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Sample records for ptx loaded nanoparticles

  1. PTX-loaded three-layer PLGA/CS/ALG nanoparticle based on layer-by-layer method for cancer therapy.

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    Wang, Fang; Yuan, Jian; Zhang, Qian; Yang, Siqian; Jiang, Shaohua; Huang, Chaobo

    2018-05-17

    Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are an ideal paclitaxel (PTX)-carrying system due to its biocompatibility and biodegradability. But it possessed disadvantage of drug burst release. In this research, a layer-by-layer deposition of chitosan (CS) and sodium alginate (ALG) was applied to modify the PLGA nanoparticles. The surface charges and morphology of the PLGA, PLGA/CS and PLGA/CS/ALG particles was measured by capillary electrophoresis and SEM and TEM, respectively. The drug encapsulation and loading efficiency were confirmed by ultraviolet spectrophotometer. The nanoparticles were stable and exhibited controlled drug release performance, with good cytotoxicity to human lung carcinoma cells (HepG 2). Cumulatively, our research suggests that this kind of three-layer nanoparticle with LbL-coated shield has great properties to act as a novel drug-loaded system.

  2. Human Albumin Fragments Nanoparticles as PTX Carrier for Improved Anti-cancer Efficacy

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    Liang Ge

    2018-06-01

    Full Text Available For enhanced anti-cancer performance, human serum albumin fragments (HSAFs nanoparticles (NPs were developed as paclitaxel (PTX carrier in this paper. Human albumins were broken into fragments via degradation and crosslinked by genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading and sustained drug release. Compared with crosslinked human serum albumin NPs, the HSAF-NPs showed relative smaller particle size, higher drug loading, and improved sustained release. Cellular and animal results both indicated that the PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the anticancer results confirmed that NPs with fast cellular internalization showed better tumor inhibition. These findings will not only provide a safe and robust drug delivery NP platform for cancer therapy, but also offer fundamental information for the optimal design of albumin based NPs.

  3. The enhanced activity of mass-selected PtxGd nanoparticles for oxygen electroreduction

    DEFF Research Database (Denmark)

    Velazquez-Palenzuela, Amado Andres; Masini, Federico; Pedersen, Anders Filsøe

    2015-01-01

    Mass-selected platinum–gadolinium alloy nanoparticles (PtxGd NPs) are synthesized for the first time as oxygen reduction reaction (ORR) electrocatalysts using the gas aggregation technique, under ultrahigh vacuum (UHV) conditions. The morphology of the PtxGd catalysts is characterized, and their ......Mass-selected platinum–gadolinium alloy nanoparticles (PtxGd NPs) are synthesized for the first time as oxygen reduction reaction (ORR) electrocatalysts using the gas aggregation technique, under ultrahigh vacuum (UHV) conditions. The morphology of the PtxGd catalysts is characterized...

  4. Exploring the phase space of time of flight mass selected PtxY nanoparticles

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    Masini, Federico; Hernandez-Fernandez, Patricia; Deiana, Davide

    2014-01-01

    the importance of transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and ion scattering spectroscopy (ISS) for verifying the morphology, size distribution and chemical composition of the nanoparticles. Furthermore, we correlate the morphology and the composition of the Ptx...

  5. Novel free paclitaxel-loaded poly(L-γ-glutamylglutamine–paclitaxel nanoparticles

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    Danbo Yang

    2011-01-01

    Full Text Available Danbo Yang1, Sang Van2, Xinguo Jiang3, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, Oceanside, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People's Republic of ChinaAbstract: The purpose of this study was to develop a novel formulation of paclitaxel (PTX that would improve its therapeutic index. Here, we combined a concept of polymer–PTX drug conjugate with a concept of polymeric micelle drug delivery to form novel free PTX-loaded poly(L-γ-glutamylglutamine (PGG–PTX conjugate nanoparticles. The significance of this drug formulation emphasizes the simplicity, novelty, and flexibility of the method of forming nanoparticles that contain free PTX and conjugated PTX in the same drug delivery system. The results of effectively inhibiting tumor growth in mouse models demonstrated the feasibility of the nanoparticle formulation. The versatility and potential of this dual PTX drug delivery system can be explored with different drugs for different indications. Novel and simple formulations of PTX-loaded PGG–PTX nanoparticles could have important implications in translational medicines.Keywords: paclitaxel, polymeric micelle, poly(L-γ-glutamylglutamine–paclitaxel, nanoconjugate, nanoparticles

  6. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

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    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

    2015-01-15

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  7. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    International Nuclear Information System (INIS)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan

    2015-01-01

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose

  8. Development of a hybrid paclitaxel-loaded arsenite nanoparticle (HPAN) delivery system for synergistic combined therapy of paclitaxel-resistant cancer

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    Chen, Fei-yan; Zhang, Yu [Nanchang University, College of Chemistry (China); Chen, Xiang-yu [Xiangya No.2 Hospital of Central South University, Department of Radiology (China); Li, Jia-qian; Xiao, Xiao-ping; Yu, Lu-lu; Tang, Qun, E-mail: tangqun@ncu.edu.cn [Nanchang University, Institute for Advanced Study (China)

    2017-04-15

    Multidrug resistance (MDR) is a major reason for failure of chemotherapy in a variety of human tumors. For instance, paclitaxel (PTX) has been widely used as a first-line anticancer drug, but resistance to PTX is becoming increasingly serious. Herein, we propose a strategy of combined therapy to overcome MDR of PTX by introducing a hybrid paclitaxel-loaded gadolinium arsenite nanoparticle (HPAN), where PTX was conjugated with rod-shaped gadolinium arsenite (GdAsO{sub x}) nanoparticle (NP). Triggered by endogenous inorganic phosphate (Pi), the hybrid nanoparticles readily collapse, thereby releasing PTX and arsenic trioxide (ATO). An MTT assay indicated IC50 values for HPAN one order of magnitude lower than for a simple equivalent mixture of PTX and ATO against PTX-resistant human colon cancer cells (HCT 166), indicating remarkable synergistic effect. Species type-dependent cellular uptake, induced apoptosis, and cell cycle modulation were also evaluated. Cellular uptake tests indicate that the HPAN presents higher PTX intracellular loading for the PTX-resistant cells and longer intracellular retention time, displaying resistance to drug efflux from the cancer cell than pristine PTX or the equivalent mixture of PTX and ATO. Cell cycle and apoptosis tests consistently proved that addition of HPAN resulted in higher G2/M and apoptosis in PTX-resistant cells. In vivo anticancer experiments evidenced that HPAN had better therapeutic effect on the resistant tumor in the murine xenograft model than pristine PTX or a mixture of PTX and ATO. Our results suggest that HPAN might enhance the therapeutic index and overcome PTX resistance and also demonstrate that the combined therapy is not only related to the species of combined agents but also their physiochemical states.

  9. Targeting property and toxicity of a novel ultrasound contrast agent microbubble carrying the targeting and drug-loaded complex FA-CNTs-PTX on MCF7 cells.

    Science.gov (United States)

    Zhang, Jie; Zhang, Yu; Liu, Junxi; Li, Guozhong; Wen, Zhaohui; Zhao, Yue; Zhang, Xiangyu; Liu, Fenghua

    2017-10-01

    The application of ultrasound contrast agents not only is confined to the enhancement of ultrasound imaging but also has started to be used as a drug system for diagnosis and treatment. In this paper, Span60 and PEG1500 were used as membrane materials, and a new targeting and drug-loading multifunctional ultrasound contrast agent microbubble enveloping the FA-CNTs-PTX complex was successfully prepared by acoustic cavitation. With the breast cancer cell line MCF7 as the research target, the effects of the microbubble with FA-CNTs-PTX on the proliferation and toxicity of MCF7 cells were studied using a CCK-8 and AO/EB double-staining method. The influences of the microbubbles with FA-CNTs-PTX on the cellular morphology and apoptosis period of the MCF7 cells were detected using an inverted fluorescence microscope. The apoptosis of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was investigated with flow cytometry and an annexin and PI double staining fluorescence quantitative analysis. The results indicated that the ultrasound contrast agent microbubble with FA-CNTs-PTX remarkably inhibited the proliferation of MCF7 cells, which was mainly controlled by the drug loading rate and the nanometer size of the microbubbles. Moreover, the proliferative inhibition rate of the microbubbles with FA-CNTs-PTX was related to the cell apoptosis period of MCF7 cells. Its inhibition degree on the proliferation of MCF7 cells was higher than that of the hepatoma HepG2 cells. The apoptosis rate of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was higher than that of normal human umbilical vein endothelial cells (HUVECs), and the microbubbles with FA-CNTs-PTX could target the MCF7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Paclitaxel-loaded KMnF3 nanoparticles for cancer imaging and therapy in vivo

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    Song, Xiao-xia; Wan, Hong-ping; Zhang, Jin-sheng; Tang, Qun

    2014-11-01

    Biocompatible nanoparticles (NPs) responding to the light, thermal, or magnetic excitation are attracting more attention for diagnosis and therapy of cancer. Design of an effective multifunctional complex based on those NPs is a key issue to be addressed, for example, integration of anti-tumor agents with nanoprobes has been considered as one of the successful strategies for combined cancer diagnosis and therapy. In this paper, we develop paclitaxel (PTX)-loaded PEGylation KMnF3 NP, with the size ranged from 18 to 23 nm, as MRI contrast agents for cancer imaging and drug delivery for chemotherapy. Preliminary cell tests demonstrated that PTX@PEG-KMnF3 NP is highly biocompatible. The NP has high loading capacity of PTX (0.7 mg PTX/mg Mn ions), enhanced solubility of PTX (0.16 mg PTX/ml vs 0.02 mg PTX/ml), and high releasing ratio (90 %) in the weak acid solution. As it was applied for in vivo imaging and therapy, the NP enhanced contrast of tumor's MR images and PTX's anti-tumor effect profoundly. The signal noise ratio of the cancer image increased 170 % as comparison to pre-injection with the injection dose of 1.15 mg Mn/kg. The drug delivery's efficacy was also substantially improved, as the tumor growth inhibition effects reached 50 %, meanwhile only 30 % for pristine PTX. Our studies suggest that PTX-loaded KMnF3 NP might be useful as MR image-guided drug delivery for tumor treatment.

  11. Synchrotron Based Structural Investigations of Mass-Selected PtxGd Nanoparticles and a Gd/Pt(111) Single Crystal for Electrochemical Oxygen Reduction

    DEFF Research Database (Denmark)

    Pedersen, Anders Filsøe; Velazquez-Palenzuela, Amado Andres; Masini, Federico

    2015-01-01

    . 134, 16476–16479 (2012). 3. Velazquez-Palenzuela, A. et al. The enhanced activity of mass-selected PtxGd nanoparticles for oxygen electroreduction. J. Catal. [in press] (2015). doi:10.1016/j.jcat.2014.12.012 4. Perez-Alonso, F. J. et al. The Effect of Size on the Oxygen Electroreduction Activity...

  12. In vitro evaluation of paclitaxel loaded amorphous chitin nanoparticles for colon cancer drug delivery.

    Science.gov (United States)

    Smitha, K T; Anitha, A; Furuike, T; Tamura, H; Nair, Shantikumar V; Jayakumar, R

    2013-04-01

    Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150±50 nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200±50 nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

    Science.gov (United States)

    Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

    2012-06-01

    A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Surface modification of paclitaxel-loaded tri-block copolymer PLGA-b-PEG-b-PLGA nanoparticles with protamine for liver cancer therapy

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    Gao, Nansha [Chinese Academy of Science, Research Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology (China); Chen, Zhihong [Guangdong Medical College, Analysis Centre (China); Xiao, Xiaojun [Shenzhen University, Institute of Allergy and Immunology, School of Medicine (China); Ruan, Changshun [Chinese Academy of Science, Research Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology (China); Mei, Lin [Tsinghua University, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen (China); Liu, Zhigang, E-mail: lzg@szu.edu.cn [Shenzhen University, Institute of Allergy and Immunology, School of Medicine (China); Zeng, Xiaowei, E-mail: zeng.xiaowei@sz.tsinghua.edu.cn [Tsinghua University, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen (China)

    2015-08-15

    In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA-b-PEG-b-PLGA was synthesized by ring-opening polymerization and characterized by {sup 1}H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol{sup ®} as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol{sup ®} did. All the results suggested that surface modification of PTX-loaded PLGA-b-PEG-b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

  15. The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes

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    Ye YJ

    2015-07-01

    Full Text Available Ya-Jing Ye,1 Yun Wang,1 Kai-Yan Lou,1 Yan-Zuo Chen,1 Rongjun Chen,2 Feng Gao1,3,4 1Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Department of Chemical Engineering, Imperial College London, London, United Kingdom; 3Shanghai Key Laboratory of Functional Materials Chemistry, 4Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, People’s Republic of China Abstract: A novel biocompatible and biodegradable drug-delivery nanoparticle (NP has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl-β-cyclodextrin (DM-β-CD, using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS to form NPs (with a size of 323.9–407.8 nm in diameter using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol®, the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC0→24h (the area under the plasma drug concentration–time curve over the period of 24 hours and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the

  16. Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment.

    Science.gov (United States)

    Song, Yu; Cai, Han; Yin, Tingjie; Huo, Meirong; Ma, Ping; Zhou, Jianping; Lai, Wenfang

    2018-01-01

    Lung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment. The redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model. This HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 μg mL -1 . Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol ® , PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles

  17. Albumin and Hyaluronic Acid-Coated Superparamagnetic Iron Oxide Nanoparticles Loaded with Paclitaxel for Biomedical Applications

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    Elena Vismara

    2017-06-01

    Full Text Available Super paramagnetic iron oxide nanoparticles (SPION were augmented by both hyaluronic acid (HA and bovine serum albumin (BSA, each covalently conjugated to dopamine (DA enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe3O4·DA-BSA/HA in water. Fe3O4·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX. The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe3O4·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system.

  18. Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

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    Ahmed A. Markeb

    2016-01-01

    Full Text Available Purpose. The antitumor activity of a novel alginate (ALG polymer-based particle that contained paclitaxel (PTX was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM and high performance liquid chromatography (HPLC fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV/visible (VIS, HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.

  19. Folate-modified, curcumin and paclitaxel co-loaded PLA-TPGS nanoparticles: preparation, optimization and in vitro cytotoxicity assays

    Science.gov (United States)

    Doan Do, Hai; Le Thi, Hao; Huong Le Thi, Thu; Nguyen, Hoai Nam; Khanh Bui, Van; Nhung Hoang Thi, My; Thu Ha, Phuong

    2018-06-01

    Development of chemoresistance is a significant restriction on the success of cancer treatment. Combination chemotherapy and drug delivery nanosystem are two promising strategies to overcome this limitation. Administration of two or more anticancer drugs at the same time can promote synergistic effect and suppress drug resistance through distinct mechanisms of action. Drug delivery nanosystem, on the other hand, improves delivery, efficacy and safety of drugs, and also can escape from some mechanisms of drug resistance. In this study we prepared drug delivery nanosystems from copolymers of lactic acid (PLA) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The nanosystems incorporated with folic acid as targeting agent were used to load curcumin (Cur) and paclitaxel (PTX) contemporaneously and denoted as (Cur  +  PTX)-PLA-TPGS-Fol. The results showed that (Cur  +  PTX)-PLA-TPGS-Fol nanoparticles has average size range of 100–200 nm depending on the ratio between PLA and TPGS. Loading efficacy of the two drugs was about 35%–83% with the highest encapsulation efficiency belonged to the system with the highest ratio of PLA. All of the prepared nanosystems with single drug or in combination exhibited strong cytotoxicity to cancer cells, but the combination was more effective in case of A549 cancer cell line. These results showed that our combination of Cur and PTX in our drug delivery nanosystem can be a promising candidate for cancer treatment.

  20. Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

    Science.gov (United States)

    Li, Ranwei; Liu, Tiecheng; Wang, Ke

    2017-02-01

    Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.

  1. Paclitaxel-loaded poly(glycolide-co-ε-caprolactone-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

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    Zhao TJ

    2013-05-01

    Full Text Available Tiejun Zhao,1 Hezhong Chen,1 Yuchao Dong,2 Jiajun Zhang,1 Haidong Huang,2 Ji Zhu,1 Wei Zhang21Institute of Cardiothoracic Surgery, 2Respiratory Department, Changhai Hospital, Shanghai, People's Republic of ChinaAbstract: In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS2k NPs was prepared. The novel amphiphilic copolymer (PGA-co-PCL-b-TPGS2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL-b -TPGS2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL-b -TPGS2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL-b -TPGS2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.Keywords: (PGA-co-PCL-b TPGS2k, paclitaxel, nanoparticles, drug delivery, lung cancer

  2. Gyrospun antimicrobial nanoparticle loaded fibrous polymeric filters

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    Eranka Illangakoon, U.; Mahalingam, S.; Wang, K. [Department of Mechanical Engineering, University College London, London WC1E 7JE (United Kingdom); Cheong, Y.-K. [School of Engineering and Technology, University of Hertfordshire, Hatfield AL10 9AB (United Kingdom); Canales, E. [Department of Civil, Environmental and Geomatic Engineering, University College London, London WC1E 7JE (United Kingdom); Ren, G.G. [School of Engineering and Technology, University of Hertfordshire, Hatfield AL10 9AB (United Kingdom); Cloutman-Green, E. [Department of Microbiology, Virology, and Infection Prevention Control, Great Ormond Street Hospital NHS Foundation Trust, London WCIN 3JH (United Kingdom); Edirisinghe, M., E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, London WC1E 7JE (United Kingdom); Ciric, L. [Department of Civil, Environmental and Geomatic Engineering, University College London, London WC1E 7JE (United Kingdom)

    2017-05-01

    A one step approach to prepare hybrid nanoparticle embedded polymer fibres using pressurised gyration is presented. Two types of novel antimicrobial nanoparticles and poly(methylmethacrylate) polymer were used in this work. X-ray diffraction analysis of the nanoparticles revealed Ag, Cu and W are the main elements present in them. The concentration of the polymer solution and the nanoparticle concentration had a significant influence on the fibre diameter, pore size and morphology. Fibres with a diameter in the range of 6–20 μm were spun using 20 wt% polymer solutions containing 0.1, 0.25 and 0.5 wt% nanoparticles under 0.3 MPa working pressure and a rotational speed of 36,000 rpm. Continuous, bead-free fibre morphologies were obtained for each case. The pore size in the fibres varied between 36 and 300 nm. Successful incorporation of the nanoparticles in polymer fibres was confirmed by energy dispersive x-ray analysis. The fibres were also gyrospun on to metallic discs to prepare filters which were tested for their antibacterial activity on a suspension of Pseudomonas aeruginosa. Nanoparticle loaded fibres showed higher antibacterial efficacy than pure poly(methylmethacrylate) fibres. - Highlights: • Nanoparticles containing Ag, Cu and W were studied for antimicrobial activity. • Hybrid nanoparticle-polymeric fibres were prepared using pressurised gyration. • Fibre characteristics were tailored using material and forming process variables. • Nanoparticle loaded fibre mats show higher antibacterial efficacy.

  3. Enhanced apoptotic and anticancer potential of paclitaxel loaded biodegradable nanoparticles based on chitosan.

    Science.gov (United States)

    Gupta, Umesh; Sharma, Saurabh; Khan, Iliyas; Gothwal, Avinash; Sharma, Ashok K; Singh, Yuvraj; Chourasia, Manish K; Kumar, Vipin

    2017-05-01

    Taxanes have established and proven effectivity against different types of cancers; in particular breast cancers. However, the high hemolytic toxicity and hydrophobic nature of paclitaxel and docetaxel have always posed challenges to achieve safe and effective delivery. Use of bio-degradable materials with an added advantage of nanotechnology could possibly improve the condition so as to achieve better and safe delivery. In the present study paclitaxel loaded chitosan nanoparticles were formulated and optimized using simple w/o nanoemulsion technique. The observed average size, pdi, zeta potential, entrapment efficiency and drug loading for the optimized paclitaxel loaded chitosan nanoparticle formulation (PTX-CS-NP-10) was 226.7±0.70nm, 0.345±0.039, 37.4±0.77mV, 79.24±2.95% and 11.57±0.81%; respectively. Nanoparticles were characterized further for size by Transmission Electron Microscopy (TEM). In vitro release studies exhibited sustained release pattern and more than 60% release was observed within 24h. Enhanced in vitro anticancer activity was observed as a result of MTT assay against triple negative MDA-MB-231 breast cancer cell lines. The observed IC 50 values obtained for PTX-CS-NP-10 was 9.36±1.13μM and was almost 1.6 folds (psafe as observed for haemolytic toxicity which was almost 4 folds less (psafe nanoformulation of paclitaxel was developed, characterized and evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Novel thermo-sensitive core-shell nanoparticles for targeted paclitaxel delivery

    International Nuclear Information System (INIS)

    Li Yuanpei; Pan Shirong; Zhang Wei; Du Zhuo

    2009-01-01

    Novel thermo-sensitive nanoparticles self-assembled from poly(N,N-diethylacrylamide- co-acrylamide)-block-poly(γ-benzyl L-glutamate) were designed for targeted drug delivery in localized hyperthermia. The lower critical solution temperature (LCST) of nanoparticles was adjusted to a level between physiological body temperature (37 deg. C) and that used in local hyperthermia (about 43 deg. C). The temperature-dependent performances of the core-shell nanoparticles were systemically studied by nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering (DLS), and atom force microscopy (AFM). The mean diameter of the nanoparticles increased slightly from 110 to 129 nm when paclitaxel (PTX), a poorly water-soluble anti-tumor drug, was encapsulated. A stability study in bovine serum albumin (BSA) solution indicated that the PTX loaded nanoparticles may have a long circulation time under physiological environments as the LCST was above physiological body temperature and the shell remained hydrophilic at 37 deg.C. The PTX release profiles showed thermo-sensitive controlled behavior. The proliferation inhibiting activity of PTX loaded nanoparticles was evaluated against Hela cells in vitro, compared with Taxol (a formulation of paclitaxel dissolved in Cremophor EL and ethanol). The cytotoxicity of PTX loaded nanoparticles increased obviously when hyperthermia was performed. The nanoparticles synthesized here could be an ideal candidate for thermal triggered anti-tumor PTX delivery system.

  5. Fluoride loaded polymeric nanoparticles for dental delivery.

    Science.gov (United States)

    Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

    2017-06-15

    The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D., E-mail: sakthi@toyo.jp

    2013-10-15

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions. - Highlights: • Aptamer escorted, theranostic biodegradable PLGA carriers were developed. • Can target cancer cells, control drug release, image and magnetically guide. • Highly specific to the targeted cancer cells thus delivering

  7. Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer.

    Science.gov (United States)

    He, Zelai; Huang, Jingwen; Xu, Yuanyuan; Zhang, Xiangyu; Teng, Yanwei; Huang, Can; Wu, Yufeng; Zhang, Xi; Zhang, Huijun; Sun, Wenjie

    2015-12-08

    An amphiphilic copolymer, folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) was prepared and explored as a nanometer carrier for the co-delivery of cisplatin (cis-diaminodichloroplatinum, CDDP) and paclitaxel (PTX). CDDP and PTX were encapsulated inside the hydrophobic inner core and chelated to the middle shell, respectively. PEG provided the outer corona for prolonged circulation. An in vitro release profile of the CDDP + PTX-encapsulated nanoparticles revealed that the PTX chelation cross-link prevented an initial burst release of CDDP. After an incubation period of 24 hours, the CDDP+PTX-encapsulated nanoparticles exhibited a highly synergistic effect for the inhibition of A549 (FA receptor negative) and M109 (FA receptor positive) lung cancer cell line proliferation. Pharmacokinetic experiment and distribution research shows that nanoparticles have longer circulation time in the blood and can prolong the treatment times of chemotherapeutic drugs. For the in vivo treatment of A549 cells xeno-graft lung tumor, the CDDP+PTX-encapsulated nanoparticles displayed an obvious tumor inhibiting effect with an 89.96% tumor suppression rate (TSR). This TSR was significantly higher than that of free chemotherapy drug combination or nanoparticles with a single drug. For M109 cells xeno-graft tumor, the TSR was 95.03%. In vitro and in vivo experiments have all shown that the CDDP+PTX-encapsulated nanoparticles have better targeting and antitumor effects in M109 cells than CDDP+PTX-loaded PEG-PLGA nanoparticles (p nanoparticles came with reduced side-effects. No obvious body weight loss or functional changes occurred within blood components, liver, or kidneys during the treatment of A549 and M109 tumor-bearing mice with the CDDP+PTX-encapsulated nanoparticles. Thus, the FA modified amphiphilic copolymer-based combination of CDDP and PTX may provide useful guidance for effective and safe cancer chemotherapy, especially in tumors with

  8. A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models

    Science.gov (United States)

    Bhattacharyya, Jayanta; Bellucci, Joseph J.; Weitzhandler, Isaac; McDaniel, Jonathan R.; Spasojevic, Ivan; Li, Xinghai; Lin, Chao-Chieh; Chi, Jen-Tsan Ashley; Chilkoti, Ashutosh

    2015-08-01

    Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumour-specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into ~60 nm near-monodisperse nanoparticles that increased the systemic exposure of PTX by sevenfold compared with free drug and twofold compared with the Food and Drug Administration-approved taxane nanoformulation (Abraxane). The tumour uptake of the CP-PTX nanoparticle was fivefold greater than free drug and twofold greater than Abraxane. In a murine cancer model of human triple-negative breast cancer and prostate cancer, CP-PTX induced near-complete tumour regression after a single dose in both tumour models, whereas at the same dose, no mice treated with Abraxane survived for >80 days (breast) and 60 days (prostate), respectively. These results show that a molecularly engineered nanoparticle with precisely engineered design features outperforms Abraxane, the current gold standard for PTX delivery.

  9. Transfection Agent Induced Nanoparticle Cell Loading

    Directory of Open Access Journals (Sweden)

    Karin Montet-Abou

    2005-07-01

    Full Text Available Loading cells with magnetic nanoparticles, and tracking their fate in vivo by high resolution MRI, is an attractive approach for enhancing the efficacy of cell-based therapies including those utilizing hematopoietic stem cells, neuroprogenitor cells, and T cells. The transfection agent (internalization agent assisted loading with the Feridex IV® nanoparticle is an attractive method of loading because of the low cost of materials, and possible low regulatory barriers for eventual clinical use. We therefore explored the interaction between Feridex IV® and three internalization agents protamine (PRO, polylysine (PLL, and lipofectamine (LFA. Feridex reacted with internalization agents to form aggregates, except when either the internalization agent or Feridex was present in large excess. When Jurkat T cells were incubated with Feridex/LFA or Feridex/PRO mixtures, and washed by centrifugation, nanoparticle aggregates co-purified with cells. With C17.2 cells large iron oxide particles adhered to the cell surface. At 30 μg/mL Feridex and 3 μg/mL LFA, internalization was largely mediated by LFA and was largely cytoplasmic. However, we found that the conditions used to label cells with Feridex and transfection agents need to be carefully selected to avoid the problems of surface adsorption and nanoparticle precipitation.

  10. Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer.

    Science.gov (United States)

    Min, Sun Young; Byeon, Hyeong Jun; Lee, Changkyu; Seo, Jisoo; Lee, Eun Seong; Shin, Beom Soo; Choi, Han-Gon; Lee, Kang Choon; Youn, Yu Seok

    2015-10-15

    Nanoparticle albumin-bound (nab™) technology is an effective way of delivering hydrophobic chemotherapeutics. We developed a one-pot/one-step formulation of paclitaxel (PTX)-bound albumin nanoparticles with embedded tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/PTX HSA-NP) for the treatment of pancreatic cancer. TRAIL/PTX HSA-NPs were fabricated using a high-pressure homogenizer at a TRAIL feeding ratio of 0.2%, 1.0%, and 2.0%. TRAIL/PTX HSA-NPs were spherical and became larger in size (170-230 nm) with increasing TRAIL amount (0.2-2.0%). The loading efficiencies of PTX were in the range of ∼86.4% and significantly low at 2.0% TRAIL (60.4%). Specifically, the inhibitory concentrations (IC50) of TRAIL (1.0 or 2.0%)/PTX HSA-NPs were >20-fold lower than that of plain PTX-HSA NP (0.032±0.06, 0.022±0.005, and 0.96±0.15 ng/ml, respectively) in pancreatic Mia Paca-2 cells. Considering TRAIL loading, bioactivity, and particle size, TRAIL(1.0%)/PTX HSA-NPs were determined as the optimal candidate for further studies. TRAIL(1.0%)/PTX HSA-NPs displayed substantially greater apoptotic activity than plain PTX HSA-NP in both FACS and TUNEL analysis. The loaded PTX and TRAIL were gradually released from the TRAIL(1.0%)/PTX HSA-NPs until ∼24 h, which is considered to be a sufficient time for delivery to the tumor tissue. TRAIL(1.0%)/PTX HSA-NP displayed markedly more antitumor efficacy than plain PTX HSA-NP in Mia Paca-2 cell-xenografted mice in terms of tumor volume (size) and weight (213.9 mm(3) and 0.18 g vs. 1126.8 mm(3) and 0.80 g, respectively). These improved in vitro and in vivo performances were due to the combined synergistic effects of PTX and TRAIL. We believe that this TRAIL/PTX HSA-NP would have potential as a novel apoptosis-based anticancer agent. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa.

    Science.gov (United States)

    Sabaeifard, Parastoo; Abdi-Ali, Ahya; Soudi, Mohammad Reza; Gamazo, Carlos; Irache, Juan Manuel

    2016-10-10

    Amikacin is a very effective aminoglycoside antibiotic but according to its high toxicity, the use of this antibiotic has been limited. The aim of this study was to formulate and characterize amikacin loaded PLGA nanoparticles. Nanoparticles were synthetized using a solid-in-oil-in-water emulsion technique with different ratio of PLGA 50:50 (Resomer 502H) to drug (100:3.5, 80:3.5 and 60:3.5), two different concentrations of stabilizer (pluronic F68) (0.5% or 1%) and varied g forces to recover the final products. The most efficient formulation based on drug loading (26.0±1.3μg/mg nanoparticle) and encapsulation efficiency (76.8±3.8%) was the one obtained with 100:3.5 PLGA:drug and 0.5% luronic F68, recovered by 20,000×g for 20min. Drug release kinetic study indicated that about 50% of the encapsulated drug was released during the first hour of incubation in phospahte buffer, pH7.4, 37°C, 120rpm. Using different cell viability/cytotoxicity assays, the optimized formulation showed no toxicity against RAW macrophages after 2 and 24h of exposure. Furthermore, released drug was active and maintained its bactericidal activity against Pseudomonas aeruginosa in vitro. These results support the effective utilization of the PLGA nanoparticle formulation for amikacin in further in vivo studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy

    Directory of Open Access Journals (Sweden)

    Xiong W

    2015-04-01

    Full Text Available Wei Xiong,1,2 Lixia Peng,1,2 Hongbo Chen,3 Qin Li1,2 1Southern Medical University, Guangzhou, 2Department of Plastic Surgery, General Hospital of Guangzhou Military Command of PLA, Guangzhou, People’s Republic of China; 3Division of Life Sciences and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People’s Republic of China Abstract: To enhance the therapeutic effects of chemotherapy on malignant melanoma, paclitaxel (PTX-loaded methoxy poly(ethylene glycol-b-poly(ε-caprolactone nanoparticles (MPEG-b-PCL NPs that had their surfaces modified with polydopamine (PTX-loaded MPEG-b-PCL NPs@PDA were prepared as drug vehicles. The block copolymer MPEG-b-PCL was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded NPs were prepared by a modified nanoprecipitation technique. The PTX-loaded NPs and PTX-loaded NPs@PDA were characterized in terms of size and size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin-6-loaded NPs@PDA could be internalized by human melanoma cell line A875 cells. The cellular uptake efficiency of NPs was greatly enhanced after PDA modification. The antitumor efficacy of the PTX-loaded NPs@PDA was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and in vivo by a xenograft tumor model. The PTX-loaded NPs@PDA could significantly inhibit tumor growth compared to Taxol® and precursor PTX-loaded NPs. All the results suggested that the PTX-loaded MPEG-b-PCL NPs that had their surfaces modified with PDA are promising nanocarriers for malignant melanoma therapy. Keywords: cancer nanotechnology, drug delivery, surface modification, polydopamine, malignant melanoma

  13. Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles

    Science.gov (United States)

    Nguyen, Hoai Nam; Thu Ha, Phuong; Sao Nguyen, Anh; Nguyen, Dac Tu; Doan Do, Hai; Nguyen Thi, Quy; Nhung Hoang Thi, My

    2016-06-01

    Theranostics, which is the combination of both therapeutic and diagnostic capacities in one dose, is a promising tool for both clinical application and research. Although there are many chromophores available for optical imaging, their applications are limited due to the photobleaching property or intrinsic toxicity. Curcumin, a natural compound extracted from the rhizome of curcuma longa, is well known thanks to its bio-pharmaceutical activities and strong fluorescence as biocompatible probe for bio-imaging. In this study, we aimed to fabricate a system with dual functions: diagnostic and therapeutic, based on poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) micelles co-loaded curcumin (Cur) and paclitaxel (PTX). Two kinds of curcumin nanoparticle (NP) were fabricated and characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscopy and dynamic light scattering methods. The cellular uptake and fluorescent activities of curcumin in these systems were also tested by bioassay studies, and were compared with paclitaxe-oregon. The results showed that (Cur + PTX)-PLA-TPGS NPs is a potential system for cancer theranostics.

  14. Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles

    International Nuclear Information System (INIS)

    Nguyen, Hoai Nam; Ha, Phuong Thu; Do, Hai Doan; Nguyen, Anh Sao; Nguyen, Dac Tu; Thi, Quy Nguyen; Thi, My Nhung Hoang

    2016-01-01

    Theranostics, which is the combination of both therapeutic and diagnostic capacities in one dose, is a promising tool for both clinical application and research. Although there are many chromophores available for optical imaging, their applications are limited due to the photobleaching property or intrinsic toxicity. Curcumin, a natural compound extracted from the rhizome of curcuma longa, is well known thanks to its bio-pharmaceutical activities and strong fluorescence as biocompatible probe for bio-imaging. In this study, we aimed to fabricate a system with dual functions: diagnostic and therapeutic, based on poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) micelles co-loaded curcumin (Cur) and paclitaxel (PTX). Two kinds of curcumin nanoparticle (NP) were fabricated and characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscopy and dynamic light scattering methods. The cellular uptake and fluorescent activities of curcumin in these systems were also tested by bioassay studies, and were compared with paclitaxe-oregon. The results showed that (Cur + PTX)-PLA-TPGS NPs is a potential system for cancer theranostics. (paper)

  15. Development of drug-loaded chitosan hollow nanoparticles for delivery of paclitaxel to human lung cancer A549 cells.

    Science.gov (United States)

    Jiang, Jie; Liu, Ying; Wu, Chao; Qiu, Yang; Xu, Xiaoyan; Lv, Huiling; Bai, Andi; Liu, Xuan

    2017-08-01

    In this study, biodegradable chitosan hollow nanospheres (CHN) were fabricated using polystyrene nanospheres (PS) as templates. CHN were applied to increase the solubility of poorly water-soluble drugs. The lung cancer drug paclitaxel (PTX), which is used as a model drug, was loaded into CHN by the adsorption equilibrium method. The drug-loaded sample (PTX-CHN) offered sustained PTX release and good bioavailability. The state characterization of PTX by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that the PTX absorbed into CHN existed in an amorphous state. An in vitro toxicity experiment indicated that CHN were nontoxic as carriers of poorly water-soluble drugs. The PTX-CHN produced a marked inhibition of lung cancer A549 cells proliferation and encouraged apoptosis. A cell uptake experiment indicated that PTX-CHN was successfully taken up by lung cancer A549 cells. Furthermore, a degradation experiment revealed that CHN were readily biodegradable. These findings state clearly that CHN can be regarded as promising biomaterials for lung cancer treatment.

  16. Facile Synthesis of Curcumin-Loaded Starch-Maleate Nanoparticles

    OpenAIRE

    Suh Cem Pang; Soon Hiang Tay; Suk Fun Chin

    2014-01-01

    We have demonstrated the loading of curcumin onto starch maleate (SM) under mild conditions by mixing dissolved curcumin and SM nanoparticles separately in absolute ethanol and ethanol/aqueous (40 : 60 v/v), respectively. Curcumin-loaded starch-maleate (CurSM) nanoparticles were subsequently precipitated from a homogeneous mixture of these solutions in absolute ethanol based on the solvent exchange method. TEM analysis indicated that the diameters of CurSM nanoparticles were ranged between 30...

  17. Loading technique for preparing radionuclide containing nanoparticles

    DEFF Research Database (Denmark)

    2011-01-01

    associated with leaky blood vessels. The composition and methods of the invention find particular use in diagnosing and imaging cancerous tissue and, in general, pathological conditions associated with leaky blood vessels in a subject. The present invention provides a new diagnostic tool for the utilization......Source: US2012213698A The present invention relates to a novel composition and method for loading delivery systems such as liposome compositions with radionuclides useful in targeted diagnostic and/or therapy of target site, such as cancerous tissue and, in general, pathological conditions...... of positron emission tomography (PET) imaging technique. One specific aspect of the invention is directed to a method of producing nanoparticles with desired targeting properties for diagnostic and/or radio-therapeutic applications....

  18. The Plasmoid Thruster Experiment (PTX)

    Science.gov (United States)

    Eskridge, Richard; Martin, Adam; Koelfgen, Syri; Lee, Mike; Smith, James W.

    2003-01-01

    A plasmoid is a compact plasma structure with an integral magnetic field. They have been studied extensively in controlled fusion research and are categorized according to the relative strength of the poloidal and toroidal magnetic field (B(phi), and B(tau), respectively). An object with B(phi)/B(tau) >> 1 is classified as a Field Reverse Configuration (FRC); if B(phi) = B(tau), it is called a Spheromak. There are a number of possible advantages to using accelerated plasmoids for in-space propulsion. A thruster based on this concept would operate by repetitively producing plasmoids and ejecting them from the device at high velocity. The plasmoid is formed inside of a single turn conical theta-pinch coil; as this process is inductive, there are no life-limiting electrodes. Similar experiments have yielded plasmoid velocities of at least 50 km/s (l), and calculations indicate that velocities in excess of 100 km/s are possible. A thruster based on this concept would be capable of producing an I(sp) in the range of 5,000 - 10,OOO s, with thrust densities of order 10(exp 5) N/m(exp 2). The current experiment is designed to produce jet powers in the range of 5-10 kW, although the concept should be scalable to higher power. The purpose of this experiment is to determine the feasibility of this plasma propulsion concept. To accomplish this, it will be necessary to determine: a.) specific impulse and thrust, b.) efficiency and mass utilization, c.) which type of plasmoid (FRC-like or Spheromak-like) gives the best performance, and d.) the characteristics required of actual thruster components (i.e., switch and capacitor technology). The plasmoid mass and velocity will be measured with a variety of diagnostics, including internal and external B-dot probes, flux loops, Langmuir probes, high-speed cameras, and an interferometer. Simulations of the plasmoid thruster using MOQUI, a time dependent MHD code, will be carried out concurrently with experimental testing. The PTX

  19. Facile Synthesis of Curcumin-Loaded Starch-Maleate Nanoparticles

    Directory of Open Access Journals (Sweden)

    Suh Cem Pang

    2014-01-01

    Full Text Available We have demonstrated the loading of curcumin onto starch maleate (SM under mild conditions by mixing dissolved curcumin and SM nanoparticles separately in absolute ethanol and ethanol/aqueous (40 : 60 v/v, respectively. Curcumin-loaded starch-maleate (CurSM nanoparticles were subsequently precipitated from a homogeneous mixture of these solutions in absolute ethanol based on the solvent exchange method. TEM analysis indicated that the diameters of CurSM nanoparticles were ranged between 30 nm and 110 nm with a mean diameter of 50 nm. The curcumin loading capacity of SM as a function of loading duration was investigated using the UV-visible spectrophotometer. The loading of curcumin onto SM increased rapidly initially with loading duration, and the curcumin loading capacity of 15 mg/g was reached within 12 hours. CurSM nanoparticles exhibited substantially higher water solubility of 6.0 × 10−2 mg/mL which is about 300 times higher than that of pure curcumin. With enhanced water solubility and bioaccessibility of curcumin, the potential utility of CurSM nanoparticles in various biomedical applications is therefore envisaged.

  20. Novel titanium oxide nanoparticles for effective delivery of paclitaxel to human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mund, R., E-mail: rachnamund@gmail.com; Panda, N., E-mail: niladri1panda@gmail.com [National Institute of Technology, Department of Biotechnology and Medical Engineering (India); Nimesh, S., E-mail: surendranimesh@curaj.ac.in [Central University of Rajasthan, Department of Biotechnology, School of Life Sciences (India); Biswas, A., E-mail: amitb79@gmail.com [National Institute of Technology, Department of Biotechnology and Medical Engineering (India)

    2014-12-15

    Novel titanium oxide (TiO{sub 2}) nanoparticles were fabricated via a modified propanol drying step. These nanoparticles were loaded with anti-cancer drug paclitaxel (PTX) to yield PTX-TiO{sub 2} nanocomposites. The nanocomposites were characterized for their size and surface morphology employing nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM). The SEM images showed spherical particles with smooth surface and narrow size distribution of ∼30–40 nm, which was also supported by NTA analysis data. The drug loading efficiency of the air-dried nanoparticles was observed to be ∼63.61 % while those prepared through propanol-induced drying step showed ∼69.70 %, thereby demonstrating higher efficiency of the latter. In vitro pH-dependent release of the loaded PTX was observed with higher release at acidic pH compared with physiological pH. Cell uptake studies suggested of time-dependent internalization of nanocomposites with significant improvement in uptake by increasing incubation time from 2 to 24 h, as evidenced by flow cytometry. Further, the cell viability as a measure of anti-cancer activity revealed that cell viability upon exposure to PTX only was 40.5 % while that of PTX-TiO{sub 2} nanocomposite showed 21.6 % viability after 24 h, suggesting better anti-cancer efficacy of nanocomposites. Apoptosis studies revealed that cells treated with PTX-TiO{sub 2} nanocomposites possessed more amount of apoptotic bodies as compared to those treated with PTX only.

  1. Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

    Science.gov (United States)

    Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

    2016-09-01

    The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Immunological evaluation of chitosan nanoparticles loaded with tetanus toxoid.

    Science.gov (United States)

    Ghalavand, M; Saadati, M; Ahmadi, A; Abbasi, E; Salimian, J

    2018-01-01

    The present study was aimed at comparing tetanus toxoid (TT)‑loaded-chitosan nanoparticles with aluminum hydroxide as a common vaccine adjuvant. Tetanus remains to be a major public health problem. Nanoparticles have been extensively used as immune adjuvants. Tetanus toxoid (TT) encapsulated in chitosan nanoparticles is considered to be a promising tetanus vaccine candidate. TT‑loaded chitosan nanoparticles were prepared by the ionic gelation method. The nanoparticles were studied by SEM for their size and morphology. In vivo study was conducted to evaluate the immunity response using mice divided into 4 groups and injected with encapsulated toxoid. The immune responses were then measured using indirect ELISA. The purity and integrity of antigen were confirmed by SDS-PAGE electrophoresis. The size of nanoparticles was estimated at 100 nm. As a result, the IgG antibody levels were 1.9, 1.76, and 0.87 in chitosan nanoparticles, aluminum hydroxide, and TT alone groups, respectively. Also, the immune responses were significantly higher in immunized groups compared to control groups vaccinated with free adjuvant vaccines (p chitosan nanoparticles were reasonable. It enhanced the immune responses as much as aluminum hydroxide adjuvant does and thus may be a good alternative candidate (Tab. 1, Fig. 3, Ref. 16).

  3. The Cytotoxicity, Characteristics, and Optimization of Insulin-loaded Nanoparticles

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    Yasemin Budama-Kilinc

    2017-04-01

    Full Text Available Controlled release systems for insulin are frequent subjects of research, because it is rapidly degraded by proteolytic enzymes in the gastrointestinal tract and minimally absorbed after oral administration. Controlled release systems also provide significant contribution to its stability.  Different techniques are used for the preparation of drug-loaded nanoparticles, and many novel techniques are being developed. The size and morphology of insulin-loaded nanoparticles may vary according to performed techniques, even if the same polymer is used. The aim of this study was to demonstrate the cytotoxicity of insulin loaded nanoparticles and the effect of various synthesis parameters on the particle size, polydispersity index (PdI, loading efficiency, and particle morphology. In the experiments, poly(lactic-co-glycolic acid (PLGA and insulin-loaded PLGA nanoparticles were prepared using the double emulsion (w/o/w method. The characterization of the nanoparticles were performed with a UV spectrometer, the Zeta-sizer system, FTIR spectroscopy, and a scanning probe microscope. Cell toxicity of different concentrations was assayed with MTT methods on L929 fibroblast cells. The optimum size of the insulin-loaded PLGA nanoparticle was obtained with a 96.5% encapsulation efficiency, a 224.5 nm average particle size, and a 0.063 polydispersity index. This study obtained and characterized spherical morphology, determined that the nanoparticles have very low toxicity, and showed the effect of different parameters on particle size and polydispersity. DOI: http://dx.doi.org/10.17807/orbital.v9i1.934 

  4. Drug loaded magnetic nanoparticles for cancer therapy

    International Nuclear Information System (INIS)

    Jurgons, R; Seliger, C; Hilpert, A; Trahms, L; Odenbach, S; Alexiou, C

    2006-01-01

    Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. In medicine they are used for several approaches such as magnetic cell separation or magnetic resonance imaging (MRI). The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is the focus of medical research, especially for the treatment of cancer and diseases of the vascular system. In an experimental cancer model, we performed targeted drug delivery and used magnetic iron oxide nanoparticles, bound to a chemotherapeutic agent, which were attracted to an experimental tumour in rabbits by an external magnetic field (magnetic drug targeting). Complete tumour remission could be achieved. An important advantage of these carriers is the possibility for detecting these nanoparticles after treatment with common imaging techniques (i.e. x-ray-tomography, magnetorelaxometry, magnetic resonance imaging), which can be correlated to histology

  5. Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Jin Cheng [Fourth Military Medical University, Department of Radiation Medicine (China); Bai Ling [Xi' an Gaoxin Hospital, Department of Clinical Laboratories (China); Wu Hong [Fourth Military Medical University, Department of Pharmacy (China); Teng Zenghui [Fourth Military Medical University, Department of Pharmacology (China); Guo Guozhen, E-mail: guozhengg@tom.co [Fourth Military Medical University, Department of Radiation Medicine (China); Chen Jingyuan, E-mail: jy_chen@fmmu.edu.c [Fourth Military Medical University, Department of Occupational and Environmental Health (China)

    2008-08-15

    SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug.

  6. Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles

    International Nuclear Information System (INIS)

    Jin Cheng; Bai Ling; Wu Hong; Teng Zenghui; Guo Guozhen; Chen Jingyuan

    2008-01-01

    SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug.

  7. Paclitaxel loaded magnetic nanocomposites with folate modified chitosan/carboxymethyl surface; a vehicle for imaging and targeted drug delivery.

    Science.gov (United States)

    Bano, Shazia; Afzal, Muhammad; Waraich, Mustansar Mahmood; Alamgir, Khalid; Nazir, Samina

    2016-11-20

    In this study, Paclitaxel (PTX) containing, bovine serum albumin (BSA) nanoparticles were fabricated via a simple approach. Folic acid (FA) was conjugated to chitosan (CS)/carboxymethyl cellulose (CMC) through an esterification reaction to produce BSA-CS-FA or BSA-CMC-FA conjugates. NiFe 2 O 4 noncore (NFs) and PTX were loaded through a heat treatment and by a diffusion process. NFs-BSA-CS and NFs-BSA-CMC-FA with size of about 80nm, showed superior transversal R 2 relaxation rate of 349 (mM) -1 s -1 along with folate receptor-targeted and magnetically directed functions. NFs-BSA-CS-FA or NFs-BSA-CS-FA were found stable and biocompatible. Application of an external magnetic field effectively enhanced the PTX release from PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA and hence tumor inhibition rate. This study validate that NFs-BSA-CS-FA or NFs-BSA-CMC-FA and PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA are suitable systems for tumor diagnosis and therapy. Copyright © 2016. Published by Elsevier B.V.

  8. Evaluation of expansile nanoparticle tumor localization and efficacy in a cancer stem cell-derived model of pancreatic peritoneal carcinomatosis

    Science.gov (United States)

    Herrera, Victoria LM; Colby, Aaron H; Tan, Glaiza AL; Moran, Ann M; O’Brien, Michael J; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W

    2016-01-01

    Aim: To evaluate the tumor localization and efficacy pH-responsive expansile nanoparticles (eNPs) as a drug delivery system for pancreatic peritoneal carcinomatosis (PPC) modeled in nude rats. Methods & materials: A Panc-1-cancer stem cell xeno1graft model of PPC was validated in vitro and in vivo. Tumor localization was tracked via in situ imaging of fluorescent eNPs. Survival of animals treated with paclitaxel-loaded eNPs (PTX-eNPs) was evaluated in vivo. Results: The Panc-1-cancer stem cell xenograft model recapitulates significant features of PPC. Rhodamine-labeled eNPs demonstrate tumor-specific, dose- and time-dependent localization to macro- and microscopic tumors following intraperitoneal injection. PTX-eNPs are as effective as free PTX in treating established PPC; but, PTX-eNPs result in fewer side effects. Conclusion: eNPs are a promising tool for the detection and treatment of PPC. PMID:27078118

  9. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    International Nuclear Information System (INIS)

    Li, Su; Wang, Anxun; Jiang, Wenqi; Guan, Zhongzhen

    2008-01-01

    It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t 1/2 , 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (V D , 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05). In our

  10. Characterization and Antiproliferative Activity of Nobiletin-Loaded Chitosan Nanoparticles

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    Ana G. Luque-Alcaraz

    2012-01-01

    Full Text Available Nobiletin is a polymethoxyflavonoid with a remarkable antiproliferative effect. In order to overcome its low aqueous solubility and chemical instability, the use of nanoparticles as carriers has been proposed. This study explores the possibility of binding nobiletin to chitosan nanoparticles, as well as to evaluate their antiproliferative activity. The association and loading efficiencies are 69.1% and 7.0%, respectively. The formation of an imine bond between chitosan amine groups and the carbonyl group of nobiletin, via Schiff-base, is proposed. Nobiletin-loaded chitosan nanoparticles exhibit considerable inhibition (IC50=8 μg/mL of cancerous cells, revealing their great potential for applications in cancer chemotherapy.

  11. Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis

    International Nuclear Information System (INIS)

    Pillai, Rajeev Raghavan; Rabinovich, Monica; Gonsalves, Kenneth E; Somayaji, Shankari N; Hudson, Michael C

    2008-01-01

    The goal of this investigation is to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of antibiotics such as nafcillin to osteoblasts. This is important in order to treat Staphylococcus aureus-mediated osteomyelitis. The latter is often chronic and highly resistant to antibiotics. Nafcillin (a penicillinase-resistant penicillin)-loaded nanoparticles were prepared by a single emulsion/solvent evaporation method. In vitro drug release studies were conducted in an incubator shaker at 37 deg. C in phosphate buffer saline. Drug loading and release were determined by UV-Vis spectroscopy. A viability study was conducted in S. aureus-infected mouse osteoblasts. In vitro release study showed an initial burst release and a second phase of slow release. Following 24 and 48 h of incubation, all formulations of nanoparticles loaded with nafcillin either killed or significantly reduced all of the intracellular bacteria. Our data demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin

  12. Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Pillai, Rajeev Raghavan; Rabinovich, Monica; Gonsalves, Kenneth E [Polymer Nanotechnology Laboratory at Center for Optoelectronics and Department of Chemistry, University of North Carolina, Charlotte, NC 28223 (United States); Somayaji, Shankari N; Hudson, Michael C [Department of Biology, University of North Carolina, Charlotte, NC 28223 (United States)], E-mail: kegonsal@uncc.edu

    2008-09-01

    The goal of this investigation is to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of antibiotics such as nafcillin to osteoblasts. This is important in order to treat Staphylococcus aureus-mediated osteomyelitis. The latter is often chronic and highly resistant to antibiotics. Nafcillin (a penicillinase-resistant penicillin)-loaded nanoparticles were prepared by a single emulsion/solvent evaporation method. In vitro drug release studies were conducted in an incubator shaker at 37 deg. C in phosphate buffer saline. Drug loading and release were determined by UV-Vis spectroscopy. A viability study was conducted in S. aureus-infected mouse osteoblasts. In vitro release study showed an initial burst release and a second phase of slow release. Following 24 and 48 h of incubation, all formulations of nanoparticles loaded with nafcillin either killed or significantly reduced all of the intracellular bacteria. Our data demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin.

  13. Preparation and characterization of Tribulus terrestris-loaded nanoparticles

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    M. Khanavi*

    2017-11-01

    Full Text Available Background and objectives: Tribulus terrestris is a flowering herb (Zygophyllaceae with several properties in folk medicine such as diuretic, tonic, aphrodisiac, analgesic, astringent, and stomachic-lithotripter activities. Although, some extracts and phytochemicals represent excellent bio-activity in vitro, less or no in vivo activity is observed due to their improper molecular size. The intend of this research was investigation of the feasibility of encapsulating T. terrestris into [poly (lactic-co-glycolic acid] PLGA nanoparticles. Methods: Aerial parts of the plant were extracted with aqueous ethanol 85% by percolation apparatus. The nanoparticles of T. terrestris-loaded were prepared using a modified simultaneous double-emulsion solvent evaporation/diffusion method. Elucidations were made on the basis of scanning electron microscopy (SEM and differential scanning calorimetry (DSC. The content of nanoparticles was analyzed by HPLC with indirect method. Results: The results stated that increasing the portion of plant extract could cause bigger size with no considerable increase in polydispersity index (PDI. The encapsulation efficiency of T. terrestris-loaded nanoparticles was 40.3 to 78.5 and the drug loadings were 0.806 to 6.104, with different ratios of extract. The overall pattern of the release in SDS 1% in dialysis bag in all formulations showed similar and biphasic release kinetic, an initial burst release in the first day followed by constant release over 10 days. Conclusion: An effective approach for the preparation of T. terrestris-loaded PLGA nanoparticles was performed. The controlled release profile showed that these biodegradable PLGA nanoparticles had great potential and should be given particular consideration in further biological researches.

  14. Resveratrol-loaded Nanoparticles Induce Antioxidant Activity against Oxidative Stress

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    Jae-Hwan Kim

    2016-02-01

    Full Text Available Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS. The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549 against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value compared to trolox and vitamin E since the concentration of resveratrol was more than 50 μM. Nanoparticles prepared from β-lactoglobulin (β-lg were successfully developed. The β-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with β-lg nanoparticles. Fluorescein isothiocynate-conjugated β-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored H2O2-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1 signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds.

  15. Human Serum Albumin Nanoparticles for Use in Cancer Drug Delivery: Process Optimization and In Vitro Characterization

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    Nikita Lomis

    2016-06-01

    Full Text Available Human serum albumin nanoparticles (HSA-NPs are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and in vitro release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized. Results indicate a size of 143.4 ± 0.7 nm and 170.2 ± 1.4 nm with a surface charge of −5.6 ± 0.8 mV and −17.4 ± 0.5 mV for HSA-NPs and PTX-HSA-NPs (0.5 mg/mL of PTX, respectively. The yield of the PTX-HSA-NPs was ~93% with an encapsulation efficiency of ~82%. To investigate the safety and effectiveness of the PTX-HSA-NPs, an in vitro drug release and cytotoxicity assay was performed on human breast cancer cell line (MCF-7. The PTX-HSA-NPs showed dose-dependent toxicity on cells of 52%, 39.3% and 22.6% with increasing concentrations of PTX at 8, 20.2 and 31.4 μg/mL, respectively. In summary, all parameters involved in HSA-NPs’ preparation, its anticancer efficacy and scale-up are outlined in this research article.

  16. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    Directory of Open Access Journals (Sweden)

    Jiang Wenqi

    2008-04-01

    Full Text Available Abstract Background It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU loaded block copolymers, with poly(γ-benzyl-L-glutamate (PBLG as the hydrophobic block and poly(ethylene glycol (PEG as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. Methods 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM and transmission electron microscopy (TEM were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC. To study in vivo effects, LoVo cells (human colon cancer cell line or Tca8113 cells (human oral squamous cell carcinoma cell line were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. Results 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min, lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L, and greater distribution volume (VD, 0.114 L vs. 0.069 L. Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p 0.05. Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles

  17. PTX3: A Potential Biomarker in Thyroid Associated Ophthalmopathy

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    Pei Mou

    2018-01-01

    Full Text Available Background. Thyroid associated ophthalmopathy (TAO is an autoimmune disease, which involves inflammation and tissue remodeling. Pentraxin-3 (PTX3 is a component of innate immune system and recently implicated in autoimmunity. This observation may indicate that PTX3 participates in the inflammatory process of TAO. Methods. All studies were performed on TAO patients and healthy controls (45: 28 in total. RNA-seq was used to detect differential gene expression of orbital adipose-connective tissue. Quantitative PCR was performed to verify the results. PTX3 protein in orbital adipose-connective tissues was visualized by immunohistochemistry (IHC. PTX3 concentration in serum was determined by enzyme-linked immunosorbent assay (ELISA. Results. RNA-seq showed 1.86-log⁡2FC higher PTX3 expression in the orbital adipose-connective tissues from TAO group than controls (FDR = 0.0059. qPCR confirmed the difference (5.59-fold increase, p=0.0012. The presence of PTX3 protein was demonstrated. Orbital adipose tissue from healthy controls showed weak staining for PTX3 while tissue from TAO group was strongly positive. Serum PTX3 concentration was significantly elevated in patients when compared to the control group (1.9-fold increase; p<0.0001. Conclusions. Patients with TAO showed increased presence of PTX3 in orbital tissue and serum, which may suggest a potential relationship of PTX3 and TAO.

  18. PTX3: A Potential Biomarker in Thyroid Associated Ophthalmopathy

    Science.gov (United States)

    Chen, Ziyu

    2018-01-01

    Background Thyroid associated ophthalmopathy (TAO) is an autoimmune disease, which involves inflammation and tissue remodeling. Pentraxin-3 (PTX3) is a component of innate immune system and recently implicated in autoimmunity. This observation may indicate that PTX3 participates in the inflammatory process of TAO. Methods All studies were performed on TAO patients and healthy controls (45: 28 in total). RNA-seq was used to detect differential gene expression of orbital adipose-connective tissue. Quantitative PCR was performed to verify the results. PTX3 protein in orbital adipose-connective tissues was visualized by immunohistochemistry (IHC). PTX3 concentration in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results RNA-seq showed 1.86-log⁡2FC higher PTX3 expression in the orbital adipose-connective tissues from TAO group than controls (FDR = 0.0059). qPCR confirmed the difference (5.59-fold increase, p = 0.0012). The presence of PTX3 protein was demonstrated. Orbital adipose tissue from healthy controls showed weak staining for PTX3 while tissue from TAO group was strongly positive. Serum PTX3 concentration was significantly elevated in patients when compared to the control group (1.9-fold increase; p < 0.0001). Conclusions Patients with TAO showed increased presence of PTX3 in orbital tissue and serum, which may suggest a potential relationship of PTX3 and TAO. PMID:29675428

  19. Redox-sensitive self-assembled nanoparticles based on alpha-tocopherol succinate-modified heparin for intracellular delivery of paclitaxel.

    Science.gov (United States)

    Yang, Xiaoye; Cai, Xiaoqing; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2017-06-15

    To remedy the problems riddled in cancer chemotherapy, such as poor solubility, low selectivity, and insufficient intra-cellular release of drugs, novel heparin-based redox-sensitive polymeric nanoparticles were developed. The amphiphilic polymer, heparin-alpha-tocopherol succinate (Hep-cys-TOS) was synthesized by grafting hydrophobic TOS to heparin using cystamine as the redox-sensitive linker, which could self-assemble into nanoparticles in phosphate buffer saline (PBS) with low critical aggregation concentration (CAC) values ranging from 0.026 to 0.093mg/mL. Paclitaxel (PTX)-loaded Hep-cys-TOS nanoparticles were prepared via a dialysis method, exhibiting a high drug-loading efficiency of 18.99%. Physicochemical properties of the optimized formulation were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM) and differential scanning calorimetry (DSC). Subsequently, the redox-sensitivity of Hep-cys-TOS nanoparticles was confirmed by the changes in size distribution, morphology and appearance after dithiothreitol (DTT) treatment. Besides, the in vitro release of PTX from Hep-cys-TOS nanoparticles also exhibited a redox-triggered profile. Also, the uptake behavior and pathways of coumarin 6-loaded Hep-cys-TOS nanoparticles were investigated, suggesting the nanoparticles could be taken into MCF-7 cells in energy-dependent, caveolae-mediated and cholesterol-dependent endocytosis manners. Later, MTT assays of different PTX-free and PTX-loaded formulations revealed the desirable safety of PTX-free nanoparticles and the enhanced anti-cancer activity of PTX-loaded Hep-cys-TOS nanoparticles (IC 50 =0.79μg/mL). Apoptosis study indicated the redox-sensitive formulation could induce more apoptosis of MCF-7 cells than insensitive one (55.2% vs. 41.7%), showing the importance of intracellular burst release of PTX. Subsequently, the hemolytic toxicity confirmed the safety of the nanoparticles for intravenous administration. The results

  20. Essential oil-loaded lipid nanoparticles for wound healing.

    Science.gov (United States)

    Saporito, Francesca; Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Boselli, Cinzia; Icaro Cornaglia, Antonia; Mannucci, Barbara; Grisoli, Pietro; Vigani, Barbara; Ferrari, Franca

    2018-01-01

    Chronic wounds and severe burns are diseases responsible for severe morbidity and even death. Wound repair is a crucial process and tissue regeneration enhancement and infection prevention are key factors to minimize pain, discomfort, and scar formation. The aim of this work was the development of lipid nanoparticles (solid lipid nanoparticles and nanostructured lipid carriers [NLC]), to be loaded with eucalyptus or rosemary essential oils and to be used, as medical devices, to enhance healing of skin wounds. Lipid nanoparticles were based on natural lipids: cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids. Lecithin was chosen as surfactant to stabilize nanoparticles and to prevent their aggregation. The systems were prepared by high shear homogenization followed by ultrasound application. Nanoparticles were characterized for physical-chemical properties, bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward normal human dermal fibroblasts. Antimicrobial activity of nanoparticles was evaluated against two reference microbial strains, one of Staphylococcus aureus , the other of Streptococcus pyogenes . Finally, the capability of nanoparticles to promote wound healing in vivo was evaluated on a rat burn model. NLC based on olive oil and loaded with eucalyptus oil showed appropriate physical-chemical properties, good bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward fibroblasts, associated to antimicrobial properties. Moreover, the in vivo results evidenced the capability of these NLC to enhance the healing process. Olive oil, which is characterized by a high content of oleic acid, proved to exert a synergic effect with eucalyptus oil with respect to antimicrobial activity and wound repair promotion.

  1. In vitro digestion of curcuminoid-loaded lipid nanoparticles

    International Nuclear Information System (INIS)

    Noack, Andreas; Oidtmann, Johannes; Kutza, Johannes; Mäder, Karsten

    2012-01-01

    Curcuminoid-loaded lipid nanoparticles were produced by melt homogenization. The used lipid matrices were medium chain triglycerides, trimyristin (TM), and tristearin. The mean particle size of the preparations was between 130 and 180 nm. The incorporated curcuminoids revealed a good stability over a period of 12 months. The curcuminoid-loaded lipid nanoparticles were intended for the oral delivery of curcuminoids. Therefore, the fate of the triglyceride matrix in simulated gastric and simulated intestinal media under the influence of pepsin and pancreatin, respectively, was assessed. The degradation of the triglycerides was monitored by the pH–stat method and with high performance thin layer chromatography in connection with spectrodensitometry to quantify the different lipid fractions. The TM nanoparticles were not degraded in simulated gastric fluid (SGF), but the decomposition of the triglyceride matrix was rapid in the intestinal media. The digestion process was faster in the simulated fed state medium compared to the simulated fasted state medium. Additionally, the stability of the incorporated drug was tested in the respective physiological media. The curcuminoids showed an overall good stability in the different test media. The release of the curcuminoids from the lipid nanoparticles was determined by fluorescence imaging techniques. A slow release of the drug was found in phosphate buffer. In contrast, a more distinct release of the curcuminoids was verifiable in SGF and in simulated intestinal fluids. Overall, it was considered that the transfer of the drug into the outer media was mainly triggered by the lipid degradation and not by drug release.

  2. Fabrication of interconnected microporous biomaterials with high hydroxyapatite nanoparticle loading

    International Nuclear Information System (INIS)

    Zhang Wei; Yao Donggang; Zhang Qingwei; Lelkes, Peter I; Zhou, Jack G

    2010-01-01

    Hydroxyapatite (HA) is known to promote osteogenicity and enhance the mechanical properties of biopolymers. However, incorporating a large amount of HA into a porous biopolymer still remains a challenge. In the present work, a new method was developed to produce interconnected microporous poly(glycolic-co-lactic acid) (PLGA) with high HA nanoparticle loading. First, a ternary blend comprising PLGA/PS (polystyrene)/HA (40/40/20 wt%) was prepared by melt blending under conditions for formation of a co-continuous phase structure. Next, a dynamic annealing stage under small-strain oscillation was applied to the blend to facilitate nanoparticle redistribution. Finally, the PS phase was sacrificially extracted, leaving a porous matrix. The results from different characterizations suggested that the applied small-strain oscillation substantially accelerated the migration of HA nanoparticles during annealing from the PS phase to the PLGA phase; nearly all HA particles were uniformly presented in the PLGA phase after a short period of annealing. After dissolution of the PS phase, a PLGA material with interconnected microporous structure was successfully produced, with a high HA loading above 30 wt%. The mechanisms beneath the experimental observations, particularly on the enhanced particle migration process, were discussed, and strategies for producing highly particle loaded biopolymers with interconnected microporous structures were proposed.

  3. Anti-EGFR-iRGD recombinant protein conjugated silk fibroin nanoparticles for enhanced tumor targeting and antitumor efficiency

    Directory of Open Access Journals (Sweden)

    Bian X

    2016-05-01

    Full Text Available Xinyu Bian,* Puyuan Wu,* Huizi Sha, Hanqing Qian, Qing Wang, Lei Cheng, Yang Yang, Mi Yang, Baorui LiuComprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, we report a novel kind of targeting with paclitaxel (PTX-loaded silk fibroin nanoparticles conjugated with iRGD–EGFR nanobody recombinant protein (anti-EGFR-iRGD. The new nanoparticles (called A-PTX-SF-NPs were prepared using the carbodiimide-mediated coupling procedure and their characteristics were evaluated. The cellular cytotoxicity and cellular uptake of A-PTX-SF-NPs were also investigated. The results in vivo suggested that NPs conjugated with the recombinant protein exhibited more targeting and anti-neoplastic property in cells with high EGFR expression. In the in vivo antitumor efficacy assay, the A-PTX-SF-NPs group showed slower tumor growth and smaller tumor volumes than PTX-SF-NPs in a HeLa xenograft mouse model. A real-time near-infrared fluorescence imaging study showed that A-PTX-SF-NPs could target the tumor more effectively. These results suggest that the anticancer activity and tumor targeting of A-PTX-SF-NPs were superior to those of PTX-SF-NPs and may have the potential to be used for targeted delivery for tumor therapies. Keywords: EGFR, nanobody, iRGD, recombinant protein, targeting drug carriers, antitumor efficiency

  4. Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles.

    Science.gov (United States)

    Lee, Amani L; Gee, Clifford T; Weegman, Bradley P; Einstein, Samuel A; Juelfs, Adam R; Ring, Hattie L; Hurley, Katie R; Egger, Sam M; Swindlehurst, Garrett; Garwood, Michael; Pomerantz, William C K; Haynes, Christy L

    2017-06-27

    Oxygen homeostasis is important in the regulation of biological function. Disease progression can be monitored by measuring oxygen levels, thus producing information for the design of therapeutic treatments. Noninvasive measurements of tissue oxygenation require the development of tools with minimal adverse effects and facile detection of features of interest. Fluorine magnetic resonance imaging ( 19 F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for anatomical imaging, cell tracking, and oxygen sensing. However, the highly hydrophobic and lipophobic properties of perfluorocarbons require the formation of emulsions for biological studies, though stabilizing these emulsions has been challenging. To enhance the stability and biological loading of perfluorocarbons, one option is to incorporate perfluorocarbon liquids into the internal space of biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19 F MRI detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles (UMNs) have large internal cavities (average = 1.8 cm 3 g -1 ), facilitating an average 17% loading efficiency of PFCs, meeting the threshold fluorine concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs have the highest equivalent nuclei per PFC molecule and a spin-lattice (T 1 ) relaxation-based oxygen sensitivity of 0.0032 mmHg -1 s -1 at 16.4 T. The option of loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell syntheses, allows for use of a broad range of PFC liquids from a single material. The biocompatible and tunable chemistry of UMNs combined with the intrinsic properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical imaging, cell tracking, and metabolic spectroscopy with improved stability.

  5. Synthesis of Pyrimethanil-Loaded Mesoporous Silica Nanoparticles and Its Distribution and Dissipation in Cucumber Plants.

    Science.gov (United States)

    Zhao, Pengyue; Cao, Lidong; Ma, Dukang; Zhou, Zhaolu; Huang, Qiliang; Pan, Canping

    2017-05-16

    Mesoporous silica nanoparticles are used as pesticide carries in plants, which has been considered as a novel method to reduce the indiscriminate use of conventional pesticides. In the present work, mesoporous silica nanoparticles with particle diameters of 200-300 nm were synthesized in order to obtain pyrimethanil-loaded nanoparticles. The microstructure of the nanoparticles was observed by scanning electron microscopy. The loading content of pyrimethanil-loaded nanoparticles was investigated. After treatment on cucumber leaves, the concentrations of pyrimethanil were determined in different parts of cucumber over a period of 48 days using high performance liquid chromatography tandem mass spectrometry. It was shown that the pyrimethanil-loaded mesoporous silica nanoparticles might be more conducive to acropetal, rather than basipetal, uptake, and the dosage had almost no effect on the distribution and dissipation rate in cucumber plants. The application of the pesticide-loaded nanoparticles in leaves had a low risk of pyrimethanil accumulating in the edible part of the plant.

  6. Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery

    Directory of Open Access Journals (Sweden)

    Zhang L

    2015-03-01

    Full Text Available Linhua Zhang,1 Dunwan Zhu,1 Xia Dong,1 Hongfan Sun,1 Cunxian Song,1 Chun Wang,2 Deling Kong1 1Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People’s Republic of China; 2Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA Abstract: The purpose of this study was to develop a novel lipid–polymer hybrid drug carrier comprised of folate (FA modified lipid-shell and polymer-core nanoparticles (FLPNPs for sustained, controlled, and targeted delivery of paclitaxel (PTX. The core-shell NPs consist of 1 a poly(ε-caprolactone hydrophobic core based on self-assembly of poly(ε-caprolactone–poly(ethylene glycol–poly(ε-caprolactone (PCL-PEG-PCL amphiphilic copolymers, 2 a lipid monolayer formed with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol-2000] (DSPE-PEG2000, 3 a targeting ligand (FA on the surface, and were prepared using a thin-film hydration and ultrasonic dispersion method. Transmission electron microscopy and dynamic light scattering analysis confirmed the coating of the lipid monolayer on the hydrophobic polymer core. Physicochemical characterizations of PTX-loaded FLPNPs, such as particle size and size distribution, zeta potential, morphology, drug loading content, encapsulation efficiency, and in vitro drug release, were also evaluated. Fluorescent microscopy proved the internalization efficiency and targeting ability of the folate conjugated on the lipid monolayer for the EMT6 cancer cells which overexpress folate receptor. In vitro cytotoxicity assay demonstrated that the cytotoxic effect of PTX-loaded FLPNPs was lower than that of Taxol®, but higher than that of PTX-loaded LPNPs (without folate conjugation. In EMT6 breast tumor model, intratumoral administration of PTX-loaded FLPNPs showed similar antitumor efficacy but low toxicity compared to Taxol®. More

  7. Microfluidic generation of droplets with a high loading of nanoparticles.

    Science.gov (United States)

    Wan, Jiandi; Shi, Lei; Benson, Bryan; Bruzek, Matthew J; Anthony, John E; Sinko, Patrick J; Prudhomme, Robert K; Stone, Howard A

    2012-09-18

    Microfluidic approaches for controlled generation of colloidal clusters, for example, via encapsulation of colloidal particles in droplets, have been used for the synthesis of functional materials including drug delivery carriers. Most of the studies, however, use a low concentration of an original colloidal suspension (60 wt %) particle concentrations. Three types of microfluidic devices, PDMS flow-focusing, PDMS T-junction, and microcapillary devices, are investigated for direct encapsulation of a high concentration of polystyrene (PS) nanoparticles in droplets. In particular, it is shown that PDMS devices fabricated by soft lithography can generate droplets from a 25 wt % PS suspension, whereas microcapillary devices made from glass capillary tubes are able to produce droplets from a 67 wt % PS nanoparticle suspension. When the PS concentration is between 0.6 and 25 wt %, the size of the droplets is found to change with the oil-to-water flow rate ratio and is independent of the concentration of particles in the initial suspensions. Drop sizes from ~12 to 40 μm are made using flow rate ratios Q(oil)/Q(water) from 20 to 1, respectively, with either of the PDMS devices. However, clogging occurs in PDMS devices at high PS concentrations (>25 wt %) arising from interactions between the PS colloids and the surface of PDMS devices. Glass microcapillary devices, on the other hand, are resistant to clogging and can produce droplets continuously even when the concentration of PS nanoparticles reaches 67 wt %. We believe that our findings indicate useful approaches and guidelines for the controlled generation of emulsions filled with a high loading of nanoparticles, which are useful for drug delivery applications.

  8. Microfluidic generation of droplets with a high loading of nanoparticles

    Science.gov (United States)

    Wan, Jiandi; Shi, Lei; Benson, Bryan; Bruzek, Matthew J.; Anthony, John E.; Sinko, Patrick J.; Prudhomme, Robert K.; Stone, Howard A.

    2012-01-01

    Microfluidic approaches for controlled generation of colloidal clusters, e.g., via encapsulation of colloidal particles in droplets, have been used for the synthesis of functional materials including drug delivery carriers. Most of the studies, however, use a low concentration of an original colloidal suspension ( 60 wt%) particle concentrations. Three types of microfluidic devices, PDMS flow-focusing, PDMS T-junction, and microcapillary devices, are investigated for direct encapsulation of a high concentration of polystyrene (PS) nanoparticles in droplets. In particular, it is shown that PDMS devices fabricated by soft lithography can generate droplets from a 25 wt% PS suspension, whereas microcapillary devices made from glass capillary tubes are able to produce droplets from a 67 wt% PS nanoparticle suspension. When the PS concentration is between 0.6 and 25 wt%, the size of the droplets is found to change with the oil-to-water flow rate ratio and is independent of the concentration of particles in the initial suspensions. Drop sizes from ~12 to 40 μm are made using flow rate ratios Qoil/Qwater from 20 to 1, respectively, with either of the PDMS devices. However, clogging occurs in PDMS devices at high PS concentrations (> 25 wt%) arising from interactions between the PS colloids and the surface of PDMS devices. Glass microcapillary devices, on the other hand, are resistant to clogging and can produce droplets continuously even when the concentration of PS nanoparticles reaches 67 wt%. We believe that our findings indicate useful approaches and guidelines for the controlled generation of emulsions of microparticles that are filled with a high loading of nanoparticles and which are useful for drug delivery applications. PMID:22934976

  9. Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

    Directory of Open Access Journals (Sweden)

    Zhang Z

    2017-02-01

    Full Text Available Zhen Zhang,1 Hanqing Qian,2 Mi Yang,2 Rutian Li,2 Jing Hu,1 Li Li,1 Lixia Yu,2 Baorui Liu,1,2 Xiaoping Qian1,2 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, 2Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute, Nanjing University, Nanjing, China Abstract: Gambogic acid (GA is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe­rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid (PLGA with red blood-cell membrane (RBCm, and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier. Keywords: gambogic acid, nanocarriers, RBCm-GA/PLGA nanoparticles, colorectal cancer

  10. Ocular pharmacoscintigraphic and aqueous humoral drug availability of ganciclovir-loaded mucoadhesive nanoparticles in rabbits

    NARCIS (Netherlands)

    Akhter, Sohail; Ramazani, Farshad; Ahmad, Mohammad Zaki; Ahmad, Farjam Jalees; Rahman, Ziyaur; Bhatnagar, Aseem; Storm, Gerrit

    2013-01-01

    The present report describes the improved ocular retention and aqueous humoral drug availability of ganciclovir (GCV) when administered via topical instillation of different kind of nanoparticles onto the rabbit eye. GCV was loaded into PLGA nanoparticles, chitosan-coated nanoparticles and

  11. Drug loading and release on tumor cells using silk fibroin–albumin nanoparticles as carriers

    International Nuclear Information System (INIS)

    Subia, B; Kundu, S C

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin–albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin–albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules. (paper)

  12. An efficient targeted drug delivery through apotransferrin loaded nanoparticles.

    Directory of Open Access Journals (Sweden)

    Athuluri Divakar Sai Krishna

    Full Text Available BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano, and showed further increase in dimension (75-95 etam in conjugated nanoparticles (conj-nano. The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus (b pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in

  13. Genes for carbon metabolism and the ToxA virulence factor in Pseudomonas aeruginosa are regulated through molecular interactions of PtxR and PtxS.

    Directory of Open Access Journals (Sweden)

    Abdelali Daddaoua

    Full Text Available Homologs of the transcriptional regulator PtxS are omnipresent in Pseudomonas, whereas PtxR homologues are exclusively found in human pathogenic Pseudomonas species. In all Pseudomonas sp., PtxS with 2-ketogluconate is the regulator of the gluconate degradation pathway and controls expression from its own promoter and also from the P(gad and P(kgu for the catabolic operons. There is evidence that PtxS and PtxR play a central role in the regulation of exotoxin A expression, a relevant primary virulence factor of Pseudomonas aeruginosa. We show using DNaseI-footprint analysis that in P. aeruginosa PtxR binds to the -35 region of the P(toxA promoter in front of the exotoxin A gene, whereas PtxS does not bind to this promoter. Bioinformatic and DNaseI-footprint analysis identified a PtxR binding site in the P(kgu and P(gad promoters that overlaps the -35 region, while the PtxS operator site is located 50 bp downstream from the PtxR site. In vitro, PtxS recognises PtxR with nanomolar affinity, but this interaction does not occur in the presence of 2-ketogluconate, the specific effector of PtxS. DNAaseI footprint assays of P(kgu and P(gad promoters with PtxS and PtxR showed a strong region of hyper-reactivity between both regulator binding sites, indicative of DNA distortion when both proteins are bound; however in the presence of 2-ketogluconate no protection was observed. We conclude that PtxS modulates PtxR activity in response to 2-ketogluconate by complex formation in solution in the case of the P(toxA promoter, or via the formation of a DNA loop as in the regulation of gluconate catabolic genes. Data suggest two different mechanisms of control exerted by the same regulator.

  14. Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy

    Directory of Open Access Journals (Sweden)

    Oh KS

    2016-03-01

    Full Text Available Keun Sang Oh,1,* Kyungim Kim,1,* Byeong Deok Yoon,1 Hye Jin Lee,1 Dal Yong Park,1 Eun-yeong Kim,1 Kiho Lee,1 Jae Hong Seo,2 Soon Hong Yuk1,2 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea University Guro Hospital, Guro-gu, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: A mixture of docetaxel (DTX and Solutol® HS 15 (Solutol transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs with a DTX-loaded Solutol nanodroplet (as template NPs core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm were observed to have an increased average diameter (from 11.7 nm to 156.1 nm and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects. Keywords: multilayer nanoparticles, Solutol, Pluronic F-68, docetaxel, cancer therapy

  15. Functionalized PLA polymers to control loading and/or release properties of drug-loaded nanoparticles.

    Science.gov (United States)

    Thauvin, Cédric; Schwarz, Bettina; Delie, Florence; Allémann, Eric

    2017-11-15

    Advantages associated with the use of polylactic acid (PLA) nano- or microparticles as drug delivery systems have been widely proven in the field of pharmaceutical sciences. These biodegradable and biocompatible carriers have demonstrated different loading and release properties depending on interactions with the cargo, preparation methods, particles size or molecular weight of PLA. In this study, we sought to show the possibility of influencing these properties by modifying the structure of the constituting polymer. Seven non-functionalized or functionalized PLA polymers were specifically designed and synthesized by microwave-assisted ring-opening polymerization of d,l-lactide. They presented short hydrophobic and/or hydrophilic groups thanks to the use of C20 aliphatic chain, mPEG1000, sorbitan esters (Spans ® ) or polysorbates (Tweens ® ), their PEGylated analogues, as initiators. Then, seven types of drug-loaded nanoparticles (NP) were prepared from these polymers and compared in terms of physico-chemical characteristics, drug loading and release profiles. Although the loading properties were not improved with any of the functionalized PLA NP, different release profiles were observed in an aqueous medium at 37 °C and over a period of five days. The presence of PEG moieties in the core of PLA-polysorbates NP induced a faster release while the addition of a single aliphatic chain induced a slower release due to better interactions with the active molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Magnetic poly(D,L-lactide) nanoparticles loaded with aliskiren: A promising tool for hypertension treatment

    International Nuclear Information System (INIS)

    Antal, Iryna; Kubovcikova, Martina; Zavisova, Vlasta; Koneracka, Martina; Pechanova, Olga; Barta, Andrej; Cebova, Martina; Antal, Vitaliy; Diko, Pavel; Zduriencikova, Martina; Pudlak, Michal; Kopcansky, Peter

    2015-01-01

    In this study anti-hypertensive drug called aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles by the modified nanoprecipitation method. The effect of magnetite and drug concentrations on the size distribution and zeta potential of polymer nanoparticles was investigated. The optimized loadings were as follows: theoretical magnetite loading was 20 mg/100 mg polymer nanoparticles and aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles at theoretical loading 0.6 mg aliskiren/100 mg magnetic polymer nanoparticles. The physicochemical characteristics of nanoparticles were studied, with spherical shape of nanoparticles sized between 58 and 227 nm being one of the observed results. Differential scanning calorimetry and infrared spectroscopy confirmed that aliskiren was successfully identified in the magnetic poly(D,L-lactide) nanoparticles. The in vivo experiments indicated that encapsulated aliskiren decreased blood pressure of the studied male spontaneously hypertensive rat even more significantly than common administered drug. - Highlights: • Anti-hypertensive drug called aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles by modified nanoprecipitation method. • The optimisation of magnetite and drug loading with regard to the size distribution and zeta potential was investigated. • The physicochemical characteristics of nanoparticles were studied by different techniques. • The in vivo experiments indicated that encapsulated aliskiren decreased blood pressure of the studied male spontaneously hypertensive rat even more significantly than common administered drug

  17. Magnetic poly(D,L-lactide) nanoparticles loaded with aliskiren: A promising tool for hypertension treatment

    Energy Technology Data Exchange (ETDEWEB)

    Antal, Iryna, E-mail: iryna.antal@saske.sk [Institute of Experimental Physics, SAS, Watsonova 47, 040 01 Kosice (Slovakia); Kubovcikova, Martina; Zavisova, Vlasta; Koneracka, Martina [Institute of Experimental Physics, SAS, Watsonova 47, 040 01 Kosice (Slovakia); Pechanova, Olga; Barta, Andrej; Cebova, Martina [Institute of Normal and Pathological Physiology, SAS, Bratislava (Slovakia); Antal, Vitaliy; Diko, Pavel [Institute of Experimental Physics, SAS, Watsonova 47, 040 01 Kosice (Slovakia); Zduriencikova, Martina [Cancer Research Institute, SAS, Bratislava (Slovakia); Pudlak, Michal; Kopcansky, Peter [Institute of Experimental Physics, SAS, Watsonova 47, 040 01 Kosice (Slovakia)

    2015-04-15

    In this study anti-hypertensive drug called aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles by the modified nanoprecipitation method. The effect of magnetite and drug concentrations on the size distribution and zeta potential of polymer nanoparticles was investigated. The optimized loadings were as follows: theoretical magnetite loading was 20 mg/100 mg polymer nanoparticles and aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles at theoretical loading 0.6 mg aliskiren/100 mg magnetic polymer nanoparticles. The physicochemical characteristics of nanoparticles were studied, with spherical shape of nanoparticles sized between 58 and 227 nm being one of the observed results. Differential scanning calorimetry and infrared spectroscopy confirmed that aliskiren was successfully identified in the magnetic poly(D,L-lactide) nanoparticles. The in vivo experiments indicated that encapsulated aliskiren decreased blood pressure of the studied male spontaneously hypertensive rat even more significantly than common administered drug. - Highlights: • Anti-hypertensive drug called aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles by modified nanoprecipitation method. • The optimisation of magnetite and drug loading with regard to the size distribution and zeta potential was investigated. • The physicochemical characteristics of nanoparticles were studied by different techniques. • The in vivo experiments indicated that encapsulated aliskiren decreased blood pressure of the studied male spontaneously hypertensive rat even more significantly than common administered drug.

  18. Fe3O4 nanoparticle loaded paclitaxel induce multiple myeloma apoptosis by cell cycle arrest and increase cleavage of caspases in vitro

    Science.gov (United States)

    Yang, Cuiping; He, Xiangfeng; Chen, Junsong; Chen, Dengyu; Liu, Yunjing; Xiong, Fei; Shi, Fangfang; Dou, Jun; Gu, Ning

    2013-08-01

    Multiple myeloma (MM) still remains an incurable disease in spite of extending the patient survival by new therapies. The hypothesis of cancer stem cells (CSCs) states that although chemotherapy kills most tumor cells, it is believed to leave a reservoir of CSCs that allows the tumor cell propagation. The objective of this research was to evaluate the therapeutic effect of new paclitaxel-Fe3O4 nanoparticles (PTX-NPs) with an average size range of 7.17 ± 1.31 nm on MM CSCs in vitro. The characteristics of CD138-CD34- cells, isolated from human MM RPMI 8226 and NCI-H929 cell lines by the magnetic associated cell sorting method, were identified by the assays of colony formation, cell proliferation, drug resistance, cell migration, and tumorigenicity in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, respectively. Inhibitory effects of PTX-NPs on CD138-CD34- cells were evaluated by a variety of assays in vitro. The results showed that the CD138-CD34- cells were capable of forming colonies, exhibited high proliferative and migratory ability, possessed a strong drug resistance, and had powerful tumorigenicity in NOD/SCID mice compared to non-CD138-CD34- cells. PTX-NPs significantly inhibited CD138- CD34- cell viability and invasive ability, and resulted in G0/G1 cell cycle arrest and apoptosis compared with PTX alone. We concluded that the CD138-CD34- phenotype cells might be CSCs in RPMI 8226 and NCI-H929 cell lines. PTX-NPs had an obvious inhibitory effect on MM CD138-CD34- CSCs. The findings may provide a guideline for PTX-NPs' treatment of MM CSCs in preclinical investigation.

  19. Fe{sub 3}O{sub 4} nanoparticle loaded paclitaxel induce multiple myeloma apoptosis by cell cycle arrest and increase cleavage of caspases in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Cuiping [Medical School, Southeast University, Department of Pathogenic Biology and Immunology (China); He, Xiangfeng [Affiliated Tumor Hospital of Nantong University, Department of Medical Oncology (China); Chen, Junsong; Chen, Dengyu; Liu, Yunjing [Medical School, Southeast University, Department of Pathogenic Biology and Immunology (China); Xiong, Fei [Southeast University, School of Biological Science and Medical Engineering (China); Shi, Fangfang [Zhongda Hospital, Southeast University, Department of Oncology (China); Dou, Jun, E-mail: njdoujun@yahoo.com.cn [Medical School, Southeast University, Department of Pathogenic Biology and Immunology (China); Gu, Ning, E-mail: guning@seu.edu.cn [Southeast University, School of Biological Science and Medical Engineering (China)

    2013-08-15

    Multiple myeloma (MM) still remains an incurable disease in spite of extending the patient survival by new therapies. The hypothesis of cancer stem cells (CSCs) states that although chemotherapy kills most tumor cells, it is believed to leave a reservoir of CSCs that allows the tumor cell propagation. The objective of this research was to evaluate the therapeutic effect of new paclitaxel-Fe{sub 3}O{sub 4} nanoparticles (PTX-NPs) with an average size range of 7.17 {+-} 1.31 nm on MM CSCs in vitro. The characteristics of CD138{sup -}CD34{sup -} cells, isolated from human MM RPMI 8226 and NCI-H929 cell lines by the magnetic associated cell sorting method, were identified by the assays of colony formation, cell proliferation, drug resistance, cell migration, and tumorigenicity in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, respectively. Inhibitory effects of PTX-NPs on CD138{sup -}CD34{sup -} cells were evaluated by a variety of assays in vitro. The results showed that the CD138{sup -}CD34{sup -} cells were capable of forming colonies, exhibited high proliferative and migratory ability, possessed a strong drug resistance, and had powerful tumorigenicity in NOD/SCID mice compared to non-CD138{sup -}CD34{sup -} cells. PTX-NPs significantly inhibited CD138{sup -} CD34{sup -} cell viability and invasive ability, and resulted in G0/G1 cell cycle arrest and apoptosis compared with PTX alone. We concluded that the CD138{sup -}CD34{sup -} phenotype cells might be CSCs in RPMI 8226 and NCI-H929 cell lines. PTX-NPs had an obvious inhibitory effect on MM CD138{sup -}CD34{sup -} CSCs. The findings may provide a guideline for PTX-NPs' treatment of MM CSCs in preclinical investigation.

  20. Fe3O4 nanoparticle loaded paclitaxel induce multiple myeloma apoptosis by cell cycle arrest and increase cleavage of caspases in vitro

    International Nuclear Information System (INIS)

    Yang, Cuiping; He, Xiangfeng; Chen, Junsong; Chen, Dengyu; Liu, Yunjing; Xiong, Fei; Shi, Fangfang; Dou, Jun; Gu, Ning

    2013-01-01

    Multiple myeloma (MM) still remains an incurable disease in spite of extending the patient survival by new therapies. The hypothesis of cancer stem cells (CSCs) states that although chemotherapy kills most tumor cells, it is believed to leave a reservoir of CSCs that allows the tumor cell propagation. The objective of this research was to evaluate the therapeutic effect of new paclitaxel-Fe 3 O 4 nanoparticles (PTX-NPs) with an average size range of 7.17 ± 1.31 nm on MM CSCs in vitro. The characteristics of CD138 − CD34 − cells, isolated from human MM RPMI 8226 and NCI-H929 cell lines by the magnetic associated cell sorting method, were identified by the assays of colony formation, cell proliferation, drug resistance, cell migration, and tumorigenicity in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, respectively. Inhibitory effects of PTX-NPs on CD138 − CD34 − cells were evaluated by a variety of assays in vitro. The results showed that the CD138 − CD34 − cells were capable of forming colonies, exhibited high proliferative and migratory ability, possessed a strong drug resistance, and had powerful tumorigenicity in NOD/SCID mice compared to non-CD138 − CD34 − cells. PTX-NPs significantly inhibited CD138 − CD34 − cell viability and invasive ability, and resulted in G0/G1 cell cycle arrest and apoptosis compared with PTX alone. We concluded that the CD138 − CD34 − phenotype cells might be CSCs in RPMI 8226 and NCI-H929 cell lines. PTX-NPs had an obvious inhibitory effect on MM CD138 − CD34 − CSCs. The findings may provide a guideline for PTX-NPs’ treatment of MM CSCs in preclinical investigation

  1. Drug loading to lipid-based cationic nanoparticles

    International Nuclear Information System (INIS)

    Cavalcanti, Leide P.; Konovalov, Oleg; Torriani, Iris L.; Haas, Heinrich

    2005-01-01

    Lipid-based cationic nanoparticles are a new promising option for tumor therapy, because they display enhanced binding and uptake at the neo-angiogenic endothelial cells, which a tumor needs for its nutrition and growth. By loading suitable cytotoxic compounds to the cationic carrier, the tumor endothelial and consequently also the tumor itself can be destroyed. For the development of such novel anti-tumor agents, the control of drug loading and drug release from the carrier matrix is essential. We have studied the incorporation of the hydrophobic anti-cancer agent Paclitaxel (PXL) into a variety of lipid matrices by X-Ray reflectivity measurements. Liposome suspensions from cationic and zwitterionic lipids, comprising different molar fractions of Paclitaxel, were deposited on planar glass substrates. After drying at controlled humidity, well ordered, oriented multilayer stacks were obtained, as proven by the presence of bilayer Bragg peaks to several orders in the reflectivity curves. The presence of the drug induced a decrease of the lipid bilayer spacing, and with an excess of drug, also Bragg peaks of drug crystals could be observed. From the results, insight into the solubility of Paclitaxel in the model membranes was obtained and a structural model of the organization of the drug in the membrane was derived. Results from subsequent pressure/area-isotherm and grazing incidence diffraction (GID) measurements performed with drug/lipid Langmuir monolayers were in accordance with these conjectures

  2. Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy.

    Science.gov (United States)

    Oh, Keun Sang; Kim, Kyungim; Yoon, Byeong Deok; Lee, Hye Jin; Park, Dal Yong; Kim, Eun-Yeong; Lee, Kiho; Seo, Jae Hong; Yuk, Soon Hong

    2016-01-01

    A mixture of docetaxel (DTX) and Solutol(®) HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects.

  3. Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

    International Nuclear Information System (INIS)

    Ying Xiaoying; Du Yongzhong; Hong Linghong; Yuan Hong; Hu Fuqiang

    2011-01-01

    Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and -30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs. - Research highlights: → A simple solvent diffusion method was developed to prepare magnetic lipid nanoparticles. → The doxorubicin-loaded magnetic lipid nanoparticles could be controlled by preparation recipe. → Magnetic lipid nanoparticles had internalization ability into tumor cells.

  4. Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Meng Meng [Tsinghua University, Department of Chemical Engineering (China); Kang, Yoon Joong [Jungwon University, Department of Biomedical Science (Korea, Republic of); Sohn, Youngjoo [Kyung Hee University, Department of Anatomy, College of Korean Medicine (Korea, Republic of); Kim, Do Kyung, E-mail: eurokorean@gmail.com, E-mail: dokyung@konyang.ac.kr [Konyang University, Industry Cooperation Foundation (Korea, Republic of)

    2015-06-15

    A double targeting strategy of anti-neoplastic agent paclitaxel (PTX) was developed by incorporating magnetic nanoparticles and RGD peptide for enhanced cell cytotoxicity effect at lower dosage. A dual targeting mechanism including magnetic targeting and RGD ligand-specific targeting enhanced the overall cytotoxicity and reduced the effective dosage of PTX to achieve enhanced and sustained release of PTX in vitro. We addressed the issues of water-insolubility of oleic acid (OA)-stabilized SPIONs and low incorporation efficiency of hydrophobic PTX with SPION nanocarriers by using an amphiphilic polymer poly[(N-isopropylacrylamide-r-acrylamide)-b-l-lactic acid] (PNAL) as micelle-forming materials. A targeting moiety, GGGGRGD peptide, a RGD sequence-containing peptide with a short linker, is attached to the surface of PNAL-SPIONs via a homo-crosslinker. Confocal microscopy image analysis revealed that the cellular uptake was increased from (1.5 ± 0.5 % (PNAL) to 11.7 ± 0.8 % (RGD-PNAL-SPIONs) at 6 h incubation, once both RGD peptide and magnetic force attraction were incorporated into the carriers. Such multi-targeting nanocarriers showed promising potential in cancer-oriented diagnosis and therapy.

  5. Nanoembedded Microparticles for Stabilization and Delivery of Drug-Loaded Nanoparticles

    DEFF Research Database (Denmark)

    Bohr, Adam; Water, Jorrit; Beck-Broichsitter, Moritz

    2015-01-01

    Nanoparticle-based pharmaceutical products are currently finding their way onto the market as a popular strategy to improve the therapeutic efficacy of numerous drugs, hereunder medications for a targeted treatment of severe diseases (e.g., cancer). Drug-loaded polymer and lipid nanoparticles...

  6. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

    Science.gov (United States)

    Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

    2014-10-15

    Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Ciprofloxacin-loaded PLGA nanoparticles against Cystic Fibrosis P. aeruginosa Lung Infections.

    OpenAIRE

    Günday Türeli, Nazende; Torge, Afra; Juntke, Jenny; Schwarz, Bianca C; Schneider-Daum, Nicole; Türeli, Akif Emre; Lehr, Claus-Michael; Schneider, Marc

    2017-01-01

    Current pulmonary treatments against Pseudomonasaeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with c...

  8. Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Sanyuan Hu

    2010-11-01

    Full Text Available Sanyuan Hu1, Yangde Zhang21Xiangya School of Medicine and 2National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Changsha, Hunan Province, People’s Republic of ChinaAbstract: Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol modified poly (DL-lactide-co-glycolide (PEG-PLGA by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM, photon correlation spectroscopy (PCS, and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak

  9. Eugenol-loaded chitosan nanoparticles: II. Application in bio-based plastics for active packaging.

    Science.gov (United States)

    Woranuch, Sarekha; Yoksan, Rangrong

    2013-07-25

    The aim of the present research was to study the possibility of using eugenol-loaded chitosan nanoparticles as antioxidants for active bio-based packaging material. Eugenol-loaded chitosan nanoparticles were incorporated into thermoplastic flour (TPF) - a model bio-based plastic - through an extrusion process at temperatures above 150°C. The influences of eugenol-loaded chitosan nanoparticles on crystallinity, morphology, thermal properties, radical scavenging activity, reducing power, tensile properties and barrier properties of TPF were investigated. Although the incorporation of 3% (w/w) of eugenol-loaded chitosan nanoparticles significantly reduced the extensibility and the oxygen barrier property of TPF, it provided antioxidant activity and improved the water vapor barrier property. In addition, TPF containing eugenol-loaded chitosan nanoparticles exhibited superior radical scavenging activity and stronger reducing power compared with TPF containing naked eugenol. The results suggest the applicability of TPF containing eugenol-loaded chitosan nanoparticles as an antioxidant active packaging material. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Development of Drug Loaded Nanoparticles Binding to Hydroxyapatite Based on a Bisphosphonate Modified Nonionic Surfactant

    Directory of Open Access Journals (Sweden)

    Jiabin Zhang

    2015-01-01

    Full Text Available This study aimed at development of drug loaded nanoparticles which could bind to hydroxyapatite (HA to construct drug or growth factor releasing bone graft substitutes. To this end, the terminal hydroxyl group of a nonionic surfactant Brij 78 (polyoxyethylene (20 stearyl ether was first modified with pamidronate (Pa. Using Pa-Brij 78 as both a surfactant and an affinity ligand to HA, three different Pa surface functionalized nanoparticles were prepared, named as solid lipid nanoparticles (Pa-SNPs, nanoemulsions (Pa-NEMs, and PLGA nanoparticles (Pa-PNPs. A model drug curcumin was successfully encapsulated in the three nanoparticles. The sizes of Pa-NEM and Pa-PNP were around 150 nm and the size of Pa-SNP was around 90 nm with polydispersity indexes (PDIs less than 0.20. Drug encapsulation efficiencies of the three nanoparticles were all greater than 85%. Furthermore, the order of binding affinity of the nanoparticles to HA was Pa-PNP>Pa-NEM=Pa-SNP. After lyophilization, the sizes of the three nanoparticles were increased about 0.5–2.0-fold but their binding affinities to HA were almost the same as the fresh prepared nanoparticles. In conclusion, a Pa-modified Brij 78 was synthesized and used for fabrication of a series of drug loaded nanoparticles to construct drug-eluting HA-based bone graft substitutes.

  11. Hydroxycamptothecin-loaded nanoparticles enhance target drug delivery and anticancer effect

    Directory of Open Access Journals (Sweden)

    Li Su

    2008-05-01

    Full Text Available Abstract Background Hydroxycamptothecin (HCPT has been shown to have activity against a broad spectrum of cancers. In order to enhance its tissue-specific delivery and anticancer activity, we prepared HCPT-loaded nanoparticles made from poly(ethylene glycol-poly(γ-benzyl-L-glutamate (PEG-PBLG, and then studied their release characteristics, pharmacokinetic characteristics, and anticancer effects. PEG-PBLG nanoparticles incorporating HCPT were prepared by a dialysis method. Scanning electron microscopy (SEM was used to observe the shape and diameter of the nanoparticles. The HCPT release characteristics in vitro were evaluated by ultraviolet spectrophotometry. A high-performance liquid chromatography (HPLC detection method for determining HCPT in rabbit plasma was established. The pharmacokinetic parameters of HCPT/PEG-PBLG nanoparticles were compared with those of HCPT. Results The HCPT-loaded nanoparticles had a core-shell spherical structure, with a core diameter of 200 nm and a shell thickness of 30 nm. Drug-loading capacity and drug encapsulation were 7.5 and 56.8%, respectively. The HCPT release profile was biphasic, with an initial abrupt release, followed by sustained release. The terminal elimination half-lives (t 1/2 β of HCPT and HCPT-loaded nanoparticles were 4.5 and 10.1 h, respectively. Peak concentrations (Cmax of HCPT and HCPT-loaded nanoparticles were 2627.8 and 1513.5 μg/L, respectively. The apparent volumes of distribution of the HCPT and HCPT-loaded nanoparticles were 7.3 and 20.0 L, respectively. Compared with a blank control group, Lovo cell xenografts or Tca8113 cell xenografts in HCPT or HCPT-loaded nanoparticle treated groups grew more slowly and the tumor doubling times were increased. The tumor inhibition effect in the HCPT-loaded nanosphere-treated group was significantly higher than that of the HCPT-treated group (p 0.05. Conclusion Compared to the HCPT- and control-treated groups, the HCPT-loaded nanoparticle

  12. Core-shell nanocarriers with high paclitaxel loading for passive and active targeting

    Science.gov (United States)

    Jin, Zhu; Lv, Yaqi; Cao, Hui; Yao, Jing; Zhou, Jianping; He, Wei; Yin, Lifang

    2016-06-01

    Rapid blood clearance and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor tumor selectivity. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide homing to αVβ3 integrins. Herein, core-shell nanocapsules (NCs) and iRGD-modified NCs (iRGD-NCs) with high drug payload for paclitaxel (PTX) were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Improved in vitro and in vivo tumor targeting and penetration were observed with NCs and iRGD-NCs; the latter exhibited better antitumor activity because iRGD enhanced the accumulation and penetration of NCs in tumors. The NCs were cytocompatible, histocompatible, and non-toxic to other healthy tissues. The endocytosis of NCs was mediated by lipid rafts in an energy-dependent manner, leading to better cytotoxicity of PTX against cancer cells. In contrast with commercial product, PTX-loaded NCs (PTX-NCs) increased area under concentration-time curve (AUC) by about 4-fold, prolonged mean resident time (MRT) by more than 8-fold and reduced the elimination rate constant by greater than 68-fold. In conclusion, the present nanocarriers with high drug-loading capacity represent an efficient tumor-targeting drug delivery system with promising potential for cancer therapy.

  13. Wettability alteration properties of fluorinated silica nanoparticles in liquid-loaded pores: An atomistic simulation

    International Nuclear Information System (INIS)

    Sepehrinia, Kazem; Mohammadi, Aliasghar

    2016-01-01

    Highlights: • Properties of fluorinated silica nanoparticles were investigated in water or decane-loaded pores of mineral silica using molecular dynamics simulation. • The water or decane-loaded pores represent liquid bridging. • Addition of nanoparticles to liquid-loaded pores results in weakening of the liquid bridge. • The hydrophobicity of the pore wall increases in the presence of adsorbed fluorinated silica nanoparticles. - Abstract: Control over the wettability of reservoir rocks is of crucial importance for enhancing oil and gas recovery. In order to develop chemicals for controlling the wettability of reservoir rocks, we present a study of functionalized silica nanoparticles as candidates for wettability alteration and improved gas recovery applications. In this paper, properties of fluorinated silica nanoparticles were investigated in water or decane-loaded pores of mineral silica using molecular dynamics simulation. Trifluoromethyl groups as water and oil repellents were placed on the nanoparticles. Simulating a pore in the presence of trapped water or decane molecules leads to liquid bridging for both of the liquids. Adsorption of nanoparticles on the pore wall reduces the density of liquid molecules adjacent to the wall. The density of liquid molecules around the nanoparticles decreases significantly with increasing the number of trifluoromethyl groups on the nanoparticles’ surfaces. An increased hydrophobicity of the pore wall was observed in the presence of adsorbed fluorinated silica nanoparticles. Also, it is observed that increasing the number of the trifluoromethyl groups results in weakening of liquid bridges. Moreover, the free energy of adsorption on mineral surface was evaluated to be more favorable than that of aggregation of nanoparticles, which suggests nanoparticles adsorb preferably on mineral surface.

  14. Wettability alteration properties of fluorinated silica nanoparticles in liquid-loaded pores: An atomistic simulation

    Energy Technology Data Exchange (ETDEWEB)

    Sepehrinia, Kazem; Mohammadi, Aliasghar, E-mail: amohammadi@sharif.edu

    2016-05-15

    Highlights: • Properties of fluorinated silica nanoparticles were investigated in water or decane-loaded pores of mineral silica using molecular dynamics simulation. • The water or decane-loaded pores represent liquid bridging. • Addition of nanoparticles to liquid-loaded pores results in weakening of the liquid bridge. • The hydrophobicity of the pore wall increases in the presence of adsorbed fluorinated silica nanoparticles. - Abstract: Control over the wettability of reservoir rocks is of crucial importance for enhancing oil and gas recovery. In order to develop chemicals for controlling the wettability of reservoir rocks, we present a study of functionalized silica nanoparticles as candidates for wettability alteration and improved gas recovery applications. In this paper, properties of fluorinated silica nanoparticles were investigated in water or decane-loaded pores of mineral silica using molecular dynamics simulation. Trifluoromethyl groups as water and oil repellents were placed on the nanoparticles. Simulating a pore in the presence of trapped water or decane molecules leads to liquid bridging for both of the liquids. Adsorption of nanoparticles on the pore wall reduces the density of liquid molecules adjacent to the wall. The density of liquid molecules around the nanoparticles decreases significantly with increasing the number of trifluoromethyl groups on the nanoparticles’ surfaces. An increased hydrophobicity of the pore wall was observed in the presence of adsorbed fluorinated silica nanoparticles. Also, it is observed that increasing the number of the trifluoromethyl groups results in weakening of liquid bridges. Moreover, the free energy of adsorption on mineral surface was evaluated to be more favorable than that of aggregation of nanoparticles, which suggests nanoparticles adsorb preferably on mineral surface.

  15. PLGA nanoparticles from nano-emulsion templating as imaging agents: Versatile technology to obtain nanoparticles loaded with fluorescent dyes.

    Science.gov (United States)

    Fornaguera, C; Feiner-Gracia, N; Calderó, G; García-Celma, M J; Solans, C

    2016-11-01

    The interest in polymeric nanoparticles as imaging systems for biomedical applications has increased notably in the last decades. In this work, PLGA nanoparticles, prepared from nano-emulsion templating, have been used to prepare novel fluorescent imaging agents. Two model fluorescent dyes were chosen and dissolved in the oil phase of the nano-emulsions together with PLGA. Nano-emulsions were prepared by the phase inversion composition (PIC) low-energy method. Fluorescent dye-loaded nanoparticles were obtained by solvent evaporation of nano-emulsion templates. PLGA nanoparticles loaded with the fluorescent dyes showed hydrodynamic radii lower than 40nm; markedly lower than those reported in previous studies. The small nanoparticle size was attributed to the nano-emulsification strategy used. PLGA nanoparticles showed negative surface charge and enough stability to be used for biomedical imaging purposes. Encapsulation efficiencies were higher than 99%, which was also attributed to the nano-emulsification approach as well as to the low solubility of the dyes in the aqueous component. Release kinetics of both fluorescent dyes from the nanoparticle dispersions was pH-independent and sustained. These results indicate that the dyes could remain encapsulated enough time to reach any organ and that the decrease of the pH produced during cell internalization by the endocytic route would not affect their release. Therefore, it can be assumed that these nanoparticles are appropriate as systemic imaging agents. In addition, in vitro toxicity tests showed that nanoparticles are non-cytotoxic. Consequently, it can be concluded that the preparation of PLGA nanoparticles from nano-emulsion templating represents a very versatile technology that enables obtaining biocompatible, biodegradable and safe imaging agents suitable for biomedical purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy.

    Science.gov (United States)

    Xu, Wujun; Thapa, Rinez; Liu, Dongfei; Nissinen, Tuomo; Granroth, Sari; Närvänen, Ale; Suvanto, Mika; Santos, Hélder A; Lehto, Vesa-Pekka

    2015-11-02

    In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. In vitro cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs.

  17. Electrospun polyacrylonitrile nanofibers loaded with silver nanoparticles by silver mirror reaction

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yongzheng; Li, Yajing; Zhang, Jianfeng; Yu, Zhongzhen; Yang, Dongzhi, E-mail: yangdz@mail.buct.edu.cn

    2015-06-01

    The silver mirror reaction (SMR) method was selected in this paper to modify electrospun polyacrylonitrile (PAN) nanofibers, and these nanofibers loaded with silver nanoparticles showed excellent antibacterial properties. PAN nanofibers were first pretreated in AgNO{sub 3} aqueous solution before the SMR process so that the silver nanoparticles were distributed evenly on the outer surface of the nanofibers. The final PAN nanofibers were characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), transmission electron microscopy (TEM), TEM-selected area electron diffraction (SAED), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). SEM, TEM micrographs and SAED patterns confirmed homogeneous dispersion of the silver nanoparticles which were composed of monocrystals with diameters 20–30 nm. EDS and XRD results showed that these monocrystals tended to form face-centered cubic single silver. TGA test indicated that the nanoparticles loaded on the nanofibers reached above 50 wt.%. This material was also evaluated by the viable cell-counting method. The results indicated that PAN nanofibers loaded with silver nanoparticles exhibited excellent antimicrobial activities against gram-negative Escherichia coli (E. coli), gram-positive Staphylococcus aureus (S. aureus) and the fungus Monilia albicans. Thus, this material had many potential applications in biomedical fields. - Highlights: • Silver mirror reaction was used to prepare nanofibers loaded with silver nanoparticles. • The SAED patterns demonstrated the monocrystallinity of silver nanocrystals. • The XRD results showed nanoparticles tended to be face-centered cubic single silver. • The material showed excellent antimicrobial activities against bacteria and fungi.

  18. Electrospun polyacrylonitrile nanofibers loaded with silver nanoparticles by silver mirror reaction

    International Nuclear Information System (INIS)

    Shi, Yongzheng; Li, Yajing; Zhang, Jianfeng; Yu, Zhongzhen; Yang, Dongzhi

    2015-01-01

    The silver mirror reaction (SMR) method was selected in this paper to modify electrospun polyacrylonitrile (PAN) nanofibers, and these nanofibers loaded with silver nanoparticles showed excellent antibacterial properties. PAN nanofibers were first pretreated in AgNO 3 aqueous solution before the SMR process so that the silver nanoparticles were distributed evenly on the outer surface of the nanofibers. The final PAN nanofibers were characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), transmission electron microscopy (TEM), TEM-selected area electron diffraction (SAED), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). SEM, TEM micrographs and SAED patterns confirmed homogeneous dispersion of the silver nanoparticles which were composed of monocrystals with diameters 20–30 nm. EDS and XRD results showed that these monocrystals tended to form face-centered cubic single silver. TGA test indicated that the nanoparticles loaded on the nanofibers reached above 50 wt.%. This material was also evaluated by the viable cell-counting method. The results indicated that PAN nanofibers loaded with silver nanoparticles exhibited excellent antimicrobial activities against gram-negative Escherichia coli (E. coli), gram-positive Staphylococcus aureus (S. aureus) and the fungus Monilia albicans. Thus, this material had many potential applications in biomedical fields. - Highlights: • Silver mirror reaction was used to prepare nanofibers loaded with silver nanoparticles. • The SAED patterns demonstrated the monocrystallinity of silver nanocrystals. • The XRD results showed nanoparticles tended to be face-centered cubic single silver. • The material showed excellent antimicrobial activities against bacteria and fungi

  19. Evaluation of self-assembled HCPT-loaded PEG-b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles.

    Science.gov (United States)

    Yang, Xiangrui; Wu, Shichao; Wang, Yange; Li, Yang; Chang, Di; Luo, Yin; Ye, Shefang; Hou, Zhenqing

    2014-12-01

    We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(D,L-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

  20. Development of flurbiprofen-loaded nanoparticles with a narrow size distribution using sucrose.

    Science.gov (United States)

    Oh, Dong Hoon; Yan, Yi-Dong; Kim, Dong Wuk; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2014-02-01

    A novel flurbiprofen-loaded nanoemulsion which gave uniform emulsion droplets with a narrow size distribution was previously reported to be prepared using membrane emulsification method. The purpose of this study is to develop a novel flurbiprofen-loaded nanoparticle with a narrow size distribution and improved bioavailability. The nanoparticle was prepared by solidifying nanoemulsion using sucrose as a carrier via spray drying method. Its physicochemical properties were investigated using SEM, DSC and PXRD. Furthermore, dissolution and bioavailability in rats were evaluated compared to a flurbiprofen-loaded commercial product. The flurbiprofen-loaded nanoparticles with flurbiprofen/sucrose/surfactant mixture (1/20/2, weight ratio) gave good solidification and no stickiness. They associated with about 70,000-fold improved drug solubility and had a mean size of about 300 nm with a narrow size distribution. Flurbiprofen was present in a changed amorphous state in these nanoparticles. Moreover, the nanoparticles gave significantly shorter Tmax, and higher AUC and Cmax of the drug compared to the commercial product (p flurbiprofen-loaded nanoparticles prepared with sucrose by the membrane emulsification and spray drying method would be a potential candidate for orally delivering poorly water-soluble flurbiprofen with enhanced bioavailability.

  1. Storage Stabilisation of Albumin-Loaded Chitosan Nanoparticles by ...

    African Journals Online (AJOL)

    The rate of BSA leakage from the nanoparticles containing trehalose was reduced from 92 ... water. CS/DS nanoparticles were simultaneously prepared by adding 4 ml of DS solution dropwise ... performed in triplicate at 25 oC with a detection.

  2. Formulation and characterization of solid lipid nanoparticles loaded Neem oil for topical treatment of acne

    Directory of Open Access Journals (Sweden)

    V. Vijayan

    2013-01-01

    Conclusion: The result concluded that Neem oil loaded solid lipid nanoparticles with more lecithin content in their colloid exhibit sustained effect which satisfactorily produced the antibacterial action on Acne microbes. Therefore Neem oil loaded SLN was used successfully for prolonged treatment of Acne.

  3. Probing the impact of loading rate on the mechanical properties of viral nanoparticles

    NARCIS (Netherlands)

    Snijder, J.; Ivanovska, I.L.; Baclayon, M.; Roos, W.H.; Wuite, G.J.L.

    2012-01-01

    The effects of changes in the loading rate during the forced dissociation of single bonds have been studied for a wide variety of interactions. Less is known on the loading rate dependent behaviour of more complex systems that consist of multiple bonds. Here we focus on viral nanoparticles, in

  4. Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation.

    Science.gov (United States)

    Dim, Nneka; Perepelyuk, Maryna; Gomes, Olukayode; Thangavel, Chellappagounder; Liu, Yi; Den, Robert; Lakshmikuttyamma, Ashakumary; Shoyele, Sunday A

    2015-09-26

    siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated. It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells. This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1

  5. The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation.

    Science.gov (United States)

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2017-12-01

    Therapeutic peptides are conventionally administered via subcutaneous injection. Chitosan-based nanoparticles are gaining increased attention for their ability to serve as a carrier for oral delivery of peptides and vaccination. They offered superior biocompatibiltiy, controlled drug release profile and facilitated gastrointestinal (GI) absorption. The encapsulated peptides can withstand enzymatic degradation and various pH. Chitosan-based nanoparticles can also be modified by ligand conjugation to the surface of nanoparticle for transcellular absorption and specific-targeted delivery of macromolecules to the tissue of interest. Current research suggests that chitosan-based nanoparticles can deliver therapeutic peptide for the treatment of several medical conditions such as diabetes, bacterial infection and cancer. This review summarises the role of chitosan in oral nanoparticle delivery and identifies the clinical application of peptide-loaded chitosan-based nanoparticles.

  6. Folate receptor targeted 17-allylamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric nanoparticles for breast cancer.

    Science.gov (United States)

    Saxena, Vipin; Naguib, Youssef; Hussain, M Delwar

    2012-06-01

    Low water solubility and hepatotoxicity limited the clinical use of 17-allylamino-17-demethoxy geldanamycin (17-AAG), an inhibitor of heat shock protein 90 (HSP90). Folate targeted polylactide-co-glycolide-polyethylene glycol-folic acid (PLGA-PEG-FA) nanoparticles containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared nanoparticles were determined in MCF-7 human breast cancer cells. The particle size of 17-AAG loaded folate targeted nanoparticles was 238.67±3.52 nm, drug loading was 8.25±2.49% and about 80% of drug was released from the nanoparticles over 10 days. Cellular uptake studies showed much higher intracellular uptake of folate targeted nanoparticle as compared to nontargeted nanoparticles. Cytotoxicity study showed 2 fold increase (PAAG loaded PLGA-PEG-FA nanoparticles might be developed as a targeted delivery system for breast and other cancer treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Peptide-Loaded Solid Lipid Nanoparticles Prepared through Coacervation Technique

    Directory of Open Access Journals (Sweden)

    Marina Gallarate

    2011-01-01

    Full Text Available Stearic acid solid lipid nanoparticles were prepared according to a new technique, called coacervation. The main goal of this experimental work was the entrapment of peptide drugs into SLN, which is a difficult task, since their chemical characteristics (molecular weight, hydrophilicity, and stability hamper peptide-containing formulations. Insulin and leuprolide, chosen as model peptide drugs, were encapsulated within nanoparticles after hydrophobic ion pairing with anionic surfactants. Peptide integrity was maintained after encapsulation, and nanoparticles can act in vitro as a sustained release system for peptide.

  8. Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.

    Science.gov (United States)

    de Araújo, Thiago M; Teixeira, Zaine; Barbosa-Sampaio, Helena C; Rezende, Luiz F; Boschero, Antonio C; Durán, Nelson; Höehr, Nelci F

    2013-06-01

    The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.

  9. Improved photodynamic action of nanoparticles loaded with indium (III) phthalocyanine on MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Souto, Carlos Augusto Zanoni [Federal Institute of Espirito Santo (Brazil); Madeira, Klesia Pirola [Federal University of Espirito Santo, Biotechnology Program/RENORBIO, Health Sciences Center (Brazil); Rettori, Daniel [Federal University of Sao Paulo, Department of Exact Sciences and Earth (Brazil); Baratti, Mariana Ozello [University of Campinas, Department of Cellular Biology (Brazil); Rangel, Leticia Batista Azevedo [Federal University of Espirito Santo, Department of Pharmaceutical Sciences (Brazil); Razzo, Daniel [University of Campinas, Department of Physical Chemistry, Institute of Chemistry (Brazil); Silva, Andre Romero da, E-mail: aromero@ifes.edu.br [Federal Institute of Espirito Santo (Brazil)

    2013-09-15

    Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly(d,l-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. The efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. The influence of photosensitizer (PS) concentration (1.8-7.5 {mu}mol/L), incubation time (1-2 h), and laser power (10-100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 {+-} 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. The InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. For a light dose of 7.5 J/cm{sup 2} and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 {+-} 3 % while for free InPc was 60 {+-} 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. The nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. The participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc.

  10. Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin.

    Science.gov (United States)

    Aluani, Denitsa; Tzankova, Virginia; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Nikolova, Elena; Odzhakov, Feodor; Apostolov, Alexandar; Markova, Tzvetanka; Yoncheva, Krassimira

    2017-10-01

    The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe 2+ /AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B.

    Science.gov (United States)

    Khatri, Kapil; Goyal, Amit K; Gupta, Prem N; Mishra, Neeraj; Vyas, Suresh P

    2008-04-16

    This work investigates the preparation and in vivo efficacy of plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Chitosan pDNA nanoparticles were prepared using a complex coacervation process. Prepared nanoparticles were characterized for size, shape, surface charge, plasmid loading and ability of nanoparticles to protect DNA against nuclease digestion and for their transfection efficacy. Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level. However, intramuscular administration of naked DNA and alum adsorbed HBsAg did not elicit sIgA titre in mucosal secretions that was induced by nasal immunization with chitosan nanoparticles. Similarly, cellular responses (cytokine levels) were poor in case of alum adsorbed HBsAg. Chitosan nanoparticles thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. The study signifies the potential of chitosan nanoparticles as DNA vaccine carrier and adjuvant for effective immunization through non-invasive nasal route.

  12. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    International Nuclear Information System (INIS)

    Tuan Anh, Nguyen; Tuyen Dao, T P; Nhan Le, N T; Mau Chien, Dang; To Hoai, Nguyen; T Chi, Nguyen; Tran, T Khai

    2012-01-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid. (paper)

  13. Preparation and Optimization OF Palm-Based Lipid Nanoparticles Loaded with Griseofulvin.

    Science.gov (United States)

    Huei Lim, Wen; Jean Tan, Yann; Sin Lee, Choy; Meng Er, Hui; Fung Wong, Shew

    2017-01-01

    Palm-based lipid nanoparticle formulation loaded with griseofulvin was prepared by solvent-free hot homogenization method. The griseofulvin loaded lipid nanoparticles were prepared via stages of optimisation, by altering the high pressure homogenisation (HPH) parameters, screening on palm-based lipids and Tween series surfactants and selection of lipid to surfactant ratios. A HPLC method has been validated for the drug loading capacity study. The optimum HPH parameter was determined to be 1500 bar with 5 cycles and among the palm-based lipid materials; Lipid C (triglycerides) was selected for the preparation of lipid nanoparticles. Tween 80 was chosen from the Tween series surfactants for its highest saturated solubility of griseofulvin at 53.1 ± 2.16 µg/mL. The optimum formulation of the griseofulvin loaded lipid nanoparticles demonstrated nano-range of particle size (179.8 nm) with intermediate distribution index (PDI) of 0.306, zeta potential of -27.9 mV and drug loading of 0.77%. The formulation was stable upon storage for 1 month at room temperature (25 ° C) and 45 ° C with consistent drug loading capacity.

  14. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

    Science.gov (United States)

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S.; Tremoli, Elena; Catapano, Alberico L.; Norata, Giuseppe D.; Bottazzi, Barbara; Garlanda, Cecilia

    2015-01-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  15. Effects of curcumin-loaded PLGA nanoparticles on the RG2 rat glioma model.

    Science.gov (United States)

    Orunoğlu, Merdan; Kaffashi, Abbas; Pehlivan, Sibel Bozdağ; Şahin, Selma; Söylemezoğlu, Figen; Oğuz, Kader Karli; Mut, Melike

    2017-09-01

    Curcumin, the active ingredient of turmeric, has a remarkable antitumor activity against various cancers, including glioblastoma. However, it has poor absorption and low bioavailability; thus, to cross the blood-brain barrier and reach tumor tissue, it needs to be transferred to tumor site by special drug delivery systems, such as nanoparticles. We aimed to evaluate the antitumor activity of curcumin on glioblastoma tissue in the rat glioma-2 (RG2) tumor model when it is loaded on poly(lactic-co-glycolic acid)-1,2-distearoyl-glycerol-3-phospho-ethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt (PLGA-DSPE-PEG) hybrid nanoparticles. Glioblastoma was induced in 42 adult female Wistar rats (250-300g) by RG2 tumor model. The curcumin-loaded nanoparticles were injected by intravenous (n=6) or intratumoral route (n=6). There were five control groups, each containing six rats. First control group was not applied any treatment. The remaining four control groups were given empty nanoparticles or curcumin alone by intravenous or intratumoral route, respectively. The change in tumor volume was assessed by magnetic resonance imaging and histopathology before and 5days after drug injections. Tumor size decreased significantly after 5days of intratumoral injection of curcumin-loaded nanoparticle (from 66.6±44.6 to 34.9±21.7mm 3 , p=0.028), whereas it significantly increased in nontreated control group (from 33.9±21.3 to 123.7±41.1mm 3 , p=0.036) and did not significantly change in other groups (p>0.05 for all). In this in vivo experimental model, intratumoral administration of curcumin-loaded PLGA-DSPE-PEG hybrid nanoparticles was effective against glioblastoma. Curcumine-loaded nanoparticles may have potential application in chemotherapy of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

    Science.gov (United States)

    Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

    2011-01-01

    Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

  17. Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells.

    Science.gov (United States)

    Menale, Ciro; Piccolo, Maria Teresa; Favicchia, Ilaria; Aruta, Maria Grazia; Baldi, Alfonso; Nicolucci, Carla; Barba, Vincenzo; Mita, Damiano Gustavo; Crispi, Stefania; Diano, Nadia

    2015-02-01

    Combined treatment based on cisplatin-loaded Poly(D,L-lactic-co-glicolic)acid (PLGA) nanoparticles (NP-C) plus the NSAID piroxicam was used as novel treatment for mesothelioma to reduce side effects related to cisplatin toxicity. PLGA nanoparticles were prepared by double emulsion solvent evaporation method. Particle size, drug release profile and in vitro cellular uptake were characterized by TEM, DLS, LC/MS and fluorescence microscopy. MSTO-211H cell line was used to analyse NP-C biological efficacy by FACS and protein analysis. Cisplatin was encapsulated in 197 nm PLGA nanoparticles with 8.2% drug loading efficiency and 47% encapsulation efficiency. Cisplatin delivery from nanoparticles reaches 80% of total encapsulated drug in 14 days following a triphasic trend. PLGA nanoparticles in MSTO-211H cells were localized in the perinuclear space NP-C in combination with piroxicam induced apoptosis using a final cisplatin concentration 1.75 fold less than free drug. Delivered cisplatin cooperated with piroxicam in modulating cell cycle regulators as caspase-3, p53 and p21. Cisplatin loaded PLGA nanoparticles plus piroxicam showed a good efficacy in exerting cytotoxic activity and inducing the same molecular apoptotic effects of the free drugs. Sustained cisplatin release allowed to use less amount of drug, decreasing toxic side effects. This novel approach could represent a new strategy for mesothelioma treatment.

  18. Cyclodextrin-PEG conjugate-wrapped magnetic ferrite nanoparticles for enhanced drug loading and release

    Science.gov (United States)

    Enoch, Israel V. M. V.; Ramasamy, Sivaraj; Mohiyuddin, Shanid; Gopinath, Packirisamy; Manoharan, R.

    2018-05-01

    Magnetic nanoparticles are envisaged to overcome the impediments in the methods of targeted drug delivery and hence cure cancer effectively. We report herein, manganese ferrite nanoparticles, coated with β-cyclodextrin-modified polyethylene glycol as a carrier for the drug, camptothecin. The particles are of the size of 100 nm and they show superparamagnetic behaviour. The saturation magnetization does not get diminished on polymer coverage of the nanoparticles. The β-cyclodextrin-polyethylene glycol conjugates are characterized using NMR and mass spectrometric techniques. By coating the magnetic nanoparticles with the cyclodextrin-tethered polymer, the drug-loading capacity is enhanced and the observed release of the drug is slow and sustained. The cell viability of HEK293 and HCT15 cells is evaluated and the cytotoxicity is enhanced when the drug is loaded in the polymer-coated magnetic nanoparticles. The noncovalent-binding based and enhanced drug loading on the nanoparticles and the sustained release make the nanocarrier a promising agent for carrying the payload to the target.

  19. Artesunate-loaded chitosan/lecithin nanoparticles: preparation, characterization, and in vivo studies.

    Science.gov (United States)

    Chadha, Renu; Gupta, Sushma; Pathak, Natasha

    2012-12-01

    Artesunate (AST), the most widely used artemisnin derivative, has poor aqueous solubility and suffers from low oral bioavailability (~40%). Under these conditions, nanoparticles with controlled and sustained released properties can be a suitable solution for improving its biopharmaceuticals properties. This work reports the preparation and characterization of auto-assembled chitosan/lecithin nanoparticles loaded with AST and AST complexed with β-cyclodextrin (β-CD) to boost its antimalarial activity. The nanoparticles prepared by direct injection of lecithin alcoholic solution into chitosan/water solution have shown the particle size distribution below 300 nm. Drug entrapment efficiency was found to be maximum (90%) for nanoparticles containing 100 mg of AST. Transmission electron microscopy images show spherical shape with contrasted corona (chitosan) surrounded by a lipidic core (lecithin + isopropyl myristate). Differential scanning calorimeter thermograms demonstrated the presence of drug in drug-loaded nanoparticles along with the disappearance of decomposition exotherm suggesting the increased physical stability of drug in prepared formulations. Negligible changes in the characteristic peaks of drug in Fourier-transform infrared spectra indicated the absence of any interaction among the various components entrapped in the nanoparticle formulation. In vitro drug release behavior was found to be influenced by pH value. Increased in vivo antimalarial activity in terms of less mean percent parasitemia was observed in infected Plasmodium berghei mice after the oral administration of all the prepared nanoparticle formulations.

  20. [Development of Inhalable Dry Powder Formulations Loaded with Nanoparticles Maintaining Their Original Physical Properties and Functions].

    Science.gov (United States)

    Okuda, Tomoyuki

    2017-01-01

     Functional nanoparticles, such as liposomes and polymeric micelles, are attractive drug delivery systems for solubilization, stabilization, sustained release, prolonged tissue retention, and tissue targeting of various encapsulated drugs. For their clinical application in therapy for pulmonary diseases, the development of dry powder inhalation (DPI) formulations is considered practical due to such advantages as: (1) it is noninvasive and can be directly delivered into the lungs; (2) there are few biocomponents in the lungs that interact with nanoparticles; and (3) it shows high storage stability in the solid state against aggregation or precipitation of nanoparticles in water. However, in order to produce effective nanoparticle-loaded dry powders for inhalation, it is essential to pursue an innovative and comprehensive formulation strategy in relation to composition and powderization which can achieve (1) the particle design of dry powders with physical properties suitable for pulmonary delivery through inhalation, and (2) the effective reconstitution of nanoparticles that will maintain their original physical properties and functions after dissolution of the powders. Spray-freeze drying (SFD) is a relatively new powderization technique combining atomization and lyophilization, which can easily produce highly porous dry powders from an aqueous sample solution. Previously, we advanced the optimization of components and process conditions for the production of SFD powders suitable to DPI application. This review describes our recent results in the development of novel DPI formulations effectively loaded with various nanoparticles (electrostatic nanocomplexes for gene therapy, liposomes, and self-assembled lipid nanoparticles), based on SFD.

  1. Photodynamic effects of methylene blue-loaded polymeric nanoparticles on dental plaque bacteria.

    Science.gov (United States)

    Klepac-Ceraj, Vanja; Patel, Niraj; Song, Xiaoqing; Holewa, Colleen; Patel, Chitrang; Kent, Ralph; Amiji, Mansoor M; Soukos, Nikolaos S

    2011-09-01

    Photodynamic therapy (PDT) is increasingly being explored for treatment of oral infections. Here, we investigate the effect of PDT on human dental plaque bacteria in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles with a positive or negative charge and red light at 665 nm. Dental plaque samples were obtained from 14 patients with chronic periodontitis. Suspensions of plaque microorganisms from seven patients were sensitized with anionic, cationic PLGA nanoparticles (50 µg/ml equivalent to MB) or free MB (50 µg/ml) for 20 min followed by exposure to red light for 5 min with a power density of 100 mW/cm2 . Polymicrobial oral biofilms, which were developed on blood agar in 96-well plates from dental plaque inocula obtained from seven patients, were also exposed to PDT as above. Following the treatment, survival fractions were calculated by counting the number of colony-forming units. The cationic MB-loaded nanoparticles exhibited greater bacterial phototoxicity in both planktonic and biofilm phase compared to anionic MB-loaded nanoparticles and free MB, but results were not significantly different (P > 0.05). Cationic MB-loaded PLGA nanoparticles have the potential to be used as carriers of MB for PDT systems. Copyright © 2011 Wiley-Liss, Inc.

  2. Dual drug-loaded nanoparticles on self-integrated scaffold for controlled delivery

    Directory of Open Access Journals (Sweden)

    Bennet D

    2012-07-01

    Full Text Available Devasier Bennet,1 Mohana Marimuthu,1 Sanghyo Kim,1 Jeongho An21Department of Bionanotechnology, Gachon University, Gyeonggi, Republic of Korea; 2Department of Polymer Science and Engineering, SunKyunKwan University, Gyeonggi, Republic of KoreaAbstract: Antioxidant (quercetin and hypoglycemic (voglibose drug-loaded poly-D,L-lactide-co-glycolide nanoparticles were successfully synthesized using the solvent evaporation method. The dual drug-loaded nanoparticles were incorporated into a scaffold film using a solvent casting method, creating a controlled transdermal drug-delivery system. Key features of the film formulation were achieved utilizing several ratios of excipients, including polyvinyl alcohol, polyethylene glycol, hyaluronic acid, xylitol, and alginate. The scaffold film showed superior encapsulation capability and swelling properties, with various potential applications, eg, the treatment of diabetes-associated complications. Structural and light scattering characterization confirmed a spherical shape and a mean particle size distribution of 41.3 nm for nanoparticles in the scaffold film. Spectroscopy revealed a stable polymer structure before and after encapsulation. The thermoresponsive swelling properties of the film were evaluated according to temperature and pH. Scaffold films incorporating dual drug-loaded nanoparticles showed remarkably high thermoresponsivity, cell compatibility, and ex vivo drug-release behavior. In addition, the hybrid film formulation showed enhanced cell adhesion and proliferation. These dual drug-loaded nanoparticles incorporated into a scaffold film may be promising for development into a transdermal drug-delivery system.Keywords: quercetin, voglibose, biocompatible materials, encapsulation, transdermal

  3. Design and Optimization of PLGA-Based Diclofenac Loaded Nanoparticles

    Science.gov (United States)

    Cooper, Dustin L.; Harirforoosh, Sam

    2014-01-01

    Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or 1%) or didodecyldimethylammonium bromide (DMAB) (0.1, 0.25, 0.5, 0.75, or 1%) stabilizers centrifuged at 8,800 rpm or 12,000 rpm. The resultant nanoparticles were evaluated based on particle size, zeta potential, and entrapment efficacy. DMAB formulated NPs showed the lowest particle size (108±2.1 nm) and highest zeta potential (−27.71±0.6 mV) at 0.1 and 0.25% respectively, after centrifugation at 12,000 rpm. Results of the PVA based NP formulation showed the smallest particle size (92.4±7.6 nm) and highest zeta potential (−11.14±0.5 mV) at 0.25% and 1% w/v, respectively, after centrifugation at 12,000 rpm. Drug entrapment reached 77.3±3.5% and 80.2±1.2% efficiency with DMAB and PVA formulations, respectively. The results of our study indicate the use of DMAB for increased nanoparticle stability during formulation. Our study supports the effective utilization of PLGA based nanoparticle formulation for diclofenac. PMID:24489896

  4. Design and optimization of PLGA-based diclofenac loaded nanoparticles.

    Directory of Open Access Journals (Sweden)

    Dustin L Cooper

    Full Text Available Drug based nanoparticle (NP formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide (PLGA based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA (0.1, 0.25, 0.5, or 1% or didodecyldimethylammonium bromide (DMAB (0.1, 0.25, 0.5, 0.75, or 1% stabilizers centrifuged at 8,800 rpm or 12,000 rpm. The resultant nanoparticles were evaluated based on particle size, zeta potential, and entrapment efficacy. DMAB formulated NPs showed the lowest particle size (108 ± 2.1 nm and highest zeta potential (-27.71 ± 0.6 mV at 0.1 and 0.25% respectively, after centrifugation at 12,000 rpm. Results of the PVA based NP formulation showed the smallest particle size (92.4 ± 7.6 nm and highest zeta potential (-11.14 ± 0.5 mV at 0.25% and 1% w/v, respectively, after centrifugation at 12,000 rpm. Drug entrapment reached 77.3 ± 3.5% and 80.2 ± 1.2% efficiency with DMAB and PVA formulations, respectively. The results of our study indicate the use of DMAB for increased nanoparticle stability during formulation. Our study supports the effective utilization of PLGA based nanoparticle formulation for diclofenac.

  5. Curcumin-bortezomib loaded polymeric nanoparticles for synergistic cancer therapy

    Czech Academy of Sciences Publication Activity Database

    Medel, S.; Syrová, Z.; Kováčik, L.; Hrdý, J.; Hornacek, M.; Jäger, Eliezer; Hrubý, Martin; Lund, R.; Cmarko, D.; Štěpánek, Petr; Raška, I.; Nyström, B.

    2017-01-01

    Roč. 93, August (2017), s. 116-131 ISSN 0014-3057 R&D Projects: GA MŠk(CZ) 7F14009 Institutional support: RVO:61389013 Keywords : polymeric nanoparticles * light scattering * flow cytometry Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.531, year: 2016

  6. Storage Stabilisation of Albumin-Loaded Chitosan Nanoparticles by ...

    African Journals Online (AJOL)

    In contrast, the other lyoprotectants (inulin and histidine) did not show stabilizing effects. Moreover, trehalose also reduced the degree of particle aggregation from 329 ± 16 to 836 ± 21 nm upon storage for 24 h as compared to CS/DS nanoparticles without trehalose; from 438 ± 14 to 1298 ± 18 (p < 0.05). The rate of BSA ...

  7. Isoniazid loaded gelatin-cellulose whiskers nanoparticles for ...

    Indian Academy of Sciences (India)

    Controlled drug delivery system represents one of the most advancing areas .... was added drop by drop as cross-linker to crosslink the nanoparticles. ... The distribution of isoni- ... (JEOL JSM – 6390LV) with an acceleration voltage of. 15 kV.

  8. Production of Curcumin-Loaded Silk Fibroin Nanoparticles for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Mercedes G. Montalbán

    2018-02-01

    Full Text Available Curcumin, extracted from the rhizome of Curcuma longa, has been widely used in medicine for centuries due to its anti-inflammatory, anti-cancer, anti-oxidant and anti-microbial effects. However, its bioavailability during treatments is poor because of its low solubility in water, slow dissolution rate and rapid intestinal metabolism. For these reasons, improving the therapeutic efficiency of curcumin using nanocarriers (e.g., biopolymer nanoparticles has been a research focus, to foster delivery of the curcumin inside cells due to their small size and large surface area. Silk fibroin from the Bombyx mori silkworm is a biopolymer characterized by its biocompatibility, biodegradability, amphiphilic chemistry, and excellent mechanical properties in various material formats. These features make silk fibroin nanoparticles useful vehicles for delivering therapeutic drugs, such as curcumin. Curcumin-loaded silk fibroin nanoparticles were synthesized using two procedures (physical adsorption and coprecipitation more scalable than methods previously described using ionic liquids. The results showed that nanoparticle formulations were 155 to 170 nm in diameter with a zeta potential of approximately −45 mV. The curcumin-loaded silk fibroin nanoparticles obtained by both processing methods were cytotoxic to carcinogenic cells, while not decreasing viability of healthy cells. In the case of tumor cells, curcumin-loaded silk fibroin nanoparticles presented higher efficacy in cytotoxicity against neuroblastoma cells than hepatocarcinoma cells. In conclusion, curcumin-loaded silk fibroin nanoparticles constitute a biodegradable and biocompatible delivery system with the potential to treat tumors by local, long-term sustained drug delivery.

  9. Production of Curcumin-Loaded Silk Fibroin Nanoparticles for Cancer Therapy

    Science.gov (United States)

    Coburn, Jeannine M.; Cenis, José L.; Víllora, Gloria; Kaplan, David L.

    2018-01-01

    Curcumin, extracted from the rhizome of Curcuma longa, has been widely used in medicine for centuries due to its anti-inflammatory, anti-cancer, anti-oxidant and anti-microbial effects. However, its bioavailability during treatments is poor because of its low solubility in water, slow dissolution rate and rapid intestinal metabolism. For these reasons, improving the therapeutic efficiency of curcumin using nanocarriers (e.g., biopolymer nanoparticles) has been a research focus, to foster delivery of the curcumin inside cells due to their small size and large surface area. Silk fibroin from the Bombyx mori silkworm is a biopolymer characterized by its biocompatibility, biodegradability, amphiphilic chemistry, and excellent mechanical properties in various material formats. These features make silk fibroin nanoparticles useful vehicles for delivering therapeutic drugs, such as curcumin. Curcumin-loaded silk fibroin nanoparticles were synthesized using two procedures (physical adsorption and coprecipitation) more scalable than methods previously described using ionic liquids. The results showed that nanoparticle formulations were 155 to 170 nm in diameter with a zeta potential of approximately −45 mV. The curcumin-loaded silk fibroin nanoparticles obtained by both processing methods were cytotoxic to carcinogenic cells, while not decreasing viability of healthy cells. In the case of tumor cells, curcumin-loaded silk fibroin nanoparticles presented higher efficacy in cytotoxicity against neuroblastoma cells than hepatocarcinoma cells. In conclusion, curcumin-loaded silk fibroin nanoparticles constitute a biodegradable and biocompatible delivery system with the potential to treat tumors by local, long-term sustained drug delivery. PMID:29495296

  10. Farnesylthiosalicylic acid-loaded lipid-polyethylene glycol-polymer hybrid nanoparticles for treatment of glioblastoma.

    Science.gov (United States)

    Kaffashi, Abbas; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Sarısözen, Can; Vural, İmran; Koşucu, Hüsnü; Demir, Taner; Buğdaycı, Kadir Emre; Söylemezoğlu, Figen; Karlı Oğuz, Kader; Mut, Melike

    2017-08-01

    We aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma. Farnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both in vitro (in comparison with non-malignant cell line, L929) and in vivo. Scanning electron microscopy studies showed that all formulations prepared had smooth surface and spherical in shape. FTA and FTA-loaded nanoparticles have cytotoxic activity against RG2 glioma cell lines in cell culture studies, which further increases with addition of DOTAP. Magnetic resonance imaging and histopathologic evaluation on RG2 tumour cells in rat glioma model (49 female Wistar rats, 250-300 g) comparing intravenous and intratumoral injections of the drug have been performed and FTA-loaded nanoparticles reduced tumour size significantly in in-vivo studies, with higher efficiency of intratumoral administration than intravenous route. Farnesylthiosalicylic acid-loaded PLGA-DSPE-PEG-DOTAP hybrid nanoparticles are proven to be effective against glioblastoma in both in-vitro and in-vivo experiments. © 2017 Royal Pharmaceutical Society.

  11. D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery

    Directory of Open Access Journals (Sweden)

    Wu YP

    2015-08-01

    Full Text Available Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,41Tongji School of Pharmacy, 2Department of Oncology, Tongji Hospital, Tongji Medical School, 3Hubei Engineering Research Center for NDDS, 4National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: Paclitaxel (PTX is one of the most effective antineoplastic drugs. Its current clinical administration Taxol® is formulated in Cremophor EL, which causes serious side effects. Nanoparticles (NP with lower systemic toxicity and enhanced therapeutic efficiency may be an alternative formulation of the Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4-arm-PEG-TPGS derivatives, the conjugation of D-α-tocopherol polyethylene glycol succinate (TPGS and 4-arm-polyethylene glycol (4-arm-PEG with different molecular weights, have been successfully synthesized and used as carriers for the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG5K-TPGS NP exhibited the smallest particle size, highest drug-loading efficiency, negligible hemolysis rate, and high physiologic stability. Therefore, it was chosen for further in vitro and in vivo investigations. Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG5K-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780, non-small cell lung cancer (A549, and breast adenocarcinoma cancer (MCF-7 cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG5K-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol® in S180 sarcoma-bearing mice models. This study suggested

  12. Study of Copolymer Composition on Drug Loading Efficiency of Enalapril in Polymersomes and Cytotoxicity of Drug Loaded Nanoparticles.

    Science.gov (United States)

    Danafar, H; Manjili, H K; Najafi, M

    2016-09-01

    Enalapril was used for hypertension and congestive heart failure. Di-block mPEG-PCL copolymers were synthesized and used to prepare of polymersomes for controlled release of enalapril as a hydrophilic drug. The various methods such as HNMR, FTIR, GPC, DSC, PCS and AFM performed for characterization of the polymersomes. The results of AFM showed that the polymersomes had spherical structure and the size of nanoparticles was 97 nm. Drug-loading efficiency of nanoparticles from copolymers with compositions of mPEG1-PCL1, mPEG2-PCL2, and mPEG3-PCL3 were 14.43%, 19.8%, and 12.33% respectively. The release profile of enalapril for drug loaded nanoparticles prepared from mPEG3-PCL3 was very fast and release profile for the nanoparticles prepared from mPEG1-PCL1 and mPEG2-PCL2 was sustained. The IC 50 value of enalapril was determined to be 8 μM while EPM/m-PEG-PCL nanoparticles did not show significant toxicity at equal concentrations in comparison with enalapril drug. Therapeutic preparations of mPEG-PCL micelle are calibrated by the mouse LD 50 assay. A dose-finding scheme of the polymeric micelle showed a safe dose of mPEG-PCL micelles was approximately 330 mg/kg in mice. The relationship between the numbers of animals, number of doses, duration of the assay used to estimate the LD 50 and the precision of the assay were investigated. Overall, the results was showed that m-PEG-PCL polymersomes can be considered as a promising carrier for hydrophilic drugs. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Development of Acyclovir-Loaded Albumin Nanoparticles and Improvement of Acyclovir Permeation Across Human Corneal Epithelial T Cells.

    Science.gov (United States)

    Suwannoi, Panita; Chomnawang, Mullika; Sarisuta, Narong; Reichl, Stephan; Müller-Goymann, Christel C

    2017-12-01

    The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitro transcorneal permeation results revealed that ACV could permeate through the HCE-T cell multilayers significantly higher from BSA nanoparticles than from aqueous ACV solutions. The ACV-loaded BSA nanoparticles could be prepared by desolvation method without glutaraldehyde in the formulation. ACV could increasingly permeate through the multilayers of HCE-T cells from the ACV-loaded BSA nanoparticles. Therefore, the ACV-loaded BSA nanoparticles could be a highly potential ocular drug delivery system.

  14. Insulin-loaded polymeric mucoadhesive nanoparticles: development, characterization and cytotoxicity evaluation

    Directory of Open Access Journals (Sweden)

    Tiago Henrique Honorato Gatti

    2018-06-01

    Full Text Available Abstract Mucoadhesive nanoparticles are particularly interesting for delivery through nasal or pulmonary routes, as an approach to overcome the mucociliary clearance. Moreover, these nanoparticles are attractive for peptide and protein delivery, particularly for insulin to treat diabetes, as an alternative to conventional parenteral administration. Thus, chitosan, a cationic mucoadhesive polysaccharide found in shells of crustaceans, and the negatively-charged dextran sulfate are able to form nanoparticles through ionic condensation, representing a potential insulin carrier. Herein, chitosan/dextran sulfate nanoparticles at various ratios were prepared for insulin loading. Formulations were characterized for particle size, zeta potential, encapsulation efficiency, scanning electron microscopy, differential scanning calorimetry, and in vitro drug release. Moreover, the interaction with mucin and the cytotoxicity against a lung cell line were studied, which altogether have not been addressed before. Results evidenced that a proper selection of polyelectrolytes is necessary for smaller particle size formation and also the composition and zeta potential impact encapsulation efficiency, which is benefited by the positive charge of chitosan. Insulin remained stable after encapsulation as evidenced by calorimetric assays, and was released in a sustained manner in the first 10 h. Positively-charged nanoparticles based on chitosan/dextran-sulfate at the ratio of 6:4 successfully interacted with mucin, which is a prerequisite for delivery to mucus-containing tissues. Finally, insulin-loaded nanoparticles displayed no cytotoxicity effect against lung cells at tested concentrations, suggesting the potential for further in vivo studies.

  15. Biodistribution of arctigenin-loaded nanoparticles designed for multimodal imaging

    OpenAIRE

    Cui, Qingxin; Hou, Yuanyuan; Wang, Yanan; Li, Xu; Liu, Yang; Ma, Xiaoyao; Wang, Zengyong; Wang, Weiya; Tao, Jin; Wang, Qian; Jiang, Min; Chen, Dongyan; Feng, Xizeng; Bai, Gang

    2017-01-01

    Background Tracking targets of natural products is one of the most challenging issues in fields ranging from pharmacognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a ?key? that opens the target ?lock?. Results We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were characteriz...

  16. Solid lipid nanoparticles by coacervation loaded with a methotrexate prodrug: preliminary study for glioma treatment.

    Science.gov (United States)

    Battaglia, Luigi; Muntoni, Elisabetta; Chirio, Daniela; Peira, Elena; Annovazzi, Laura; Schiffer, Davide; Mellai, Marta; Riganti, Chiara; Salaroglio, Iris Chiara; Lanotte, Michele; Panciani, Pierpaolo; Capucchio, Maria Teresa; Valazza, Alberto; Biasibetti, Elena; Gallarate, Marina

    2017-03-01

    Methotrexate-loaded biocompatible nanoparticles were tested for preliminary efficacy in glioma treatment. Behenic acid nanoparticles, prepared by the coacervation method, were loaded with the ester prodrug didodecylmethotrexate, which was previously tested in vitro against glioblastoma human primary cultures. Nanoparticle conjugation with an ApoE mimicking chimera peptide was performed to obtain active targeting to the brain. Biodistribution studies in healthy rats assessed the superiority of ApoE-conjugated formulation, which was tested on an F98/Fischer glioma model. Differences were observed in tumor growth rate (measured by MRI) between control and treated rats. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to explain the apoptosis observed in glioma models.

  17. Preparation, characterisation and antioxidant activities of rutin-loaded zein-sodium caseinate nanoparticles.

    Science.gov (United States)

    Zhang, Shuangling; Han, Yue

    2018-01-01

    Novel rutin-loaded zein-sodium caseinate nanoparticles (ZP) with antioxidant activity in aqueous medium were investigated. The results showed that the sodium caseinate concentrations, dosages of rutin and ethanol volume fractions significantly affected the zein nanoparticles' characteristics. Concerning the antioxidant properties, the highest values of rutin loaded ZP obtained using 2, 2-diphenyl-1-picrylhydrazyl scavenging and 2 and 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) decolourisation assays were 52.7% and 71.2%, respectively, and the total antioxidant capacity was 0.40 nmol g-1. The results suggest that zein-sodium caseinate nanoparticles can be used as a new nano carrier system for rutin or other water insoluble active ingredients.

  18. Dynamic mechanical behaviour of nanoparticle loaded biodegradable PVA films for vaginal drug delivery.

    Science.gov (United States)

    Traore, Yannick L; Fumakia, Miral; Gu, Jijin; Ho, Emmanuel A

    2018-03-01

    In this study, we investigated the viscoelastic and mechanical behaviour of polyvinyl alcohol films formulated along with carrageenan, plasticizing agents (polyethylene glycol and glycerol), and when loaded with nanoparticles as a model for potential applications as microbicides. The storage modulus, loss modulus and glass transition temperature were determined using a dynamic mechanical analyzer. Films fabricated from 2% to 5% polyvinyl alcohol containing 3 mg or 5 mg of fluorescently labeled nanoparticles were evaluated. The storage modulus and loss modulus values of blank films were shown to be higher than the nanoparticle-loaded films. Glass transition temperature determined using the storage modulus, and loss modulus was between 40-50℃ and 35-40℃, respectively. The tensile properties evaluated showed that 2% polyvinyl alcohol films were more elastic but less resistant to breaking compared to 5% polyvinyl alcohol films (2% films break around 1 N load and 5% films break around 7 N load). To our knowledge, this is the first study to evaluate the influence of nanoparticle and film composition on the physico-mechanical properties of polymeric films for vaginal drug delivery.

  19. Smart polymer platforms for in vitro drug screening assays based on drug-loaded nanoparticles

    DEFF Research Database (Denmark)

    Faralli, Adele

    -electrodes for co-localization of drug-loaded nanoparticles (liposomes) and cancer cells. PEGDA hydrogels are widely used in different fields including tissue engineering and in vivo drug delivery. A home-made setup for the fabrication of PEGDA hydrogels through visible-light photopolymerization is described...

  20. Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer.

    Science.gov (United States)

    Semkina, Alevtina S; Abakumov, Maxim A; Skorikov, Alexander S; Abakumova, Tatiana O; Melnikov, Pavel A; Grinenko, Nadejda F; Cherepanov, Sergey A; Vishnevskiy, Daniil A; Naumenko, Victor A; Ionova, Klavdiya P; Majouga, Alexander G; Chekhonin, Vladimir P

    2018-05-03

    In presented paper we have developed new system for cancer theranostics based on vascular endothelial growth factor (VEGF) targeted magnetic nanoparticles. Conjugation of anti-VEGF antibodies with bovine serum albumin coated PEGylated magnetic nanoparticles allows for improved binding with murine breast adenocarcinoma 4T1 cell line and facilitates doxorubicin delivery to tumor cells. It was shown that intravenous injection of doxorubicin loaded VEGF targeted nanoparticles increases median survival rate of mice bearing 4T1 tumors up to 50%. On the other hand magnetic resonance imaging (MRI) of 4T1 tumors 24 h after intravenous injection showed accumulation of nanoparticles in tumors, thus allowing simultaneous cancer therapy and diagnostics. Copyright © 2018. Published by Elsevier Inc.

  1. Preparation, characterization and immunological evaluation: canine parvovirus synthetic peptide loaded PLGA nanoparticles.

    Science.gov (United States)

    Derman, Serap; Mustafaeva, Zeynep Akdeste; Abamor, Emrah Sefik; Bagirova, Melahat; Allahverdiyev, Adil

    2015-10-20

    Canine parvovirus 2 (CPV-2) remains a significant worldwide canine pathogen and the most common cause of viral enteritis in dogs. The 1 L15 and 7 L15 peptides overlap each other with QPDGGQPAV residues (7-15 of VP2 capsid protein of CPV) is shown to produce high immune response. PLGA nanoparticles were demonstrated to have special properties such as; controlled antigen release, protection from degradation, elimination of booster-dose and enhancing the cellular uptake by antigen presenting cells. Nevertheless, there is no study available in literature, about developing vaccine based on PLGA nanoparticles with adjuvant properties against CPV. Thus, the aim of the present study was to synthesize and characterize high immunogenic W-1 L19 peptide (from the VP2 capsid protein of CPV) loaded PLGA nanoparticle and to evaluate their in vitro immunogenic activity. PLGA nanoparticles were produced with 5.26 ± 0.05 % loading capacity and high encapsulation efficiency with 81.2 ± 3.1 %. Additionally, it was evaluated that free NPs and W-1 L19 peptide encapsulated PLGA nanoparticles have Z-ave of 183.9 ± 12.1 nm, 221.7 ± 15.8 nm and polydispersity index of 0.107 ± 0.08, 0.135 ± 0.12 respectively. It was determined that peptide loaded PLGA nanoparticles were successfully phagocytized by macrophage cells and increased NO production at 2-folds (*P vaccine candidate against Canine Parvovirus. Studies targeting PLGA nanoparticles based delivery system must be maintained in near future in order to develop new and more effective nano-vaccine formulations.

  2. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

    International Nuclear Information System (INIS)

    Esfandyari-Manesh, Mehdi; Darvishi, Behrad; Ishkuh, Fatemeh Azizi; Shahmoradi, Elnaz; Mohammadi, Ali; Javanbakht, Mehran; Dinarvand, Rassoul; Atyabi, Fatemeh

    2016-01-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC_5_0) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

  3. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Esfandyari-Manesh, Mehdi [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Darvishi, Behrad [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ishkuh, Fatemeh Azizi [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shahmoradi, Elnaz [Department of Chemical Engineering, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Mohammadi, Ali [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Javanbakht, Mehran [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-05-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC{sub 50}) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

  4. Magnetic nanoparticle-loaded electrospun polymeric nanofibers for tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Heng [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China); Xia, JiYi [Department of Science and Technology, Southwest Medical University, Luzhou 646000 (China); Pang, XianLun [Health Management Center, The Affiliated Hospital (TCM) of Southwest Medical University, Luzhou 646000 (China); Zhao, Ming; Wang, BiQiong; Yang, LingLin [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China); Wan, HaiSu [Experiment Center of Basic Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 (China); Wu, JingBo, E-mail: wjb6147@163.com [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China); Fu, ShaoZhi, E-mail: shaozhifu513@163.com [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China)

    2017-04-01

    Magnetic nanoparticles have been one of the most attractive nanomaterials for various biomedical applications including magnetic resonance imaging (MRI), diagnostic contrast enhancement, magnetic cell separation, and targeted drug delivery. Three-dimensional (3-D) fibrous scaffolds have broad application prospects in the biomedical field, such as drug delivery and tissue engineering. In this work, a novel three-dimensional composite membrane composed of the tri-block copolymer poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) and magnetic iron oxide nanoparticles (Fe{sub 3}O{sub 4} NPs) were fabricated using electrospinning technology. The physico-chemical properties of the PCEC/Fe{sub 3}O{sub 4} membranes were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Morphological observation using scanning electron microscopy (SEM) showed that the composite fibers containing 5% Fe{sub 3}O{sub 4} nanoparticles had a diameter of 250 nm. In vitro cell culture of NIH 3T3 cells on the PCEC/Fe{sub 3}O{sub 4} membranes showed that the PCEC/Fe{sub 3}O{sub 4} fibers might be a suitable scaffold for cell adhesion. Moreover, MTT analysis also demonstrated that the membranes possessed lower cytotoxicity. Therefore, this study revealed that the magnetic PCEC/Fe{sub 3}O{sub 4} fibers might have great potential for using in skin tissue engineering. - Graphical abstract: In this study, we prepared a kind of magnetic three-dimensional scaffolds (PCEC/Fe{sub 3}O{sub 4}) using iron oxide nanoparticles (Fe{sub 3}O{sub 4} NPs) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) copolymer through electrospinning technique. Their crystallization property, thermal property, in vitro degradation, and morphology were investigated. Furthermore, the cell compatibility and toxicity were also evaluated using NIH 3T3 cells. The results showed that the Fe{sub 3}O

  5. Improved photodynamic action of nanoparticles loaded with indium (III) phthalocyanine on MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Souto, Carlos Augusto Zanoni; Madeira, Klésia Pirola; Rettori, Daniel; Baratti, Mariana Ozello; Rangel, Letícia Batista Azevedo; Razzo, Daniel; Silva, André Romero da

    2013-01-01

    Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly(d,l-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. The efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. The influence of photosensitizer (PS) concentration (1.8–7.5 μmol/L), incubation time (1–2 h), and laser power (10–100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 ± 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. The InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. For a light dose of 7.5 J/cm 2 and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 ± 3 % while for free InPc was 60 ± 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. The nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. The participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc

  6. Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections.

    Science.gov (United States)

    Günday Türeli, Nazende; Torge, Afra; Juntke, Jenny; Schwarz, Bianca C; Schneider-Daum, Nicole; Türeli, Akif Emre; Lehr, Claus-Michael; Schneider, Marc

    2017-08-01

    Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu-3 cells and CF bronchial epithelial cells (CFBE41o - ) indicated that complex-loaded PLGA NPs were non-toxic at concentrations ≫ MIC cipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex-loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Fabrication, characterization and antimicrobial activities of thymol-loaded zein nanoparticles stabilized by sodium caseinate-chitosan hydrochloride double layers.

    Science.gov (United States)

    Zhang, Yaqiong; Niu, Yuge; Luo, Yangchao; Ge, Mei; Yang, Tian; Yu, Liangli Lucy; Wang, Qin

    2014-01-01

    Thymol-loaded zein nanoparticles stabilized with sodium caseinate (SC) and chitosan hydrochloride (CHC) were prepared and characterized. The SC stabilized nanoparticles had well-defined size range and negatively charged surface. Due to the presence of SC, the stabilized zein nanoparticles showed a shift of isoelectric point from 6.18 to 5.05, and had a desirable redispersibility in water at neutral pH after lyophilization. Coating with CHC onto the SC stabilized zein nanoparticles resulted in increased particle size, reversal of zeta potential value from negative to positive, and improved encapsulation efficiency. Both thymol-loaded zein nanoparticles and SC stabilized zein nanoparticles had a spherical shape and smooth surface, while the surfaces of CHC-SC stabilized zein nanoparticles seemed rough and had some clumps. Encapsulated thymol was more effective in suppressing gram-positive bacterium than un-encapsulated thymol for a longer time period. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A Novel Docetaxel-Loaded Poly (ɛ-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

    Science.gov (United States)

    Mei, Lin; Zhang, Yangqing; Zheng, Yi; Tian, Ge; Song, Cunxian; Yang, Dongye; Chen, Hongli; Sun, Hongfan; Tian, Yan; Liu, Kexin; Li, Zhen; Huang, Laiqiang

    2009-12-01

    Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ɛ-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere® in the MCF-7 TAX30 cell culture, but the differences were not significant ( p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere® ( p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

  9. Bovine serum albumin nanoparticles loaded with Photosens photosensitizer for effective photodynamic therapy

    Science.gov (United States)

    Khanadeev, Vitaly; Khlebtsov, Boris; Packirisamy, Gopinath; Khlebtsov, Nikolai

    2017-03-01

    Polymeric nanoparticles (NPs) are widely used for drug delivery applications due to high biodegradability, low toxicity and high loading capacity. The focus of this study is the development of photosensitizer Photosens (PS) loaded albumin NPs for efficient photodynamic therapy (PDT). To fabricate PS-loaded bovine serum albumin nanoparticles (BSA-PS NPs), we used a coacervation method with glutaraldehyde followed by passive loading of PS. Successful loading of PS was confirmed by appearance of characteristic peak in absorption spectrum which allows to determine the PS loading in BSA NPs. The synthesized BSA-PS NPs demonstrated low toxicity to HeLa cells at therapeutic concentrations of loaded PS. Compared to free PS solution, the synthesized BSA-PS NPs generated the singlet oxygen more effectively under laser irradiation at 660 nm. In addition, due to presence of various chemical groups on the surface of BSA-PS NPs, they are capable to adsorb on cell surface and accumulate in cells due to cellular uptake mechanisms. Owing to combination of PD and cell uptake advantages, BSA-PS NPs demonstrated higher efficacy of photodynamic damage to cancer cells as compared to free PS at equivalent concentrations. These results suggest that non-targeted BSA-PS NPs with high PD activity and low-fabrication costs of are promising candidates for transfer to PD clinic treatments.

  10. Endothelial cell-derived microparticles loaded with iron oxide nanoparticles: feasibility of MR imaging monitoring in mice.

    Science.gov (United States)

    Al Faraj, Achraf; Gazeau, Florence; Wilhelm, Claire; Devue, Cécile; Guérin, Coralie L; Péchoux, Christine; Paradis, Valérie; Clément, Olivier; Boulanger, Chantal M; Rautou, Pierre-Emmanuel

    2012-04-01

    To assess the feasibility of loading iron oxide nanoparticles in endothelial microparticles (EMPs), thereby enabling their noninvasive monitoring with magnetic resonance (MR) imaging in mice. Experiments were approved by the French Ministry of Agriculture. Endothelial cells, first labeled with anionic superparamagnetic nanoparticles, were stimulated to generate EMPs, carrying the nanoparticles in their inner compartment. C57BL/6 mice received an intravenous injection of nanoparticle-loaded EMPs, free nanoparticles, or the supernatant of nanoparticle-loaded EMPs. A 1-week follow-up was performed with a 4.7-T MR imaging device by using a gradient-echo sequence for imaging spleen, liver, and kidney and a radial very-short-echo time sequence for lung imaging. Comparisons were performed by using the Student t test. The signal intensity loss induced by nanoparticle-loaded EMPs or free nanoparticles was readily detected within 5 minutes after injection in the liver and spleen, with a more pronounced effect in the spleen for the magnetic EMPs. The kinetics of signal intensity attenuation differed for nanoparticle-loaded EMPs and free nanoparticles. No signal intensity changes were observed in mice injected with the supernatant of nanoparticle-loaded EMPs, confirming that cells had not released free nanoparticles, but only in association with EMPs. The results were confirmed by using Perls staining and immunofluorescence analysis. The strategy to generate EMPs with magnetic properties allowed noninvasive MR imaging assessment and follow-up of EMPs and opens perspectives for imaging the implications of these cellular vectors in diseases. © RSNA, 2012.

  11. Characterization of Celecoxib-Loaded Solid Lipid Nanoparticles ...

    African Journals Online (AJOL)

    system with several advantages, including enhanced physical stability, dual loading ability for lipophilic and .... where kp is the release rate constant at the elapsed time t, n is a constant, where the value of n ≤ 0.45 indicates .... CXB and the hydrocarbon chain of the esterified fatty acids in the lipids. Upon emulsification CXB.

  12. In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma.

    Science.gov (United States)

    Katiyar, Shefali; Pandit, Jayamanti; Mondal, Rabi S; Mishra, Anil K; Chuttani, Krishna; Aqil, Mohd; Ali, Asgar; Sultana, Yasmin

    2014-02-15

    The most important risk associated with glaucoma is the onset and progression of intraocular pressure. The objective of this study was to formulate in situ gel of chitosan nanoparticles to enhance the bioavailability and efficacy of dorzolamide in the glaucoma treatment. Optimized nanoparticles were spherical in shape (particle size: 164 nm) with a loading efficiency of 98.1%. The ex vivo release of the optimized in situ gel nanoparticle formulation showed a sustained drug release as compared to marketed formulation. The gamma scintigraphic study of prepared in situ nanoparticle gel showed good corneal retention compared to marketed formulation. HET-CAM assay of the prepared formulation scored 0.33 in 5 min which indicates the non-irritant property of the formulation. Thus in situ gel of dorzolamide hydrochloride loaded nanoparticles offers a more intensive treatment of glaucoma and a better patient compliance as it requires fewer applications per day compared to conventional eye drops. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    International Nuclear Information System (INIS)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-01-01

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1–4 μm, encapsulation efficiency 80–85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  14. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant, E-mail: pmishra@dbeb.iitd.ac.in [Indian Institute of Technology Delhi, Department of Biochemical Engineering and Biotechnology (India)

    2013-03-15

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1-4 {mu}m, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 {+-} 28.6 nm, encapsulation efficiency 92.17 {+-} 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  15. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    Science.gov (United States)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-03-01

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  16. Repetitive heterocoagulation of oppositely charged particles for enhancement of magnetic nanoparticle loading into monodisperse silica particles.

    Science.gov (United States)

    Matsumoto, Hideki; Nagao, Daisuke; Konno, Mikio

    2010-03-16

    Oppositely charged particles were repetitively heterocoagulated to fabricate highly monodisperse magnetic silica particles with high loading of magnetic nanoparticles. Positively charged magnetic nanoparticles prepared by surface modification with N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TSA) were used to heterocoagulate with silica particles under basic conditions to give rise to negative silica surface charge and prevent the oxidation of the magnetic nanoparticles. The resultant particles of silica core homogeneously coated with the magnetic nanoparticles were further coated with thin silica layer with sodium silicate in order to enhance colloidal stability and avoid desorption of the magnetic nanoparticles from the silica cores. Five repetitions of the heterocoagulation and the silica coating could increase saturation magnetization of the magnetic silica particles to 27.7 emu/g, keeping the coefficient of variation of particle sizes (C(V)) less than 6.5%. Highly homogeneous loading of the magnetic component was confirmed by measuring Fe-to-Si atomic ratios of individual particles with energy dispersive X-ray spectroscopy.

  17. Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Jin [Key Laboratory of Tea Biochemistry and Biotechnology of Ministry of Education and Ministry of Agriculture, Anhui Agricultural University, Hefei 230036 (China); College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Li, Feng [College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Fang, Yong; Yang, Wenjian [College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023 (China); An, Xinxin; Zhao, Liyan; Xin, Zhihong; Cao, Lin [College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Hu, Qiuhui, E-mail: qiuhuihu@njau.edu.cn [College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023 (China)

    2014-03-01

    Tea polyphenols have strong antioxidant and antitumor activities. However, these health benefits are limited due to their poor in vivo stability and low bioavailability. Chitosan nanoparticles as delivery systems may provide an alternative approach for enhancing bioavailability of poorly absorbed drugs. In this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using two different chitosan biomaterials, and their antitumor effects were evaluated in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis, cell apoptosis and cell cycle detection. The results indicated that the tea polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous distribution in prepared suspension. MTT assay suggested that tea polyphenol-loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and the cytotoxicity rates were increased gradually and appeared an obvious dose-dependent relationship. Transmission electron microscope images showed that the HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited some typical apoptotic features, such as microvilli disappearance, margination of nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea polyphenols not only induced cancer cell apoptosis, but also promoted their necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their antitumor effects mainly through inducing cell apoptosis. Our results revealed that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on tumor cells probably depended on their controlled drug release and effective cell delivery. The chitosan nanoparticles themselves as the delivery carrier showed limited antitumor effects compared with their encapsulated drugs. - Highlights: • Tea polyphenol-loaded

  18. Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Salam Massadeh

    2016-06-01

    Full Text Available Background: PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic. In this study, methotrexate (MTX-loaded nanoparticles were prepared by the double emulsion method. Method: Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%. Results: Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion: The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

  19. Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells

    International Nuclear Information System (INIS)

    Liang, Jin; Li, Feng; Fang, Yong; Yang, Wenjian; An, Xinxin; Zhao, Liyan; Xin, Zhihong; Cao, Lin; Hu, Qiuhui

    2014-01-01

    Tea polyphenols have strong antioxidant and antitumor activities. However, these health benefits are limited due to their poor in vivo stability and low bioavailability. Chitosan nanoparticles as delivery systems may provide an alternative approach for enhancing bioavailability of poorly absorbed drugs. In this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using two different chitosan biomaterials, and their antitumor effects were evaluated in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis, cell apoptosis and cell cycle detection. The results indicated that the tea polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous distribution in prepared suspension. MTT assay suggested that tea polyphenol-loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and the cytotoxicity rates were increased gradually and appeared an obvious dose-dependent relationship. Transmission electron microscope images showed that the HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited some typical apoptotic features, such as microvilli disappearance, margination of nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea polyphenols not only induced cancer cell apoptosis, but also promoted their necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their antitumor effects mainly through inducing cell apoptosis. Our results revealed that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on tumor cells probably depended on their controlled drug release and effective cell delivery. The chitosan nanoparticles themselves as the delivery carrier showed limited antitumor effects compared with their encapsulated drugs. - Highlights: • Tea polyphenol-loaded

  20. Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

    Science.gov (United States)

    Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

    2016-01-01

    Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

  1. Paclitaxel conjugated Fe{sub 3}O{sub 4}@LaF{sub 3}:Ce{sup 3+},Tb{sup 3+} nanoparticles as bifunctional targeting carriers for Cancer theranostics application

    Energy Technology Data Exchange (ETDEWEB)

    Mangaiyarkarasi, Rajendiran; Chinnathambi, Shanmugavel; Karthikeyan, Subramani; Aruna, Prakasarao; Ganesan, Singaravelu, E-mail: sganesan@annauniv.edu

    2016-02-01

    The bi-functional Chitosan functionalized magnetite doped luminescent rare earth nanoparticles (Fe{sub 3}O{sub 4}@LaF{sub 3}: Ce{sup 3+},Tb{sup 3+}/chi NPs) as a carrier of paclitaxel (PTX) drug was designed using a co-precipitation and facile direct precipitation method. The synthesized nanoparticles are spherical in shape with a typical diameter of 19–37 nm respectively. They are water soluble, super paramagnetic and biocompatible, in which the amino groups on the nanoparticles surface are used for the conjugation with an anticancer drug, paclitaxel. The nature of PTX binding with Fe{sub 3}O{sub 4}@LaF{sub 3}: Ce{sup 3+},Tb{sup 3+}/chi nanoparticles were studied using X-ray diffraction, vibrating sample magnetometer and scanning electron micrograph. The nature of interactions between PTX and Fe{sub 3}O{sub 4}@LaF{sub 3}: Ce{sup 3+},Tb{sup 3+}/chi NPs due to complex formation were conceded out by various spectroscopic methods viz., UV–visible, steady state and excited state fluorescence spectroscopy. The photo-physical characterization reveals that the adsorption and release of PTX from Fe{sub 3}O{sub 4}@LaF{sub 3}:Tb{sup 3+}/chi nanoparticles is quicker when compared with other nanoparticles and also confirms that this may be due to the hydrogen bond formation between the hydroxyl group of drug and amino group of nanoparticles respectively. The maximum loading capacity and entrapment efficiency of 83.69% and 80.51% were attained at a ratio of 5:8 of PTX and Fe{sub 3}O{sub 4}@LaF{sub 3}: Ce{sup 3+},Tb{sup 3+}/chi NPs respectively. In addition with that, antitumoral activity study of PTX conjugated Fe{sub 3}O{sub 4}@LaF{sub 3}:Tb{sup 3+}/chi nanoparticles exhibits increased cytotoxic effects on A549 lung cancer cell lines than that of unconjugated PTX. - Highlights: • Fe{sub 3}O{sub 4}@LaF{sub 3}: Ce{sup 3+},Tb{sup 3+}/chi nanoparticles as a carrier of paclitaxel. • These particles are water soluble, super paramagnetic and biocompatible. • The maximum

  2. Magnetic nanoparticle-loaded alginate beads for local micro-actuation of in vitro tissue constructs.

    Science.gov (United States)

    Alshehri, Awatef M; Wilson, Otto C; Dahal, Bishnu; Philip, John; Luo, Xiaolong; Raub, Christopher B

    2017-11-01

    Magnetic nanoparticles (MNPs) self-align and transduce magnetic force, two properties which lead to promising applications in cell and tissue engineering. However, the toxicity of MNPs to cells which uptake them is a major impediment to applications in engineered tissue constructs. To address this problem, MNPs were embedded in millimeter-scale alginate beads, coated with glutaraldehyde cross-linked chitosan, and loaded in acellular and MDA-MB-231 cancer cell-seeded collagen hydrogels, providing local micro-actuation under an external magnetic field. Brightfield microscopy was used to assess nanoparticle diffusion from the bead. Phase contrast microscopy and digital image correlation were used to track collagen matrix displacement and estimate intratissue strain under magnetic actuation. Coating the magnetic alginate beads with glutaraldehyde-chitosan prevents bulk diffusion of nanoparticles into the surrounding microenvironment. Further, the beads exert force on the surrounding collagen gel and cells, resulting in intratissue strains of 0-10% tunable with bead dimensions, collagen density, and distance from the bead. Cells seeded adjacent to the embedded beads are subjected to strain gradients without loss of cell viability over two days culture. This study describes a simple way to fabricate crosslinked magnetic alginate beads to load in a collagen tissue construct without direct exposure of the construct to nanoparticles. The findings are significant to in vitro studies of mechanobiology in enabling precise control over dynamic mechanical loading of tissue constructs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles.

    Science.gov (United States)

    El-Naggar, Mehrez E; El-Rafie, M H; El-sheikh, M A; El-Feky, Gina S; Hebeish, A

    2015-11-01

    The current research work focuses on the medical application of the cost-effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP(®) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti-inflammatory drug (NSAID). Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes

    KAUST Repository

    Ornelas-Megiatto, Cá tia; Shah, Parth N.; Wich, Peter R.; Cohen, Jessica L.; Tagaev, Jasur A.; Smolen, Justin A.; Wright, Brian D.; Panzner, Matthew J.; Youngs, Wiley J.; Frechet, Jean; Cannon, Carolyn L.

    2012-01-01

    Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery. © 2012 American Chemical Society.

  5. Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.

    Science.gov (United States)

    Ornelas-Megiatto, Cátia; Shah, Parth N; Wich, Peter R; Cohen, Jessica L; Tagaev, Jasur A; Smolen, Justin A; Wright, Brian D; Panzner, Matthew J; Youngs, Wiley J; Fréchet, Jean M J; Cannon, Carolyn L

    2012-11-05

    Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH(2)Cl(2) (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.

  6. Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes

    KAUST Repository

    Ornelas-Megiatto, Cátia

    2012-11-05

    Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery. © 2012 American Chemical Society.

  7. Curcumin and piperine loaded zein-chitosan nanoparticles: Development and in-vitro characterisation

    Directory of Open Access Journals (Sweden)

    Yücel Baspinar

    2018-03-01

    It was succeeded to prepare curcumin and piperine loaded zein-chitosan nanoparticles having a mean particle size of approximately 500 nm and high encapsulation efficencies for curcumin (89% and piperine (87%. Using a curcumin concentration of 10–25 µg/ml resulted in reduction of the viability of approximately 50% of the neuroblastoma cells. The here developed nanoparticle formulation consisting of solely natural compounds showed good cytotoxic effects and is a promising approach with appropriate properties for final consumption.

  8. X-ray excited luminescence of polystyrene composites loaded with SrF{sub 2} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Demkiv, T.M.; Halyatkin, O.O.; Vistovskyy, V.V. [Ivan Franko National University of Lviv, 8a Kyryla i Mefodiya St., 79005 Lviv (Ukraine); Hevyk, V.B. [Ivano-Frankivsk National Technical University of Oil and Gas, 15 Karpatska St., 76019 Ivano-Frankivsk (Ukraine); Yakibchuk, P.M. [Ivan Franko National University of Lviv, 8a Kyryla i Mefodiya St., 79005 Lviv (Ukraine); Gektin, A.V. [Institute for Scintillation Materials, NAS of Ukraine, 60 Lenina Ave, 61001 Kharkiv (Ukraine); Voloshinovskii, A.S. [Ivan Franko National University of Lviv, 8a Kyryla i Mefodiya St., 79005 Lviv (Ukraine)

    2017-03-01

    The polystyrene film nanocomposites of 0.3 mm thickness with embedded SrF{sub 2} nanoparticles up to 40 wt% have been synthesized. The luminescent and kinetic properties of the polystyrene composites with embedded SrF{sub 2} nanoparticles upon the pulse X-ray excitation have been investigated. The luminescence intensity of the pure polystyrene scintillator film significantly increases when it is loaded with the inorganic SrF{sub 2} nanoparticles. The film nanocomposites show fast (∼2.8 ns) and slow (∼700 ns) luminescence decay components typical for a luminescence of polystyrene activators (p-Terphenyl and POPOP) and SrF{sub 2} nanoparticles, respectively. It is revealed that the fast decay luminescence component of the polystyrene composites is caused by the excitation of polystyrene by the photoelectrons escaped from the nanoparticles due to photoeffect, and the slow component is caused by reabsorption of the self-trapped exciton luminescence of SrF{sub 2} nanoparticles by polystyrene.

  9. Design and optimization of novel paclitaxel-loaded folate-conjugated amphiphilic cyclodextrin nanoparticles.

    Science.gov (United States)

    Erdoğar, Nazlı; Esendağlı, Güneş; Nielsen, Thorbjorn T; Şen, Murat; Öner, Levent; Bilensoy, Erem

    2016-07-25

    As nanomedicines are gaining momentum in the therapy of cancer, new biomaterials emerge as alternative platforms for the delivery of anticancer drugs with bioavailability problems. In this study, two novel amphiphilic cyclodextrins (FCD-1 and FCD-2) conjugated with folate group to enable active targeting to folate positive breast tumors were introduced. The objective of this study was to develop and characterize new folated-CD nanoparticles via 3(2) factorial design for optimal final parameters. Full physicochemical characterization studies were performed. Blank and paclitaxel loaded FCD-1 and FCD-2 nanoparticles remained within the range of 70-275nm and 125-185nm, respectively. Zeta potential values were neutral and -20mV for FCD-1 and FCD-2 nanoparticles, respectively. Drug release studies showed initial burst release followed by a longer sustained release. Blank nanoparticles had no cytotoxicity against L929 cells. T-47D and ZR-75-1 human breast cancer cells with different levels of folate receptor expression were used to assess anti-cancer efficacy. Through targeting the folate receptor, these nanoparticles were efficiently engulfed by the breast cancer cells. Additionally, breast cancer cells became more sensitive to cytotoxic and/or cytostatic effects of PCX delivered by FCD-1 and FCD-2. In conclusion, these novel folate-conjugated cyclodextrin nanoparticles can therefore be considered as promising alternative systems for safe and effective delivery of paclitaxel with a folate-dependent mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Formulation, characterization and pharmacokinetics of praziquantel-loaded hydrogenated castor oil solid lipid nanoparticles.

    Science.gov (United States)

    Xie, Shuyu; Pan, Baoliang; Wang, Ming; Zhu, Luyan; Wang, Fenghua; Dong, Zhao; Wang, Xiaofang; Zhou, WenZhong

    2010-07-01

    The purpose of this study was to formulate praziquantel (PZQ)-loaded hydrogenated castor oil (HCO) solid lipid nanoparticles (SLN) to enhance the bioavailability and prolong the systemic circulation of the drug. PZQ was encapsulated into HCO nanoparticles by a hot homogenization and ultrasonication method. The physicochemical characteristics of SLN were investigated by optical microscope, scanning electron microscopy and photon correlation spectroscopy. Pharmacokinetics were studied after oral, subcutaneous and intramuscular administration in mice. The diameter, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the nanoparticles were 344.0 +/- 15.1 nm, 0.31 +/- 0.08, -16.7 +/- 0.5 mV, 62.17 +/- 6.53% and 12.43 +/- 1.31%, respectively. In vitro release of PZQ-loaded HCO-SLN exhibited an initial burst release followed by a sustained release. SLN increased the bioavailability of PZQ by 14.9-, 16.1- and 2.6-fold, and extended the mean residence time of the drug from 7.6, 6.6 and 8.2 to 95.9, 151.6 and 48.2 h after oral, subcutaneous and intramuscular administration, respectively. The PZQ-loaded HCO-SLN could be a promising formulation to enhance the pharmacological activity of PZQ.

  11. Structural characterization of PTX3 disulfide bond network and its multimeric status in cumulus matrix organization.

    Science.gov (United States)

    Inforzato, Antonio; Rivieccio, Vincenzo; Morreale, Antonio P; Bastone, Antonio; Salustri, Antonietta; Scarchilli, Laura; Verdoliva, Antonio; Vincenti, Silvia; Gallo, Grazia; Chiapparino, Caterina; Pacello, Lucrezia; Nucera, Eleonora; Serlupi-Crescenzi, Ottaviano; Day, Anthony J; Bottazzi, Barbara; Mantovani, Alberto; De Santis, Rita; Salvatori, Giovanni

    2008-04-11

    PTX3 is an acute phase glycoprotein that plays key roles in resistance to certain pathogens and in female fertility. PTX3 exerts its functions by interacting with a number of structurally unrelated molecules, a capacity that is likely to rely on its complex multimeric structure stabilized by interchain disulfide bonds. In this study, PAGE analyses performed under both native and denaturing conditions indicated that human recombinant PTX3 is mainly composed of covalently linked octamers. The network of disulfide bonds supporting this octameric assembly was resolved by mass spectrometry and Cys to Ser site-directed mutagenesis. Here we report that cysteine residues at positions 47, 49, and 103 in the N-terminal domain form three symmetric interchain disulfide bonds stabilizing four protein subunits in a tetrameric arrangement. Additional interchain disulfide bonds formed by the C-terminal domain cysteines Cys(317) and Cys(318) are responsible for linking the PTX3 tetramers into octamers. We also identified three intrachain disulfide bonds within the C-terminal domain that we used as structural constraints to build a new three-dimensional model for this domain. Previously it has been shown that PTX3 is a key component of the cumulus oophorus extracellular matrix, which forms around the oocyte prior to ovulation, because cumuli from PTX3(-/-) mice show defective matrix organization. Recombinant PTX3 is able to restore the normal phenotype ex vivo in cumuli from PTX3(-/-) mice. Here we demonstrate that PTX3 Cys to Ser mutants, mainly assembled into tetramers, exhibited wild type rescue activity, whereas a mutant, predominantly composed of dimers, had impaired functionality. These findings indicate that protein oligomerization is essential for PTX3 activity within the cumulus matrix and implicate PTX3 tetramers as the functional molecular units required for cumulus matrix organization and stabilization.

  12. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    International Nuclear Information System (INIS)

    Hamon, Casey L.; Dorsey, Christopher L.; Özel, Tuğba; Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania

    2016-01-01

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.Graphical abstract

  13. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hamon, Casey L.; Dorsey, Christopher L. [Texas State University, Department of Chemistry and Biochemistry (United States); Özel, Tuğba [Texas State University, Materials Science, Engineering, and Commercialization Program (United States); Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania, E-mail: tb26@txstate.edu [Texas State University, Department of Chemistry and Biochemistry (United States)

    2016-07-15

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.Graphical abstract.

  14. Biodistribution of arctigenin-loaded nanoparticles designed for multimodal imaging.

    Science.gov (United States)

    Cui, Qingxin; Hou, Yuanyuan; Wang, Yanan; Li, Xu; Liu, Yang; Ma, Xiaoyao; Wang, Zengyong; Wang, Weiya; Tao, Jin; Wang, Qian; Jiang, Min; Chen, Dongyan; Feng, Xizeng; Bai, Gang

    2017-04-07

    Tracking targets of natural products is one of the most challenging issues in fields ranging from pharmacognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a "key" that opens the target "lock". We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were characterized by transmission electron microscopy (TEM), laser particle size analysis and atomic force microscopy (AFM). In addition, we studied the localization of ATG at the level of the cell and the whole animal (zebrafish and mice). We demonstrated that fluorescent NPs could be ideal carriers in the development of a feasible method for target identification. The distributions of the target proteins were found to be consistent with the pharmacological action of ATG at the cellular and whole-organism levels. The results indicated that functionalized poly-lysine NPs could be valuable in the multimodal imaging of arctigenin.

  15. Organic-Inorganic Hybrid Hollow Mesoporous Organosilica Nanoparticles for Efficient Ultrasound-Based Imaging and Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Xiaoqin Qian

    2014-01-01

    Full Text Available A novel anticancer drug delivery system with contrast-enhanced ultrasound-imaging performance was synthesized by a typical hard-templating method using monodispersed silica nanoparticles as the templates, which was based on unique molecularly organic/inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs. The highly dispersed HPMOs show the uniform spherical morphology, large hollow interior, and well-defined mesoporous structures, which are very beneficial for ultrasound-based theranostics. The obtained HPMOs exhibit excellent performances in contrast-enhanced ultrasonography both in vitro and in vivo and can be used for the real-time determination of the progress of lesion tissues during the chemotherapeutic process. Importantly, hydrophobic paclitaxel- (PTX- loaded HPMOs combined with ultrasound irradiation show fast ultrasound responsiveness for controlled drug release and higher in vitro and in vivo tumor inhibition rates compared with free PTX and PTX-loaded HPMOs, which is due to the enhanced ultrasound-triggered drug release and ultrasound-induced cavitation effect. Therefore, the achieved novel HPMOs-based nanoparticle systems will find broad application potentials in clinically ultrasound-based imaging and auxiliary tumor chemotherapy.

  16. A novel nanoparticle formulation for sustained paclitaxel delivery.

    Science.gov (United States)

    Trickler, W J; Nagvekar, A A; Dash, A K

    2008-01-01

    To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC(50) of PTX. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.

  17. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    Science.gov (United States)

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers.

    Directory of Open Access Journals (Sweden)

    Stefanie Wohlfart

    Full Text Available BACKGROUND: Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid (PLGA nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods. METHODOLOGY: The particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA or human serum albumin (PLGA/HSA as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3 × 2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density. CONCLUSION: The results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations.

  19. Resveratrol-loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles: Preparation, characterization, and targeting effect on liver tumors.

    Science.gov (United States)

    Wu, Mingfang; Lian, Bolin; Deng, Yiping; Feng, Ziqi; Zhong, Chen; Wu, Weiwei; Huang, Yannian; Wang, Lingling; Zu, Chang; Zhao, Xiuhua

    2017-08-01

    In this study, glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were prepared to establish a tumor targeting nano-sized drug delivery system. Glycyrrhizic acid was coupled to human serum albumin, and resveratrol was encapsulated in glycyrrhizic acid-conjugated human serum albumin by high-pressure homogenization emulsification. The average particle size of sample nanoparticles prepared under the optimal conditions was 108.1 ± 5.3 nm with a polydispersity index (PDI) of 0.001, and the amount of glycyrrhizic acid coupled with human serum albumin was 112.56 µg/mg. The drug encapsulation efficiency and drug loading efficiency were 83.6 and 11.5%, respectively. The glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were characterized through laser light scattering, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, and gas chromatography. The characterization results showed that resveratrol in glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles existed in amorphous state and the residual amounts of chloroform and methanol in nanoparticles were separately less than the international conference on harmonization (ICH) limit. The in vitro drug-release study showed that the nanoparticles released the drug slowly and continuously. The inhibitory rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide method. The IC50 values of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles and resveratrol were 62.5 and 95.5 µg/ml, respectively. The target ability of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles

  20. PTX3 predicts severe disease in febrile patients at the emergency department

    NARCIS (Netherlands)

    de Kruif, Martijn D.; Limper, Maarten; Sierhuis, Karlien; Wagenaar, Jiri F. P.; Spek, C. Arnold; Garlanda, Cecilia; Cotena, Alessia; Mantovani, Alberto; ten Cate, Hugo; Reitsma, Pieter H.; van Gorp, Eric C. M.

    2010-01-01

    Objectives: The long pentraxin PTX3 is a promising marker of disease severity in severely ill patients. In order to identify patients warranting critical care as quickly as possible, we investigated the value of PTX3 as a biomarker for disease severity in patients presenting with fever at the

  1. In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery

    Science.gov (United States)

    Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

    2016-01-01

    The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w/w), and a sodium deoxycholate gel (CP 0.05% w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP. PMID:28035957

  2. In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery.

    Science.gov (United States)

    Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

    2016-12-26

    The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w / w ), and a sodium deoxycholate gel (CP 0.05% w / w ) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.

  3. Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles

    Directory of Open Access Journals (Sweden)

    Fu-Heng Yang

    2015-03-01

    Full Text Available Paclitaxel (PTX, taxol, a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05. The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

  4. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    Science.gov (United States)

    Soni, Maheshkumar P.; Shelkar, Nilakash; Gaikwad, Rajiv V.; Vanage, Geeta R.; Samad, Abdul; Devarajan, Padma V.

    2014-01-01

    Background: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer circulation and biodistrbution study confirmed high RES uptake (75%) in RES organs like liver lung spleen etc. Conclusion: The high RES uptake suggests BPQ SLN as a promising approach for targeted and improved delivery in theileriosis. PMID:24459400

  5. Production of drug-loaded polymeric nanoparticles by electrospraying technology.

    Science.gov (United States)

    Sosnik, Alejandro

    2014-09-01

    The pharmaceutical industry struggles with high attrition. The outbreak of pharmaceutical micro/nanotechnology has been fundamental to overcome several (bio)pharmaceutic drawbacks of drugs such as poor aqueous solubility, physicochemical instability, short half life, inappropriate biodistribution and toxicity. The spatiotemporal release of drugs directly in the site of action and the restriction of the systemic exposure by means of nanotechnology has notoriously improved drug safety ratios. At the same time, the development of production methods that are cost-effective, scalable and reproducible under industrial settings becomes crucial to ensure the clinical translation of any development. The electrospraying process, also known as electrohydrodynamic atomization (EHDA), is a single-stage technique of liquid atomization by means of electrical forces that enables the generation of micro/nanoparticles with especially narrow size distribution. EHDA is based on the ability of an electric field to deform the interface of a liquid drop and break it into smaller mono-disperse droplets. The main advantageous features over conventional methods are the possibility to produce particles without the use of surfactants, at ambient temperature and pressure and with maximum encapsulation efficiency due to the absence of an external medium that allows the migration and/or dissolution of water-soluble cargos. In addition, the mild conditions are optimal for the encapsulation of thermo-sensitive cargos. The present article overviews the applications of this technology for the production of nano-drug delivery systems and discusses its key role to support the transfer of a broad spectrum of nanomedicines to the market.

  6. Freeze-drying of HI-6-loaded recombinant human serum albumin nanoparticles for improved storage stability.

    Science.gov (United States)

    Dadparvar, Miriam; Wagner, Sylvia; Wien, Sascha; Worek, Franz; von Briesen, Hagen; Kreuter, Jörg

    2014-10-01

    Severe intoxications with organophosphates require the immediate administration of atropine in combination with acetyl cholinesterase (AChE) reactivators such as HI-6. Although this therapy regimen enables the treatment of peripheral symptoms, the blood-brain barrier (BBB) restricts the access of the hydrophilic antidotes to the central nervous system which could lead to a fatal respiratory arrest. Therefore, HI-6-loaded albumin nanoparticles were previously developed to enhance the transport across this barrier and were able to reactivate organophosphate-(OP)-inhibited AChE in an in vitro BBB model. Since HI-6 is known to be moisture-sensitive, the feasibility of freeze-drying of the HI-6-loaded nanoparticles was investigated in the present study using different cryo- and lyoprotectants at different concentrations. Trehalose and sucrose (3%, w/v)-containing formulations were superior to mannitol concerning the physicochemical parameters of the nanoparticles whereas trehalose-containing samples were subject of a prolonged storage stability study at temperatures between -20°C and +40°C for predetermined time intervals. Shelf-life computations of the freeze-dried HI-6 nanoparticle formulations revealed a shelf-life time of 18 months when stored at -20°C. The formulations' efficacy was proven in vitro by reactivation of OP-inhibited AChE after transport over a porcine brain capillary endothelial cell layer model. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery

    International Nuclear Information System (INIS)

    Kayal, S.; Ramanujan, R.V.

    2010-01-01

    Magnetic drug targeting is a drug delivery system that can be used in locoregional cancer treatment. Coated magnetic particles, called carriers, are very useful for delivering chemotherapeutic drugs. Magnetic carriers were synthesized by coprecipitation of iron oxide followed by coating with polyvinyl alcohol (PVA). Characterization was carried out using X-ray diffraction, TEM, TGA, FTIR and VSM techniques. The magnetic core of the carriers was magnetite (Fe 3 O 4 ), with average size of 10 nm. The room temperature VSM measurements showed that magnetic particles were superparamagnetic. The amount of PVA bound to the iron oxide nanoparticles were estimated by thermogravimetric analysis (TGA) and the attachment of PVA to the iron oxide nanoparticles was confirmed by FTIR analysis. Doxorubicin (DOX) drug loading and release profiles of PVA coated iron oxide nanoparticles showed that up to 45% of adsorbed drug was released in 80 h, the drug release followed the Fickian diffusion-controlled process. The binding of DOX to the PVA was confirmed by FTIR analysis. The present findings show that DOX loaded PVA coated iron oxide nanoparticles are promising for magnetically targeted drug delivery.

  8. Effective Removal of Congo Red by Triarrhena Biochar Loading with TiO2 Nanoparticles

    Directory of Open Access Journals (Sweden)

    Peng Yu

    2018-01-01

    Full Text Available A composite of pyrolytic Triarrhena biochar loading with TiO2 nanoparticles has been synthesized by the sol-gel method. The composite shows a well-developed hollow mesoporous and macropore structure as characterized by XRD, BET, and SEM. When used as an absorbent to remove Congo red from aqueous solution, it was found that as-prepared composite performed better absorption capacity than single biochar or TiO2. The results suggest that biochar loading with TiO2 could be promisingly implemented as an environmentally friendly and inexpensive adsorbent for Congo red removal from wastewater.

  9. A general approach to mesoporous metal oxide microspheres loaded with noble metal nanoparticles

    KAUST Repository

    Jin, Zhao; Xiao, Manda; Bao, Zhihong; Wang, Peng; Wang, Jianfang

    2012-01-01

    Catalytic microspheres: A general approach is demonstrated for the facile preparation of mesoporous metal oxide microspheres loaded with noble metal nanoparticles (see TEM image in the picture). Among 18 oxide/noble metal catalysts, TiO 2/0.1 mol Pd microspheres showed the highest turnover frequency in NaBH 4 reduction of 4-nitrophenol (see picture). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma

    OpenAIRE

    Shinde, Ujwala; Ahmed, Mohammed Hadi; Singh, Kavita

    2013-01-01

    Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) ...

  11. A general approach to mesoporous metal oxide microspheres loaded with noble metal nanoparticles

    KAUST Repository

    Jin, Zhao

    2012-04-26

    Catalytic microspheres: A general approach is demonstrated for the facile preparation of mesoporous metal oxide microspheres loaded with noble metal nanoparticles (see TEM image in the picture). Among 18 oxide/noble metal catalysts, TiO 2/0.1 mol Pd microspheres showed the highest turnover frequency in NaBH 4 reduction of 4-nitrophenol (see picture). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. pH and ion strength modulated ionic species loading in mesoporous silica nanoparticles

    International Nuclear Information System (INIS)

    Liu, Wei; Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Yang, Meng; Li, Li; Xu, Jianguo

    2013-01-01

    Mesoporous silica nanoparticles (MSN) have emerged as appealing host materials to accommodate guest molecules for biomedical applications, and recently various methods have been developed to modulate the loading of guest molecules in the silica matrix. Herein, it was demonstrated that pH and ion strength showed great influence on the loading of charged species into the nanoparticles, taking MCM-41 as a host MSN model and methylviologen (MV 2+ ) and 1,5-naphthalene disulfonate (NDS 2− ) as typical charged ionic guest molecules. As the pH increased from 3.0 to 8.0, the loading amount of MV 2+ increased gradually, while on the contrary, it decreased gradually for NDS 2− , for the solution pH changed the electrostatic interaction between the silica matrix and the ionic guest molecules. Additionally, the adding of NaCl reduced the electrostatic interaction, which resulted in a decreasing of the electrostatic rejection and electrostatic accumulation for the molecules carrying the same and the opposite charge to the particle respectively. Thus, pH and ion strength can be employed as simple approaches to modulate the loading of charged molecules and permselectivity in MSN. This work has a definite guidance function for molecule loading, transport modulation, controlled release as well as sensors based on MSN. (paper)

  13. Gum tragacanth stabilized green gold nanoparticles as cargos for Naringin loading: A morphological investigation through AFM.

    Science.gov (United States)

    Rao, Komal; Imran, Muhammad; Jabri, Tooba; Ali, Imdad; Perveen, Samina; Shafiullah; Ahmed, Shakil; Shah, Muhammad Raza

    2017-10-15

    Gold nanoparticles (AuNPs) have attracted greater scientific interests for the construction of drugs loading cargos due to their biocompatibility, safety and facile surface modifications. This study deals with the fabrication of gum tragacanth (GT) green AuNPs as carrier for Naringin, a less water soluble therapeutic molecule. The optimized AuNPs were characterized through UV-vis spectroscopy, FT-IR and atomic force microscope (AFM). Naringin loaded nanoparticles were investigated for their bactericidal potentials using Tetrazolium Microplate assay. Morphological studies conducted via AFM revealed spherical shape for AuNPs with nano-range size and stabilized by GT multi-functional groups. The AuNPs acted as carrier for increased amount of Naringin. Upon loading in AuNPs, Naringin An increased in the bactericidal potentials of Naringin was observed after loading on AuNPs against various tested bacterial strains. This was further authenticated by the surface morphological analysis, showing enhanced membrane destabilizing effects of loaded Naringin. The results suggest that GT stabilized green AuNPs can act as effective delivery vehicles for enhancing bactericidal potentials of Naringin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Improved insulin loading in poly (lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids

    DEFF Research Database (Denmark)

    Garcia Diaz, Maria; Foged, Camilla; Nielsen, Hanne Mørck

    2015-01-01

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading...... of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique...... efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid–insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer...

  15. Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells.

    Science.gov (United States)

    Liang, Jin; Li, Feng; Fang, Yong; Yang, Wenjian; An, Xinxin; Zhao, Liyan; Xin, Zhihong; Cao, Lin; Hu, Qiuhui

    2014-03-01

    Tea polyphenols have strong antioxidant and antitumor activities. However, these health benefits are limited due to their poor in vivo stability and low bioavailability. Chitosan nanoparticles as delivery systems may provide an alternative approach for enhancing bioavailability of poorly absorbed drugs. In this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using two different chitosan biomaterials, and their antitumor effects were evaluated in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis, cell apoptosis and cell cycle detection. The results indicated that the tea polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous distribution in prepared suspension. MTT assay suggested that tea polyphenol-loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and the cytotoxicity rates were increased gradually and appeared an obvious dose-dependent relationship. Transmission electron microscope images showed that the HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited some typical apoptotic features, such as microvilli disappearance, margination of nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea polyphenols not only induced cancer cell apoptosis, but also promoted their necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their antitumor effects mainly through inducing cell apoptosis. Our results revealed that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on tumor cells probably depended on their controlled drug release and effective cell delivery. The chitosan nanoparticles themselves as the delivery carrier showed limited antitumor effects compared with their encapsulated drugs. Copyright © 2013. Published by

  16. PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer.

    Science.gov (United States)

    Garlanda, Cecilia; Bottazzi, Barbara; Magrini, Elena; Inforzato, Antonio; Mantovani, Alberto

    2018-04-01

    Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial, and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis). Moreover, it has a complex regulatory role in inflammation, such as ischemia/reperfusion injury and cancer-related inflammation, as well as in extracellular matrix organization and remodeling, with profound implications in physiology and pathology. Finally, PTX3 acts as an extrinsic oncosuppressor gene by taming tumor-promoting inflammation in murine and selected human tumors. Thus evidence suggests that PTX3 is a key homeostatic component at the crossroad of innate immunity, inflammation, tissue repair, and cancer. Dissecting the complexity of PTX3 pathophysiology and human genetics paves the way to diagnostic and therapeutic exploitation.

  17. Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

    Science.gov (United States)

    David, Karolyn Infanta; Jaidev, Leela Raghav; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2015-11-01

    Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

    Directory of Open Access Journals (Sweden)

    Ilaiyaraja Nallamuthu

    2015-06-01

    Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

  19. Doxorubicin Loaded Chitosan-W18 O49 Hybrid Nanoparticles for Combined Photothermal-Chemotherapy.

    Science.gov (United States)

    Yuan, Shanmei; Hua, Jisong; Zhou, Yinyin; Ding, Yin; Hu, Yong

    2017-08-01

    Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan-W 18 O 49 nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W 18 O 49 nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near-infrared fluorescence imaging, and tumor growth inhibition experiment. These nanoparticles have a mean size around 110 nm and show a pH sensitive drug release behavior. After irradiation by the 980 nm laser, these nanoparticles show more pronounced cytotoxicity against HeLa cells than that of free doxorubicin or photothermal therapy alone. The in vivo experiments confirm that their antitumor ability is significantly improved, resulting in superior efficiency in impeding tumor growth and extension of the lifetime of mice. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Drug-polymer interaction studies of cytarabine loaded chitosan nanoparticles

    International Nuclear Information System (INIS)

    Madni, A.; Kashif, P.M.; Nazir, I.; Rehman, M.

    2017-01-01

    Assessment of possible incompatibilities between drug and excipients is an important parameter of preformulation stage during the pharmaceutical product development of active pharmaceutical ingredient (API). The potential physical and chemical interaction among the components of a delivery system can affect the chemical nature, bioavailability, stability, and subsequently therapeutic efficacy of drugs. In this study, ATR-FTIR spectroscopy was employed to investigate the possible intermolecular interaction of Cytarabine with deacetylated chitosan and tripolyphosphate in the resulting physical blends and crosslinked nanoparticulate system. Two different strategies, physical blending and ionotropic gelation, were adopted to prepare binary or tertiary mixtures and nanoparticulate formulation, respectively. The IR spectra of CB showed characteristic peaks at 3438.27 cm-1 (primary amine), 3264.74 cm-1 (hydroxyl group) and 1654.98 cm-1 (C=O stretch in cyclic ring); CS at 3361.47 cm-1 (N-H stretching), 1646.18 cm-1 (C=O of Amide I), 1582.36 cm-1 (C=O of Amide II), and sTPP at 1135.77 cm-1 (P=O). CS-sTPP chemical interaction was confirmed from the shift in the absorption band of carbonyl groups (amide I, II) to 1634.66 cm-1 and 1541.17 cm-1 in blank chitosan nanoparticles, and 1636.87 cm-1, 1543.33 cm-1 in CSNP1 (2:6:1), and at 1646.15 cm-1 and 1557.04 cm-1 in CSNP2 (1:3:1). The characteristic peaks of CB were also present in chitosan formulation with a slight shift in the amino group at 3429.43 cm-1 and 3423.21 cm-1, in the hydroxyl group at 3274.54 cm-1 and 3270.73 cm-1, CSNP1 and CSNP2, respectively. The findings counseled no significant interaction in IR absorption pattern of cytarabine functional groups after encapsulation in CS-sTPP complex, which projected the potential of chitosan nanoparticulate system to entrap cytarabine. (author)

  1. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    Directory of Open Access Journals (Sweden)

    Maheshkumar P Soni

    2014-01-01

    Full Text Available Background: Buparvaquone (BPQ, a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES organs. The present study investigates development of solid lipid nanoparticles (SLN of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C. Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC, powder X-ray diffraction (XRD and scanning electron microscope (SEM study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8% and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52% uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed

  2. Loading of atorvastatin and linezolid in β-cyclodextrin–conjugated cadmium selenide/silica nanoparticles: A spectroscopic study

    International Nuclear Information System (INIS)

    Antony, Eva Janet; Shibu, Abhishek; Ramasamy, Sivaraj; Paulraj, Mosae Selvakumar; Enoch, Israel V.M.V.

    2016-01-01

    The preparation of β–cyclodextrin–conjugated cadmium selenide–silica nanoparticles, the loading of two drugs viz., Atorvastatin and linezolid in the cyclodextrin cavity, and the fluorescence energy transfer between CdSe/SiO_2 nanoparticles and the drugs encapsulated in the cyclodextrin cavity are reported in this paper. IR spectroscopy, X-ray diffractometry, transmission electron microscopy, and particle size analysis by light–scattering experiment were used as the tools of characterizing the size and the crystal system of the nanoparticles. The nanoparticles fall under hexagonal system. The silica–shell containing CdSe nanoparticles were functionalized by reaction with aminoethylamino–β–cyclodextrin. Fluorescence spectra of the nanoparticles in their free and drug–encapsulated forms were studied. The FÖrster distances between the encapsulated drugs and the CdSe nanoparticles are below 3 nm. The change in the FÖrster resonance energy parameters under physiological conditions may aid in tracking the release of drugs from the cavity of the cyclodextrin. - Highlights: • CdSe/SiO_2 nanoparticles of crystallite size 15 nm are prepared. • β-Cyclodextrin is attached to the surface of the nanoparticles. • Atorvastatin and linezolid get encapsulated in the cyclodextrin cavity. • FRET efficiency between the nanoparticles and the loaded drugs are determined.

  3. Loading of atorvastatin and linezolid in β-cyclodextrin–conjugated cadmium selenide/silica nanoparticles: A spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Antony, Eva Janet; Shibu, Abhishek [Department of Nanosciences & Technology, Karunya University, Coimbatore 641114, Tamil Nadu (India); Ramasamy, Sivaraj; Paulraj, Mosae Selvakumar [Department of Chemistry, Karunya University, Coimbatore 641114, Tamil Nadu (India); Enoch, Israel V.M.V., E-mail: drisraelenoch@gmail.com [Department of Nanosciences & Technology, Karunya University, Coimbatore 641114, Tamil Nadu (India); Department of Chemistry, Karunya University, Coimbatore 641114, Tamil Nadu (India)

    2016-08-01

    The preparation of β–cyclodextrin–conjugated cadmium selenide–silica nanoparticles, the loading of two drugs viz., Atorvastatin and linezolid in the cyclodextrin cavity, and the fluorescence energy transfer between CdSe/SiO{sub 2} nanoparticles and the drugs encapsulated in the cyclodextrin cavity are reported in this paper. IR spectroscopy, X-ray diffractometry, transmission electron microscopy, and particle size analysis by light–scattering experiment were used as the tools of characterizing the size and the crystal system of the nanoparticles. The nanoparticles fall under hexagonal system. The silica–shell containing CdSe nanoparticles were functionalized by reaction with aminoethylamino–β–cyclodextrin. Fluorescence spectra of the nanoparticles in their free and drug–encapsulated forms were studied. The FÖrster distances between the encapsulated drugs and the CdSe nanoparticles are below 3 nm. The change in the FÖrster resonance energy parameters under physiological conditions may aid in tracking the release of drugs from the cavity of the cyclodextrin. - Highlights: • CdSe/SiO{sub 2} nanoparticles of crystallite size 15 nm are prepared. • β-Cyclodextrin is attached to the surface of the nanoparticles. • Atorvastatin and linezolid get encapsulated in the cyclodextrin cavity. • FRET efficiency between the nanoparticles and the loaded drugs are determined.

  4. Synthesis of MgO nanoparticle loaded mesoporous Al2O3 and its defluoridation study

    International Nuclear Information System (INIS)

    Dayananda, Desagani; Sarva, Venkateswara R.; Prasad, Sivankutty V.; Arunachalam, Jayaraman; Parameswaran, Padmanabhan; Ghosh, Narendra N.

    2015-01-01

    Highlights: • Simple and cost effective preparation of MgO nanoparticles loaded mesoporous Al 2 O 3 . • Adsorbents possess high surface area and mesoporous structure. • Higher fluoride removal capacity of MgO loaded Al 2 O 3 than that of pure Al 2 O 3 . • Faster fluoride adsorption kinetics of MgO loaded Al 2 O 3 from water. - Abstract: MgO nanoparticle loaded mesoporous alumina has been synthesized using a simple aqueous solution based cost effective method for removal of fluoride from water. Wide angle powder X-ray diffraction, nitrogen adsorption desorption analysis, transmission electron microscopy techniques and energy dispersive X-ray spectroscopy were used to characterize the synthesized adsorbents. Synthesized adsorbents possess high surface area with mesoporous structure. The adsorbents have been thoroughly investigated for the adsorption of F − using batch adsorption method. MgO nanoparticle loading on mesoporous Al 2 O 3 enhances the F − adsorption capacity of Al 2 O 3 from 56% to 90% (initial F − concentration = 10 mg L −1 ). Kinetic study revealed that adsorption kinetics follows the pseudo-second order model, suggesting the chemisorption mechanism. The F − adsorption isotherm data was explained by both Langmuir and Freundlich model. The maximum adsorption capacity of 40MgO@Al 2 O 3 was 37.35 mg g −1 . It was also observed that, when the solutions having F − concentration of 5 mg L −1 and 10 mg L −1 was treated with 40MgO@Al 2 O 3 , the F − concentration in treated water became <1 mg L −1 , which is well below the recommendation of WHO

  5. Hypericin-loaded nanoparticles for the photodynamic treatment of ovarian cancer.

    Science.gov (United States)

    Zeisser-Labouèbe, Magali; Lange, Norbert; Gurny, Robert; Delie, Florence

    2006-12-01

    A photodynamic approach has been suggested to improve diagnosis and therapy of ovarian cancer. As Hypericin (Hy), a natural photosensitizer (PS) extracted from Hypericum perforatum, has been shown to be efficient in vitro and in vivo for the detection or treatment of other cancers, Hy could also be a potent tool for the treatment and detection of ovarian cancer. Due to its hydrophobicity, systemic administration of Hy is problematic. Thus, polymeric nanoparticles (NPs) of polylactic acid (PLA) or polylactic-co-glycolic acid (PLGA) were used as a drug delivery system. Hy-loaded NPs were produced with the following characteristics: (i) size in the 200-300 nm range, (ii) negative zeta potential, (iii) low residual PVAL and (iv) drug loading from 0.03 to 0.15% (w/w). Their in vitro photoactivity was investigated on the NuTu-19 ovarian cancer cell model derived from Fischer 344 rats and compared to free drug. Hy-loaded PLA NPs exhibited a higher photoactivity than free drug. Increasing light dose or incubation time with cells induced an enhanced activity of Hy-loaded PLA NPs. Increased NP drug loading had a negative effect on their photoactivity on NuTu-19 cells: at the same Hy concentration, the higher was the drug loading, the lower was the phototoxic effect. The influence of NP drug loading on the Hy release from NPs was also investigated.

  6. Synthesis and Characterization of BSA Conjugated Silver Nanoparticles (Ag/BSA Nanoparticles) and Evaluation of Biological Properties of Ag/BSA Nanoparticles and Ag/BSA Nanoparticles Loaded Poly(hydroxy butyrate valerate) PHBV Films

    Science.gov (United States)

    Ambaye, Almaz

    Ag/BSA nanoparticles was found to be in a range of 9-13 nm. X-ray photo electron spectroscopy measurements of argon sputtered Ag/BSA nanoparticles provided evidence that the outer and inner region of nanoparticles are mainly composed of BSA and silver, respectively. Having characterized the nanoparticles, the next phase of the study was to evaluate the antibacterial activity and cytotoxicity level of BSA stabilized silver nanoparticles. The antibacterial efficacy of Ag/BSA nanoparticles against E. coli and S. aureus was evaluated, and minimum lethal concentration was found to be 2ppm and 7ppm, respectively. E. coli showed a higher susceptibility to silver nanoparticles than S. aureus, which could be attributed to the difference in the cell wall structure. We have also investigated the cytotoxicity level of Ag/BSA nanoparticles towards MC3T3-E1 osteoblast cells. The minimum bactericidal concentration found for both strains is lower than the silver nanoparticles concentration that was toxic to the osteoblast cells. Preliminary studies of Ag/BSA nanoparticles loaded collagen immobilized PHBV film showed that the Ag/BSA nanoparticles loaded PHBV film inhibit bacterial growth. The findings of our study can be extremely useful in the design of novel scaffold to address the critical needs of bone tissue engineering community.

  7. Development and evaluation of Desvenlafaxine loaded PLGA-chitosan nanoparticles for brain delivery

    Directory of Open Access Journals (Sweden)

    Gui-Feng Tong

    2017-09-01

    Full Text Available Depression is a debilitating psychiatric condition that remains the second most common cause of disability worldwide. Currently, depression affects more than 4 per cent of the world’s population. Most of the drugs intended for clinical management of depression augment the availability of neurotransmitters at the synapse by inhibiting their neuronal reuptake. However, the therapeutic efficacy of antidepressants is often compromised as they are unable to reach brain by the conventional routes of administration. The purpose of the present study was to reconnoiter the potential of mucoadhesive PLGA-chitosan nanoparticles for the delivery of encapsulated Desvenlafaxine to the brain by nose to brain delivery route for superior pharmacokinetic and pharmacodynamic profile of Desvenlafaxine. Desvenlafaxine loaded PLGA-chitosan nanoparticles were prepared by solvent emulsion evaporation technique and optimized for various physiochemical characteristics. The antidepressant efficacy of optimized Desvenlafaxine was evaluated in various rodent depression models together with the biochemical estimation of monoamines in their brain. Further, the levels of Desvenlafaxine in brain and blood plasma were determined at various time intervals for calculation of different pharmacokinetic parameters. The optimized Desvenlafaxine loaded PLGA-chitosan nanoparticles (∼172 nm/+35 mV on intranasal administration significantly reduced the symptoms of depression and enhanced the level of monoamines in the brain in comparison with orally administered Desvenlafaxine. Nose to brain delivery of Desvenlafaxine PLGA-chitosan nanoparticles also enhanced the pharmacokinetic profile of Desvenlafaxine in brain together with their brain/blood ratio at different time points. Thus, intranasal mucoadhesive Desvenlafaxine PLGA-chitosan nanoparticles could be potentially used for the treatment of depression.

  8. Chitosan nanoparticles as non-viral gene delivery systems: determination of loading efficiency.

    Science.gov (United States)

    Carrillo, Carolina; Suñé, Josep Maria; Pérez-Lozano, Pilar; García-Montoya, Encarna; Sarrate, Rocío; Fàbregas, Anna; Miñarro, Montserrat; Ticó, Josep Ramon

    2014-07-01

    Chitosan has been studied for use in particle delivery systems for therapeutic purposes, since one of its most important applications is as a non-viral vector in gene therapy. Due to its positive charge, it is capable of forming DNA complexes (polyplexes) obtained through several methods and with the property of protecting nucleic acids. Two methods for obtaining the nanoparticles of chitosan-nucleic acids are reported in this study: simple complexation (of depolymerized chitosan or of different chitosan salts with plasmid) and ionic gelation (by adsorption of plasmid in the nanoparticles or by encapsulation of plasmid into nanoparticles). The determination of the loading efficiency of chitosan nanoparticles with the plasmid is carried out by electrophoretic mobility of the samples on agarose gel. Furthermore, the nanoparticles have been characterized according to their morphology, size and surface charge using AFM, TEM, laser diffraction and dynamic light scattering techniques. The polyplexes obtained have been found to be spherical and nanometric in size (between 100-230nm) with a zeta potential between 37 and 48mV. Positive results have been obtained by agarose gel electrophoresis for all studied cases: a concentration of between 20 and 30μg/mL of chitosan salts is required while for the remaining chitosan samples studied, 100% loading efficiency does not occur until a concentration equal to 100μg/mL (regardless of previous depolymerisation and the method performed). Chitosan-plasmid nanocapsules have been obtained at the polymer concentrations worked with (between 0.025 and 0.2%). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Synthesis and catalytic properties of Pd nanoparticles loaded nanoporous TiO2 material

    International Nuclear Information System (INIS)

    Xu, Wence; Zhu, Shengli; Li, Zhaoyang; Cui, Zhenduo; Yang, Xianjin

    2013-01-01

    In the present work, Pd nanoparticles were loaded on the nanoporous TiO 2 material by a simple chemical deposition. The amount of Pd nanoparticles was determined by the loading times. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and chronoamperometry (CA) methods were used to characterize the surface morphology, composition and electro-catalyst activity of the nanoporous Pd/TiO 2 material. CV and CA results exhibited the excellent methanol electro-oxidation performance of 6 times loaded sample. The effects of methanol concentration, H 2 SO 4 concentration and upper scan limits on the electro-oxidation performance of six times loaded sample were investigated. In the solution with low methanol concentration, electro-oxidation of methanol was influenced by the amount of methanol molecules on Pd active sites. In the solution with high methanol concentration, electro-oxidation of methanol was controlled by intermediates diffusion. With increasing H 2 SO 4 concentration, driving force of methanol oxidation decreased. However, the increase of bisulfate adsorption, the reduction of thermodynamic tendency and solution conductivity would result in the suppression of peak current density. The upper scanning limit had obvious influence on the active sites for the methanol oxidation reaction in the backward scanning stage. The generation of PdO at high potential was undesired for methanol electro–oxidation

  10. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martina.pospisilova@contipro.com; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir [Contipro Biotech (Czech Republic)

    2015-09-15

    Hyaluronan (HA) represents an interesting polymer for nanoparticle coating due to its biocompatibility and enhanced cell interaction via CD44 receptor. Here, we describe incorporation of oleate-capped β–NaYF{sub 4}:Yb{sup 3+}, Er{sup 3+} nanoparticles (UCNP-OA) into amphiphilic HA by microemulsion method. Resulting structures have a spherical, micelle-like appearance with a hydrodynamic diameter of 180 nm. UCNP-OA-loaded HA micelles show a good stability in PBS buffer and cell culture media. The intensity of green emission of UCNP-OA-loaded HA micelles in water is about five times higher than that of ligand-free UCNP, indicating that amphiphilic HA effectively protects UCNP luminescence from quenching by water molecules. We found that UCNP-OA-loaded HA micelles in concentrations up to 50 μg mL{sup −1} increase cell viability of normal human dermal fibroblasts (NHDF), while viability of human breast adenocarcinoma cells MDA–MB–231 is reduced at these concentrations. The utility of UCNP-OA-loaded HA micelles as a bio-imaging probe was demonstrated in vitro by successful labelling of NHDF and MDA–MB–231 cells overexpressing the CD44 receptor.

  11. Transient loading of CD34+ hematopoietic progenitor cells with polystyrene nanoparticles

    Directory of Open Access Journals (Sweden)

    Deville S

    2017-01-01

    Full Text Available Sarah Deville,1,2 Wahyu Wijaya Hadiwikarta,1 Nick Smisdom,1,2 Bart Wathiong,1,3 Marcel Ameloot,2 Inge Nelissen,1 Jef Hooyberghs1,3 1VITO, Flemish Institute for Technological Research, Mol, Belgium; 2Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium; 3Theoretical Physics, Hasselt University, Diepenbeek, Belgium Abstract: CD34+ hematopoietic progenitor cells (HPCs offer great opportunities to develop new treatments for numerous malignant and non-malignant diseases. Nanoparticle (NP-based strategies can further enhance this potential, and therefore a thorough understanding of the loading behavior of HPCs towards NPs is essential for a successful application. The present study focusses on the interaction kinetics of 40 nm sized carboxylated polystyrene (PS NPs with HPCs. Interestingly, a transient association of the NPs with HPCs is observed, reaching a maximum within 1 hour and declining afterwards. This behavior is not seen in dendritic cells (CD34-DCs differentiated from HPCs, which display a monotonic increase in NP load. We demonstrate that this transient interaction requires an energy-dependent cellular process, suggesting active loading and release of NPs by HPCs. This novel observation offers a unique approach to transiently equip HPCs. A simple theoretical approach modeling the kinetics of NP loading and release is presented, contributing to a framework of describing this phenomenon. Keywords: nanoparticles, hematopoietic progenitor cells, dendritic cells, uptake, release

  12. Silver nanoparticle-loaded chitosan-starch based films: Fabrication and evaluation of tensile, barrier and antimicrobial properties

    International Nuclear Information System (INIS)

    Yoksan, Rangrong; Chirachanchai, Suwabun

    2010-01-01

    The fabrication of silver nanoparticles was accomplished by γ-ray irradiation reduction of silver nitrate in a chitosan solution. The obtained nanoparticles were stable in the solution for more than six months, and showed the characteristic surface plasmon band at 411 nm as well as a positively charged surface with 40.4 ± 2.0 mV. The silver nanoparticles presented a spherical shape with an average size of 20-25 nm, as observed by TEM. Minimum inhibitory concentration (MIC) against E. coli, S. aureus and B. cereus of the silver nanoparticles dispersed in the γ-ray irradiated chitosan solution was 5.64 μg/mL. The silver nanoparticle-loaded chitosan-starch based films were prepared by a solution casting method. The incorporation of silver nanoparticles led to a slight improvement of the tensile and oxygen gas barrier properties of the polysaccharide-based films, with diminished water vapor/moisture barrier properties. In addition, silver nanoparticle-loaded films exhibited enhanced antimicrobial activity against E. coli, S. aureus and B. cereus. The results suggest that silver nanoparticle-loaded chitosan-starch based films can be feasibly used as antimicrobial materials for food packaging and/or biomedical applications.

  13. Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment.

    Science.gov (United States)

    Katiyar, Sameer S; Muntimadugu, Eameema; Rafeeqi, Towseef Amin; Domb, Abraham J; Khan, Wahid

    2016-09-01

    P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

  14. Synthesis of curcumin-loaded chitosan phosphate nanoparticle and study of its cytotoxicity and antimicrobial activity.

    Science.gov (United States)

    Deka, C; Aidew, L; Devi, N; Buragohain, A K; Kakati, D K

    2016-11-01

    Curcumin has acquired an important position in the treatment of various diseases. But its use, as a chemotherapeutic agent, is limited due to its low water solubility, poor bioavailability, and its sensitive nature at the physiological pH. To overcome this, curcumin was loaded into chitosan phosphate nanoparticles (CPNs). The loading efficiency was found to be 84%. DLS studies revealed the average particle size of CPNs and curcumin-loaded CPNs as 53 and 91 nm, respectively, and TEM results supplemented these values. A sustained release pattern was noticed and the amount of curcumin released in acidic pH was higher than at physiological pH. The curcumin nanoformulation exhibited proficient activity against both Gram-positive and Gram-negative bacteria as well as fungus. Cytocompatibility of the nanoformulations against peripheral blood mononuclear cells (PBMCs) and murine monocyte-macrophage cell line was confirmed by incubating with PBMCs and murine monocyte-macrophage cell line.

  15. Preparation of curcumin-loaded pluronic F127/chitosan nanoparticles for cancer therapy

    International Nuclear Information System (INIS)

    Phuc Le, Thi Minh; Pham, Van Phuc; Lua Dang, Thi Minh; Huyen La, Thi; Le, Thi Hanh; Le, Quang Huan

    2013-01-01

    Nanoparticles (NPs) have been proven to be an effective delivery system with few side effects for anticancer drugs. In this study, curcumin-loaded NPs have been prepared by an ionic gelation method using chitosan (Chi) and pluronic ® F-127 (PF) as carriers to deliver curcumin to the target cancer cells. Prepared NPs were characterized using Zetasizer, fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Our results showed that the encapsulation efficiency of curcumin was approximately 50%. The average size of curcumin-loaded PF/Chi NPs was 150.9 nm, while the zeta potential was 5.09 mV. Cellular uptake of curcumin-loaded NPs into HEK293 cells was confirmed by fluorescence microscopy. (paper)

  16. Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

    Science.gov (United States)

    Gayathri, N K; Aparna, V; Maya, S; Biswas, Raja; Jayakumar, R; Mohan, C Gopi

    2017-12-01

    We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. MO-FG-BRA-05: Next Generation Radiotherapy Biomaterials Loaded With Gold Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Cifter, G; Ngwa, W [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (United States); Univ Massachusetts Lowell, Lowell, MA (United States); Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Korideck, H; Cormack, R; Makrigiorgos, G [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (United States); Kumar, R [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (United States); Northeastern University, Boston, MA (United States); Sridhar, S [Northeastern University, Boston, MA (United States)

    2015-06-15

    Purpose: It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. In this work, we developed prototypes of such RT biomaterials and investigated the sustained release of GNPs from the biomaterials as a function of design parameters. Methods: Prototype smart biomaterials were produced by incorporating the GNPs in poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. For comparison, commercially available spacers were also coated with a polymer film loaded with fluorescent GNP. Optical/spectroscopy methods were used to monitor in vitro release of GNPs over time as a function of different design parameters: polymer weighting, type, and initial (loading) GNP concentrations. Inductively coupled plasma mass spectrometry was employed to verify GNP release. Results: Results showed that gold nanoparticles could be successfully loaded in the new RT biomaterial prototypes. Burst release of GNPs could be achieved within 1 to 25 days depending on the preparation approach. Burst release was followed by sustained release profile over time. The amount of released GNP increased with increasing loading concentration as expected. The release profiles could also be customized as a function of polymer weighting, or preparation approaches. Conclusion: Considered together, our results highlight potential for the development of next generation RT biomaterials loaded with GNPs customizable to different RT schedules. Such biomaterials could be employed as needed instead of currently used inert spacers/fiducials at no additional inconvenience to patients, to enhance RT.

  18. MO-FG-BRA-05: Next Generation Radiotherapy Biomaterials Loaded With Gold Nanoparticles

    International Nuclear Information System (INIS)

    Cifter, G; Ngwa, W; Sajo, E; Korideck, H; Cormack, R; Makrigiorgos, G; Kumar, R; Sridhar, S

    2015-01-01

    Purpose: It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. In this work, we developed prototypes of such RT biomaterials and investigated the sustained release of GNPs from the biomaterials as a function of design parameters. Methods: Prototype smart biomaterials were produced by incorporating the GNPs in poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. For comparison, commercially available spacers were also coated with a polymer film loaded with fluorescent GNP. Optical/spectroscopy methods were used to monitor in vitro release of GNPs over time as a function of different design parameters: polymer weighting, type, and initial (loading) GNP concentrations. Inductively coupled plasma mass spectrometry was employed to verify GNP release. Results: Results showed that gold nanoparticles could be successfully loaded in the new RT biomaterial prototypes. Burst release of GNPs could be achieved within 1 to 25 days depending on the preparation approach. Burst release was followed by sustained release profile over time. The amount of released GNP increased with increasing loading concentration as expected. The release profiles could also be customized as a function of polymer weighting, or preparation approaches. Conclusion: Considered together, our results highlight potential for the development of next generation RT biomaterials loaded with GNPs customizable to different RT schedules. Such biomaterials could be employed as needed instead of currently used inert spacers/fiducials at no additional inconvenience to patients, to enhance RT

  19. Preparation and characterization of DOX loaded keratin nanoparticles for pH/GSH dual responsive release

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanmei; Zhi, Xuelian [Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); Lin, Jiantao [Guangdong Medical University, Dongguan 523808 (China); You, Xin [Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); Yuan, Jiang, E-mail: jyuan@njnu.edu.cn [Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China)

    2017-04-01

    Smart drug carriers are the current need of the hour in controlled drug delivery applications. In this work, pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated through two-step strategies. Keratin nanoparticles were first prepared by desolvation method and chemical crosslinking, followed by electrostatic adsorbing doxorubicin (DOX) to afford drug loaded keratin nanoparticles (KDNPs). The size, size distribution, and morphology of the KDNPs were characterized with dynamic light scattering (DLS) and Scan electronic microscope (SEM). Drug delivery profiles showed that KDNPs exhibited pH and glutathione (GSH) dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting nitric oxide (NO) release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine. - Graphical abstract: pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated by desolvation with chemical crosslinking, followed by electrostatic adsorbing DOX to afford DOX loaded keratin nanoparticles (KDNPs). Drug delivery profiles showed that KDNPs exhibited pH and GSH dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay

  20. Palladium Loaded on Magnetic Nanoparticles as Efficient and Recyclable Catalyst for the Suzuki- Miyaura Reaction

    Directory of Open Access Journals (Sweden)

    H. Khojasteh

    2015-07-01

    Full Text Available Palladium is the best metal catalyst for Suzuki cross coupling reaction for synthesize of unsymmetrical biaryl compounds. But its high cost limits its application in wide scale. Using of nanoscale particles as active catalytic cites is a good approach for reducing needed noble metal. By loading precious nanoparticles on magnetic nanocores as a support, recycling and reusing of catalyst will be possible. Magnetic nanoparticles have super paramagnetic feature and applying an external magnetic field can collect the supported catalyst from reaction milieu simply. In this work new palladium catalyst immobilized on modified magnetic nanoparticles containing NNO donor atoms were synthesized. Then the catalyst characterized by FT-IR spectroscopy, thermogravimetric analysis, X-ray diffraction and ICP. Prepared catalyst showed high activity in the Suzuki– Miyaura cross-coupling reaction of phenylboronic acid with aryl halides. Activity, Pd loading, reusability and Pd leaching of catalyst were studied. Results showed that the supported catalyst has the advantage to be completely recoverable with the simple application of an external magnetic field.

  1. G-CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo.

    Science.gov (United States)

    Tanha, Shima; Rafiee-Tehrani, Morteza; Abdollahi, Mohamad; Vakilian, Saeid; Esmaili, Zahra; Naraghi, Zahra Safaei; Seyedjafari, Ehsan; Javar, Hamid Akbari

    2017-10-01

    Sustained release of functional growth factors can be considered as a beneficial methodology for wound healing. In this study, recombinant human granulocyte colony-stimulating factor (G-CSF)-loaded chitosan nanoparticles were incorporated in Poly(ε-caprolactone) (PCL) nanofibers, followed by surface coating with collagen type I. Physical and mechanical properties of the PCL nanofibers containing G-CSF loaded chitosan nanoparticles PCL/NP(G-CSF) and in vivo performance for wound healing were investigated. G-CSF structural stability was evaluated through SDS_PAGE, reversed phase (RP) HPLC and size-exclusion chromatography, as well as circular dichroism. Nanofiber/nanoparticle composite scaffold was demonstrated to have appropriate mechanical properties as a wound dresser and a sustained release of functional G-CSF. The PCL/NP(G-CSF) scaffold showed a suitable proliferation and well-adherent morphology of stem cells. In vivo study and histopathological evaluation outcome revealed that skin regeneration was dramatically accelerated under PCL/NP(G-CSF) as compared with control groups. Superior fibroblast maturation, enhanced collagen deposition and minimum inflammatory cells were also the beneficial properties of PCL/NP(G-CSF) over the commercial dressing. The synergistic effect of extracellular matrix-mimicking nanofibrous membrane and G-CSF could develop a suitable supportive substrate in order to extensive utilization for the healing of skin wounds. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2830-2842, 2017. © 2017 Wiley Periodicals, Inc.

  2. Polyinosinic:polycytidylic acid loading onto different generations of PAMAM dendrimer-coated magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Khodadust, Rouhollah, E-mail: raoul.1357@gmail.com [Middle East Technical University, Department of Biotechnology (Turkey); Mutlu, Pelin [Middle East Technical University, Central Laboratory, Molecular Biology and Biotechnology R and D Center (Turkey); Yalc Latin-Small-Letter-Dotless-I n, Serap [Ahi Evran University, Department of Food Engineering (Turkey); Unsoy, Gozde; Gunduz, Ufuk, E-mail: ufukg@metu.edu.tr [Middle East Technical University, Department of Biotechnology (Turkey)

    2013-08-15

    Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor cells. The immobilization of Poly (I:C) onto nanoparticles is important for the fabrication of targeted delivery systems. In this study, different generations of newly synthesized PAMAM dendron-coated magnetic nanoparticles (DcMNP) which can be targeted to the tumor site under magnetic field were efficiently loaded for the first time with Poly (I:C). Different generations of DcMNPs (G{sub 2}, G{sub 3}, G{sub 4}, G{sub 5}, G{sub 6}, and G{sub 7}) were synthesized. Poly (I:C) activation was achieved in the presence of EDC and 1-methylimidazole. Loading of Poly (I:C) onto DcMNPs was followed by agarose gel electrophoresis. Acidic reaction conditions were found as superior to basic and neutral for binding of Poly (I:C). In addition, having more functional groups at the surface, higher generations (G{sub 7}, G{sub 6}, and G{sub 5}) of PAMAM DcMNPs were found more suitable as a delivery system for Poly (I:C). Further in vitro and in vivo analyses of Poly (I:C)/PAMAM magnetic nanoparticles may provide new opportunities for the selective targeting and killing of tumor cells.

  3. Human pentraxin 3 (PTX3 as a novel biomarker for the diagnosis of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yuichi Tamura

    Full Text Available BACKGROUND: Although inflammation is an important feature of pulmonary arterial hypertension (PAH, the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3, a local inflammatory marker, would be a useful biomarker for detecting PAH. METHODS: Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH, and six with congenital heart disease, 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP and C-reactive protein (CRP were also determined. RESULTS: Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001. Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001. There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866 is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%. CONCLUSION: Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

  4. The role of the acute phase protein PTX3 in the ventilator-induced lung injury

    Directory of Open Access Journals (Sweden)

    JM Real

    2008-06-01

    Full Text Available The pentraxin 3 (PTX3 is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI, representing a major cause of iatrogenic lung damage in intensive units. Our objective was to investigate the role of PTX3 in VILI. PTX3 transgenic, knockout and Wt control mice (n = 12/group were ventilated (45ml·kg–1 until respiratory system Elastance increased 50% (Ers150%, an indicator of VILI. Histological analysis demonstrated that using a Ers150% was appropriate for our analysis since identical degrees of inflammation were observed in Tg, KO and Wt mice as assessed by leukocyte infiltration, oedema, alveolar collapse and number of breaks in alveolar septa. However, Tg mice reached Ers150% faster than Wt controls (p = 0.0225. We also showed that the lack of PTX3 does not abolish the occurrence of VILI in KOs. Gene expression profile of PTX3, IL-1beta, IL-6, KC, IFNgamma, TGFbeta and PCIII were investigated by QPCR. MV drastically up modulated PTX3 as well as IL-1beta, IL-6, IFNgamma and KC. Alternatively, mice were ventilated for 20, 40 and 60 min. The faster kinetics of Tg mice to reach Ers150% was accompanied by an earlier augmentation of IL-1b and PTX3 expression. The kinetics of local PTX3 expression in the lungs of ventilated mice strongly suggests the involvement of this pentraxin in the pathogenesis of VILI.

  5. SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation.

    Science.gov (United States)

    Dimchevska, Simona; Geskovski, Nikola; Petruševski, Gjorgji; Chacorovska, Marina; Popeski-Dimovski, Riste; Ugarkovic, Sonja; Goracinova, Katerina

    2017-03-01

    One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol ® F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

  6. Impact of enzyme loading on the efficacy and recovery of cellulolytic enzymes immobilized on enzymogel nanoparticles.

    Science.gov (United States)

    Samaratunga, Ashani; Kudina, Olena; Nahar, Nurun; Zakharchenko, Andrey; Minko, Sergiy; Voronov, Andriy; Pryor, Scott W

    2015-03-01

    Cellulase and β-glucosidase were adsorbed on a polyacrylic acid polymer brush grafted on silica nanoparticles to produce enzymogels as a form of enzyme immobilization. Enzyme loading on the enzymogels was increased to a saturation level of approximately 110 μg (protein) mg(-1) (particle) for each enzyme. Enzymogels with varied enzyme loadings were then used to determine the impact on hydrolysis rate and enzyme recovery. Soluble sugar concentrations during the hydrolysis of filter paper and Solka-Floc with the enzymogels were 45 and 53%, respectively, of concentrations when using free cellulase. β-Glucosidase enzymogels showed lower performance; hydrolyzate glucose concentrations were just 38% of those using free enzymes. Increasing enzyme loading on the enzymogels did not reduce net efficacy for cellulase and improved efficacy for β-glucosidase. The use of free cellulases and cellulase enzymogels resulted in hydrolyzates with different proportions of cellobiose and glucose, suggesting differential attachment or efficacy of endoglucanases, exoglucanases, and β-glucosidases present in cellulase mixtures. When loading β-glucosidase individually, higher enzyme loadings on the enzymogels produced higher hydrolyzate glucose concentrations. Approximately 96% of cellulase and 66 % of β-glucosidase were recovered on the enzymogels, while enzyme loading level did not impact recovery for either enzyme.

  7. Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

    Science.gov (United States)

    Brandhonneur, N; Hatahet, T; Amela-Cortes, M; Molard, Y; Cordier, S; Dollo, G

    2018-04-01

    We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo 6 Br 14 cluster unit, (TBA) 2 Mo 6 Br 14 , presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA) 2 Mo 6 Br 14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA) 2 Mo 6 Br 14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Cisplatin Loaded Hyaluronic Acid Modified TiO2 Nanoparticles for Neoadjuvant Chemotherapy of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Enling Liu

    2015-01-01

    Full Text Available Novel tumor-targeting titanium dioxide (TiO2 nanoparticles modified with hyaluronic acid (HA were developed to explore the feasibility of exploiting the pH-responsive drug release property of TiO2 and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP delivery system (HA-TiO2 for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2 nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2 nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo real-time imaging assay revealed that HA-TiO2 nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.

  9. Atorvastatin calcium loaded chitosan nanoparticles: in vitro evaluation and in vivo pharmacokinetic studies in rabbits

    Directory of Open Access Journals (Sweden)

    Abdul Baquee Ahmed

    2015-06-01

    Full Text Available In this study, we prepared atorvastatin calcium (AVST loaded chitosan nanoparticles to improve the oral bioavailability of the drug. Nanoparticles were prepared by solvent evaporation technique and evaluated for its particle size, entrapment efficiency, zeta potential, in vitro release and surface morphology by scanning electron microscopy (SEM. In addition, the pharmacokinetics of AVST from the optimized formulation (FT5 was compared with marketed immediate release formulation (Atorva(r in rabbits. Particle size of prepared nanoparticles was ranged between 179.3 ± 7.12 to 256.8 ± 8.24 nm with a low polydispersity index (PI value. Zeta potential study showed that the particles are stable with positive values between 13.03 ± 0.32 to 46.90 ± 0.49 mV. FT-IR studies confirmed the absence of incompatibility of AVST with excipient used in the formulations. In vitro release study showed that the drug release was sustained for 48 h. Results of pharmacokinetics study showed significant changes in the pharmacokinetic parameter (2.2 fold increase in AUC of the optimized formulation as compared to marketed formulation (Atorva(r. Thus, the developed nanoparticles evidenced the improvement of oral bioavailability of AVST in rabbit model.

  10. BSA nanoparticle loaded atorvastatin calcium--a new facet for an old drug.

    Science.gov (United States)

    Sripriyalakshmi, S; Anjali, C H; George, Priya Doss C; Rajith, B; Ravindran, Aswathy

    2014-01-01

    Currently, the discovery of effective chemotherapeutic agents poses a major challenge to the field of cancer biology. The present study focuses on enhancing the therapeutic and anti cancer properties of atorvastatin calcium loaded BSA (ATV-BSA) nanoparticles in vitro. BSA-ATV nanoparticles were prepared using desolvation technique. The process parameters were optimized based on the amount of desolvating agent, stabilization conditions as well as the concentration of the cross linker. The anti cancer properties of the protein coated ATV nanoparticles were tested on MiaPaCa-2 cell lines. In vitro release behavior of the drug from the carrier suggests that about 85% of the drug gets released after 72 hrs. Our studies show that ATV-BSA nanoparticles showed specific targeting and enhanced cytotoxicity to MiaPaCa-2 cells when compared to the bare ATV. We hereby propose that the possible mechanism of cellular uptake of albumin bound ATV could be through caveolin mediated endocytosis. Hence our studies open up new facet for an existing cholesterol drug as a potent anti-cancer agent.

  11. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

    Science.gov (United States)

    Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

    2017-11-21

    Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  12. Bioactive Glass Nanoparticles-Loaded Poly(ɛ-caprolactone Nanofiber as Substrate for ARPE-19 Cells

    Directory of Open Access Journals (Sweden)

    Tadeu Henrique Lima

    2016-01-01

    Full Text Available Bioactive glass nanoparticles-loaded poly(ɛ-caprolactone nanofibers (BIOG PCL nanofibers were synthesized and evaluated as substrates for ocular cells (ARPE-19. BIOG PCL nanofibers were characterized using SEM, FTIR, and DSC, and the in vitro degradation profile was also investigated. The in vitro ocular biocompatibility of nanofibers was exploited in Müller glial cells (MIO-M1 cells and in chorioallantoic membrane (CAM; and the proliferative capacity, cytotoxicity, and functionality were evaluated. Finally, ARPE-19 cells were seeded onto BIOG PCL nanofibers and they were investigated as supports for in vitro cell adhesion and proliferation. SEM images revealed the incorporation of BIOG nanoparticles into PCL nanofibers. Nanoparticles did not induce modifications in the chemical structure and semicrystalline nature of PCL in the nanofiber, as shown by FTIR and DSC. MIO-M1 cells exposed to BIOG PCL nanofibers showed viability, and they were able to proliferate and to express GFAP, indicating cellular functionality. Moreover, nanofibers were well tolerated by CAM. These findings suggested the in vitro ocular biocompatibility and absence of toxicity of these nanofibers. Finally, the BIOG nanoparticles modulated the protein adsorption, and, subsequently, ARPE-19 cells adhered and proliferated onto the nanostructured supports, establishing cell-substrate interactions. In conclusion, the biodegradable and biocompatible BIOG PCL nanofibers supported the ARPE-19 cells.

  13. Purification of Drug Loaded PLGA Nanoparticles Prepared by Emulsification Solvent Evaporation Using Stirred Cell Ultrafiltration Technique.

    Science.gov (United States)

    Paswan, Suresh K; Saini, T R

    2017-12-01

    The emulsifiers in an exceedingly higher level are used in the preparation of drug loaded polymeric nanoparticles prepared by emulsification solvent evaporation method. This creates great problem to the formulator due to their serious toxicities when it is to be administered by parenteral route. The final product is therefore required to be freed from the used surfactants by the conventional purification techniques which is a cumbersome job. The solvent resistant stirred cell ultrafiltration unit (Millipore) was used in this study using polyethersulfone ultrafiltration membrane (Biomax®) having pore size of NMWL 300 KDa as the membrane filter. The purification efficiency of this technique was compared with the conventional centrifugation technique. The flow rate of ultrafiltration was optimized for removal of surfactant (polyvinyl alcohol) impurities to the acceptable levels in 1-3.5 h from the nanoparticle dispersion of tamoxifen prepared by emulsification solvent evaporation method. The present investigations demonstrate the application of solvent resistant stirred cell ultrafiltration technique for removal of toxic impurities of surfactant (PVA) from the polymeric drug nanoparticles (tamoxifen) prepared by emulsification solvent evaporation method. This technique offers added benefit of producing more concentrated nanoparticles dispersion without causing significant particle size growth which is observed in other purification techniques, e.g., centrifugation and ultracentrifugation.

  14. Interactions of the humoral pattern recognition molecule PTX3 with the complement system

    DEFF Research Database (Denmark)

    Doni, Andrea; Garlanda, Cecilia; Bottazzi, Barbara

    2012-01-01

    The innate immune system comprises a cellular and a humoral arm. The long pentraxin PTX3 is a fluid phase pattern recognition molecule, which acts as an essential component of the humoral arm of innate immunity. PTX3 has antibody-like properties including interactions with complement components....... PTX3 interacts with C1q, ficolin-1 and ficolin-2 as well as mannose-binding lectin, recognition molecules in the classical and lectin complement pathways. The formation of these heterocomplexes results in cooperative pathogen recognition and complement activation. Interactions with C4b binding protein...

  15. Controlling the interparticle spacing of Au-salt loaded micelles and Au nanoparticles on flat surfaces.

    Science.gov (United States)

    Bansmann, J; Kielbassa, S; Hoster, H; Weigl, F; Boyen, H G; Wiedwald, U; Ziemann, P; Behm, R J

    2007-09-25

    The self-organization of diblock copolymers into micellar structures in an appropriate solvent allows the deposition of well ordered arrays of pure metal and alloy nanoparticles on flat surfaces with narrow distributions in particle size and interparticle spacing. Here we investigated the influence of the materials (substrate and polymer) and deposition parameters (temperature and emersion velocity) on the deposition of metal salt loaded micelles by dip-coating from solution and on the order and inter-particle spacing of the micellar deposits and thus of the metal nanoparticle arrays resulting after plasma removal of the polymer shell. For identical substrate and polymer, variation of the process parameters temperature and emersion velocity enables the controlled modification of the interparticle distance within a certain length regime. Moreover, also the degree of hexagonal order of the final array depends sensitively on these parameters.

  16. Study on synthesis and properties of nanoparticles loaded with amaryllidaceous alkaloids

    Directory of Open Access Journals (Sweden)

    Duan Lihong

    2017-11-01

    Full Text Available Alzheimer’s disease (AD is the most common disease among the elderly people and a major social and medical problem. Amaryllidaceous alkaloids, acting as acetylcholinesterase inhibitors, represent a potential treatment of AD. However, they also have some deficiencies, such as extensive toxicity and widespread side effects. In order to improve the bioavailability and reduce the toxic and side effects, brain targeting of amaryllidaceous alkaloids was enhanced by considering low density lipoprotein (LDL receptors of blood-brain barrier (BBB endothelial cells as therapeutic targets. Amaryllidaceous alkaloids were highly selectively and quantitatively riveted to the surface of low density lipoproteins by using a new method - mild click chemistry. The structure of products has been characterized by NMR, FT-IR, and other methods. In addition, drug loading rate, encapsulation rate, and drug release by the nanoparticles were determined to assess the quality of the nanoparticles.

  17. Estradiol-loaded PLGA nanoparticles for improving low bone mineral density of cancellous bone caused by osteoporosis: Application of enhanced charged nanoparticles with iontophoresis.

    Science.gov (United States)

    Takeuchi, Issei; Kobayashi, Shiori; Hida, Yukari; Makino, Kimiko

    2017-07-01

    Postmenopausal osteoporosis among older women, which occurs by an ovarian hormone deficiency, is one of the major public health problems. 17 β-estradiol (E2) is used to prevent and treat this disease as a drug of hormone replacement therapy. In oral administration, E2 is significantly affected by first-pass hepatic metabolism, and high dose administration must be needed to obtain drug efficacy. Therefore, alternative administration route is needed, and we have focused on the transdermal drug delivery system. In this study, we have prepared E2-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles for osteoporosis by using a combination of an antisolvent diffusion method with preferential solvation. The average particle diameter of the nanoparticles was 110.0±41.0nm and the surface charge number density was 82 times higher than that of conventional E2-loaded PLGA nanoparticles. Therapeutic evaluation of E2-loaded PLGA nanoparticles was carried out using ovariectomized female rats. Therapeutic efficacy was evaluated to measure bone mineral density of cancellous bone using an X-ray CT system. When the E2-loaded PLGA nanoparticles were administrated once a week, bone mineral density was significantly higher than that of the non-treated group at 60days after the start of treatment. Also, in the group administered this nanoparticle twice a week, the bone mineral density increased significantly at 45days after the start of treatment. From these results, it was revealed that E2-loaded PLGA nanoparticles with iontophoresis were useful to recover bone mineral density of cancellous bone, and it was also suggested that they extend the dosing interval of E2. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Jing, E-mail: joemj1005@163.com, E-mail: miaojing@zju.edu.cn [Zhejiang University, Department of Pharmacy, the First Affiliated Hospital, College of Medicine (China); Du, Yongzhong; Yuan, Hong [Zhejiang University, College of Pharmaceutical Sciences (China); Zhang, Xingguo; Li, Qian; Rao, Yuefeng [Zhejiang University, Department of Pharmacy, the First Affiliated Hospital, College of Medicine (China); Zhao, Mengdan [Zhejiang University, Women’s Hospital, College of Medicine (China); Hu, Fuqiang, E-mail: hufq@zju.edu.cn [Zhejiang University, College of Pharmaceutical Sciences (China)

    2015-01-15

    Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC{sub 50}) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL{sup −1}, respectively, while the IC{sub 50} of Taxol{sup TM} was 1.72 ± 0.09 µg mL{sup −1}. For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC.

  19. Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

    International Nuclear Information System (INIS)

    Miao, Jing; Du, Yongzhong; Yuan, Hong; Zhang, Xingguo; Li, Qian; Rao, Yuefeng; Zhao, Mengdan; Hu, Fuqiang

    2015-01-01

    Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC 50 ) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL −1 , respectively, while the IC 50 of Taxol TM was 1.72 ± 0.09 µg mL −1 . For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC

  20. Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors.

    Science.gov (United States)

    Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong; Li, He; Li, Yaogang; Duan, Yourong

    2016-01-19

    Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately -16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy.

  1. Efficient production of nanoparticle-loaded orodispersible films by process integration in a stirred media mill.

    Science.gov (United States)

    Steiner, Denise; Finke, Jan Henrik; Kwade, Arno

    2016-09-25

    Orodispersible films possess a great potential as a versatile platform for nanoparticle-loaded oral dosage forms. In this case, poorly water-soluble organic materials were ground in a stirred media mill and embedded into a polymer matrix. The aim of this study was the shortening of this manufacturing process by the integration of several process steps into a stirred media mill without facing disadvantages regarding the film quality. Furthermore, this process integration is time conserving due to the high stress intensities provided in the mill and applicable for high solids contents and high suspension viscosities. Two organic materials, the model compound Anthraquinone and the active pharmaceutical ingredient Naproxen were investigated in this study. Besides the impact of the film processing on the crystallinity of the particles in the orodispersible film, a particle load of up to 50% was investigated with the new developed processing route. Additionally, a disintegration test was developed, combining an appropriate amount of saliva substitute and a clear endpoint determination. In summary, high nanoparticle loads in orodispersible films with good particle size preservation after film redispersion in water as well as a manufacturing of the film casting mass within a few minutes in a stirred media mill was achieved. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

    International Nuclear Information System (INIS)

    Sanz, Vanesa; Conde, João; Hernández, Yulán; Baptista, Pedro V.; Ibarra, M. R.; Fuente, Jesús M. de la

    2012-01-01

    The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold–thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs (∼14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

  3. Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process.

    Science.gov (United States)

    Aniesrani Delfiya, D S; Thangavel, K; Amirtham, D

    2016-04-01

    In this study, acetone was used as a desolvating agent to prepare the curcumin-loaded egg albumin nanoparticles. Response surface methodology was employed to analyze the influence of process parameters namely concentration (5-15%w/v) and pH (5-7) of egg albumin solution on solubility, curcumin loading and entrapment efficiency, nanoparticles yield and particle size. Optimum processing conditions obtained from response surface analysis were found to be the egg albumin solution concentration of 8.85%w/v and pH of 5. At this optimum condition, the solubility of 33.57%, curcumin loading of 4.125%, curcumin entrapment efficiency of 55.23%, yield of 72.85% and particles size of 232.6 nm were obtained and these values were related to the values which are predicted using polynomial model equations. Thus, the model equations generated for each response was validated and it can be used to predict the response values at any concentration and pH.

  4. Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sanz, Vanesa; Conde, Joao; Hernandez, Yulan [Universidad de Zaragoza, Instituto de Nanociencia de Aragon (Spain); Baptista, Pedro V. [Universidade Nova de Lisboa, Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Centro de Investigacao em Genetica Molecular Humana (Portugal); Ibarra, M. R.; Fuente, Jesus M. de la, E-mail: jmfuente@unizar.es [Universidad de Zaragoza, Instituto de Nanociencia de Aragon (Spain)

    2012-06-15

    The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold-thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs ({approx}14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

  5. Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

    Science.gov (United States)

    Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

    2012-01-01

    Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug. PMID:22275837

  6. Fabrication and characterization of novel antimicrobial films derived from thymol-loaded zein-sodium caseinate (SC) nanoparticles.

    Science.gov (United States)

    Li, Kang-Kang; Yin, Shou-Wei; Yang, Xiao-Quan; Tang, Chuan-He; Wei, Zi-Hao

    2012-11-21

    The objective of this research was to fabricate novel antimicrobial films based on zein colloidal nanoparticles coated with sodium caseinate (SC), an emulsifier/stabilizer. Thymol-loaded zein-SC nanoparticles were prepared using an antisolvent technique, with the average particle size and zeta potential about 200 ± 20 nm and -40 mV, respectively. Zein-SC nanoparticle-based films exhibited higher mechanical resistance and water barrier capacity than the SC films and concomitant good extensibility as compared with zein films. Thymol loadings endowed zein-SC nanoparticle-based films with antimicrobial activity against Escherichia coli and Salmonella as well as DPPH radical scavenging activity. Water vapor permeability, microstructure, mechanical, and controlled release properties of the films were evaluated. The possible relationship between some selected physical properties and microstructure were also discussed. Atomic force microscopy (AFM) analysis indicated that thymol loadings resulted in the emergence phenomena of the nanoparticles to form large particles or packed structure, consisting of clusters of nanoparticles, within the film matrix, in a thymol loading dependent manner. The appearance of large particles or an agglomerate of particles may weaken the compactness of protein network of films and thus impair the water barrier capacity, mechanical resistance, and extensibility of the films. The release kinetics of thymol from nanoparticle-based films can be described as a two-step biphasic process, that is, an initial burst effect followed by subsequent slower release, and zein-SC nanoparticles within the films matrices gave them the ability to sustain the release of thymol. In addition, a schematic illustration of the formation pathway of zein-SC nanoparticle-based films with or without thymol was proposed to illuminate the possible relationship between some selected physical properties and the microstructure of the films.

  7. Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

    Science.gov (United States)

    Wang, Fengzhen; Chen, Li; Jiang, Sunmin; He, Jun; Zhang, Xiumei; Peng, Jin; Xu, Qunwei; Li, Rui

    2014-09-01

    The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

  8. Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters.

    Science.gov (United States)

    Oliveira, Camila Areias de; Peres, Daniela D'Almeida; Graziola, Fabiana; Chacra, Nádia Araci Bou; Araújo, Gabriel Lima Barros de; Flórido, Ana Catarina; Mota, Joana; Rosado, Catarina; Velasco, Maria Valéria Robles; Rodrigues, Luís Monteiro; Fernandes, Ana Sofia; Baby, André Rolim

    2016-01-01

    The encapsulation of natural ingredients, such as rutin, can offer improvements in sun protection effectiveness. This strategy can provide enhanced flavonoid content and produces an improved bioactive compound with new physical and functional characteristics. As an alternative to common synthetic-based sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate (EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose of this study was to develop rutin-loaded gelatin nanoparticles and characterize their physicochemical, thermal, functional and safety properties. Rutin-loaded gelatin nanoparticles increased antioxidant activity by 74% relative to free-rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor (SPF) by 48%, indicating its potential as a raw material for bioactive sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA) decreased HaCaT cell viability in a concentration/time-dependent manner. However, both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good performance on skin compatibility tests. These results functionally characterized rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in association with UV filters. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Preparation of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles by a microchannel technology.

    Science.gov (United States)

    Guo, Fangyuan; Guo, Dingjia; Zhang, Wei; Yan, Qinying; Yang, Yan; Hong, Weiyong; Yang, Gensheng

    2017-03-01

    Biodegradable polymeric nanoparticles (NPs) have potential therapeutic applications; however, preparing NPs of a specific diameter and uniform size distribution is a challenge. In this work, we fabricated a microchannel system for the preparation of curcumin (Cur)-loaded NPs by the interfacial precipitation method, which rapidly and consistently generated stable NPs with a relatively smaller diameter, narrow size distribution, and higher drug-loading capacity and entrapment efficiency. Poly(ε-caprolactone)-poly(ethylene glycol)-poly (ε-caprolactone) triblock copolymers(PCEC) used as the carrier material was synthesized and characterized. Cur-loaded PCEC NPs had an average size of 167.2nm with a zeta potential of -29.23mV, and showed a loading capacity and drug entrapment efficiency of 15.28%±0.23% and 96.11%±0.13%, respectively. Meanwhile, the NPs demonstrated good biocompatibility and bioavailability, efficient cellular uptake, and long circulation time and a possible liver targeting effect in vivo. These results indicate that the Cur-loaded PCEC NPs can be used as drug carriers in controlled delivery systems and other biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Lycopene loaded gelatin nanoparticles induces internucleosmal DNA fragmentation and apoptosis in human breast adenocarcinoma cells

    Science.gov (United States)

    Preetha, K. Mary Anne; Devasena, T.

    2018-06-01

    The complex disease, cancer is caused by genetic uncertainty and various molecular alterations. Due to the present ineffective diagnostic and prognostic classifications, the complete heterogeneity of a tumor is not revealed which in turn affects the selection of suitable treatment and patient outcome. Cancer nanotechnology is an emerging interdisciplinary research field that covers important aspects of chemistry, engineering, biology and medicine, leading to the advancement of cancer diagnosis and treatment. Hence the main aim of this study is to develop lycopene loaded gelatin nanoparticles and evaluate its in vitro anticancer activity using breast adenocarcinoma cells.

  11. Advances in research of targeting delivery and controlled release of drug-loaded nanoparticles

    International Nuclear Information System (INIS)

    Tan Zhonghua

    2003-01-01

    Biochemistry drug, at present, is still the main tool that human struggle to defeat the diseases. So, developing safe and efficacious technique of drug targeting delivery and controlled release is key to enhance curative effect, decrease drug dosage, and lessen its side effect. Drug-loaded nanoparticles, which is formed by conjugate between nanotechnology and modern pharmaceutics, is a new fashioned pharmic delivery carrier. Because of advantages in pharmic targeting transport and controlled or slow release and improving bioavailability, it has been one of developing trend of modern pharmaceutical dosage forms

  12. Two-phase model of hydrogen transport to optimize nanoparticle catalyst loading for hydrogen evolution reaction

    DEFF Research Database (Denmark)

    Kemppainen, Erno; Halme, Janne; Hansen, Ole

    2016-01-01

    is the evolution and transport of gaseous H2, since HER leads to the continuous formation of H2 bubbles near the electrode. We present a numerical model that includes the transport of both gaseous and dissolved H2, as well as mass exchange between them, and combine it with a kinetic model of HER at platinum (Pt......) nanoparticle electrodes. We study the effect of the diffusion layer thickness and H2 dissolution rate constant on the importance of gaseous transport, and the effect of equilibrium hydrogen coverage and Pt loading on the kinetic and mass transport overpotentials. Gaseous transport becomes significant when...

  13. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

    Science.gov (United States)

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

  14. QDP-JIT/PTX: A QDP++ Implementation for CUDA-Enabled GPUs

    Energy Technology Data Exchange (ETDEWEB)

    Winter, Frank T. [JLAB; Edwards, Robert G. [JLAB

    2014-11-01

    These proceedings describe briefly the QDP-JIT/PTX framework for lattice field theory calcula- tions on the CUDA architecture. The framework generates compute kernels in the PTX assembler language which can be compiled to efficient GPU machine code by the NVIDIA JIT compiler. A comprehensive memory management was added to the framework so that applications, e.g. Chroma, can run unaltered on GPU clusters and supercomputers.

  15. Simultaneous diagnosis and drug delivery by silymarin-loaded magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Maryam Khalkhali

    2015-07-01

    Full Text Available Objective(s: The aim of this work was to prepare and characterize magnetic nanoparticles (MNPs as theranostic system to act simultaneously as drug carrier and MRI contrast agent. Chitosan-coated MNPs (CMNPs were prepared and loaded with silymarin. Silymarin-loaded CMNPs were characterized with various techniques and their potential as MRI contrast agent was also evaluated. Materials and Methods:The chitosan-coated MNPs were prepared by coprecipitation method and were loaded with silymarin. The synthesized nanoparticles were characterized by various techniques including SEM, TEM, X‐ray diffraction (XRD, FTIR and vibrating sample magnetometer (VSM. In vitro drug release of silymarin was evaluated at 37 ˚C at pH 5.3 and 7.4. Then, their proton relaxivity was evaluated to study the potential of CMNPs as MRI contrast agent in terms of r1 and r2.Results:Silymarin-loaded CMNPs were successfully prepared and characterized by FTIR and XRD techniques. VSM analysis revealed superparamagnetic properties of CMNPs. The release study showed that the maximum drug release accessible for CMNPs in pH=5.3 was higher than pH=7.4. Finally, the r2/r1 value of CMNPs was found to be close to 20 indicating that CMNPs has a strong efficiency as T2 contrast agents for MRI imaging.  Conclusion:The findings demonstrated the potential of CMNPs as efficient MRI contrast agent as well as silymarin drug delivery.

  16. Formulation and in vitro interaction of rhodamine-B loaded PLGA nanoparticles with cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Antranik Jonderian

    2016-12-01

    Full Text Available This study aims to characterize rhodamine B (Rh B loaded poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized nanoparticles were about 184 nm, 0.19, 40% and -21.7 mV respectively. In vitro release showed that 29% of the Rh B was released within the first 8 hours. Scanning electron microscopy (SEM measurements performed on the optimized nanoparticles showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on fetal cardiac myocytes after 24 and 48 hours of exposure with concentrations up to 200 µg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the first hours. Interestingly, our data show an increase in the nanoparticles’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

  17. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    Science.gov (United States)

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

    2014-08-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  18. Antibacterial performance on plasma polymerized heptylamine films loaded with silver nanoparticles

    Science.gov (United States)

    Lin, Yu-Chun; Lin, Chia-Chun; Lin, Chih-Hao; Wang, Meng-Jiy

    2017-01-01

    The antibacterial performance of the plasma-polymerized (pp) heptylamine thin films loaded with silver nanoparticles was evaluated against the colonization of Escherichia coli and Staphylococcus aureus. The properties including the thickness and chemical composition of the as deposited HApp films were modulated by adjusting plasma parameters. The acquired results showed that the film thickness was controlled in the range of 20 to 400 nm by adjusting deposition time. The subsequent immersion of the HApp thin films in silver nitrate solutions result in the formation of amine-metal complexes, in which the silver nanoparticles were reduced directly on the matrices to form Ag@HApp. The reduction reaction of silver was facilitated by applying NaBH4 as a reducing agent. The results of physicochemical analyses including morphological analysis and ellipsometry revealed that the silver nanoparticles were successfully reduced on the HApp films, and the amount of reduced silver was closely associated which the thickness of the plasma-polymerized films, the concentration of applied metal ions solutions, and the time of immobilization. Regarding the antibacterial performance, the Ag@HApp films reduced by NaBH4 showed antibacterial abilities of 70.1 and 68.2% against E. coli and S. aureus, respectively.

  19. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    International Nuclear Information System (INIS)

    Banerjee, Subhamoy; Ghosh, Siddhartha Sankar; Sahoo, Amaresh Kumar; Chattopadhyay, Arun

    2014-01-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV–vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells. (paper)

  20. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax.

    Science.gov (United States)

    Kheradmandnia, Soheila; Vasheghani-Farahani, Ebrahim; Nosrati, Mohsen; Atyabi, Fatemeh

    2010-12-01

    Solid lipid nanoparticles (SLNs) have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. Ketoprofen as a model drug was incorporated into SLNs prepared from a mixture of beeswax and carnauba wax using Tween 80 and egg lecithin as emulsifiers. The characteristics of the SLNs with various lipid and surfactant composition were investigated. The mean particle size of drug-loaded SLNs decreased upon mixing with Tween 80 and egg lecithin as well as upon increasing total surfactant concentration. SLNs of 75 ± 4 nm with a polydispersity index of 0.2 ± 0.02 were obtained using 1% (vol/vol) mixed surfactant at a ratio of 60:40 Tween 80 to egg lecithin. The zeta potential of these SLNs varied in the range of -15 to -17 (mV), suggesting the presence of similar interface properties. High drug entrapment efficiency of 97% revealed the ability of SLNs to incorporate a poorly water-soluble drug such as ketoprofen. Differential scanning calorimetry thermograms and high-performance liquid chromatographic analysis indicated the stability of nanoparticles with negligible drug leakage after 45 days of storage. It was also found that nanoparticles with more beeswax content in their core exhibited faster drug release as compared with those containing more carnauba wax in their structure. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles.

    Science.gov (United States)

    Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

    2016-09-01

    The aim of this research was to prepare and optimize calcium carbonate (CaCO3) nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure, with the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the speed of homogenization (X3) as the independent variables. The particle size and entrapment efficiency were considered as response variables. Mathematical equations and response surface plots were used, along with the counter plots, to relate the dependent and independent variables. The results indicated that the speed of homogenization was the main variable contributing to particle size and entrapment efficiency. The combined effect of all three independent variables was also evaluated. Using the response optimization design, the optimized Xl-X3 levels were predicted. An optimized formulation was then prepared according to these levels, resulting in a particle size of 80.23 nm and an entrapment efficiency of 30.80%. It was concluded that the chemical precipitation technique, together with the Box-Behnken experimental design methodology, could be successfully used to optimize the formulation of drug-incorporated calcium carbonate nanoparticles.

  2. Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles

    Directory of Open Access Journals (Sweden)

    Zhang J

    2017-12-01

    Full Text Available Jiayu Zhang,1 Shiqing Ma,1 Zihao Liu,1 Hongjuan Geng,1 Xin Lu,1 Xi Zhang,1 Hongjie Li,1 Chenyuan Gao,2 Xu Zhang,1 Ping Gao1 1School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, 2Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, People’s Republic of China Introduction: Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS contained in an asymmetric collagen-chitosan membrane (CCM. Methods: In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg. The drug release behavior of ACS was studied. Transmission electron microscopy (TEM and scanning electron microscopy (SEM were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM. In vitro bone mesenchymal stem cells (BMSCs were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration.Results: Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group.Conclusion: This

  3. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

    Science.gov (United States)

    Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

    2010-05-01

    The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2017-05-01

    Full Text Available A biodegradable poly(lactic-co-glycolic acid loading atorvastatin calcium (AC nanoparticles (AC-PLGA-NPs were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGA-NPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

  5. Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Di Martino, Antonio; Kucharczyk, Pavel; Capakova, Zdenka; Humpolicek, Petr; Sedlarik, Vladimir, E-mail: sedlarik@ft.utb.cz [Tomas Bata University in Zlín, Centre of Polymer Systems, University Institute (Czech Republic)

    2017-02-15

    In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150–180 nm, was able to accommodate up to 800 μg of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7.4 where the hydrolysis in the inactive metabolite was clearly delayed. CS-SPLA nanoparticles demonstrated a pH-dependent TMZ release kinetics with the opportunity to increase or decrease the rate. Mass spectroscopy, UV-Vis analysis, and in vitro cell tests confirmed the improvement in temozolomide stability and effectiveness when loaded into the polymeric carrier, in comparison with the free drug.

  6. Microfluidic platform for dynamic in vitro optimization of methotrexate-loaded lipid nanoparticle delivery for personalized osteosarcoma treatment

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz-Hernando, M.; Macias, P.; Abella, M.; Desco, M.; Sharpe, S.; Vaquero, J.J.; Muñoz-Barrutia, M.

    2016-07-01

    Cancer is a leading cause of mortality in the world, with osteosarcoma being one of the most common types among children between 1 and 14 years old. The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment. However, current techniques for in vitro testing of these vehicles have shown little validity due to their static nature, in which nanoparticles sediment onto the bottom of the wells and kill the cells via asphyxiation, hiding the real effect achieved by the nanoparticles. In this work, a microfluidic platform capable of determining the optimum dose of methotrexate-loaded lipid nanoparticles in osteosarcoma treatment is presented as a promising alternative to current nanoparticle characterization assays. (Author)

  7. Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-01-01

    Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

  8. In Situ Loading of Basic Fibroblast Growth Factor Within Porous Silica Nanoparticles for a Prolonged Release

    Directory of Open Access Journals (Sweden)

    Postovit Lynne-Marie

    2009-01-01

    Full Text Available Abstract Basic fibroblast growth factor (bFGF, a protein, plays a key role in wound healing and blood vessel regeneration. However, bFGF is easily degraded in biologic systems. Mesoporous silica nanoparticles (MSNs with well-tailored porous structure have been used for hosting guest molecules for drug delivery. Here, we report an in situ route to load bFGF in MSNs for a prolonged release. The average diameter (d of bFGF-loaded MSNs is 57 ± 8 nm produced by a water-in-oil microemulsion method. The in vitro releasing profile of bFGF from MSNs in phosphate buffer saline has been monitored for 20 days through a colorimetric enzyme linked immunosorbent assay. The loading efficiency of bFGF in MSNs is estimated at 72.5 ± 3%. In addition, the cytotoxicity test indicates that the MSNs are not toxic, even at a concentration of 50 μg/mL. It is expected that the in situ loading method makes the MSNs a new delivery system to deliver protein drugs, e.g. growth factors, to help blood vessel regeneration and potentiate greater angiogenesis.

  9. Transient loading of CD34+ hematopoietic progenitor cells with polystyrene nanoparticles.

    Science.gov (United States)

    Deville, Sarah; Hadiwikarta, Wahyu Wijaya; Smisdom, Nick; Wathiong, Bart; Ameloot, Marcel; Nelissen, Inge; Hooyberghs, Jef

    2017-01-01

    CD34 + hematopoietic progenitor cells (HPCs) offer great opportunities to develop new treatments for numerous malignant and non-malignant diseases. Nanoparticle (NP)-based strategies can further enhance this potential, and therefore a thorough understanding of the loading behavior of HPCs towards NPs is essential for a successful application. The present study focusses on the interaction kinetics of 40 nm sized carboxylated polystyrene (PS) NPs with HPCs. Interestingly, a transient association of the NPs with HPCs is observed, reaching a maximum within 1 hour and declining afterwards. This behavior is not seen in dendritic cells (CD34-DCs) differentiated from HPCs, which display a monotonic increase in NP load. We demonstrate that this transient interaction requires an energy-dependent cellular process, suggesting active loading and release of NPs by HPCs. This novel observation offers a unique approach to transiently equip HPCs. A simple theoretical approach modeling the kinetics of NP loading and release is presented, contributing to a framework of describing this phenomenon.

  10. Rosemary Essential Oil-Loaded Lipid Nanoparticles: In Vivo Topical Activity from Gel Vehicles

    Directory of Open Access Journals (Sweden)

    Lucia Montenegro

    2017-10-01

    Full Text Available Although rosemary essential oil (EO shows many biological activities, its topical benefits have not been clearly demonstrated. In this work, we assessed the effects on skin hydration and elasticity of rosemary EO after topical application via gel vehicles in human volunteers. To improve its topical efficacy, rosemary EO was loaded into lipid nanoparticles (NLCs consisting of cetyl palmitate as a solid lipid, and non-ionic surfactants. Such NLCs were prepared using different ratios of EO/solid lipid and those containing EO 3% w/w and cetyl pamitate 7% w/w were selected for in vivo studies, showing the best technological properties (small particle size, low polydispersity index and good stability. Gels containing free EO or EO-loaded NLCs were applied on the hand skin surface of ten healthy volunteers twice a day for one week. Skin hydration and elasticity changes were recorded using the instrument Soft Plus. Gels containing EO-loaded NLCs showed a significant increase in skin hydration in comparison with gels containing free EO. Skin elasticity increased, as well, although to a lesser extent. The results of this study point out the usefulness of rosemary EO-loaded NLCs for the treatment of cutaneous alterations involving loss of skin hydration and elasticity.

  11. Lysozyme-loaded lipid-polymer hybrid nanoparticles: preparation, characterization and colloidal stability evaluation.

    Science.gov (United States)

    Devrim, Burcu; Kara, Aslı; Vural, İmran; Bozkır, Asuman

    2016-11-01

    Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles. The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme. Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method. Poly-ɛ-caprolactone (PCL) was used as polymeric core material and tripalmitin:lechitin mixture was used to form a lipid shell around the LPNPs. LPNPs were evaluated for particle size distribution, zeta potential, morphology, encapsulation efficiency, in vitro drug release, stability and cytotoxicity. The DLS measurement results showed that the particle size of LPNPs ranged from 58.04 ± 1.95 nm to 2009.00 ± 0.52 nm. The AFM and TEM images of LPNPs demonstrate that LPNPs are spherical in shape. The protein-loading capacity of LPNPs ranged from 5.81% to 60.32%, depending on the formulation parameters. LPNPs displayed a biphasic drug release pattern with a burst release within 1 h, followed by sustained release afterward. Colloidal stability results of LPNPs in different media showed that particle size and zeta potential values of particles did not change significantly in all media except of FBS 100% for 120 h. Finally, the results of a cellular uptake study showed that LPNPs were significantly taken up by 83.3% in L929 cells. We concluded that the LPNPs prepared with PCL as polymeric core material and tripalmitin:lechitin mixture as lipid shell should be a promising choice for protein delivery.

  12. Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

    DEFF Research Database (Denmark)

    Sacco, Pasquale; Decleva, Eva; Tentor, Fabio

    2017-01-01

    that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...... of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...

  13. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

    Science.gov (United States)

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-08-15

    This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Stability and antimicrobial effect of amikacin-loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Solmaz Ghaffari

    2010-12-01

    Full Text Available Solmaz Ghaffari1, Jaleh Varshosaz1, Afrooz Saadat2, Fatemeh Atyabi21Department of Pharmaceutics, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; 2Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Solid lipid nanoparticles (SLNs of amikacin were designed in this study for pulmonary delivery to reduce the dose or its administration intervals leading to reduction of its toxicities especially in long term treatment. Nanoparticles of amikacin were prepared from cholesterol by solvent diffusion technique and homogenization. The size, zeta potential, loading efficiency, and release profile of the nanoparticles were studied. The conventional broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC and minimum bacteriostatic concentration (MBC of amikacin SLNs with respect to Pseudomonas aeruginosa in vitro. To guarantee the stability of desired SLNs, they were lyophilized using cryoprotectants. Results showed that considering the release profile of amikacin from the studied nanocarrier, MIC and MBC of amikacin could be about two times less in SLNs of amikacin compared to the free drug. Therefore, fewer doses of amikacin in SLNs can clear the infection with less adverse effects and more safety. Particle size enlargement after lyophilization of desired SLNs after two months storage was limited in comparison with non-lyophilized particles, 996 and 194 nm, respectively. Zeta potential of lyophilized particles was increased to +17 mV from +4 mV before lyophilization. Storage of particles in higher temperature caused accelerated drug release.Keywords: amikacin, antimicrobial effects, Pseudomonas aeruginosa, solid lipid nanoparticles, stability

  15. [Combination Chemotherapy Including Intraperitoneal(IP)Administration of Paclitaxel(PTX)followed by PTX, CDDP and S-1Triplet Chemotherapy for CY1P0 Gastric Cancer].

    Science.gov (United States)

    Shinkai, Masayuki; Imano, Motohiro; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Kimura, Yutaka; Imamoto, Haruhiko; Furukawa, Hiroshi; Yasuda, Takushi

    2017-11-01

    We evaluate the feasibility and efficacy of combination chemotherapy including single intraperitoneal( IP)administration of paclitaxel(PTX), followed by triplet chemotherapy(PTX, cisplatin[CDDP]and S-1: PCS)for CY1P0 gastric cancer. First of all, we performed staging laparoscopy and confirmed CY1P0, and secondary, administrated PTX intraperitoneally. Thirdly, patients received PCS chemotherapy for 2 courses. After antitumor effect had been confirmed, we performed second look laparoscopy. In the case of CY0P0, we performed gastrectomy with D2 lymph nodes dissection. Total 4 patients were enrolled. Grade 3 leukopenia and neutropenia were observed in one patient while intraperitoneal and systemic-chemotherapy. One patients showed PR and 3 patients showed SD. All patients underwent second look laparoscopy. CY0P0 was observed in all patients and gastrectomy with D2 dissection was performed for all patients. Postoperative complications were observed in 2 patients. Two patients were still alive without recurrence, while the remaining 2 had died of liver metastasis and #16 LN metastasis. Combination chemotherapy including single IP PTX followed by PCS systemic-chemotherapy for CY1P0 gastric cancer is feasible and efficient.

  16. Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release

    Directory of Open Access Journals (Sweden)

    Ju-Heon Kim

    2017-12-01

    Full Text Available Houttuynia cordata (H. cordata has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS, differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy (FT-IR, and scanning electron microscopy (SEM. Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin were 92.9–95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.

  17. Nutlin-3a and Cytokine Co-loaded Spermine-Modified Acetalated Dextran Nanoparticles for Cancer Chemo-Immunotherapy

    DEFF Research Database (Denmark)

    Bauleth-Ramos, Tomás; Shahbazi, Mohammad-Ali; Liu, Dongfei

    2017-01-01

    The combination of chemo- and immunotherapy represents one promising strategy to overcome the existent challenges in the present-day anticancer therapy. Here, spermine-modified acetalated dextran nanoparticles (Sp-AcDEX NPs), co-loaded with the non-genotoxic molecule Nutlin-3a (Nut3a), and the cy......The combination of chemo- and immunotherapy represents one promising strategy to overcome the existent challenges in the present-day anticancer therapy. Here, spermine-modified acetalated dextran nanoparticles (Sp-AcDEX NPs), co-loaded with the non-genotoxic molecule Nutlin-3a (Nut3a...

  18. Polyethylenimine-mediated synthetic insertion of gold nanoparticles into mesoporous silica nanoparticles for drug loading and biocatalysis.

    Science.gov (United States)

    Pandey, Prem C; Pandey, Govind; Narayan, Roger J

    2017-03-27

    Mesoporous silica nanoparticles (MSNPs) have been used as an efficient and safe carrier for drug delivery and biocatalysis. The surface modification of MSNPs using suitable reagents may provide a robust framework in which two or more components can be incorporated to give multifunctional capabilities (e.g., synthesis of noble metal nanoparticles within mesoporous architecture along with loading of a bioactive molecule). In this study, the authors reported on a new synthetic route for the synthesis of gold nanoparticles (AuNPs) within (1) unmodified MSNPs and (2) 3-trihydroxysilylpropyl methylphosphonate-modified MSNPs. A cationic polymer, polyethylenimine (PEI), and formaldehyde were used to mediate synthetic incorporation of AuNPs within MSNPs. The AuNPs incorporated within the mesoporous matrix were characterized by transmission electron microscopy, energy dispersive x-ray analysis, and high-resolution scanning electron microscopy. PEI in the presence of formaldehyde enabled synthetic incorporation of AuNPs in both unmodified and modified MSNPs. The use of unmodified MSNPs was associated with an increase in the polycrystalline structure of the AuNPs within the MSNPs. The AuNPs within modified MSNPs showed better catalytic activity than those within unmodified MSNPs. MSNPs with an average size of 200 nm and with a pore size of 4-6 nm were used for synthetic insertion of AuNPs. It was found that the PEI coating enabled AuNPs synthesis within the mesopores in the presence of formaldehyde or tetrahydrofuran hydroperoxide at a temperature between 10 and 25 °C or at 60 °C in the absence of organic reducing agents. The as-made AuNP-inserted MSNPs exhibited enhanced catalytic activity. For example, these materials enabled rapid catalytic oxidation of the o-dianisidine substrate to produce a colored solution in proportion to the amount of H 2 O 2 generated as a function of glucose oxidase-catalyzed oxidation of glucose; a linear concentration range from 80 to

  19. Novel approach for a PTX/VEGF dual drug delivery system in cardiovascular applications-an innovative bulk and surface drug immobilization.

    Science.gov (United States)

    Wulf, Katharina; Teske, Michael; Matschegewski, Claudia; Arbeiter, Daniela; Bajer, Dalibor; Eickner, Thomas; Schmitz, Klaus-Peter; Grabow, Niels

    2018-06-01

    The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated. The advantage of this DDDS is that the bulk incorporation of fluorescein diacetate (FDAc) (model drug for paclitaxel (PTX)) via spray coating enhanced the subsequent cleavable surface coupling of vascular endothelial growth factor (VEGF) via the crosslinker bissulfosuccinimidyl suberate (BS 3 ). In the presence of the embedded FDAc, the VEGF loading and release are about twice times higher than in absence. Furthermore, the DDDS combines the diffusion drug delivery (FDAc or PTX) and the chemical controlled drug release, VEGF via hydrolysable ester bonds, without loss in quantity and quality of the drug release curves. Additionally, the performed in vitro biocompatibility study showed the bimodal influences of PTX and VEGF on human endothelial EA.hy926 cells. In conclusion, it was possible to show the feasibility to develop a novel DDDS which has a high potential for the medical application due to the possible easy and short modification of a polymer-based PTX delivery system.

  20. Fabrication of curcumin-loaded bovine serum albumin (BSA)-dextran nanoparticles and the cellular antioxidant activity.

    Science.gov (United States)

    Fan, Yuting; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

    2018-01-15

    Bovine serum albumin (BSA)-dextran conjugate was prepared with glycation. Self-assembly nanoparticles were synthesized with a green, and facile approach. The effects of dry-heating time on the fabrication and characteristics of BSA-dextran conjugate nanoparticles were examined. Stable nanoparticles (dextran was grafted onto the BSA to provide significant steric hindrance. Particle size decreased with the increase of dry-heating time and the lowest particle size (51.2nm) was obtained after 24h dry-heating. The nanoparticles were stable in a wide pH range (pH 2.0-7.0). The particle size of nanoparticles increased to 115nm after curcumin incorporation and was stable even after one-month storage. TEM results demonstrated that curcumin-loaded nanoparticles displayed a spherical structure and were homogeneously dispersed. Curcumin in BSA-dextran nanoparticle showed better stability, compared to free curcumin. In addition, BSA-dextran nanoparticles can improve the cellular antioxidant activity of curcumin in Caco-2 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylori.

    Science.gov (United States)

    Seabra, Catarina Leal; Nunes, Cláudia; Gomez-Lazaro, Maria; Correia, Marta; Machado, José Carlos; Gonçalves, Inês C; Reis, Celso A; Reis, Salette; Martins, M Cristina L

    2017-03-15

    Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5 ® , Miglyol-812 ® ) and a surfactant (Tween 60 ® ). Homogeneous NLC with 302±14nm diameter, -28±3mV surface charge (dynamic and electrophoretic light scattering) and containing 66±7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25μM) than free DHA (>100μM). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

    International Nuclear Information System (INIS)

    Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Morshedi, Dina; Arpanaei, Ayyoob; Marvian, Amir Tayaranian

    2015-01-01

    Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain

  3. Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas, E-mail: shoja-sa@modares.ac.ir [Tarbiat Modares University, Biotechnology Group, Faculty of Chemical Engineering (Iran, Islamic Republic of); Morshedi, Dina; Arpanaei, Ayyoob [National Institute of Genetic Engineering and Biotechnology, Department of Industrial and Environmental Biotechnology (Iran, Islamic Republic of); Marvian, Amir Tayaranian [Aarhus University, Department of Biomedicine (Denmark)

    2015-04-15

    Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain.

  4. Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

    Science.gov (United States)

    Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Morshedi, Dina; Arpanaei, Ayyoob; Marvian, Amir Tayaranian

    2015-04-01

    Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)- N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain.

  5. Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides.

    Science.gov (United States)

    das Neves, José; Sarmento, Bruno

    2015-05-01

    Polymeric nanoparticles (NPs) have the potential to provide effective and safe delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal microbicides. Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were produced by an emulsion-solvent evaporation method, optimized for colloidal properties using a 3-factor, 3-level Box-Behnken experimental design, and characterized for drug loading, production yield, morphology, thermal behavior, drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory potential. Also, drug permeability/membrane retention in well-established HEC-1-A and CaSki cell monolayer models as mediated by NPs was assessed in the absence or presence of mucin. Box-Behnken design allowed optimizing monodisperse 170nm drug-loaded NPs. Drug release experiments showed an initial burst effect up to 4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken up by different genital and macrophage cell lines as assessed by fluorescence microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as compared to the free drug, with up to around one-log increase in half-maximal cytotoxic concentration values. In all cases, no relevant changes in cell pro-inflammatory cytokine/chemokine production were observed. Dapivirine transport across cell monolayers was significantly decreased when mucin was present at the donor side with either NPs or the free drug, thus evidencing the influence of this natural glycoprotein in membrane permeability. Moreover, drug retention in cell monolayers was significantly higher for NPs in comparison with the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting technological and biological features that may contribute to their use as novel safe and effective vaginal microbicides. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Development of silver nanoparticles loaded chitosan-alginate constructs with biomedical potentialities.

    Science.gov (United States)

    Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M N; Li, Chuanlong; Hu, Hongbo; Zhang, Xuehong

    2017-12-01

    Herein, a facile biosynthesis of silver nanoparticles (AgNPs) and AgNPs-loaded chitosan-alginate constructs with biomedical potentialities is reported. The UV-vis spectroscopic profile confirmed the synthesis of AgNPs using methanolic leaves extract of Euphorbia helioscopia. The newly developed AgNPs were characterized using various analytical and imaging techniques including UV-vis and FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The optimally yielded AgNPs at 24h reaction period were loaded onto various chitosan-alginate constructs. A maximum of 95% loading efficiency (LE) was recorded with a chitosan: alginate ratio at 2:1, followed by 81% at 2:2 ratios. The anti-bacterial activities of AgNPs and AgNPs loaded chitosan-alginate constructs were tested against six bacterial strains i.e. Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Morganella morganii and Haemophilus influenza. A significant reduction in the log values was recorded for all test constructs, in comparison to the initial bacterial count (control value, i.e., 1.5×10 8 CFU/mL). The cytotoxicity profile revealed complete biocompatibility against normal cell line i.e. L929. Almost all constructs showed considerable cytotoxicity up to certain extant against human epithelial cells (HeLa) cancer cells. In summary, the highest antibacterial activities along with anti-cancer behavior both suggest the biomedical potentialities of newly engineered AgNPs and AgNPs-loaded chitosan-alginate constructs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Nanoparticle-neural stem cells for targeted ovarian cancer treatment: optimization of silica nanoparticles for efficient drug loading

    Science.gov (United States)

    Patel, Z.; Berlin, J.; Abidi, W.

    2018-02-01

    One of the drugs used to treat ovarian cancer is cisplatin. However, cisplatin kills normal surrounding tissue in addition to cancer cells. To improve tumor targeting efficiency, our lab uses neural stem cells (NSCs), which migrate directly to ovarian tumors. If free cisplatin is loaded into NSCs for targeted drug delivery, it will kill the NSCs. To prevent the drug cisplatin from killing both the NSCs and normal surrounding tissue, our lab synthesizes silica nanoparticles (SiNPs) that act as a protective carrier. The big picture here is to maximize efficiency of tumor targeting using NSCs and minimize toxicity to these NSCs using SiNPs. The goal of this project is to optimize the stability of SiNPs, which is important for efficient drug loading. To do this, the concentration of tetraethyl orthosilicate (TEOS), one of the main components of SiNPs, was varied. We hypothesized that more TEOS equates to more stable SiNPs because TEOS contributes carbon to SiNPs, and thus a tightly-packed chemical structure results in a stable particle. Then, the stability of the SiNPs were checked in cell media and phosphate buffered saline (PBS). Lastly, the SiNPs were analyzed for their porosity using the transmission electron microscope (TEM). TEM imaging showed white spots in the 200-800 μL TEOS batches and no white spots in the 1000-1800 μL TEOS batches. The white spots were pores, which indicate instability. We concluded that the ultimate factor that determines the stability of SiNPs (100 nm) is the concentration of organic substance.

  8. Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Omwoyo WN

    2014-08-01

    Full Text Available Wesley Nyaigoti Omwoyo,1,2 Bernhards Ogutu,3,4 Florence Oloo,3,5 Hulda Swai,6 Lonji Kalombo,6 Paula Melariri,6 Geoffrey Maroa Mahanga,2 Jeremiah Waweru Gathirwa3,4 1Department of Chemistry, Maasai Mara University, Narok, Kenya; 2Department of Chemistry, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya; 3Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 4Kenya Medical Research Institute, Nairobi, Kenya; 5Department of Chemical Sciences and Technology, Technical University of Kenya, Nairobi, Kenya; 6Department of Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa Abstract: Primaquine (PQ is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs (PQ-SLNs as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from -6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence

  9. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression

    Science.gov (United States)

    Pi, Fengmei; Binzel, Daniel W.; Lee, Tae Jin; Li, Zhefeng; Sun, Meiyan; Rychahou, Piotr; Li, Hui; Haque, Farzin; Wang, Shaoying; Croce, Carlo M.; Guo, Bin; Evers, B. Mark; Guo, Peixuan

    2018-01-01

    Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

  10. Evaluation of hypericin-loaded solid lipid nanoparticles: physicochemical properties, photostability and phototoxicity.

    Science.gov (United States)

    Youssef, Tareq; Fadel, Maha; Fahmy, Rania; Kassab, Kawser

    2012-01-01

    Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200-300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (Phypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure. © 2012 Informa Healthcare USA, Inc.

  11. Selective in vitro anticancer effect of superparamagnetic iron oxide nanoparticles loaded in hyaluronan polymeric micelles.

    Science.gov (United States)

    Smejkalová, Daniela; Nešporová, Kristina; Huerta-Angeles, Gloria; Syrovátka, Jakub; Jirák, Daniel; Gálisová, Andrea; Velebný, Vladimír

    2014-11-10

    Due to its native origin, excellent biocompatibility and biodegradability, hyaluronan (HA) represents an attractive polymer for superparamagnetic iron oxide nanoparticles (SPION) coating. Herein, we report HA polymeric micelles encapsulating oleic acid coated SPIONs, having a hydrodynamic size of about 100 nm and SPION loading capacity of 1-2 wt %. The HA-SPION polymeric micelles were found to be selectively cytotoxic toward a number of human cancer cell lines, mainly those of colon adenocarcinoma (HT-29). The selective inhibition of cell growth was even observed when the SPION loaded HA polymeric micelles were incubated with a mixture of control and cancer cells. The selective in vitro inhibition could not be connected with an enhanced CD44 uptake or radical oxygen species formation and was rather connected with a different way of SPION intracellular release. While aggregated iron particles were visualized in control cells, nonaggregated solubilized iron oxide particles were detected in cancer cells. In vivo SPION accumulation in intramuscular tumor following an intravenous micelle administration was confirmed by magnetic resonance (MR) imaging and histological analysis. Having a suitable hydrodynamic size, high magnetic relaxivity, and being cancer specific and able to accumulate in vivo in tumors, SPION-loaded HA micelles represent a promising platform for theranostic applications.

  12. Reduced bacteria adhesion on octenidine loaded mesoporous silica nanoparticles coating on titanium substrates.

    Science.gov (United States)

    Xu, Gaoqiang; Shen, Xinkun; Dai, Liangliang; Ran, Qichun; Ma, Pingping; Cai, Kaiyong

    2017-01-01

    Bacterial infection is one of the most severe postoperative complications leading to implantation failure. The early bacterial stage (4-6h) was proved to be the "decisive period" for long-term bacteria-related infection. Thus, to endow potential early antibacterial capacity for a titanium (Ti) based implant, an effective antiseptic agent of octenidine dihydrochloride (OCT) was effectively loaded on the mesoporous silica nanoparticles (MSNs)-incorporated titania coating which was fabricated by an electrophoretic-enhanced micro-arc oxidation technique. The surface characteristic of the coatings were characterized by various methods (SEM, AFM, XPS, XRD, etc.), and its corrosion resistance was also examined by the potentiodynamic polarization curves. The composite coating without OCT loading not only displayed good cytocompatibility but also exhibited certain anti-bacterial property. After loading with OCT, its antibacterial efficiency of the titanium substrates with composite coating was greatly enhanced without compromising their cytocompatibility. The study provides an approach for the fabrication of anti-bacterial Ti implant for potential orthopedic application. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  14. Antitumor activity of docetaxel-loaded polymeric nanoparticles fabricated by Shirasu porous glass membrane-emulsification technique

    Directory of Open Access Journals (Sweden)

    Yu YN

    2013-07-01

    Full Text Available Yunni Yu,1,* Songwei Tan,1,2,* Shuang Zhao,1 Xiangting Zhuang,1 Qingle Song,1 Yuliang Wang,1 Qin Zhou,2,3 Zhiping Zhang1,2 1Tongji School of Pharmacy, 2National Engineering Research Center for Nanomedicine, 3College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Docetaxel (DTX has excellent efficiency against a wide spectrum of cancers. However, the current clinical formulation has limited its usage, as it causes some severe side effects. Various polymeric nanoparticles have thus been developed as alternative formulations of DTX, but they have been mostly fabricated on a laboratory scale. Previously, we synthesized a novel copolymer, poly(lactide-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS, and found that it exhibited great potential in drug delivery with improved properties. In this study, we applied the Shirasu porous glass (SPG membrane-emulsification technique to prepare the DTX-loaded PLA-TPGS nanoparticles on a pilot scale. The effect of several formulation variables on the DTX-loaded nanoparticle properties, including particle size, zeta potential, and drug-encapsulation efficiency, were investigated based on surfactant type and concentration in the aqueous phase, organic/aqueous phase volumetric ratio, membrane-pore size, transmembrane cycles, and operation pressure. The DTX-loaded nanoparticles were obtained with sizes of 306.8 ± 5.5 nm and 334.1 ± 2.7 nm (mean value ± standard deviation, and drug-encapsulation efficiency of 81.8% ± 4.5% and 64.5% ± 2.7% for PLA-TPGS and poly(lactic-co-glycolic acid (PLGA nanoparticles, respectively. In vivo pharmacokinetic study exhibited a significant advantage of PLA-TPGS nanoparticles over PLGA nanoparticles and Taxotere. Drug-loaded PLA-TPGS nanoparticles exhibited 1.78-, 6.34- and 3.35-fold higher values for area under the curve, half-life, and mean

  15. Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue.

    Science.gov (United States)

    Gawde, Kaustubh A; Kesharwani, Prashant; Sau, Samaresh; Sarkar, Fazlul H; Padhye, Subhash; Kashaw, Sushil K; Iyer, Arun K

    2017-06-15

    Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. One-step Synthesis of Pt Nanoparticles Highly Loaded on Graphene Aerogel as Durable Oxygen Reduction Electrocatalyst

    International Nuclear Information System (INIS)

    Huang, Qinghong; Tao, Feifei; Zou, Liangliang; Yuan, Ting; Zou, Zhiqing; Zhang, Haifeng; Zhang, Xiaogang; Yang, Hui

    2015-01-01

    Synthesis of highly active and durable Pt based catalysts with a high metal loading for fuel cells’ applications still remains a big challenge. The three-dimensional (3D) graphene aerogel (GA) not only possess the intrinsic property of graphene, but also have abundant pore architecture for anchoring metal nanoparticles, thus would be suitable as metal catalysts’ support. This work reports a simple and mild one-step co-reduction synthesis of Pt nanoparticles highly loaded on 3D GA and the use as durable oxygen reduction catalyst. Both X-ray diffraction and TEM measurements confirm that Pt nanoparticles (ca. 60 wt.% Pt loading) with an average diameter of ca. 3.2 nm are uniformly decorated on the homogeneously interconnected pores of 3D GA even after a heat treatment at 300 °C. Such a Pt/GA catalyst exhibits significantly enhanced electrocatalytic activity and improved durability for the oxygen reduction reaction. The enhancement in both catalytic activity and durability may result from the unique 3-D architecture structure of GA, the uniform dispersion of Pt nanoparticles, and the interaction between the Pt nanoparticles and GA. The GA-supported Pt can serve as a highly active catalyst for fuel cell applications

  17. Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil nanoparticle suspensions of different particle sizes.

    Science.gov (United States)

    Chen, Xiaojin; Wang, Ting; Lu, Mengmeng; Zhu, Luyan; Wang, Yan; Zhou, WenZhong

    2014-01-01

    Three tilmicosin-loaded hydrogenated castor oil nanoparticle (TMS-HCO-NP) suspensions of different particle sizes were prepared with different polyvinyl alcohol surfactant concentrations using a hot homogenization and ultrasonic technique. The in vitro release, in vitro antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability study were conducted to evaluate the characteristics of the suspensions. The in vitro tilmicosin release rate, antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability of the suspensions were evaluated. When prepared with polyvinyl alcohol concentrations of 0.2%, 1%, and 5%, the mean diameters of the nanoparticles in the three suspensions were 920±35 nm, 452±10 nm, and 151±4 nm, respectively. The three suspensions displayed biphasic release profiles similar to that of freeze-dried TMS-HCO-NP powders, with the exception of having a faster initial release. Moreover, suspensions of smaller-sized particles showed faster initial release, and lower minimum inhibitory concentrations and minimum bactericidal concentrations. Time-kill curves showed that within 12 hours, the suspension with the 151 nm particles had the most potent bactericidal activity, but later, the suspensions with larger-sized particles showed increased antibacterial activity. None of the three suspensions were cytotoxic at clinical dosage levels. At higher drug concentrations, all three suspensions showed similar concentration-dependent cytotoxicity. The suspension with the smallest-sized particle showed significantly more acute toxicity in mice, perhaps due to faster drug release. All three suspensions exhibited good stability at 4°C and at room temperature for at least 6 months. These results demonstrate that TMS-HCO-NP suspensions can be a promising formulation for tilmicosin, and that nanoparticle size can be an important consideration for formulation development.

  18. Preliminary focus on the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles

    Directory of Open Access Journals (Sweden)

    T. Russo

    2017-09-01

    As reported in the literature, the stress distribution may be altered in bones after the implantation of a total joint prosthesis. Some scientific works have also correlated uncemented TKA to a progressive decrease of bone density below the tibial component. Antibiotic-loaded bone cements are commonly employed in conjunction with systemic antibiotics to treat infections. Furthermore, nanoparticles with antimicrobial activity have been widely analysed. Accordingly, the current research was focused on a preliminary analysis of the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles. The obtained results demonstrated that nanocomposite cements with a specific concentration of gold nanoparticles improved the punching performance and antibacterial activity. However, critical aspects were found in the optimization of the nanocomposite bone cement.

  19. Palladium Nanoparticle-Loaded Cellulose Paper: A Highly Efficient, Robust, and Recyclable Self-Assembled Composite Catalytic System.

    Science.gov (United States)

    Zheng, Guangchao; Kaefer, Katharina; Mourdikoudis, Stefanos; Polavarapu, Lakshminarayana; Vaz, Belén; Cartmell, Samantha E; Bouleghlimat, Azzedine; Buurma, Niklaas J; Yate, Luis; de Lera, Ángel R; Liz-Marzán, Luis M; Pastoriza-Santos, Isabel; Pérez-Juste, Jorge

    2015-01-15

    We present a novel strategy based on the immobilization of palladium nanoparticles (Pd NPs) on filter paper for development of a catalytic system with high efficiency and recyclability. Oleylamine-capped Pd nanoparticles, dispersed in an organic solvent, strongly adsorb on cellulose filter paper, which shows a great ability to wick fluids due to its microfiber structure. Strong van der Waals forces and hydrophobic interactions between the particles and the substrate lead to nanoparticle immobilization, with no desorption upon further immersion in any solvent. The prepared Pd NP-loaded paper substrates were tested for several model reactions such as the oxidative homocoupling of arylboronic acids, the Suzuki cross-coupling reaction, and nitro-to-amine reduction, and they display efficient catalytic activity and excellent recyclability and reusability. This approach of using NP-loaded paper substrates as reusable catalysts is expected to open doors for new types of catalytic support for practical applications.

  20. Kinetics and Isotherm of Sunset Yellow Dye Adsorption on Cadmium Sulfide Nanoparticle Loaded on Activated Carbon

    Directory of Open Access Journals (Sweden)

    N. Mosallanejad, A. Arami

    2012-03-01

    Full Text Available The objective of this study was to assess the potential of cadmium sulfide nanoparticles loaded onto activated carbon (CdSN-AC for the removal of sunset yellow (SY dye from aqueous solution. Adsorption studies were conducted in a batch mode varying solution pH, contact time, initial dye concentration, CdSN-AC dose. In order to investigate the efficiency of SY adsorption on CdSN-AC, pseudo-first-order, pseudo-second-order kinetic models were studied. It was observed that the pseudo-second-order kinetic model fits better than other kinetic models with good correlation coefficient. Equilibrium data were fitted to the Langmuir model. It was found that the sorption of SY onto CdSN-AC is followed by these results. 

  1. Synthesis of drug loaded magnetic nanoparticles and their uptake into immune cells

    International Nuclear Information System (INIS)

    Prinz, Eva-Marie; Hempelmann, Rolf; Eggers, Ruth; Lee, Hyeck-Hee; Steinfeld, Ute

    2010-01-01

    Ferrite nanoparticles (Mn 0,8 Zn 0,2 Fe 2 O 4 ) are synthesized by the co-precipitation method and characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. The particles are functionalized with dextran which is activated via amino or carboxymethyl groups. The chemotherapeutic drug doxorubicin (DOX) is attached to these dextran derivates in different ways. One method is based on the attachment of DOX to amino dextran by its keto group; the other is a bond to the primary amino group of DOX. The characterization of drug loaded dextran derivates is performed by Raman, FT-IR-, UV/VIS-and fluorescence spectroscopy. The biofunctionalized particles are intended for use in adoptive cancer immunotherapy as a new approach, where immune cells (T lymphocytes) will be used as new autonomous highly target specific drug delivery systems. The uptake efficiency of these particles into T lymphocytes is investigated by fluorescence and convocal microscopy.

  2. Implication of the oligomeric state of the N-terminal PTX3 domain in cumulus matrix assembly.

    Science.gov (United States)

    Ievoli, Elena; Lindstedt, Ragnar; Inforzato, Antonio; Camaioni, Antonella; Palone, Francesca; Day, Anthony J; Mantovani, Alberto; Salvatori, Giovanni; Salustri, Antonietta

    2011-06-01

    Pentraxin 3 (PTX3) plays a key role in the formation of the hyaluronan-rich matrix of the cumulus oophorus surrounding ovulated eggs that is required for successful fertilization and female fertility. PTX3 is a multimeric protein consisting of eight identical protomers held together by a combination of non-covalent interactions and disulfide bonds. Recent findings suggest that the oligomeric status of PTX3 is important for stabilizing the cumulus matrix. Because the role of PTX3 in the cumulus resides in the unique N-terminal sequence of the protomer, we investigated further this issue by testing the ability of distinct Cys/Ser mutants of recombinant N-terminal region of PTX3 (N(_)PTX3) with different oligomeric arrangement to promote in vitro normal expansion in cumuli from Ptx3-null mice. Here we report that the dimer of the N(_)PTX3 is unable to rescue cumulus matrix organization, and that the tetrameric assembly of the protein is the minimal oligomeric state required for accomplishing this function. We have previously demonstrated that PTX3 binds to HCs of IαI and TSG-6, which are essential for cumulus matrix formation and able to interact with hyaluronan. Interestingly, here we show by solid-phase binding experiments that the dimer of the N(_)PTX3 retains the ability to bind to both IαI and TSG-6, suggesting that the octameric structure of PTX3 provides multiple binding sites for each of these ligands. These findings support the hypothesis that PTX3 contributes to cumulus matrix organization by cross-linking HA polymers through interactions with multiple HCs of IαI and/or TSG-6. The N-terminal PTX3 tetrameric oligomerization was recently reported to be also required for recognition and inhibition of FGF2. Given that this growth factor has been detected in the mammalian preovulatory follicle, we wondered whether FGF2 negatively influences cumulus expansion and PTX3 may also serve in vivo to antagonize its activity. We found that a molar excess of FGF2, above

  3. Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

    International Nuclear Information System (INIS)

    Alexiou, Christoph; Tietze, Rainer; Schreiber, Eveline; Jurgons, Roland; Richter, Heike; Trahms, Lutz; Rahn, Helene; Odenbach, Stefan; Lyer, Stefan

    2011-01-01

    The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: →Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. → Histology evidences the intravasation of particles enter the intracellular space. → Non-invasive imaging techniques can display the spatial arrangement of particles. → HPLC-analysis show outstanding drug enrichment in tumors after MDT.

  4. Cancer therapy with drug loaded magnetic nanoparticles-magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Alexiou, Christoph, E-mail: c.alexiou@web.d [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Tietze, Rainer; Schreiber, Eveline [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany); Jurgons, Roland [Franz Penzoldt Center, University Hospital Erlangen (Germany); Richter, Heike; Trahms, Lutz [PTB Berlin (Germany); Rahn, Helene; Odenbach, Stefan [TU Dresden, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Lyer, Stefan [Department of Oto-rhino-laryngology, Head and Neck Surgery, University Hospital Erlangen, Section for Experimental Oncology and Nanomedicine at the Else Kroener-Fresenius-Stiftung-Professorship (Germany)

    2011-05-15

    The aim of magnetic drug targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the overall dose is reduced. This can be achieved with coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intra arterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field gradient leads to an accumulation in the region of interest (i.e. tumor). The particle enrichment and thereby the drug-load in the tumor during MDT has been proven by several analytical and imaging methods. Moreover, in pilot studies we investigated in an experimental in vivo tumor model the effectiveness of this approach. Complete tumor regressions without any negative side effects could be observed. - Research Highlights: Iron oxide nanoparticles can be enriched in tumors by external magnetic fields. Histology evidences the intravasation of particles enter the intracellular space. Non-invasive imaging techniques can display the spatial arrangement of particles. HPLC-analysis show outstanding drug enrichment in tumors after MDT.

  5. Enhanced therapeutic benefit of quercetin-loaded phytosome nanoparticles in ovariectomized rats.

    Science.gov (United States)

    Abd El-Fattah, Abeer I; Fathy, Mohamed M; Ali, Zeinab Y; El-Garawany, Abd El-Rahman A; Mohamed, Ehsan K

    2017-06-01

    Quercetin, a dietary flavonol phytoestrogen, has many health benefits but it is poorly absorbed when administered orally. To improve its bioavailability, we prepared quercetin-loaded phytosome nanoparticles (QP) using the thin film hydration method. The prepared nano-formulations were characterized using different techniques. Transmission electron microscopy revealed the homogeneously spherical, well and uniformly dispersed, nano-sized nature of QP. Dynamic light scattering measurements of QP (70 ± 7.44 nm) also confirmed this. Stability of the formed nanoparticles was established via zeta potential determination. The prepared QP exhibited very high encapsulation efficiency (98.4%). The estrogenic activity of QP, concerning inflammation, oxidative stress, bone, lipid profile, blood glucose level and weight gain, was investigated in ovariectomized rat model using 10 and 50 mg/kg/day oral doses for 4 weeks. Treatment with QP showed significant increase in serum calcium, inorganic phosphorus and glutathione content. Whereas, it significantly decreased serum alkaline phosphatase, acid phosphatase, malondialdehyde level, tumor necrosis factor-alpha and glucose level and improved lipid profile. Consequently, the results obtained confirm the superiority of QP over free quercetin at the same doses as a promising hormone replacement therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Carboxymethylated ɩ-carrageenan conjugated amphotericin B loaded gelatin nanoparticles for treating intracellular Candida glabrata infections.

    Science.gov (United States)

    Aparna, V; Melge, Anu Rohit; Rajan, V K; Biswas, Raja; Jayakumar, R; Gopi Mohan, C

    2018-04-15

    Intercellular Candida glabrata infections are difficult to treat due to poor penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B) into the macrophages where the pathogen inhabits is an effective solution. We are studying the macrophage targeting proficiency of ɩ-carrageenan for the delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A was the outcome of in silico inspections where the amino functionalized polymer having the best docking score with Amp B was selected. We prepared a sustained release formulation of amp B loaded carboxymethyl ɩ-carrageenan conjugated gelatin nanoparticles (CMC-Amp B-GNPs) with size 343±12nm and -25±5.3mV zeta potential. The formulations were found to be stable, biocompatible and non-haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced antifungal activity than bare Amp B and Amp B-GNPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Asymmetric photoelectric property of transparent TiO2 nanotube films loaded with Au nanoparticles

    International Nuclear Information System (INIS)

    Wang, Hui; Liang, Wei; Liu, Yiming; Zhang, Wanggang; Zhou, Diaoyu; Wen, Jing

    2016-01-01

    Highlights: • Highly transparent films of TiO 2 nanotube arrays were directly fabricated on FTO glasses. • Semitransparent TNT-Au composite films were obtained and exhibited excellent photoelectrocatalytic ability. • Back-side of TNT-Au composite films was firstly irradiated and tested to compare with front-side of films. - Abstract: Semitransparent composite films of Au loaded TiO 2 nanotubes (TNT-Au) were prepared by sputtering Au nanoparticles on highly transparent TiO 2 nanotubes films, which were fabricated directly on FTO glasses by anodizing the Ti film sputtered on the FTO glasses. Compared with pure TNT films, the prepared TNT-Au films possessed excellent absorption ability and high photocurrent response and improved photocatalytic activity under visible-light irradiation. It could be concluded that Au nanoparticles played important roles in improving the photoelectrochemical performance of TNT-Au films. Moreover, in this work, both sides of TNT-Au films were researched and compared owing to theirs semitransparency. It was firstly found that the photoelectric activity of TNT-Au composite films with back-side illumination was obviously superior to front-side illumination.

  8. Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles

    Directory of Open Access Journals (Sweden)

    Marta Machado-Pereira

    2017-01-01

    Full Text Available Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2. RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state, promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases.

  9. Asymmetric photoelectric property of transparent TiO{sub 2} nanotube films loaded with Au nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui [College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, Shanxi 030024 (China); College of Applied Science, Taiyuan University of Science and Technology, Taiyuan, Shanxi 030024 (China); Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan, Shanxi 030024 (China); Liang, Wei, E-mail: 986903124@qq.com [College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, Shanxi 030024 (China); Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan, Shanxi 030024 (China); Liu, Yiming; Zhang, Wanggang; Zhou, Diaoyu; Wen, Jing [College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, Shanxi 030024 (China); Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan, Shanxi 030024 (China)

    2016-11-15

    Highlights: • Highly transparent films of TiO{sub 2} nanotube arrays were directly fabricated on FTO glasses. • Semitransparent TNT-Au composite films were obtained and exhibited excellent photoelectrocatalytic ability. • Back-side of TNT-Au composite films was firstly irradiated and tested to compare with front-side of films. - Abstract: Semitransparent composite films of Au loaded TiO{sub 2} nanotubes (TNT-Au) were prepared by sputtering Au nanoparticles on highly transparent TiO{sub 2} nanotubes films, which were fabricated directly on FTO glasses by anodizing the Ti film sputtered on the FTO glasses. Compared with pure TNT films, the prepared TNT-Au films possessed excellent absorption ability and high photocurrent response and improved photocatalytic activity under visible-light irradiation. It could be concluded that Au nanoparticles played important roles in improving the photoelectrochemical performance of TNT-Au films. Moreover, in this work, both sides of TNT-Au films were researched and compared owing to theirs semitransparency. It was firstly found that the photoelectric activity of TNT-Au composite films with back-side illumination was obviously superior to front-side illumination.

  10. A novel technology using transscleral ultrasound to deliver protein loaded nanoparticles.

    Science.gov (United States)

    Huang, Di; Wang, Lili; Dong, Yixuan; Pan, Xin; Li, Ge; Wu, Chuanbin

    2014-09-01

    This study was designed to investigate the feasibility of silk fibroin nanoparticles (SFNs) for sustained drug delivery in transscleral ultrasound. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA, MW 66.45 kDa) was chosen as a model macromolecular protein drug and SFNs were used as nano-carrier systems suitable for ocular drug delivery. Drug loaded nanoparticles (FITC-BSA-SFNs) were first prepared and characterized. In vitro transscleral study under ultrasound exposure (1MHz, 0.5 W/cm(2), 5 min continuous wave) using isolated sclera of rabbit was performed. The posterior eye segment of rabbit was examined for adverse effect by slit-lamp and histology. It was found that FITC-BSA-SFNs possessed sustained release, bioadhesive, and co-permeation characteristics. The ultrasound application significantly improved the penetration efficiency of FITC-BSA-SFNs as compared with passive delivery, meanwhile caused no damages to the ocular tissue and particles themselves. The distribution profile of SFNs revealed rapid and lasting adhesion on the outer scleral tissues, followed by migration into the interior up to one week after treatment. This research suggested a novel non-invasive transscleral administration of macromolecular protein drugs using SFN carriers combining with ultrasound technology. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain

    Directory of Open Access Journals (Sweden)

    Shanshan Liu

    2018-01-01

    Full Text Available Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs. The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm with high drug loading (around 35% and high entrapment efficiency (around 80%. The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.

  12. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

    Directory of Open Access Journals (Sweden)

    Raquel Martínez-González

    2016-07-01

    Full Text Available There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs as contrast agents (CAs for magnetic resonance imaging (MRI, due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T2 relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r2, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.

  13. Production, characterisation, and in vitro nebulisation performance of budesonide-loaded PLA nanoparticles.

    Science.gov (United States)

    Amini, Mohammad Ali; Faramarzi, Mohammad Ali; Gilani, Kambiz; Moazeni, Esmaeil; Esmaeilzadeh-Gharehdaghi, Elina; Amani, Amir

    2014-01-01

    The aim of this study is to prepare a nanosuspension of budesonide for respiratory delivery using nebuliser by optimising its particle size and characterising its in vitro deposition behaviour. PLA (poly lactic acid)-budesonide nanosuspension (BNS) was prepared using high-pressure emulsification/solvent evaporation method. To optimise particle size, different parameters such as PLA concentration, sonication time, and amplitude were investigated. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscope (SEM) analyses were performed to characterise the prepared PLA-budesonide nanoparticles. The in vitro aerodynamic characteristics of the PLA-BNS using a jet nebuliser were estimated and compared with that of commercially available suspension formulation of budesonide. Budesonide-loaded PLA nanoparticles with fine particle size (an average size of 224-360 nm), narrow size distribution, and spherical and smooth surface were prepared. The optimum condition for preparation of fine particle size for aerosolisation was found to be at PLA concentration of 1.2 mg/ml and amplitude of 70 for 75 s sonication time. The in vitro aerosolisation performance of PLA-BNS compared to that of commercial budesonide indicated that it has significantly (p PLA-BNS could be considered as a promising alternative suspension formulation for deep lung delivery of the drug using nebuliser.

  14. Preparation of starch nanoparticles in a water-in-ionic liquid microemulsion system and their drug loading and releasing properties.

    Science.gov (United States)

    Zhou, Gang; Luo, Zhigang; Fu, Xiong

    2014-08-13

    An ionic liquid microemulsion consisting of 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF₆), surfactant TX-100, 1-butanol, and water was prepared. The water-in-[Bmim]PF₆ (W/IL), bicontinuous, and [Bmim]PF₆-in-water (IL/W) microregions of the microemulsion were identified by conductivity measurements. Starch nanoparticles with a mean diameter of 91.4 nm were synthesized with epichlorohydrin as cross-linker through W/IL microemulsion cross-linking reaction at 50 °C for 4 h. Fourier transform infrared spectroscopy (FTIR) data demonstrated the formation of cross-linking bonds in starch molecules. Scanning electron microscopy (SEM) revealed that starch nanoparticles were spherical and that some particles showed aggregation formation. Furthermore, drug loading and releasing properties of starch nanoparticles were investigated with mitoxantrone hydrochloride as a drug model. This work provides an efficient and environmentally friendly approach for the preparation of starch nanoparticles, which is beneficial to their further application.

  15. Preparation, characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids.

    Science.gov (United States)

    Xie, Shuyu; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Wang, Yan; Li, Xihe; Zhou, WenZhong

    2011-04-01

    Enrofloxacin-loaded solid lipid nanoparticles (SLN) were prepared using fatty acids (tetradecanoic acid, palmitic acid, stearic acid) as lipid matrix by hot homogenization and ultrasonication method. The effect of fatty acids on the characteristics and pharmacokinetics of the SLN were investigated. The results showed that the encapsulation efficiency and loading capacity of nanoparticles varied with fatty acids in the order of stearic acid>palmitic acid>tetradecanoic acid. Furthermore, stearic acid-SLN had larger particle size, bigger polydispersity index (PDI) and higher zeta potential compared with the other two fatty acid formulated SLN. The SLN showed sustained releases in vitro and the released enrofloxacin had the same antibacterial activity as that of the native enrofloxacin. Although in vitro release exhibited similar patterns, within 24 h the releasing rates of the three formulations were significantly different (tetradecanoic acid-SLN>palmitic acid-SLN>stearic acid-SLN). Pharmacokinetic study after a single dose of intramuscular administration to mice demonstrated that tetradecanoic acid-SLN, palmitic acid-SLN, and stearic acid-SLN increased the bioavailability by 6.79, 3.56 and 2.39 folds, and extended the mean residence time (MRT) of the drug from 10.60 h to 180.36, 46.26 and 19.09 h, respectively. These results suggest that the enrofloxacin-fatty acid SLN are promising formulations for sustained release while fatty acids had significant influences on the characteristics and performances of the SLN. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer

    Directory of Open Access Journals (Sweden)

    Qu N

    2016-07-01

    Full Text Available Na Qu,1 Robert J Lee,1,2 Yating Sun,1 Guangsheng Cai,1 Junyang Wang,1 Mengqiao Wang,1 Jiahui Lu,1 Qingfan Meng,1 Lirong Teng,1 Di Wang,1 Lesheng Teng1,3 1School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA; 3State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, People’s Republic of China Abstract: Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween. A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%, and superior blood biocompatibility based on in vitro hemolysis assay. Blood circulation, tumor uptake, and antitumor activity of Cbz-NPs were assessed in prostatic cancer xenograft-bearing nude mice. Cbz-NPs exhibited prolonged blood circulation and greater accumulation of Cbz in tumors along with reduced toxicity compared to Cbz-Tween. Moreover, hematoxylin and eosin histopathological staining of organs revealed consistent results. The levels of blood urea nitrogen and serum creatinine in drug-treated mice showed that Cbz-NPs were less toxic than Cbz-Tween to the kidneys. In conclusion, Cbz-NPs provide a promising therapeutic for prostate cancer. Keywords: cabazitaxel, human serum albumin, nanoparticle, drug delivery, toxicity, pros­tate cancer

  17. Aripiprazole loaded poly(caprolactone) nanoparticles: Optimization and in vivo pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Sawant, Krutika; Pandey, Abhijeet; Patel, Sneha

    2016-09-01

    In the present investigation, a Quality by Design strategy was applied for formulation and optimization of aripiprazole (APZ) loaded PCL nanoparticles (APNPs) using nanoprecipitation method keeping entrapment efficiency (%EE) and particle size (PS) as critical quality attributes. Establishment of design space was done followed by analysis of its robustness and sensitivity. Characterization of optimized APNPs was done using DSC, FT-IR, PXRD and TEM studies and was evaluated for drug release, hemocompatibility and nasal toxicity. PS, zeta potential and %EE of optimized APNPs were found to be 199.2 ± 5.65 nm, − 21.4 ± 4.6 mV and 69.2 ± 2.34% respectively. In vitro release study showed 90 ± 2.69% drug release after 8 h. Nasal toxicity study indicated safety of developed formulation for intranasal administration. APNPs administered via intranasal route facilitated the brain distribution of APZ incorporated with the AUC{sub 0→8} in rat brain approximately 2 times higher than that of APNPs administered via intravenous route. Increase in C{sub max} was observed which might help in dose reduction along with reduction in dose related side effects. The results of the study indicate that intranasally administered APZ loaded PCL NPs can potentially transport APZ via nose to brain and can serve as a non-invasive alternative for the delivery of APZ to brain. - Highlights: • It explores intra-nasal route for treatment of schizophrenia. • Quality by Design strategy has been used for optimization and assessesment of design space robustness. • PCL nanoparticles enhance penetration of drug into brain leading to increased C{sub max} and decrease in T{sub max}. • It can act as potential platform for treatment of schizophrenia with decreased dose related toxicities.

  18. Preparation and functional studies of hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody

    Directory of Open Access Journals (Sweden)

    Yang J

    2014-05-01

    Full Text Available Jingjing Yang,1,3,* Xiaoping Huang,1,3,* Fanghong Luo,1 Xiaofeng Cheng,3 Lianna Cheng,3 Bin Liu,4 Lihong Chen,2 Ruyi Hu,1,3 Chunyan Shi,1,3 Guohong Zhuang,1,3 Ping Yin2 1Anti-Cancer Research Center, Medical College, Xiamen University, Fujian, People's Republic of China, 2The Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China, 3Organ transplantation institution, Xiamen University, Xiamen, People's Republic of China, 4Jilin Vocational College of Industry and Technology, Jilin, People's Republic of China  *These authors contributed equally to this work Objective: To prepare hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody, and study their characteristics, functions, and mechanisms of action. Materials and methods: The anti-human death receptor 5 single-chain antibody was constructed and expressed. Protein-loaded hydroxyethyl chitosan nanoparticles were prepared, and their size, morphology, particle-size distribution and surface zeta potential were measured by scanning electron microscopy and laser particle-size analysis. Mouse H22 hepatocellular carcinoma cells were cultured, and growth inhibition was examined using the CellTiter-Blue cell-viability assay. Flow cytometry and Hoechst 33342 were employed to measure cell apoptosis. Kunming mice with H22 tumor models were treated with protein-loaded hydroxyethyl chitosan nanoparticles, and their body weight and tumor size were measured, while hematoxylin and eosin staining was used to detect antitumor effects in vivo and side effects from tumors. Results: The protein-loaded hydroxyethyl chitosan nanoparticles had good stability; the zeta potential was -24.2±0.205, and the dispersion index was 0.203. The inhibition of the protein-loaded hydroxyethyl chitosan nanoparticles on H22 growth was both time- and dose-dependent. Increased expressions of active caspase 8, active caspase 3, and BAX were detected

  19. Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes.

    Science.gov (United States)

    Jin, Mingji; Jin, Guangming; Kang, Lin; Chen, Liqing; Gao, Zhonggao; Huang, Wei

    2018-01-01

    The co-delivery of chemotherapeutic agents and small interfering RNA (siRNA) within one cargo can enhance the anticancer outcomes through its synergistic therapeutic effects. We prepared smart polymeric nanoparticles (NPs) with pH-responsive and poly(ethylene glycol) (PEG)-detachable properties to systemically co-deliver paclitaxel (PTX) and siRNA against survivin gene for lung cancer therapy. The cationic polyethyleneimine-block-polylactic acid (PEI-PLA) was first synthesized and characterized, with good biocompatibility. PTX was encapsulated into the hydrophobic core of the PEI-PLA polymers by dialysis, and then the survivin siRNA was loaded onto the PTX-loaded NPs (PEI-PLA/PTX) through electrostatic interaction between siRNA and PEI block. Finally, the negatively charged poly(ethylene glycol)-block-poly(L-aspartic acid sodium salt) (PEG-PAsp) was coated onto the surface of NPs by electrostatic interaction to form final smart polymeric NPs with mean particle size of 82.4 nm and zeta potential of 4.1 mV. After uptake of NPs by tumor cells, the PEG-PAsp segments became electrically neutral owing to the lower endosome pH and consequently detached from the smart NPs. This process allowed endosomal escape of the NPs through the proton-sponge effect of the exposed PEI moiety. The resulting NPs achieved drug loading of 6.04 wt% and exhibited good dispersibility within 24 h in 10% fetal bovine serum (FBS). At pH 5.5, the NPs presented better drug release and cellular uptake than at pH 7.4. The NPs with survivin siRNA effectively knocked down the expression of survivin mRNA and protein owing to enhanced cell uptake of NPs. Cell counting kit-8 (CCK-8) assay showed that the NPs presented low systemic toxicity and improved antiproliferation effect of PTX on A549 cells. Moreover, in vivo studies demonstrated that accumulated NPs in the tumor site were capable of inhibiting the tumor growth and extending the survival rate of the mice by silencing the survivin gene and

  20. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao, E-mail: 11140021@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Hu, Youdong [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China); Tan, Jianying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Shihui [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Chen, Junying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Guo, Xin; Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Li, Xia, E-mail: xial_li@qq.com [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China)

    2017-02-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  1. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    International Nuclear Information System (INIS)

    Liu, Tao; Hu, Youdong; Tan, Jianying; Liu, Shihui; Chen, Junying; Guo, Xin; Pan, Changjiang; Li, Xia

    2017-01-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  2. Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study.

    Science.gov (United States)

    Badri, Waisudin; Miladi, Karim; Robin, Sophie; Viennet, Céline; Nazari, Qand Agha; Agusti, Géraldine; Fessi, Hatem; Elaissari, Abdelhamid

    2017-09-01

    This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin. Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used. The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from -19 to -13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well. The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

  3. Poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate) Nanoparticles: Synthesis and Characterization, Enzymatic and Cellular Degradation, Micellar Solubilization of Paclitaxel, and in Vitro and in Vivo Evaluation.

    Science.gov (United States)

    Jäger, Alessandro; Jäger, Eliézer; Syrová, Zdeňka; Mazel, Tomas; Kováčik, Lubomír; Raška, Ivan; Höcherl, Anita; Kučka, Jan; Konefal, Rafal; Humajova, Jana; Poučková, Pavla; Štěpánek, Petr; Hrubý, Martin

    2018-04-11

    Polyester-based nanostructures are widely studied as drug-delivery systems due to their biocompatibility and biodegradability. They are already used in the clinic. In this work, we describe a new and simple biodegradable and biocompatible system as the Food and Drug Administration approved polyesters (poly-ε-caprolactone, polylactic acid, and poly(lactic- co-glycolic acid)) for the delivery of the anticancer drug paclitaxel (PTX) as a model drug. A hydrophobic polyester, poly(propylene succinate) (PPS), was prepared from a nontoxic alcohol (propylene glycol) and monomer from the Krebs's cycle (succinic acid) in two steps via esterification and melt polycondensation. Furthermore, their amphiphilic block copolyester, poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate) (mPEO- b-PPS), was prepared by three steps via esterification followed by melt polycondensation and the addition of mPEO to the PPS macromolecules. Analysis of the in vitro cellular behavior of the prepared nanoparticle carriers (NPs) (enzymatic degradation, uptake, localization, and fluorescence resonance energy-transfer pair degradation studies) was performed by fluorescence studies. PTX was loaded to the NPs of variable sizes (30, 70, and 150 nm), and their in vitro release was evaluated in different cell models and compared with commercial PTX formulations. The mPEO- b-PPS copolymer analysis displays glass transition temperature hydrolysis during transport in bloodstream, and simultaneous enzymatic degradability after uptake into the cells. The detailed cytotoxicity in vitro and in vivo tumor efficacy studies have shown the superior efficacy of the NPs compared with PTX and PTX commercial formulations.

  4. One-pot synthesis and characterization of rhodamine derivative-loaded magnetic core-shell nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jin, E-mail: jzhang@eng.uwo.ca; Li Jiaxin [University of Western Ontario, Department of Chemical and Biochemical Engineering (Canada); Razavi, Fereidoon S. [Brock University, Department of Physics (Canada); Mumin, Abdul Md. [University of Western Ontario, Department of Chemical and Biochemical Engineering (Canada)

    2011-05-15

    A new method to produce elaborate nanostructure with magnetic and fluorescent properties in one entity is reported in this article. Magnetite (Fe{sub 3}O{sub 4}) coated with fluorescent silica (SiO{sub 2}) shell was produced through the one-pot reaction, in which one reactor was utilized to realize the synthesis of superparamagnetic core of Fe{sub 3}O{sub 4}, the formation of SiO{sub 2} coating through the condensation and polymerization of tetraethylorthosilicate (TEOS), and the encapsulation of tetramethyl rhodamine isothiocyanate-dextran (TRITC-dextran) within silica shell. Transmission electron microscopy (TEM), energy dispersive X-ray (EDX) analysis, and X-ray diffraction (XRD) were carried out to investigate the core-shell structure. The magnetic core of the core-shell nanoparticles is 60 {+-} 10 nm in diameter. The thickness of the fluorescent SiO{sub 2} shell is estimated at 15 {+-} 5 nm. In addition, the fluorescent signal of the SiO{sub 2} shell has been detected by the laser confocal scanning microscopy (LCSM) with emission wavelength ({lambda}{sub em}) at 566 nm. In addition, the magnetic properties of TRITC-dextran loaded silica-coating iron oxide nanoparticles (Fe{sub 3}O{sub 4}-SiO{sub 2} NPs) were studied. The hysteresis loop of the core-shell NPs measured at room temperature shows that the saturation magnetization (M{sub s}) is not reached even at the field of 70 kOe (7T). Meanwhile, the very low coercivity (H{sub c}) and remanent magnetization (M{sub r}) are 0.375 kOe and 6.6 emu/g, respectively, at room temperature. It indicates that the core-shell particles have the superparamagnetic properties. The measured blocking temperature (T{sub B}) of the TRITC-dextran loaded Fe{sub 3}O{sub 4}-SiO{sub 2} NPs is about 122.5 K. It is expected that the multifunctional core-shell nanoparticles can be used in bio-imaging.

  5. Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

    Directory of Open Access Journals (Sweden)

    Ibrahim WM

    2013-12-01

    Full Text Available Waheed M Ibrahim,1 Abdullah H AlOmrani,2 Alaa Eldeen B Yassin31Drug Sector, Saudi Food and Drug Authority, 2Department of Pharmaceutics, College of Pharmacy, King Saud University, 3Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi ArabiaBackground: Solid lipid nanoparticles (SLN, novel drug delivery carriers, can be utilized in enhancing both intestinal permeability and dissolution of poorly absorbed drugs. The aim of this work was to enhance the intestinal permeability of sulpiride by loading into SLN.Methods: A unique ultrasonic melt-emulsification method with minimum stress conditions was used for the preparation of SLN. The mixture of the drug and the melted lipids was simply dispersed in an aqueous solution of a surfactant at a temperature that was 10°C higher than the melting points of the lipids using probe sonication, and was then simultaneously dispersed in cold water. Several formulation parameters were optimized, including the drug-to-lipid ratio, and the types of lipids and surfactants used. The produced SLN were evaluated for their particle size and shape, surface charge, entrapment efficiency, crystallinity of the drug and lipids, and the drug release profile. The rat everted sac intestine model was utilized to evaluate the change in intestinal permeability of sulpiride by loading into SLN.Results: The method adopted allowed successful preparation of SLN with a monodispersed particle size of 147.8–298.8 nm. Both scanning electron microscopic and atomic force microscopic images showed uniform spherical particles and confirmed the sizes determined by the light scattering technique. Combination of triglycerides with stearic acid resulted in a marked increase in zeta potential, entrapment efficiency, and drug loading; however, the particle size was increased. The type of surfactant used was critical for particle size

  6. PEG-PLGA electrospun nanofibrous membranes loaded with Au@Fe2O3 nanoparticles for drug delivery applications

    Science.gov (United States)

    Spadaro, Salvatore; Santoro, Marco; Barreca, Francesco; Scala, Angela; Grimato, Simona; Neri, Fortunato; Fazio, Enza

    2018-02-01

    A PEGylated-PLGA random nanofibrous membrane loaded with gold and iron oxide nanoparticles and with silibinin was prepared by electrospinning deposition. The nanofibrous membrane can be remotely controlled and activated by a laser light or magnetic field to release biological agents on demand. The nanosystems were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and thermogravimetric analyses. The drug loading efficiency and drug content percentages were determined by UV-vis optical absorption spectroscopy. The nanofibrous membrane irradiated by a relatively low-intensity laser or stimulated by a magnetic field showed sustained silibinin release for at least 60 h, without the burst effect. The proposed low-cost electrospinning procedure is capable of assembling, via a one-step procedure, a stimuli-responsive drug-loaded nanosystem with metallic nanoparticles to be externally activated for controlled drug delivery.

  7. Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer.

    Science.gov (United States)

    Tomoda, Keishiro; Tam, Yu Tong; Cho, Hyunah; Buehler, Darya; Kozak, Kevin R; Kwon, Glen S

    2017-01-01

    Triolimus is a multi-drug loaded polymeric micelle containing paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP). This study examines the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells are dose dependent and at 2 × 10 -9 m, Triolimus shows significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio, PTX alone, dual drug combinations, and Triolimus treatment at 2 × 10 -9 m have radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17-AAG (P/17) >17-AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17-AAG/RAP at 15/15/7.5 mg kg -1 ) strongly inhibits A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17-AAG/RAP at 60/60/30 mg kg -1 ) before the fractionated radiation leads to tumor control for up to 24 weeks. An enhanced radiosensitizing effect is observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Studying the loading effect of acidic type antioxidant on amorphous silica nanoparticle carriers

    Science.gov (United States)

    Ravinayagam, Vijaya; Rabindran Jermy, B.

    2017-06-01

    The study investigates the suitable nanosilica carriers to transport acidic type cargo molecules for potential targeted drug delivery application. Using phenolic acidic type antioxidant gallic acid (GA) as model compound, the present study investigates the loading effect of GA (0.3-15.9 mmol GA g-1 support) on textural characteristics of amorphous silica nanoparticles such as Q10 silica (1D), structured two-dimensional Si-MCM-41 (2D), and three-dimensional Si-SBA-16 (3D). The variation in the nature of textures after GA loading was analyzed using X-ray diffraction, N2 adsorption, FT-IR, scanning electron microscopy with energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. Among the nanocarriers, high adsorption of GA was found in the following order: Si-SBA-16 (3D)˜Si-KIT-6 (3D) > Si-MCM-41 (2D) > ultralarge pore FDU-12 (ULPFDU-12; 3D) > Q10 (1D)˜mesostructured cellular silica foam (MSU-F). 3D-type silicas Si-SBA-16 and KIT-6 were shown to maintain structural integrity at acidic condition (pH ˜3) and accommodate GA in non-crystalline form. In the case of ULPFDU-12 and MSU-F cellular foam, only crystalline deposition of GA occurs with a significant variation in the surface area and pore volume. [Figure not available: see fulltext.

  9. Loading of praziquantel in the crystal lattice of solid lipid nanoparticles - studies by DSC and SAXS

    Energy Technology Data Exchange (ETDEWEB)

    Souza, A.L.R.; Cassimiro, D.L.; Almeida, A.E.; Ribeiro, C.A.; Gremiao, M.P.D. [UNESP, Araraquara, SP (Brazil); Sarmento, V.H.V. [Universidade Federal de Sergipe (UFS), Itabaiana, SE (Brazil); Andreani, T.; Silva, A.M.; Souto, E.B. [Universidade de Tras-os-Montes e Alto Douro, Vila Real (Portugal)

    2012-07-01

    Full text: Praziquantel (PZQ) is the drug of choice for oral treatment of schistosomiasis and other fluke infections that affect humans. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. In this work, solid lipid nanoparticles loaded with PZQ (PZQ-SLN) were prepared by a modified oil-in-water microemulsion method selecting stearic acid as lipid phase after solubility screening studies. The mean particle size (Z-Ave) and zeta potential (ZP) were 500 nm and -34.0 mV, respectively. Morphology and shape of PZQ-SLN were analysed by scanning electron microscopy revealing the presence of spherical particles with smooth surface. Differential scanning calorimetry suggested that SLN comprised a less ordered arrangement of crystals and the drug was molecularly dispersed in the lipid matrix. No supercooled melts were detected. The entrapment efficiency (EE) and loading capacity of PZQ, determined by high performance liquid chromatography, were 99.0 and 17.5, respectively. Effective incorporation of PZQ into the particles was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure. Stability parameters of PZQ-SLN stored at room temperature (25 deg C) and at 4 deg C were checked by analysing Z-Ave, ZP and the EE for a period of 60 days Results showed a relatively long-term physical stability after storage at 4 deg C, without drug expulsion. (author)

  10. Loading of praziquantel in the crystal lattice of solid lipid nanoparticles - studies by DSC and SAXS

    International Nuclear Information System (INIS)

    Souza, A.L.R.; Cassimiro, D.L.; Almeida, A.E.; Ribeiro, C.A.; Gremiao, M.P.D.; Sarmento, V.H.V.; Andreani, T.; Silva, A.M.; Souto, E.B.

    2012-01-01

    Full text: Praziquantel (PZQ) is the drug of choice for oral treatment of schistosomiasis and other fluke infections that affect humans. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. In this work, solid lipid nanoparticles loaded with PZQ (PZQ-SLN) were prepared by a modified oil-in-water microemulsion method selecting stearic acid as lipid phase after solubility screening studies. The mean particle size (Z-Ave) and zeta potential (ZP) were 500 nm and -34.0 mV, respectively. Morphology and shape of PZQ-SLN were analysed by scanning electron microscopy revealing the presence of spherical particles with smooth surface. Differential scanning calorimetry suggested that SLN comprised a less ordered arrangement of crystals and the drug was molecularly dispersed in the lipid matrix. No supercooled melts were detected. The entrapment efficiency (EE) and loading capacity of PZQ, determined by high performance liquid chromatography, were 99.0 and 17.5, respectively. Effective incorporation of PZQ into the particles was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure. Stability parameters of PZQ-SLN stored at room temperature (25 deg C) and at 4 deg C were checked by analysing Z-Ave, ZP and the EE for a period of 60 days Results showed a relatively long-term physical stability after storage at 4 deg C, without drug expulsion. (author)

  11. Near-infrared fluorescence imaging platform for quantifying in vivo nanoparticle diffusion from drug loaded implants.

    Science.gov (United States)

    Markovic, Stacey; Belz, Jodi; Kumar, Rajiv; Cormack, Robert A; Sridhar, Srinivas; Niedre, Mark

    2016-01-01

    Drug loaded implants are a new, versatile technology platform to deliver a localized payload of drugs for various disease models. One example is the implantable nanoplatform for chemo-radiation therapy where inert brachytherapy spacers are replaced by spacers doped with nanoparticles (NPs) loaded with chemotherapeutics and placed directly at the disease site for long-term localized drug delivery. However, it is difficult to directly validate and optimize the diffusion of these doped NPs in in vivo systems. To better study this drug release and diffusion, we developed a custom macroscopic fluorescence imaging system to visualize and quantify fluorescent NP diffusion from spacers in vivo. To validate the platform, we studied the release of free fluorophores, and 30 nm and 200 nm NPs conjugated with the same fluorophores as a model drug, in agar gel phantoms in vitro and in mice in vivo. Our data verified that the diffusion volume was NP size-dependent in all cases. Our near-infrared imaging system provides a method by which NP diffusion from implantable nanoplatform for chemo-radiation therapy spacers can be systematically optimized (eg, particle size or charge) thereby improving treatment efficacy of the platform.

  12. Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after vaginal delivery in mice.

    Science.gov (United States)

    das Neves, José; Araújo, Francisca; Andrade, Fernanda; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2014-07-01

    To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery. Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method. Genital distribution of NPs and their ability to modify the PK of dapivirine up to 24 h was assessed after vaginal instillation in a female mouse model. Also, the safety of NPs upon daily administration for 14 days was assessed by histological analysis and chemokine/cytokine content in vaginal lavages. PEO-PCL NPs (180-200 nm) were rapidly eliminated after administration but able to distribute throughout the vagina and lower uterus, and capable of tackling mucus and penetrate the epithelial lining. Nanocarriers modified the PK of dapivirine, with higher drug levels being recovered from vaginal lavages and vaginal/lower uterine tissues as compared to a drug suspension. Systemic drug exposure was reduced when NPs were used. Also, NPs were shown safe upon administration for 14 days. Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable genital drug levels, thus attesting the potential value of using this vaginal drug delivery nanosystem in the context of HIV prophylaxis.

  13. Diclofenac sodium-loaded solid lipid nanoparticles prepared by emulsion/solvent evaporation method

    Energy Technology Data Exchange (ETDEWEB)

    Liu Dongfei; Jiang Sunmin [Nanjing Medical University, School of Pharmacy (China); Shen Hong [Nanjing Brain Hospital Affiliated to Nanjing Medical University, Neuro-Psychiatric Institute (China); Qin Shan; Liu Juanjuan; Zhang Qing; Li Rui, E-mail: chongloutougao@gmail.com; Xu Qunwei, E-mail: qunweixu@163.com [Nanjing Medical University, School of Pharmacy (China)

    2011-06-15

    The preparation of solid lipid nanoparticles (SLNs) suffers from the drawback of poor incorporation of water-soluble drugs. The aim of this study was therefore to assess various formulation and process parameters to enhance the incorporation of a water-soluble drug (diclofenac sodium, DS) into SLNs prepared by the emulsion/solvent evaporation method. Results showed that the entrapment efficiency (EE) of DS was increased to approximately 100% by lowering the pH of dispersed phase. The EE of DS-loaded SLNs (DS-SLNs) had been improved by the existence of cosurfactants and increment of PVA concentration. Stabilizers and their combination with PEG 400 in the dispersed phase also resulted in higher EE and drug loading (DL). EE increased and DL decreased as the phospholipid/DS ratio became greater, while the amount of DS had an opposite effect. Ethanol turned out to be the ideal solvent making DS-SLNs. EE and DL of DS-SLNs were not affected by either the stirring speed or the viscosity of aqueous and dispersed phase. According to the investigations, drug solubility in dispersion medium played the most important role in improving EE.

  14. Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings.

    Science.gov (United States)

    Li, Dan; Yang, Ke; Li, Jie-Si; Ke, Xi-Yu; Duan, Yu; Du, Ruo; Song, Ping; Yu, Ke-Fu; Ren, Wei; Huang, Dan; Li, Xing-Huo; Hu, Xin; Zhang, Xuan; Zhang, Qiang

    2012-01-01

    Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo. The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumor-bearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice. The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC(50) of the CLA-PTX microemulsion was 1.61 ± 0.83 μM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P > 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol(®) had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD(50) of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg. CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.

  15. A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Carolina R Oliveira

    Full Text Available BACKGROUND: Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. METHODS AND FINDINGS: Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF and simulated intestinal fluid (SIF. Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. CONCLUSIONS: Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.

  16. Development of silane grafted ZnO core shell nanoparticles loaded diglycidyl epoxy nanocomposites film for antimicrobial applications.

    Science.gov (United States)

    Suresh, S; Saravanan, P; Jayamoorthy, K; Ananda Kumar, S; Karthikeyan, S

    2016-07-01

    In this article a series of epoxy nanocomposites film were developed using amine functionalized (ZnO-APTES) core shell nanoparticles as the dispersed phase and a commercially available epoxy resin as the matrix phase. The functional group of the samples was characterized using FT-IR spectra. The most prominent peaks of epoxy resin were found in bare epoxy and in all the functionalized ZnO dispersed epoxy nanocomposites (ZnO-APTES-DGEBA). The XRD analysis of all the samples exhibits considerable shift in 2θ, intensity and d-spacing values but the best and optimum concentration is found to be 3% ZnO-APTES core shell nanoparticles loaded epoxy nanocomposites supported by FT-IR results. From TGA measurements, 100wt% residue is obtained in bare ZnO nanoparticles whereas in ZnO core shell nanoparticles grafted DGEBA residue percentages are 37, 41, 45, 46 and 52% for 0, 1, 3, 5 and 7% ZnO-APTES-DGEBA respectively, which is confirmed with ICP-OES analysis. From antimicrobial activity test, it was notable that antimicrobial activity of 7% ZnO-APTES core shell nanoparticles loaded epoxy nanocomposite film has best inhibition zone effect against all pathogens under study. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

    Science.gov (United States)

    K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy

    Science.gov (United States)

    2012-01-01

    Background Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process. Methods In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, in vitro release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out. Results Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5 ± 9.8 nm and the drug loading was determined to be 10.32 ± 1.4%. The in vitro release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC0-∞) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation. Conclusions A successful effort towards

  19. Iontophoresis on minoxidil sulphate-loaded chitosan nanoparticles accelerates drug release, decreasing their targeting effect to hair follicles

    Directory of Open Access Journals (Sweden)

    Breno N. Matos

    Full Text Available The experiments described in this paper tested the hypothesis whether iontophoresis applied on a chitosan nanoparticle formulation could combine the enhanced drug accumulation into the follicular casts obtained using iontophoresis and the sustained drug release, reducing dermal exposure, provided by nanoparticles. Results showed that even though iontophoresis presented comparable minoxidil targeting potential to hair follicles than passive delivery of chitosan-nanoparticles (4.1 ± 0.9 and 5.3 ± 1.0 µg cm-2, respectively, it was less effective on preventing dermal exposure, since chitosan-nanoparticles presented a drug permeation in the receptor solution of 15.3 ± 4.3 µg cm-2 after 6 h of iontophoresis, while drug amounts from passive nanoparticle delivery were not detected. Drug release experiments showed particles were not able to sustain the drug release under the influence of a potential gradient. In conclusion, the application of MXS-loaded chitosan nanoparticles remains the best way to target MXS to the hair follicles while preventing dermal exposure.

  20. Ficolin-1-PTX3 complex formation promotes clearance of altered self-cells and modulates IL-8 production

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Doni, Andrea; Romani, Luigina

    2013-01-01

    for enhancement of phagocytosis by human monocyte-derived macrophages and downregulation of IL-8 production during phagocytosis. On A. fumigatus, PTX3 exposed the C-terminal portion of the molecule, probably resulting in steric hindrance of ficolin-1 interaction with PTX3. These results demonstrate that ficolin-1...

  1. PTX3 is up-regulated in epithelial mammary cells during S. aureus intramammary infection in goat

    Directory of Open Access Journals (Sweden)

    Joel Fernando Soares Filipe

    2015-07-01

    PTX3 was up-regulated in epithelial mammary cells and in milk cells after S. aureus infection, demonstrating that it represents a first line of immune defense in goat udder. No modulation was observed in macrophages, in the secretum and in the ductal epithelial cells. Further experiments are needed to elucidate the role of PTX3 in the pathogenesis of S. aureus infection.

  2. Dual stimuli-sensitive dendrimers: Photothermogenic gold nanoparticle-loaded thermo-responsive elastin-mimetic dendrimers.

    Science.gov (United States)

    Fukushima, Daichi; Sk, Ugir Hossain; Sakamoto, Yasuhiro; Nakase, Ikuhiko; Kojima, Chie

    2015-08-01

    Dendrimers are synthetic macromolecules with unique structures that can work as nanoplatforms for both photothermogenic gold nanoparticles (AuNPs) and thermosensitive elastin-like peptides (ELPs) with valine-proline-glycine-valine-glycine (VPGVG) repeats. In this study, photothermogenic AuNPs were loaded into thermo-responsive elastin-mimetic dendrimers (dendrimers conjugating ELPs at their periphery) to produce dual stimuli-sensitive nanoparticles. Polyamidoamine G4 dendrimers were modified with acetylated VPGVG and (VPGVG)2, and the resulting materials were named ELP1-den and ELP2-den, respectively. The AuNPs were prepared by the reduction of Au ions using a dendrimer-nanotemplated method. The AuNP-loaded elastin-mimetic dendrimers exhibited photothermal properties. ELP1-den and ELP2-den showed similar temperature-dependent changes in their conformations. Phase transitions were observed at around 55°C and 35°C for the AuNP-loaded ELP1-den and AuNP-loaded ELP2-den, respectively, but not for the corresponding PEGylated dendrimer. In contrast to the AuNP-loaded PEGylated dendrimer, AuNP-loaded ELP2-den readily associated with cells and induced efficient photocytotoxicity at 37°C. The cell association and the photocytotoxicity properties of AuNP-loaded ELP2-den could be controlled by temperature. These results therefore suggest that dual stimuli-sensitive dendrimer nanoparticles of this type could be used for photothermal therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile.

    Science.gov (United States)

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug's pharmacokinetics related to the conventional formulation. Poly(lactide- co -glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs' long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA-PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel's pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs.

  4. Preparation and antioxidant properties of selenium nanoparticles-loaded chitosan microspheres

    Directory of Open Access Journals (Sweden)

    Bai K

    2017-06-01

    Full Text Available Kaikai Bai,1,2 Bihong Hong,1,2 Jianlin He,1,2 Zhuan Hong,1,2 Ran Tan1,2 1Third Institute of Oceanography, 2Engineering Research Center of Marine Biological Resource, Comprehensive Utilization, State Oceanic Administration, Xiamen, People’s Republic of China Abstract: Selenium nanoparticles (SeNPs, as a special form of selenium (Se supplement, have attracted worldwide attention due to their favorable properties and unique bioactivities. Herein, an eco-friendly and economic way to prepare stable SeNPs is introduced. SeNPs were synthesized in aqueous chitosan (CTS and then embedded into CTS microspheres by spray-drying, forming selenium nanoparticles-loaded chitosan microspheres (SeNPs-M. The physicochemical properties including morphology, elemental state, size distribution and surface potential were investigated. Institute of Cancer Research mice were used as model animal to evaluate the bioactivities of SeNPs-M. Trigonal-phase SeNPs of ~35 nm were synthesized, and SeNPs-M physically embedding those SeNPs were successfully prepared. Amazingly, acute toxicity test indicated that SeNPs-M were much safer than selenite in terms of Se dose, with a LD50 of around 18-fold of that of selenite. In addition, SeNPs-M possessed powerful antioxidant activities, as evidenced by a dramatic increase of both Se retention and the levels of glutathione peroxidase, superoxide dismutase and catalase. The design of SeNPs-M can offer a new way for further development of SeNPs with a higher efficacy and better biosafety. Thus, SeNPs-M may be a potential candidate for further evaluation as an Se supplement with antioxidant properties and be used against Se deficiency in animals and human beings. Keywords: selenium, nano, microsphere, chitosan, antioxidant

  5. Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits

    Directory of Open Access Journals (Sweden)

    Linhua Zhang

    2009-09-01

    Full Text Available Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song11Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaAbstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX-loaded poly(lactic acid–co-glycolic acid nanoparticles (DEX-NPs in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L-1. Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.Keywords: dexamethasone, nanoparticles, intravitreal injection, pharmacokinetics

  6. Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

    Directory of Open Access Journals (Sweden)

    Ahmed TA

    2016-02-01

    Full Text Available Tarek A Ahmed1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Abstract: In this study, optimized freeze-dried finasteride nanoparticles (NPs were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM. Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD. Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful

  7. Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism

    Science.gov (United States)

    Shen, Jianan; He, Qianjun; Gao, Yu; Shi, Jianlin; Li, Yaping

    2011-10-01

    Multidrug resistance (MDR) is one of the major obstacles for successful chemotherapy in cancer. One of the effective approaches to overcome MDR is to use nanoparticle-mediated drug delivery to increase drug accumulation in drug resistant cancer cells. In this work, we first report that the performance and mechanism of an inorganic engineered delivery system based on mesoporous silica nanoparticles (MSNs) loading doxorubicin (DMNs) to overcome the MDR of MCF-7/ADR (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The experimental results showed that DMNs could enhance the cellular uptake of doxorubicin (DOX) and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells. The IC50 of DMNs against MCF-7/ADR cells was 8-fold lower than that of free DOX. However, an improved effect of DOX in DMNs against MCF-7 cells (a DOX-sensitive cancer cell line) was not found. The increased cellular uptake and nuclear accumulation of DOX delivered by DMNs in MCF-7/ADR cells was confirmed by confocal laser scanning microscopy, and could result from the down-regulation of P-gp and bypassing the efflux action by MSNs themselves. The cellular uptake mechanism of DMNs indicated that the macropinocytosis was one of the pathways for the uptake of DMNs by MCF-7/ADR cells. The in vivo biodistribution showed that DMNs induced a higher accumulation of DOX in drug resistant tumors than free DOX. These results suggested that MSNs could be an effective delivery system to overcome multidrug resistance.

  8. Preparation, characterization, and in vitro/vivo studies of oleanolic acid-loaded lactoferrin nanoparticles

    Directory of Open Access Journals (Sweden)

    Xia X

    2017-05-01

    Full Text Available Xiaojing Xia,1,2 Haowei Liu,1 Huixia Lv,1 Jing Zhang,1 Jianping Zhou,1 Zhiying Zhao3 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 2Department of Pharmaceutics, ZheJiang Pharmaceutical College, Ningbo, 3Department of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: Oleanolic acid (OA, a pentacyclic triterpene, is used to safely and economically treat hepatopathy. However, OA, a Biopharmaceutics Classification System IV category drug, has low bioavailability owing to low solubility (<1 µg/mL and biomembrane permeability. We developed a novel OA nanoparticle (OA-NP-loaded lactoferrin (Lf nanodelivery system with enhanced in vitro OA dissolution and improved oral absorption and bioavailability. The OA-NPs were prepared using NP albumin-bound technology and characterized using dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro dissolution test. The in vivo pharmacokinetics was investigated in Sprague Dawley rats using liquid chromatography-tandem mass spectrometry. OA-NPs (OA:Lf =1:6, w/w% exhibited spherical morphology, 202.2±8.3 nm particle size, +(27.1±0.32 mV ζ potential, 92.59%±3.24% encapsulation efficiency, and desirable in vitro release profiles. An effective in vivo bioavailability (340.59% was achieved compared to the free drug following oral administration to rats. The Lf novel nanodelivery vehicle enhanced the dissolution rate, intestinal absorption, and bioavailability of OA. These results demonstrate that Lf NPs are a new strategy for improving oral absorption and bioavailability of poorly soluble and poorly absorbed drugs. Keywords: oleanolic acid, nanoparticle, lactoferrin nanodelivery system, drug absorption, bioavailability

  9. Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xue M

    2013-12-01

    Full Text Available Mei Xue, Ming-xing Yang, Wei Zhang, Xiu-min Li, De-hong Gao, Zhi-min Ou, Zhi-peng Li, Su-huan Liu, Xue-jun Li, Shu-yu Yang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Abstract: The high aqueous solubility, poor permeability, and absorption of berberine (BBR result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm, zeta potential (7.87 mV, encapsulation efficiency (58%, and drug loading (4.2%. The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg oral pharmacokinetic studies in rats showed significant improvement (P<0.05 in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05, suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced. Keywords: berberine, solid lipid nanoparticles, pharmacokinetic, hypoglycemic effect

  10. Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Feng R

    2012-07-01

    Full Text Available Runliang Feng,1,* Zhimei Song,1,* Guangxi Zhai2 1Department of Pharmaceutical Engineering, College of Medicine and Life Science, University of Jinan, Jinan, Shandong Province, 2Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China*These authors contributed equally to this workBackground: Curcumin (CUR has been linked with antioxidant, anti-inflammatory, antimicrobial, anti amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability.Methods: To improve its bioavailability and water solubility, we synthesized two series of poly (ε-Caprolactone-poly (ethylene glycol-poly (ε-Caprolactone triblock copolymers by ring-opening polymerization of poly (ethylene glycol and ε-Caprolactone, with stannous 2-ethylhexanoate as the catalyst. Structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography. The nanoparticles (NPs were prepared using a probe-type ultrasonic emulsion and solvent evaporation method. To obtain an optimal delivery system, we explored the effect of the length of the copolymers' hydrophilic and hydrophobic chains on the encapsulation of hydrophobic CUR, performing entrapment efficiency and drug loading evaluations, as well as studying the particle distribution and in vitro release using the direct dispersion method. Finally, study of the in vivo pharmacokinetics of the CUR-loaded NPs was also carried out on selected copolymers in comparison with CUR solution formulations.Results: CUR was encapsulated with 94.3% and 95.5% efficiency in biodegradable nanoparticulate formulations based on NP43 and NP63, respectively. Dynamic laser light scattering and transmission electron microscopy indicated a particle diameter of 55.6 nm and 62.4 nm for NP43 and NP63, respectively. Fourier transform

  11. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

    Directory of Open Access Journals (Sweden)

    Yuan Q

    2014-10-01

    Full Text Available Qing Yuan,1 Jing Han,1,2 Wenshu Cong,1 Ying Ge,3 Dandan Ma,1,3,4 Zhaoxia Dai,3,4 Yaping Li,5 Xiaolin Bi1,3,4 1CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 2School of Life Sciences, Anhui University, Hefei, 3Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 4Graduate School, Dalian Medical University, Dalian, 5Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere® and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly

  12. Silica-coated Gd(DOTA)-loaded protein nanoparticles enable magnetic resonance imaging of macrophages

    Science.gov (United States)

    Bruckman, Michael A.; Randolph, Lauren N.; Gulati, Neetu M.; Stewart, Phoebe L.; Steinmetz, Nicole F.

    2015-01-01

    The molecular imaging of in vivo targets allows non-invasive disease diagnosis. Nanoparticles offer a promising platform for molecular imaging because they can deliver large payloads of imaging reagents to the site of disease. Magnetic resonance imaging (MRI) is often preferred for clinical diagnosis because it uses non-ionizing radiation and offers both high spatial resolution and excellent penetration. We have explored the use of plant viruses as the basis of for MRI contrast reagents, specifically Tobacco mosaic virus (TMV), which can assemble to form either stiff rods or spheres. We loaded TMV particles with paramagnetic Gd ions, increasing the ionic relaxivity compared to free Gd ions. The loaded TMV particles were then coated with silica maintaining high relaxivities. Interestingly, we found that when Gd(DOTA) was loaded into the interior channel of TMV and the exterior was coated with silica, the T1 relaxivities increased by three-fold from 10.9 mM−1 s−1 to 29.7 mM−1s−1 at 60 MHz compared to uncoated Gd-loaded TMV. To test the performance of the contrast agents in a biological setting, we focused on interactions with macrophages because the active or passive targeting of immune cells is a popular strategy to investigate the cellular components involved in disease progression associated with inflammation. In vitro assays and phantom MRI experiments indicate efficient targeting and imaging of macrophages, enhanced contrast-to-noise ratio was observed by shape-engineering (SNP > TMV) and silica-coating (Si-TMV/SNP > TMV/SNP). Because plant viruses are in the food chain, antibodies may be prevalent in the population. Therefore we investigated whether the silica-coating could prevent antibody recognition; indeed our data indicate that mineralization can be used as a stealth coating option to reduce clearance. Therefore, we conclude that the silica-coated protein-based contrast agent may provide an interesting candidate material for further investigation

  13. Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications.

    Science.gov (United States)

    Sahle, Fitsum Feleke; Gerecke, Christian; Kleuser, Burkhard; Bodmeier, Roland

    2017-01-10

    pH-sensitive nanoparticles have a great potential for dermal and transfollicular drug delivery. In this study, pH-sensitive, dexamethasone-loaded Eudragit ® L 100, Eudragit ® L 100-55, Eudragit ® S 100, HPMCP-50, HPMCP-55 and cellulose acetate phthalate nanoparticles were prepared by nanoprecipitation and characterized. The pH-dependent swelling, erosion, dissolution and drug release kinetics were investigated in vitro using dynamic light scattering and Franz diffusion cells, respectively. Their toxicity potential was assessed by the ROS and MTT assays. 100-700nm nanoparticles with high drug loading and entrapment efficiency were obtained. The nanoparticles bear no toxicity potential. Cellulose phthalates nanoparticles were more sensitive to pH than acrylates nanoparticles. They dissolved in 10mM pH 7.5 buffer and released>80% of the drug within 7h. The acrylate nanoparticles dissolved in 40mM pH 7.5 buffer and released 65-70% of the drug within 7h. The nanoparticles remained intact in 10 and 40mM pH 6.0 buffers (HPMCP nanoparticles dissolved in 40mM pH 6.0 buffer) and released slowly. The nanoparticles properties could be modulated by blending the different polymers. In conclusion, various pH-sensitive nanoparticles that could release differently on the skin surface and dissolve and release in the hair follicles were obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients.

    Science.gov (United States)

    Derakhshandeh, Katayoun; Soheili, Marzieh; Dadashzadeh, Simin; Saghiri, Reza

    2010-08-09

    The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies.

  15. Development and analytical characterization of vitamin(s)-loaded chitosan nanoparticles for potential food packaging applications

    International Nuclear Information System (INIS)

    Aresta, Antonella; Calvano, Cosima Damiana; Trapani, Adriana; Cellamare, Saverio; Zambonin, Carlo Giorgio; De Giglio, Elvira

    2013-01-01

    Most vitamins are well-known natural antioxidant agents which can be usefully employed for foods preservation to increase their shelf life. In the present study, we aimed to investigate the potential of vitamin-based chitosan nanoparticles (CSNPs) for novel food packaging application. In particular, Vitamin C- and/or E-loaded CSNPs were formulated following the ionic gelation technique and using sulfobutylether-β-cyclodextrin as cross-linking agent. The obtained CSNPs were characterized in terms of size and zeta potential measurements, leading to size range of 375–503 nm and zeta range values from +16.0 to +33.8 mV. At the solid-state, the same particles were subjected to X-ray photoelectron spectroscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. Then, the antioxidant potential of the produced vitamin(s) nanoparticulate formulations has been evaluated through 1,1-diphenyl-2-picrylhydrazyl test, a rapid spectrophotometric assay. The standardized procedure was used on vitamin(s)-modified CSNPs systems to determine both the amount of active vitamin(s) loaded in CSNPs and their release performances by in vitro release studies. Of all, high vitamins association efficiency along with an improvement of their shelf life (also under light exposure up to 7 days) were achieved. Altogether, the results suggest that Vitamin E is available in a hydrophilic delivery system able to replace organic solvents usually used for the solubilization of this antioxidant agent. In conclusion, these nanocarriers represent a promising strategy for the co-administration of Vitamin E and Vitamin C in packaging materials intended for a better storage of hydrophilic and/or lipophilic food.

  16. Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma

    Directory of Open Access Journals (Sweden)

    Ujwala Shinde

    2013-01-01

    Full Text Available Chitosan (CS is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs loaded with dorzolamide hydrochloride (DRZ. CS was reacted with monochloroacetic acid (MCA for OCM-CS synthesis and was characterized by FT-IR, DSC, and 13C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and 13C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment.

  17. Development and analytical characterization of vitamin(s)-loaded chitosan nanoparticles for potential food packaging applications

    Energy Technology Data Exchange (ETDEWEB)

    Aresta, Antonella, E-mail: antonellamaria.aresta@uniba.it; Calvano, Cosima Damiana [University of Bari, Department of Chemistry (Italy); Trapani, Adriana; Cellamare, Saverio [University of Bari, Department of Pharmacy-Drug Sciences (Italy); Zambonin, Carlo Giorgio; De Giglio, Elvira [University of Bari, Department of Chemistry (Italy)

    2013-04-15

    Most vitamins are well-known natural antioxidant agents which can be usefully employed for foods preservation to increase their shelf life. In the present study, we aimed to investigate the potential of vitamin-based chitosan nanoparticles (CSNPs) for novel food packaging application. In particular, Vitamin C- and/or E-loaded CSNPs were formulated following the ionic gelation technique and using sulfobutylether-{beta}-cyclodextrin as cross-linking agent. The obtained CSNPs were characterized in terms of size and zeta potential measurements, leading to size range of 375-503 nm and zeta range values from +16.0 to +33.8 mV. At the solid-state, the same particles were subjected to X-ray photoelectron spectroscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. Then, the antioxidant potential of the produced vitamin(s) nanoparticulate formulations has been evaluated through 1,1-diphenyl-2-picrylhydrazyl test, a rapid spectrophotometric assay. The standardized procedure was used on vitamin(s)-modified CSNPs systems to determine both the amount of active vitamin(s) loaded in CSNPs and their release performances by in vitro release studies. Of all, high vitamins association efficiency along with an improvement of their shelf life (also under light exposure up to 7 days) were achieved. Altogether, the results suggest that Vitamin E is available in a hydrophilic delivery system able to replace organic solvents usually used for the solubilization of this antioxidant agent. In conclusion, these nanocarriers represent a promising strategy for the co-administration of Vitamin E and Vitamin C in packaging materials intended for a better storage of hydrophilic and/or lipophilic food.

  18. Development of dorzolamide loaded 6-o-carboxymethyl chitosan nanoparticles for open angle glaucoma.

    Science.gov (United States)

    Shinde, Ujwala; Ahmed, Mohammed Hadi; Singh, Kavita

    2013-01-01

    Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and (13)C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and (13)C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment.

  19. Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles.

    Science.gov (United States)

    das Neves, José; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2013-11-18

    Nanocarriers may provide interesting delivery platforms for microbicide drugs and their characterization should be addressed early in development. Differently surface-engineered dapivirine-loaded, poly(epsilon-caprolactone) (PCL)-based nanoparticles (NPs) were obtained by nanoprecipitation using polyethylene oxide (PEO), sodium lauryl sulfate (SLS), or cetyltrimethylammonium bromide (CTAB) as surface modifiers. Physical-chemical properties of NP aqueous dispersions were evaluated upon storage at -20-40 °C for one year. NPs presented 170-200 nm in diameter, roundish-shape, low polydispersity index (≤0.18), and high drug association efficiency (≥97%) and loading (≥12.7%). NPs differed in zeta potential, depending on surface modifier (PEO: -27.9 mV; SLS: -54.7 mV; CTAB: +42.4 mV). No interactions among formulation components were detected by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), except for SLS-PCL NPs. Colloidal properties of NPs were lost at -20 °C storage. Negatively charged NPs were stable up to one year at 5-40°C; as for CTAB-PCL NPs, particle aggregation was observed from 30 to 90 days of storage depending on temperature. Colloidal instability affected the in vitro drug release of CTAB-PCL NPs after 360 days. In any case, no degradation of dapivirine was apparent. Overall, PEO-PCL and SLS-PCL NPs presented suitable properties as nanocarriers for dapivirine. Conversely, CTAB-PCL NPs require additional strategies in order to increase stability. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Surface properties and dye loading behavior of Zn2SnO4 nanoparticles hydrothermally synthesized using different mineralizers

    International Nuclear Information System (INIS)

    Annamalai, Alagappan; Eo, Yang Dam; Im, Chan; Lee, Man-Jong

    2011-01-01

    We present for the first time the influence of different mineralizers on the isoelectric point (IEP) of zinc stannate (Zn 2 SnO 4 ) nanoparticles hydrothermally prepared using three different mineralizers, viz., Na 2 CO 3 , KOH and tert-butyl amine, and the effect of the IEPs on the dye loading behavior of Zn 2 SnO 4 based photoelectrodes in dye sensitized solar cells (DSSCs). To produce highly crystalline, uniform sized Zn 2 SnO 4 nanoparticles, hydrothermal processing parameters, such as reaction temperature, time, and the mineralizers used have been critically adjusted. The structural and morphological features of the as-synthesized Zn 2 SnO 4 nanoparticles have been observed using both scanning and transmission electron microscopy. For the surface state characterization of shape- and size-controlled Zn 2 SnO 4 nanoparticles, the IEPs of Zn 2 SnO 4 surfaces were determined through zeta potential measurements. The IEPs were found to be 5.7, 7.4 and 8.1 for Zn 2 SnO 4 nanoparticles formed using Na 2 CO 3 , KOH and tert-butyl amine, respectively, suggesting that the surface properties of Zn 2 SnO 4 nanoparticles can be manipulated through the choice of the mineralizers used during the hydrothermal reaction. The amount of N719 dye loading on the surfaces of Zn 2 SnO 4 electrodes having different IEPs was also evaluated. It was revealed that the higher the IEP, the higher the dye loading amount, which means that the IEP mainly affects the dye loading at the dye-metal oxide interface. - Highlights: → The effect of various mineralizers on the isoelectric point of Zn 2 SnO 4 was discussed. → The IEP of Zn 2 SnO 4 can be modified by the choice of mineralizer. → Change in IEP affects the surface properties and the morphology of Zn 2 SnO 4 particles. → Modified surface affects the N719 dye loading behaviour of the Zn 2 SnO 4 based DSSCs.

  1. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun, E-mail: weiywswzy@163.com [Anhui Agricultural University, School of Life Sciences (China)

    2016-01-15

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly (d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion–solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet–Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100–150 nm. We compared the antibacterial effects of PQTs against Escherichia coli (E. coli) and Micrococcus tetragenus (M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  2. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    International Nuclear Information System (INIS)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun

    2016-01-01

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly (d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion–solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet–Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100–150 nm. We compared the antibacterial effects of PQTs against Escherichia coli (E. coli) and Micrococcus tetragenus (M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application

  3. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    Science.gov (United States)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun

    2016-01-01

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly ( d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion-solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet-Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100-150 nm. We compared the antibacterial effects of PQTs against Escherichia coli ( E. coli) and Micrococcus tetragenus ( M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  4. Solid lipid nanoparticles loaded with edaravone for inner ear protection after noise exposure.

    Science.gov (United States)

    Gao, Gang; Liu, Ya; Zhou, Chang-Hua; Jiang, Ping; Sun, Jian-Jun

    2015-01-20

    Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO 3 ) staining at 1, 4, and 6 days. The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

  5. Adsorptive desulfurization of model oil using untreated, acid activated and magnetite nanoparticle loaded bentonite as adsorbent

    Directory of Open Access Journals (Sweden)

    Muhammad Ishaq

    2017-02-01

    Full Text Available The present research work focuses on a novel ultraclean desulfurization process of model oil by the adsorption method using untreated, acid activated and magnetite nanoparticle loaded bentonite as adsorbent. The parameters investigated are effect of contact time, adsorbent dose, initial dibenzothiophene (DBT concentration and temperature. Experimental tests were conducted in batch process. Pseudo first and second order kinetic equations were used to examine the experimental data. It was found that pseudo second order kinetic equation described the data of the DBT adsorption onto all types of adsorbents very well. The isotherm data were analyzed using Langmuir and Freundlich isotherm models. The Langmuir isotherm model fits the data very well for the adsorption of DBT onto all three forms of adsorbents. The adsorption of DBT was also investigated at different adsorbent doses and was found that the percentage adsorption of DBT was increased with increasing the adsorbent dose, while the adsorption in mg/g was decreased with increasing the adsorbent dose. The prepared adsorbents were analyzed by scanning electron microscopy (SEM, energy dispersive X-ray spectrometry (EDX and X-ray diffraction (XRD.

  6. Cadmium telluride nanoparticles loaded on activated carbon as adsorbent for removal of sunset yellow

    Science.gov (United States)

    Ghaedi, M.; Hekmati Jah, A.; Khodadoust, S.; Sahraei, R.; Daneshfar, A.; Mihandoost, A.; Purkait, M. K.

    2012-05-01

    Adsorption is a promising technique for decolorization of effluents of textile dyeing industries but its application is limited due to requirement of high amounts of adsorbent required. The objective of this study was to assess the potential of cadmium telluride nanoparticles loaded onto activated carbon (CdTN-AC) for the removal of sunset yellow (SY) dye from aqueous solution. Adsorption studies were conducted in a batch mode varying solution pH, contact time, initial dye concentration, CdTN-AC dose, and temperature. In order to investigate the efficiency of SY adsorption on CdTN-AC, pseudo-first-order, pseudo-second-order, Elovich, and intra-particle diffusion kinetic models were studied. It was observed that the pseudo-second-order kinetic model fits better than other kinetic models with good correlation coefficient. Equilibrium data were fitted to the Langmuir model. Thermodynamic parameters such as enthalpy, entropy, activation energy, and sticking probability were also calculated. It was found that the sorption of SY onto CdTN-AC was spontaneous and endothermic in nature. The proposed adsorbent is applicable for SY removal from waste of real effluents including pea-shooter, orange drink and jelly banana with efficiency more than 97%.

  7. Gamma sterilization of diclofenac sodium loaded- N-trimethyl chitosan nanoparticles for ophthalmic use.

    Science.gov (United States)

    Asasutjarit, Rathapon; Theerachayanan, Thitaree; Kewsuwan, Prartana; Veeranondha, Sukitaya; Fuongfuchat, Asira; Ritthidej, Garnpimol C

    2017-02-10

    This study was conducted to investigate the effect of gamma irradiation on physicochemical properties of N-trimethyl chitosan (TMC), diclofenac sodium (DC) and diclofenac sodium loaded N-trimethylchitosan nanoparticles (DC-TMCNs), and to determine suitable doses of gamma rays for sterilization of DC-TMCNs. Physicochemical properties of TMC, DC and DC-TMCNs before and after exposure to gamma rays at various doses were investigated. It was found that gamma irradiation at doses of 5-25kGy did not cause any significant changes in physical and chemical properties of TMC, DC and DC-TMCNs. The bioburden of DC-TMCNs was 1.5×10 6 CFU/vial. The initial contaminating bacteria were radiosensitive bacteria. A number of microorganisms was reduced to 10 -6 after exposure to 9.9kGy of gamma rays. Therefore, DC-TMCNs could be sterilized by gamma irradiation at a dose of 10kGy, which did not alter their physicochemical properties and did not produce any substances toxic to the eye. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Bevacizumab loaded solid lipid nanoparticles prepared by the coacervation technique: preliminary in vitro studies

    Science.gov (United States)

    Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Solazzi, Ilaria; Giordano, Susanna Marzia Adele; Gigliotti, Casimiro Luca; Riganti, Chiara; Dianzani, Chiara

    2015-06-01

    Glioblastoma, the most common primary brain tumor in adults, has an inauspicious prognosis, given that overcoming the blood-brain barrier is the major obstacle to the pharmacological treatment of brain tumors. As neoangiogenesis plays a key role in glioblastoma growth, the US Food and Drug Administration approved bevacizumab (BVZ), an antivascular endothelial growth factor antibody for the treatment of recurrent glioblastoma in patients whose the initial therapy has failed. In this experimental work, BVZ was entrapped in solid lipid nanoparticles (SLNs) prepared by the fatty-acid coacervation technique, thanks to the formation of a hydrophobic ion pair. BVZ activity, which was evaluated by means of four different in vitro tests on HUVEC cells, increased by 100- to 200-fold when delivered in SLNs. Moreover, SLNs can enhance the permeation of fluorescently labelled BVZ through an hCMEC/D3 cell monolayer—an in vitro model of the blood brain barrier. These results are promising, even if further in vivo studies are required to evaluate the effective potential of BVZ-loaded SLNs in glioblastoma treatment.

  9. Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

    OpenAIRE

    Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

    2015-01-01

    The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an i...

  10. Antibacterial and anti-adhesion effects of the silver nanoparticles-loaded poly(L-lactide) fibrous membrane

    International Nuclear Information System (INIS)

    Liu, Shen; Zhao, Jingwen; Ruan, Hongjiang; Wang, Wei; Wu, Tianyi; Cui, Wenguo; Fan, Cunyi

    2013-01-01

    The complications of tendon injury are frequently compromised by peritendinous adhesions and tendon sheath infection. Physical barriers for anti-adhesion may increase the incidence of postoperative infection. This study was designed to evaluate the potential of silver nanoparticles (AgNPs)-loaded poly(L-lactide) (PLLA) electrospun fibrous membranes to prevent adhesion formation and infection. Results of an in vitro drug release study showed that a burst release was followed by sustained release from electrospun fibrous membranes with a high initial silver content. Fewer fibroblasts adhered to and proliferated on the AgNP-loaded PLLA electrospun fibrous membranes compared with pure PLLA electrospun fibrous membrane. In the antibacterial test, the AgNP-loaded PLLA electrospun fibrous membranes can prevent the adhesion of Gram-positive Staphylococcus aureus and Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa. Taken together, these results demonstrate that AgNP-loaded PLLA electrospun fibrous membranes have the convenient practical medical potential of reduction of infection and adhesion formation after tendon injury. - Highlights: ► Silver nanoparticles are directly electrospun into PLLA fibrous membrane. ► Long-lasting release of Ag + ions is achieved. ► Cytotoxicity of silver ions benefits the anti-proliferation of physical barriers. ► Broad anti-microbial effect of drug-loaded fibrous membrane is revealed. ► Antibacterial and anti-adhesion effects of the physical barriers are combined

  11. Silver nanoparticles-loaded activated carbon fibers using chitosan as binding agent: Preparation, mechanism, and their antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chengli, E-mail: tcl-lily@mail.zjxu.edu.cn [College of Mechanical and Electrical Engineering, Jiaxing University, Jiaxing 314001 (China); Hu, Dongmei [College of Mechanical Science and Engineering, Jilin University, Changchun 130022 (China); Cao, Qianqian [College of Mechanical and Electrical Engineering, Jiaxing University, Jiaxing 314001 (China); Yan, Wei [Department of Environmental Science and Engineering, Xi’an Jiaotong University, Xi’an 710049 (China); Xing, Bo [College of Mechanical and Electrical Engineering, Jiaxing University, Jiaxing 314001 (China)

    2017-02-01

    Highlights: • Chitosan was firstly introduced as binding agent for AgNPs loading on ACF surface. • Molecular dynamics simulation was used to explore the AgNPs loading mechanism. • Loading mechanism was proposed based on the experimental and simulation results. • Antibacterial AgNPs-loaded ACF showed use potential for water disinfection. - Abstract: The effective and strong adherence of silver nanoparticles (AgNPs) to the substrate surface is pivotal to the practical application of those AgNPs-modified materials. In this work, AgNPs were synthesized through a green and facile hydrothermal method. Chitosan was introduced as the binding agent for the effective loading of AgNPs on activated carbon fibers (ACF) surface to fabricate the antibacterial material. Apart from conventional instrumental characterizations, i. e., scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), zeta potential and Brunauer-Emmett-Teller (BET) surface area measurement, molecular dynamics simulation method was also applied to explore the loading mechanism of AgNPs on the ACF surface. The AgNPs-loaded ACF material showed outstanding antibacterial activity for S. aureus and E. coli. The combination of experimental and theoretical calculation results proved chitosan to be a promising binding agent for the fabrication of AgNPs-loaded ACF material with excellent antibacterial activity.

  12. Poly(vinyl methyl ether/maleic anhydride)-Doped PEG-PLA Nanoparticles for Oral Paclitaxel Delivery To Improve Bioadhesive Efficiency.

    Science.gov (United States)

    Wang, Qian; Li, Chan; Ren, Tianyang; Chen, Shizhu; Ye, Xiaoxia; Guo, Hongbo; He, Haibing; Zhang, Yu; Yin, Tian; Liang, Xing-Jie; Tang, Xing

    2017-10-02

    Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape and exhibited a sustained drug release compared with Taxol. m-NPs also exhibited favorable bioadhesive efficiency at the same time. Coumarin 6 or DiR-loaded nanoparticles with/without PVMMA (C6-m-NPs/DiR-m-NPs or C6-p-NPs/DiR-p-NPs) were used for cellular uptake and intestinal adhesion experiments, respectively. C6-m-NPs were shown to enhance cellular uptake, and caveolae/lipid raft mediated endocytosis was the primary route for the uptake of the nanoparticles. Favorable bioadhesive efficiency led to prolonged retention in the intestine reflected by the fluorescence in isolated intestines ex vivo. In a ligated intestinal loops model, C6-m-NPs showed a clear advantage for transporting NPs across the mucus layer over C6-p-NPs and free C6. The apparent permeability coefficient (Papp) of PTX-m-NPs through Caco-2/HT29 monolayers was 1.3- and 1.6-fold higher than PTX-p-NPs and Taxol, respectively, which was consistent with the AUC 0-t of different PTX formulations after oral administration in rats. PTX-m-NPs also exhibited a more effective anticancer efficacy, with an IC 50 of 0.2 ± 1.4 μg/mL for A549 cell lines, further demonstrating the advantage of bioadhesive nanoparticles. The bioadhesive nanoparticles m-NPs demonstrated both mucus permeation and epithelial absorption, and thus, this bioadhesive drug delivery system has the potential to improve the bioavailability of drugs that are insoluble in the gastrointestinal environment.

  13. N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination : Biological properties and immunogenicity in a mouse model

    NARCIS (Netherlands)

    Amidi, Maryam; Romeijn, Stefan G.; Verhoef, J. Coos; Junginger, Hans E.; Bungener, Laura; Huckriede, Anke; Crommelin, Daan J. A.; Jiskoot, Wim

    2007-01-01

    In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of a monovalent influenza subunit vaccine was investigated. The antigen-loaded nanoparticles were prepared by mixing a solution containing TMC and monovalent influenza A subunit H3N2

  14. Design of experiments for the development of poly(d,l-lactide-co-glycolide) nanoparticles loaded with Uncaria tomentosa

    International Nuclear Information System (INIS)

    Ribeiro, Ana Ferreira; Ferreira, Carina Torres Garruth; Santos, Juliana Fernandes dos; Cabral, Lúcio Mendes; Sousa, Valéria Pereira de

    2015-01-01

    Polymeric nanoparticles have been shown to be effective carriers for natural substances that possess anticancer properties. Incorporation of these natural substances into polymeric nanoparticles increases targeting of these drugs, thus reducing side effects. Uncaria tomentosa (UT) is a Peruvian Amazon plant (existing in the Brazilian Amazon rainforest) that possesses promising anti-tumor activity. This paper describes the development of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with UT extract. The emulsion solvent evaporation method was utilized and the initial conditions were determined for the organic phase (OP) and the aqueous phase (AP). The influence of surfactant (type and concentration), PLGA concentration and AP volume on nanoparticle size, polydispersity index (PI), and entrapment efficiency (EE) was determined using a fractional factorial design (FFD). In addition, the formulation was optimized using a Box–Behnken design. After the conditions were optimized, UT nanoparticles were obtained using an OP composed of an ethyl acetate:acetone (3:2) mixture which contained the UT alkaloids and PLGA, and an AP composed of a buffered solution of Poloxamer 188 (pH 7.5). The optimized formulation produced an EE of 64.6 %, a particle size of 107.4 nm and a PI of 0.163. The preliminary experiments provided important information regarding the behavior of the nanoparticulate system and the FFD used in this study greatly facilitated the selection of the most optimal conditions for formulation development

  15. Improved Treatment of Pancreatic Cancer With Drug Delivery Nanoparticles Loaded With a Novel AKT/PDK1 Inhibitor.

    Science.gov (United States)

    Kobes, Joseph E; Daryaei, Iman; Howison, Christine M; Bontrager, Jordan G; Sirianni, Rachael W; Meuillet, Emmanuelle J; Pagel, Mark D

    2016-09-01

    This research study sought to improve the treatment of pancreatic cancer by improving the drug delivery of a promising AKT/PDK1 inhibitor, PHT-427, in poly(lactic-co-glycolic) acid (PLGA) nanoparticles. PHT-427 was encapsulated in single-emulsion and double-emulsion PLGA nanoparticles (SE-PLGA-427 and DE-PLGA-427). The drug release rate was evaluated to assess the effect of the second PLGA layer of DE-PLGA-427. Ex vivo cryo-imaging and drug extraction from ex vivo organs was used to assess the whole-body biodistribution in an orthotopic model of MIA PaCa-2 pancreatic cancer. Anatomical magnetic resonance imaging (MRI) was used to noninvasively assess the effects of 4 weeks of nanoparticle drug treatment on tumor size, and diffusion-weighted MRI longitudinally assessed changes in tumor cellularity. DE-PLGA-427 showed delayed drug release and longer drug retention in the pancreas relative to SE-PLGA-427. Diffusion-weighted MRI indicated a consistent decrease in cellularity during drug treatment with both types of drug-loaded nanoparticles. Both SE- and DE-PLGA-427 showed a 6-fold and 4-fold reduction in tumor volume relative to untreated tumors and an elimination of primary pancreatic tumor in 68% of the mice. These results indicated that the PLGA nanoparticles improved drug delivery of PHT-427 to pancreatic tumors, which improved the treatment of MIA PaCa-2 pancreatic cancer.

  16. Preparation and Loading with Rifampicin of Sub-50 nm Poly(ethyl cyanoacrylate Nanoparticles by Semicontinuous Heterophase Polymerization

    Directory of Open Access Journals (Sweden)

    H. Saade

    2016-01-01

    Full Text Available We report the preparation of poly(ethyl cyanoacrylate (PECA nanoparticles by semicontinuous heterophase polymerization carried out at monomer starved conditions at three monomer addition rates. Particles in the nanometer range were obtained, the size of which diminishes with decreasing monomer addition rate as shown by the fact that particles with mean diameters of ca. 42 and 30 nm were obtained at the faster and intermediate dosing rates, respectively, whereas two populations of particles, one of 15.5 and the other of 36 nm in mean diameters, were produced at the slower dosing rate. The obtained molecular weights were from 2,200 to 3,500 g/mol, depending on the addition rate, which are typical of the anionic polymerizations of cyanoacrylates in aqueous dispersions at low pHs. The rifampicin (RIF loading into the nanoparticles was successful since the entire drug added was incorporated. The drug release study carried out at pH of 7.2 indicated a faster release from the free RIF at intermediate and larger release times as expected since, in the nanoparticles, first the drug has to diffuse through the nanoparticle structure. The comparison of several drug release models indicates that the RIF release from PECA nanoparticles follows that of Higuchi.

  17. Design of experiments for the development of poly(d,l-lactide-co-glycolide) nanoparticles loaded with Uncaria tomentosa

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ana Ferreira, E-mail: ana.ribeiro@ifrj.edu.br [Federal University of Rio de Janeiro, Department of Drugs and Pharmaceutics, Faculty of Pharmacy (Brazil); Ferreira, Carina Torres Garruth; Santos, Juliana Fernandes dos [Federal Institute of Education, Science and Technology of Rio de Janeiro, Faculty of Pharmacy (Brazil); Cabral, Lúcio Mendes; Sousa, Valéria Pereira de [Federal University of Rio de Janeiro, Department of Drugs and Pharmaceutics, Faculty of Pharmacy (Brazil)

    2015-02-15

    Polymeric nanoparticles have been shown to be effective carriers for natural substances that possess anticancer properties. Incorporation of these natural substances into polymeric nanoparticles increases targeting of these drugs, thus reducing side effects. Uncaria tomentosa (UT) is a Peruvian Amazon plant (existing in the Brazilian Amazon rainforest) that possesses promising anti-tumor activity. This paper describes the development of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with UT extract. The emulsion solvent evaporation method was utilized and the initial conditions were determined for the organic phase (OP) and the aqueous phase (AP). The influence of surfactant (type and concentration), PLGA concentration and AP volume on nanoparticle size, polydispersity index (PI), and entrapment efficiency (EE) was determined using a fractional factorial design (FFD). In addition, the formulation was optimized using a Box–Behnken design. After the conditions were optimized, UT nanoparticles were obtained using an OP composed of an ethyl acetate:acetone (3:2) mixture which contained the UT alkaloids and PLGA, and an AP composed of a buffered solution of Poloxamer 188 (pH 7.5). The optimized formulation produced an EE of 64.6 %, a particle size of 107.4 nm and a PI of 0.163. The preliminary experiments provided important information regarding the behavior of the nanoparticulate system and the FFD used in this study greatly facilitated the selection of the most optimal conditions for formulation development.

  18. Design of experiments for the development of poly( d, l-lactide- co-glycolide) nanoparticles loaded with Uncaria tomentosa

    Science.gov (United States)

    Ribeiro, Ana Ferreira; Ferreira, Carina Torres Garruth; dos Santos, Juliana Fernandes; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

    2015-02-01

    Polymeric nanoparticles have been shown to be effective carriers for natural substances that possess anticancer properties. Incorporation of these natural substances into polymeric nanoparticles increases targeting of these drugs, thus reducing side effects. Uncaria tomentosa (UT) is a Peruvian Amazon plant (existing in the Brazilian Amazon rainforest) that possesses promising anti-tumor activity. This paper describes the development of poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles loaded with UT extract. The emulsion solvent evaporation method was utilized and the initial conditions were determined for the organic phase (OP) and the aqueous phase (AP). The influence of surfactant (type and concentration), PLGA concentration and AP volume on nanoparticle size, polydispersity index (PI), and entrapment efficiency (EE) was determined using a fractional factorial design (FFD). In addition, the formulation was optimized using a Box-Behnken design. After the conditions were optimized, UT nanoparticles were obtained using an OP composed of an ethyl acetate:acetone (3:2) mixture which contained the UT alkaloids and PLGA, and an AP composed of a buffered solution of Poloxamer 188 (pH 7.5). The optimized formulation produced an EE of 64.6 %, a particle size of 107.4 nm and a PI of 0.163. The preliminary experiments provided important information regarding the behavior of the nanoparticulate system and the FFD used in this study greatly facilitated the selection of the most optimal conditions for formulation development.

  19. Superparamagnetic iron oxide nanoparticles (SPIONs)-loaded Trojan microparticles for targeted aerosol delivery to the lung.

    Science.gov (United States)

    Tewes, Frederic; Ehrhardt, Carsten; Healy, Anne Marie

    2014-01-01

    Targeted aerosol delivery to specific regions of the lung may improve therapeutic efficiency and minimise unwanted side effects. Targeted delivery could potentially be achieved with porous microparticles loaded with superparamagnetic iron oxide nanoparticles (SPIONs)-in combination with a target-directed magnetic gradient field. The aim of this study was to formulate and evaluate the aerodynamic properties of SPIONs-loaded Trojan microparticles after delivery from a dry powder inhaler. Microparticles made of SPIONs, PEG and hydroxypropyl-β-cyclodextrin (HPβCD) were formulated by spray drying and characterised by various physicochemical methods. Aerodynamic properties were evaluated using a next generation cascade impactor (NGI), with or without a magnet positioned at stage 2. Mixing appropriate proportions of SPIONs, PEG and HPβCD allowed Trojan microparticle to be formulated. These particles had a median geometric diameter of 2.8±0.3μm and were shown to be sensitive to the magnetic field induced by a magnet having a maximum energy product of 413.8kJ/m(3). However, these particles, characterised by a mass median aerodynamic diameter (MMAD) of 10.2±2.0μm, were considered to be not inhalable. The poor aerodynamic properties resulted from aggregation of the particles. The addition of (NH4)2CO3 and magnesium stearate (MgST) to the formulation improved the aerodynamic properties of the Trojan particles and resulted in a MMAD of 2.2±0.8μm. In the presence of a magnetic field on stage 2 of the NGI, the amount of particles deposited at this stage increased 4-fold from 4.8±0.7% to 19.5±3.3%. These Trojan particles appeared highly sensitive to the magnetic field and their deposition on most of the stages of the NGI was changed in the presence compared to the absence of the magnet. If loaded with a pharmaceutical active ingredient, these particles may be useful for treating localised lung disease such as cancer nodules or bacterial infectious foci. Copyright

  20. Paclitaxel-Fe3O4 nanoparticles inhibit growth of CD138–  CD34– tumor stem-like cells in multiple myeloma-bearing mice

    Directory of Open Access Journals (Sweden)

    Yang C

    2013-04-01

    Full Text Available Cuiping Yang,1,3,* Jing Wang,2,* Dengyu Chen,1,* Junsong Chen,1 Fei Xiong,4 Hongyi Zhang,1 Yunxia Zhang,2 Ning Gu,4 Jun Dou11Department of Pathogenic Biology and Immunology, Medical School, 2Department of Gynecology and Obstetrics, Zhongda Hospital, Southeast University, Nanjing, 3Department of Pathogenic Biology and Immunology, School of Basic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 4School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China*These authors contributed equally to this workBackground: There is growing evidence that CD138– CD34– cells may actually be tumor stem cells responsible for initiation and relapse of multiple myeloma. However, effective drugs targeted at CD138– CD34– tumor stem cells are yet to be developed. The purpose of this study was to investigate the inhibitory effect of paclitaxel-loaded Fe3O4 nanoparticles (PTX-NPs on CD138– CD34– tumor stem cells in multiple myeloma-bearing mice.Methods: CD138– CD34– cells were isolated from a human U266 multiple myeloma cell line using an immune magnetic bead sorting method and then subcutaneously injected into mice with nonobese diabetic/severe combined immunodeficiency to develop a multiple myeloma-bearing mouse model. The mice were treated with Fe3O4 nanoparticles 2 mg/kg, paclitaxel 4.8 mg/kg, and PTX-NPs 0.64 mg/kg for 2 weeks. Tumor growth, pathological changes, serum and urinary interleukin-6 levels, and molecular expression of caspase-3, caspase-8, and caspase-9 were evaluated.Results: CD138– CD34– cells were found to have tumor stem cell characteristics. All the mice developed tumors in 40 days after injection of 1 × 106 CD138– CD34– tumor stem cells. Tumor growth in mice treated with PTX-NPs was significantly inhibited compared with the controls (P <  0.005, and the groups that received nanoparticles alone (P < 0.005 or paclitaxel alone (P < 0.05. In addition

  1. An in vivo mechanism for the reduced peripheral neurotoxicity of NK105: a paclitaxel-incorporating polymeric micellar nanoparticle formulation

    Directory of Open Access Journals (Sweden)

    Nakamura I

    2017-02-01

    Full Text Available Iwao Nakamura, Eiji Ichimura, Rika Goda, Hitomi Hayashi, Hiroko Mashiba, Daichi Nagai, Hirofumi Yokoyama, Takeshi Onda, Akira Masuda Nanomedicine Group, Pharmaceutical Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan Abstract: In our previous rodent studies, the paclitaxel (PTX-incorporating polymeric micellar nanoparticle formulation NK105 had showed significantly stronger antitumor effects and reduced peripheral neurotoxicity than PTX dissolved in Cremophor® EL and ethanol (PTX/CRE. Thus, to elucidate the mechanisms underlying reduced peripheral neurotoxicity due to NK105, we performed pharmacokinetic analyses of NK105 and PTX/CRE in rats. Among neural tissues, the highest PTX concentrations were found in the dorsal root ganglion (DRG. Moreover, exposure of DRG to PTX (Cmax_PTX and AUC0-inf._PTX in the NK105 group was almost half that in the PTX/CRE group, whereas exposure of sciatic and sural nerves was greater in the NK105 group than in the PTX/CRE group. In histopathological analyses, damage to DRG and both peripheral nerves was less in the NK105 group than in the PTX/CRE group. The consistency of these pharmacokinetic and histopathological data suggests that high levels of PTX in the DRG play an important role in the induction of peripheral neurotoxicity, and reduced distribution of PTX to the DRG of NK105-treated rats limits the ensuing peripheral neurotoxicity. In further analyses of PTX distribution to the DRG, Evans blue (Eb was injected with BODIPY®-labeled NK105 into rats, and Eb fluorescence was observed only in the DRG. Following injection, most Eb dye bound to albumin particles of ~8 nm and had penetrated the DRG. In contrast, BODIPY®–NK105 particles of ~90 nm were not found in the DRG, suggesting differential penetration based on particle size. Because PTX also circulates as PTX–albumin particles of ~8 nm following injection of PTX/CRE, reduced peripheral neurotoxicity of NK105 may reflect exclusion from the

  2. Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization.

    Science.gov (United States)

    Liu, Jie; Gong, Tao; Wang, Changguang; Zhong, Zhirong; Zhang, Zhirong

    2007-08-01

    Solid lipid nanoparticles (SLNs) loaded with insulin-mixed micelles (Ins-MMs) were prepared by a novel reverse micelle-double emulsion method, in which sodium cholate (SC) and soybean phosphatidylcholine (SPC) were employed to improve the liposolubility of insulin, and the mixture of stearic acid and palmitic acid were employed to prepare insulin loaded solid lipid nanoparticles (Ins-MM-SLNs). Some of the formulation parameters were optimized to obtain high quality nanoparticles. The particle size and zeta potential measured by photon correlation spectroscopy (PCS) were 114.7+/-4.68 nm and -51.36+/-2.04 mV, respectively. Nanospheres observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed extremely spherical shape. The entrapment efficiency (EE%) and drug loading capacity (DL%) determined with high performance liquid chromatogram (HPLC) by modified ultracentrifuge method were 97.78+/-0.37% and 18.92+/-0.07%, respectively. Differential scanning calorimetry (DSC) of Ins-MM-SLNs indicated no tendency of recrystallisation. The core-shell drug loading pattern of the SLNs was confirmed by fluorescence spectra and polyacrylamide gel electrophoresis (PAGE) which also proved the integrity of insulin after being incorporated into lipid carrier. The drug release behavior was studied by in situ and externally sink method and the release pattern of drug was found to follow Weibull and Higuchi equations. Results of stability evaluation showed a relatively long-term stability after storage at 4 degrees C for 6 months. In conclusion, SLNs with small particle size, excellent physical stability, high entrapment efficiency, good loading capacity for protein drug can be produced by this novel reverse micelle-double emulsion method in present study.

  3. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

    Science.gov (United States)

    Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

    2006-02-01

    Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

  4. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Joshy, K.S. [Department of Chemistry, CMS College Kottayam, Kerala (India); International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Sharma, Chandra P. [Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram, Kerala (India); Kalarikkal, Nandakumar [International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Sandeep, K. [International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Thomas, Sabu, E-mail: sabuchathukulam@yahoo.co.uk [International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686 560, Kerala (India); Pothen, Laly A. [Department of Chemistry, Bishop Moore College, Mavelikkara, Kerala (India)

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66 ± 12.22 nm and modified solid lipid nanoparticles showed an average size of 265.61 ± 80.44 nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. - Highlights: • SLN of AZT-SA, AZT-SA-AV was developed • Better drug loading efficacy • Good uptake.

  5. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells

    International Nuclear Information System (INIS)

    Joshy, K.S.; Sharma, Chandra P.; Kalarikkal, Nandakumar; Sandeep, K.; Thomas, Sabu; Pothen, Laly A.

    2016-01-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66 ± 12.22 nm and modified solid lipid nanoparticles showed an average size of 265.61 ± 80.44 nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. - Highlights: • SLN of AZT-SA, AZT-SA-AV was developed • Better drug loading efficacy • Good uptake

  6. Folate attached, curcumin loaded Fe_3O_4 nanoparticles: A novel multifunctional drug delivery system for cancer treatment

    International Nuclear Information System (INIS)

    Thu Huong, Le Thi; Nam, Nguyen Hoai; Doan, Do Hai; My Nhung, Hoang Thi; Quang, Bui Thuc; Nam, Pham Hong; Thong, Phan Quoc; Phuc, Nguyen Xuan; Thu, Ha Phuong

    2016-01-01

    Study and development of drug delivery nanosystem for cancer treatment are attracting great attention in recent years. In this work, we studied the role of folic acid as a targeting factor on magnetic nanoparticle Fe_3O_4 based curcumin loading nanosystem. Characteristics of the nanosystems were investigated by Fourier transform infrared spectroscopy (FTIR) and field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA) and vibrating sample magnetometer (VSM), while targeting role of folic was accessed in vivo on tumor bearing mice. The results showed that folate attached Fe_3O_4 based curcumin loading nanosystem has very small size and exhibits better targeting effect compared to the counterpart without folate. In addition, magnetic induction heating of this nanosystem evidenced its potential for cancer hyperthermia. - Highlights: • Folate attached, curcumin loaded Fe3O4 nanoparticles were prepared and characterized. • The NPs have high curcumin loading capacity and good ability for hyperthermia. • Folate shows its bioactivity of effectively targeting the NPs to tumor tissues. • Chemotherapy, hyperthermia and targeting factor are all well combined in the NPs.

  7. Quantification of drug-loaded magnetic nanoparticles in rabbit liver and tumor after in vivo administration

    Energy Technology Data Exchange (ETDEWEB)

    Tietze, Rainer; Jurgons, Roland; Lyer, Stefan; Schreiber, Eveline [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany); Wiekhorst, Frank; Eberbeck, Dietmar; Richter, Heike; Steinhoff, Uwe; Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Berlin (Germany); Alexiou, Christoph [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany)], E-mail: C.Alexiou@web.de

    2009-05-15

    Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is imminent in medical research, especially for treating cancer and vascular diseases. We used drug-labeled magnetic iron oxide nanoparticles, which were attracted to an experimental tumor in rabbits with an external magnetic field (magnetic drug targeting, MDT). Aim of this study was to detect and quantify the biodistribution of the magnetic nanoparticles by magnetorelaxometry. The study shows higher amount of nanoparticles in the tumor after intraarterial application and MDT compared to intravenous administration.

  8. Radioiodination of cyclin dependent kinase inhibitor Olomoucine loaded Fe rate at Au nanoparticle and evaluation of the therapeutic efficacy on cancerous cells

    Energy Technology Data Exchange (ETDEWEB)

    Takan, Gokhan; Guldu, Ozge Kozgus; Medine, Emin Ilker [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2017-06-01

    Magnetic nanoparticles have promising biomedical applications such as drug delivery, novel therapeutics and diagnostic imaging. Magnetic drug delivery combination works on the delivery of magnetic nanoparticles loaded with drug to the target tissue by means of an external magnetic field. Gold coated iron oxide (Fe rate at Au) nanoparticles can provide useful surface chemistry and biological reactivity. Covalent conjugation to the Fe rate at Au nanoparticles through cleavable linkages can be used to deliver drugs to tumor cells, then the drug can be released by an external. In this paper, purine based cyclin dependent kinases (CDKs) inhibitor Olomoucine (Olo) [2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine] was loaded on gold coated iron oxide (Fe rate at Au) nanoparticles and radiolabeled with {sup 131}I to combine magnetic targeted drug delivery and radiotherapy. Fe rate at Au nanoparticles were synthesized by microemulsion method. The characterization of nanoparticles was examined by TEM, VSM and XRD. Amine activation was utilized by cysteamine hydrochloride and then CDI was used for conjugation of Olomoucine. Antiproliferative effect and cytotoxicity of Olomoucine loaded Fe rate at Au nanoparticles (Fe rate at Au-Olo) were investigated on MCF7 and A549 cell lines. Proliferation rate was decreased while uptake of Fe rate at Au-Olo on both cell lines was high in comparison with Olomoucine. Also, enhanced incorporation ratio was observed under external magnetic field.

  9. Radioiodination of cyclin dependent kinase inhibitor Olomoucine loaded Fe rate at Au nanoparticle and evaluation of the therapeutic efficacy on cancerous cells

    International Nuclear Information System (INIS)

    Takan, Gokhan; Guldu, Ozge Kozgus; Medine, Emin Ilker

    2017-01-01

    Magnetic nanoparticles have promising biomedical applications such as drug delivery, novel therapeutics and diagnostic imaging. Magnetic drug delivery combination works on the delivery of magnetic nanoparticles loaded with drug to the target tissue by means of an external magnetic field. Gold coated iron oxide (Fe rate at Au) nanoparticles can provide useful surface chemistry and biological reactivity. Covalent conjugation to the Fe rate at Au nanoparticles through cleavable linkages can be used to deliver drugs to tumor cells, then the drug can be released by an external. In this paper, purine based cyclin dependent kinases (CDKs) inhibitor Olomoucine (Olo) [2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine] was loaded on gold coated iron oxide (Fe rate at Au) nanoparticles and radiolabeled with "1"3"1I to combine magnetic targeted drug delivery and radiotherapy. Fe rate at Au nanoparticles were synthesized by microemulsion method. The characterization of nanoparticles was examined by TEM, VSM and XRD. Amine activation was utilized by cysteamine hydrochloride and then CDI was used for conjugation of Olomoucine. Antiproliferative effect and cytotoxicity of Olomoucine loaded Fe rate at Au nanoparticles (Fe rate at Au-Olo) were investigated on MCF7 and A549 cell lines. Proliferation rate was decreased while uptake of Fe rate at Au-Olo on both cell lines was high in comparison with Olomoucine. Also, enhanced incorporation ratio was observed under external magnetic field.

  10. Solid Lipid Nanoparticles Loaded with Edaravone for Inner Ear Protection After Noise Exposure

    Directory of Open Access Journals (Sweden)

    Gang Gao

    2015-01-01

    Full Text Available Background: Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs, in steady noise-exposed guinea pigs. Methods: SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR threshold measurements, reactive oxygen species (ROS were detected in their cochleas with electron spin resonance (ESR, and outer hair cells (OHCs were counted with silvernitrate (AgNO 3 staining at 1, 4, and 6 days. Results: The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Conclusions: Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL.

  11. Development and Evaluation of Diclofenac Sodium Loaded-N-Trimethyl Chitosan Nanoparticles for Ophthalmic Use.

    Science.gov (United States)

    Asasutjarit, Rathapon; Theerachayanan, Thitaree; Kewsuwan, Prartana; Veeranodha, Sukitaya; Fuongfuchat, Asira; Ritthidej, Garnpimol C

    2015-10-01

    The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular inflammation is presently available in the market only as an eye drop solution. Due to its low occular bioavailability, it requires frequent application leading to low patients' compliance and quality of life. This study was conducted to develop formulations of DC loaded-N-trimethyl chitosan nanoparticles (DC-TMCNs) for ophthalmic use to improve ocular biavailabiltiy of DC. DC-TMCNs varied in formulation compositions were prepared using ionic gelation technique and evaluated for their physicochemical properties, drug release, eye irritation potential, and ophthalmic absorption of diclofenac sodium. N-Trimethyl chitosan (TMC) with a 49.8% degree of quaternization was synthesized and used for DC-TMCNs production. The obtained DC-TMCNs had particle size in a range of 130-190 nm with zeta potential values of +4 to +9 mV and drug entrapment efficiencies of more than 70% depending on the content of TMC and sodium tripolyphosphate (TPP). The optimized DC-TMCNs formulation contained TMC, DC, and TPP at a weight ratio of TMC/DC/TPP = 3:1:1. Their lyophilized product reconstituted with phosphate buffer solution pH 5.5 possessed a drug release pattern that fitted within the zero-order model. The eye irritation tests showed that DC-TMCNs were safe for ophthalmic use. The in vivo ophthalmic drug absorption study performed on rabbits indicated that DC-TMCNs could improve ophthalmic bioavailability of DC. Results of this study suggested that DC-TMCNs had potential for use as an alternative to conventional DC eye drops for ophthalmic inflammation treatment.

  12. Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Arora, R; Kuhad, A; Kaur, I P; Chopra, K

    2015-08-01

    Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA. In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats. Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats. The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance. © 2014 European Pain Federation - EFIC®

  13. Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients

    Directory of Open Access Journals (Sweden)

    Katayoun Derakhshandeh

    2010-07-01

    Full Text Available Katayoun Derakhshandeh1, Marzieh Soheili1, Simin Dadashzadeh2, Reza Saghiri31Department of Pharmaceutics, Faculty of Pharmacy, University of Medical Science, Kermanshah 67145-1673, Iran; 2Department of Pharmaceutics, Faculty of Pharmacy, Shaheed Beheshti University of Medical Science, Tehran, Iran; 3Deptartment of Biochemistry, Pasteur Institute, Tehran, IranAbstract: The purpose in this study was to investigate poly(ethylene glycol-modified poly (d,l-lactide-co-glycolide nanoparticles (PLGA-PEG-NPs loading 9-nitrocamptothecin (9-NC as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84, and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs have a better physicochemical characterization

  14. Evaluation of radiolabeled curcumin-loaded solid lipid nanoparticles usage as an imaging agent in liver-spleen scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Ayan, Arif Kursad [Department of Nuclear Medicine, Ataturk University, 25240 Erzurum (Turkey); Yenilmez, Ayse, E-mail: yenilmez2014@gmail.com [Department of Nanoscience and Nanoengineering, Ataturk University, 25240 Erzurum (Turkey); Department of Molecular Biology and Genetics, Erzurum Technical University, 25240 Erzurum (Turkey); Eroglu, Hayrettin [Department of Biomedical Engineering, Ataturk University, 25240 Erzurum (Turkey)

    2017-06-01

    Curcumin-loaded solid lipid nanoparticles (C-SLNs) were prepared using micro emulsion and ultrasonication methods in the first stage of this study to determine the role of C-SLN on liver-spleen scintigraphy. It was concluded that the curcumin that was encapsulated in solid lipid nanoparticles had a β′ polymorph structure according to the X-ray diffraction (XRD) analysis. İt was concluded that these particles were at nano scale according to the laser diffraction (LD) analysis. Fourier transform infrared spectroscopy (FT-IR) analysis suggested an interaction between the curcumin and the solid lipid matrix, and the curcumin was loaded on the solid lipid nanoparticles. Moreover, the particles were concluded to be spherical and at nanoscale according to the scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. On the other hand, thermogravimetric analysis (TGA) suggested that the curcumin loaded solid nanoparticles were stable against the temperature. C-SLNs were labeled with Technetium-99 m ({sup 99m}Tc) radioisotope in the second stage of the study, then using scintigraphic methods in-vivo studies were performed on New Zealand rabbit and made a comparison with Phytate colloid, routinely used in liver-spleen scintigraphy. After analyzing the images and the biological distributions obtained from the experiments, uptake was observed in the liver and the spleen. Following from the experiment results, {sup 99m}Tc-labeled C-SLNs was concluded to be a possible imaging agent. In particular, it could be a new radiopharmaceutical alternative to {sup 99m}Tc-labeled compounds that are used in liver and spleen imaging in colloid scintigraphy. - Graphıcal abstract: Display Omitted - Hıghlıghts: • Curcumin-loaded solid lipid nanoparticles (C-SLNs) were prepared and examined characterization studies. • The C-SLNs were labeled with {sup 99m}Tc and made a comparison with Phytate colloid, routinely used in liver-spleen scintigraphy. • In vivo

  15. A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells

    Science.gov (United States)

    Rashidi, Ladan; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Atashi, Amir; Rostami, Khosrow; Gangi, Fariba; Fallahpour, Masoud; Tahouri, Mohammad Taher

    2014-03-01

    In this study, the effects of intracellular delivery of various concentrations of gallic acid (GA) as a semistable antioxidant, gallic acid-loaded mesoporous silica nanoparticles (MSNs-GA), and cellular uptake of nanoparticles into Caco-2 cells were investigated. MSNs were synthesized and loaded with GA, then characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, N2 adsorption isotherms, X-ray diffraction, and thermal gravimetric analysis. The cytotoxicity of MSNs and MSNs-GA at low and high concentrations were studied by means of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry. MSNs did not show significant toxicity in various concentrations (0-500 μg/ml) on Caco-2 cells. For MSNs-GA, cell viability was reduced as a function of incubation time and different concentrations of nanoparticles. The in vitro GA release from MSNs-GA exhibited the same antitumor properties as free GA on Caco-2 cells. Flow cytometry results confirmed those obtained using MTT assay. TEM and fluorescent microscopy confirmed the internalization of MSNs by Caco-2 cells through nonspecific cellular uptake. MSNs can easily internalize into Caco-2 cells without deleterious effects on cell viability. The cell viability of Caco-2 cells was affected during MSNs-GA uptake. MSNs could be designed as suitable nanocarriers for antioxidants delivery.

  16. Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent.

    Science.gov (United States)

    Ilk, Sedef; Saglam, Necdet; Özgen, Mustafa

    2017-08-01

    Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 ± 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture.

  17. Antibacterial Activity of Fructus forsythia Essential Oil and the Application of EO-Loaded Nanoparticles to Food-Borne Pathogens

    Directory of Open Access Journals (Sweden)

    Na Guo

    2016-10-01

    Full Text Available Fructus forsythia essential oil (FEO with excellent antibacterial activity was rarely reported. The objective of the present study was to investigate the antibacterial activity and the antibacterial mechanism of FEO against two food-borne pathogenic bacteria, Escherichia coli (E. coli and Staphylococcus aureus (S. aureus in vitro. When treated FEO, the zones of inhibition (ZOI of E. coli (20.5 ± 0.25 mm and S. aureus (24.3 ± 0.21 mm were much larger than control (p < 0.05. The minimum inhibitory concentrations (MICs of FEO were 3.13 mg/mL and 1.56 mg/mL for E. coli and S. aureus, respectively. The antibacterial mechanism of FEO against E. coil was due to the changes in permeability and integrity of cell membrane leading to the leakage of nucleic acids and proteins. With the superior antibacterial activity of FEO, the nano-encapsulation method has been applied in FEO. When compared to FEO and blank chitosan nanoparticles, FEO-loaded nanoparticles (chitosan to FEO of 1:1 can effectively inhibit the growth of E. coil above 90% at room temperature. It is necessary to consider that FEO and FEO-loaded nanoparticles will become promising antibacterial additives for food preservative, cosmetic, and pharmaceutical applications.

  18. Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

    Science.gov (United States)

    Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

    2014-12-01

    The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

  19. Designing structural features of novel benznidazole-loaded cationic nanoparticles for inducing slow drug release and improvement of biological efficacy.

    Science.gov (United States)

    Dos Santos-Silva, Alaine M; de Caland, Lilia B; de S L Oliveira, Ana Luíza C; de Araújo-Júnior, Raimundo F; Fernandes-Pedrosa, Matheus F; Cornélio, Alianda Maira; da Silva-Júnior, Arnóbio A

    2017-09-01

    Several polymers have been investigated for producing cationic nanocarriers due to their ability to cross biological barriers. Polycations such as copolymers of polymethylmethacrylate are highlighted due to their biocompatibility and low toxicity. The purpose of this study was to produce small and narrow-sized cationic nanoparticles able to overcome cell membranes and improve the biological activity of benznidazole (BNZ) in normal and cancer cells. The effect of composition and procedure parameters of the used emulsification-solvent evaporation method were controlled for this purpose. The experimental approach included particle size, polydispersity index, zeta potential, atomic force microscopy (AFM), attenuated total reflectance Fourier transforms infrared spectroscopy (ATR- FTIR), drug loading efficiency, and physical stability assays. Spherical and stable (over six weeks) sub 150nm cationic nanoparticles were optimized, with the encapsulation efficiency >80%. The used drug/copolymer ratio modulated the slow drug release, which was adjusted by the parabolic diffusion mathematical model. In addition, the ability of the cationic nanoparticles improve the BNZ uptake in the normal kidney cells (HEK 293) and the human colorectal cancer cells (HT 29) demonstrate that this novel BNZ-loaded cationic has great potential as a chemotherapeutic application of benznidazole. Copyright © 2017. Published by Elsevier B.V.

  20. Multimodal nanoporous silica nanoparticles functionalized with aminopropyl groups for improving loading and controlled release of doxorubicin hydrochloride.

    Science.gov (United States)

    Wang, Xin; Li, Chang; Fan, Na; Li, Jing; He, Zhonggui; Sun, Jin

    2017-09-01

    The purpose of this study was to develop amino modified multimodal nanoporous silica nanoparticles (M-NSNs-NH 2 ) loaded with doxorubicin hydrochloride (DOX), intended to enhance the drug loading capacity and to achieve controlled release effect. M-NSNs were functionalized with aminopropyl groups through post-synthesis. The contribution of large pore sizes and surface chemical groups on DOX loading and release were systemically studied using transmission electron microscope (TEM), nitrogen adsorption/desorption measurement, Fourier transform infrared spectroscopy (FTIR), zeta potential analysis, X-ray photoelectron spectroscopy (XPS) and ultraviolet spectrophotometer (UV). The results demonstrated that the NSNs were functionalized with aminopropyl successfully and the DOX molecules were adsorbed inside the nanopores by the hydrogen bonding. The release performance indicated that DOX loaded M-NSNs significantly controlled DOX release, furthermore DOX loaded M-NSNs-NH 2 performed slower controlled release, which was mainly attributed to its stronger hydrogen bonding forces. As expected, we developed a novel carrier with high drug loading capacity and controlled release for DOX. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation.

    Science.gov (United States)

    Cui, Fude; Shi, Kai; Zhang, Liqiang; Tao, Anjin; Kawashima, Yoshiaki

    2006-08-28

    Biodegradable nanoparticles loaded with insulin-phospholipid complex were prepared by a novel reverse micelle-solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of insulin, and biodegradable polymers as carrier materials to control drug release. Solubilization study, IR and X-ray diffraction analysis were employed to prove the complex formation. The effects of key parameters such as polymer/SPC weight ratio, organic phase and polymer type on the properties of the nanoparticles were investigated. Spherical particles of 200 nm mean diameter and a narrow size distribution were obtained under optimal conditions. The drug entrapment efficiency was up to 90%. The in vitro drug release was characterized by an initial burst and subsequent delayed release in both pH 6.8 and pH 1.2 dissolution mediums. The specific modality of drug release, i.e., free or SPC-combined, was investigated in the aid of ultracentrifugation and ultrafiltration methods. The influence of polymer type on the drug release was also discussed. The pharmacological effects of the nanoparticles made of PLGA 50/50 (Av.Mw 9500) were further evaluated to confirm their potential suitability for oral delivery. Intragastric administration of the 20 IU/kg nanoparticles reduced fasting plasma glucose levels to 57.4% within the first 8 h of administration and this continued for 12 h. PK/PD analysis indicated that 7.7% of oral bioavailability relative to subcutaneous injection was obtained.

  2. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

    Science.gov (United States)

    Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

    2011-01-01

    Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

  3. Synthesis and characterization of Cu/Ag nanoparticle loaded mullite nanocomposite system: A potential candidate for antimicrobial and therapeutic applications.

    Science.gov (United States)

    Kar, S; Bagchi, B; Kundu, B; Bhandary, S; Basu, R; Nandy, P; Das, S

    2014-11-01

    Microbial resistance to antibiotics has triggered the development of nanoscale materials as an alternative strategy. To stabilize these particles an inert support is needed. Porous nanomullite developed by sol-gel route is loaded with copper and silver nanoparticle by simple adsorption method. These nanocomposites are characterized using XRD, FTIR, TEM, SEM, EDAX and UV-visible spectrophotometer. Antibacterial activity of these nanocomposites against Gram positive and Gram negative bacteria are performed by bactericidal kinetics, flow cytometry and MTT assay. The underlying mechanisms behind the antimicrobial property and cell death are also investigated by EPR spectroscopy, intracellular ROS measurement and β-galactosidase assay. The cytocompatibility of the nanocomposites is investigated by cell viability (MTT), proliferation (Alamar blue) and wound healing assay of mammalian fibroblast cell line. Nanocomposites show a fairly uniform distribution of metal nanoparticle within mullite matrix. They show excellent antibacterial activity. Metal ions/nanoparticle is found to be released from the materials (CM and SM). Treated cells manifested high intracellular oxidative stress and β-galactosidase activity in the growth medium. The effect of nanocomposites on mammalian cell line depends on exposure time and concentration. The scratch assay shows normal cell migration with respect to control. The fabricated nanoparticles possess diverse antimicrobial mechanism and exhibit good cytocompatibility along with wound healing characteristics in mouse fibroblast cell line (L929). The newly synthesized materials are promising candidates for the development of antimicrobial ceramic coatings for biomedical devices and therapeutic applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.

    Science.gov (United States)

    Xin, Yuxuan; Qi, Qi; Mao, Zhenmin; Zhan, Xiaoping

    2017-08-07

    A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. miRNA-218-loaded carboxymethyl chitosan - Tocopherol nanoparticle to suppress the proliferation of gastrointestinal stromal tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Lin; Wang, Ming; Zhao, Wen-Yi; Zhang, Zi-Zhen; Tang, De-Feng; Zhang, Ye-Qian [Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Cao, Hui, E-mail: caohui10281@163.com [Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Zhang, Zhi-Gang, E-mail: zhangzhiganggz@hotmail.com [State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240 (China)

    2017-03-01

    Gastrointestinal stromal tumors (GIST) are one of the most common forms of mesenchymal cancers of the gastrointestinal tract. Although chemotherapeutic drugs inhibited the proliferation of GIST, however, sizable proportion of people developed resistance and therefore difficult to treat. In the present study, O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated into stable polymeric nanoparticles. The main aim of present study was to increase the therapeutic efficacy of miR-218 in GIST. The mean size of nanoparticles was ~ 110 nm with a spherical shape. The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. The miR-218 NP inhibited the cell invasion and promoted the apoptosis of GIST cancer cells. In the present study, we have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay. These findings collectively suggest the miR-218 loaded nanoparticle by virtue of effective transfection could act as a tumor suppressor miRNA in the treatment of GIST. - Highlights: • O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated in nanoparticles. • The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. • We have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay.

  6. Analytical validation of an ultraviolet-visible procedure for determining lutein concentration and application to lutein-loaded nanoparticles.

    Science.gov (United States)

    Silva, Jéssica Thaís do Prado; Silva, Anderson Clayton da; Geiss, Julia Maria Tonin; de Araújo, Pedro Henrique Hermes; Becker, Daniela; Bracht, Lívia; Leimann, Fernanda Vitória; Bona, Evandro; Guerra, Gustavo Petri; Gonçalves, Odinei Hess

    2017-09-01

    Lutein is a carotenoid presenting known anti-inflammatory and antioxidant properties. Lutein-rich diets have been associated with neurological improvement as well as reduction of the risk of vision loss due to Age-Related Macular Degeneration (AMD). Micro and nanoencapsulation have demonstrated to be effective techniques in protecting lutein against degradation and also in improving its bioavailability. However, actual lutein concentration inside the capsules and encapsulation efficiency are key parameters that must be precisely known when designing in vitro and in vivo tests. In this work an analytical procedure was validated for the determination of the actual lutein content in zein nanoparticles using ultraviolet-visible spectroscopy. Method validation followed the International Conference on Harmonisation (ICH) guidelines which evaluate linearity, detection limit, quantification limit, accuracy and precision. The validated methodology was applied to characterize lutein-loaded nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Permanent electric dipole moments of PtX (X = H, F, Cl, Br, and I) by the composite approach

    Science.gov (United States)

    Deng, Dan; Lian, Yongqin; Zou, Wenli

    2017-11-01

    Using the FPD composite approach of Peterson et. al. we calculate the permanent electric dipole moments of PtX (X = H, F, Cl, Br, and I) at the equilibrium geometries of their ground states. The dipole moment of PtF is estimated to be 3.421 Debye, being very close to the experimental value of 3.42(6) Debye. This research also suggests the ordering of dipole moments of PtX being proportional to the electronegativity of X.

  8. Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids

    Directory of Open Access Journals (Sweden)

    Annkathrin Hornung

    2015-09-01

    Full Text Available Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT employing superparamagnetic iron oxide nanoparticles (SPION loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPIONMTO are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo.

  9. The effect of the triblock properties on the morphologies and photophysical properties of nanoparticle loaded with carboxylic dendrimer phthalocyanine

    Science.gov (United States)

    Lv, Huafei; Chen, Zhe; Yu, Xinxin; Pan, Sujuan; Zhang, Tiantian; Xie, Shusen; Yang, Hongqin; Peng, Yiru

    2016-09-01

    Photodynamic therapy (PDT) is an emerging alternative treatment for various cancers and age-related macular degeneration. Phthalocyanines (Pcs) and their substituted derivatives are under intensive investigation as the second generation photosensitizers. A big challenge for the application of Pcs is poor solubility and limited accumulation in the tumor tissues, which severely reduced its PDT efficacy. Nano-delivery systems such as polymeric micelles are promising tools for increasing the solubility and improving delivery efficiency of Pcs for PDT application. In this paper, nanoparticles of amphiphilic triblock copolymer poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) were developed to encapsulate 1-2 generation carboxylic poly (benzyl aryl ether) dendrimer. The morphologies and photophysical properties of polymeric nanoparticles loaded with 1-2 generation dendritic phthalocyanines (G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m) were studied by AFM, UV/Vis and fluorescent spectroscopic method. The morphologies of self-assembled PLL-PEG-PLL aggregates exhibited concentration dependence. Its morphologies changed from cocoon-like to spheral. The diameters of G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m were in the range of 33-147 nm, increasing with the increase of the concentration of PLL-PEG-PLL. The morphologies of G2-ZnPc(COOH)16/m also changed from cocoon-like to sphere with the increase of the concentration of PLL-PEG-PLL. It was found that, the no obviously Q change was observed between the free phthalocyanines and nanoparticles. The fluorescence intensity of polymer nanoparticles were higher enhanced compared with free dendritic phthalocyanines. The dendrimer phthalocyanine loaded with poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) presented suitable physical stability, improved photophysical properties suggesting it may be considered as a promising formulation for PDT.

  10. Engineering of budesonide-loaded lipid-polymer hybrid nanoparticles using a quality-by-design approach.

    Science.gov (United States)

    Leng, Donglei; Thanki, Kaushik; Fattal, Elias; Foged, Camilla; Yang, Mingshi

    2017-08-25

    Chronic obstructive pulmonary disease (COPD) is a complex disease, characterized by persistent airflow limitation and chronic inflammation. The purpose of this study was to design lipid-polymer hybrid nanoparticles (LPNs) loaded with the corticosteroid, budesonide, which could potentially be combined with small interfering RNA (siRNA) for COPD management. Here, we prepared LPNs based on the biodegradable polymer poly(dl-lactic-co-glycolic acid) (PLGA) and the cationic lipid dioleyltrimethylammonium propane (DOTAP) using a double emulsion solvent evaporation method. A quality-by-design (QbD) approach was adopted to define the optimal formulation parameters. The quality target product profile (QTPP) of the LPNs was identified based on risk assessment. Two critical formulation parameters (CFPs) were identified, including the theoretical budesonide loading and the theoretical DOTAP loading. The CFPs were linked to critical quality attributes (CQAs), which included the intensity-based hydrodynamic particle diameter (z-average), the polydispersity index (PDI), the zeta-potential, the budesonide encapsulation efficiency, the actual budesonide loading and the DOTAP encapsulation efficiency. A response surface methodology (RSM) was applied for the experimental design to evaluate the influence of the CFPs on the CQAs, and to identify the optimal operation space (OOS). All nanoparticle dispersions displayed monodisperse size distributions (PDIPLGA increases when increasing the initial amount of budesonide. The OOS was modeled by applying the QTPP. The OOS had a budesonide encapsulation efficiency higher than 30%, a budesonide loading above 15μg budesonide/mg PLGA, a zeta-potential higher than 35mV and a DOTAP encapsulation efficiency above 50%. This study shows the importance of systematic formulation design for understanding the effect of formulation parameters on the characteristics of LPNs, eventually resulting in the identification of an OOS. Copyright © 2017 Elsevier B

  11. The sweet side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation

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    Antonio eInforzato

    2013-01-01

    Full Text Available Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs that recognise pathogen associated molecular patterns (PAMPs and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation.Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.

  12. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

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    Ji P

    2016-03-01

    Full Text Available Peng Ji, Tong Yu, Ying Liu, Jie Jiang, Jie Xu, Ying Zhao, Yanna Hao, Yang Qiu, Wenming Zhao, Chao WuCollege of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People’s Republic of ChinaAbstract: Naringenin (NRG, a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only ~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle

  13. Poly ɛ-caprolactone nanoparticles loaded with Uncaria tomentosa extract: preparation, characterization, and optimization using the Box–Behnken design

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    Ribeiro, Ana Ferreira; de Oliveira Rezende, Ricardo Leite; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

    2013-01-01

    Purpose The aim of this research was to develop and optimize a process for obtaining poly ɛ-caprolactone (PCL) nanoparticles loaded with Uncaria tomentosa (UT) extract. Methods Nanoparticles were produced by the oil-in-water emulsion solvent evaporation method. Preliminary experiments determined the initial conditions of the organic phase (OP) and of the aqueous phase (AP) that would be utilized for this study. Ultimately, a three-factor three-level Box–Behnken design (BBD) was employed during the optimization process. PCL and polyvinyl alcohol (PVA) concentrations (X1 and X2, respectively) and the AP/OP volume ratio (X3) were the independent variables studied, while entrapment efficiency (Y1), particle mean diameter (Y2), polydispersity (Y3), and zeta potential (Y4) served as the evaluated responses. Results Preliminary experiments revealed that the optimal initial conditions for the preparation of nanoparticles were as follows: OP composed of 5 mL ethyl acetate/acetone (3/2) mixture containing UT extract and PCL, and an AP of buffered PVA (pH 7.5) solution. Statistical analysis of the BBD results indicated that all of the studied factors had significant effects on the responses Y1, Y2, and Y4, and these effects are closely described or fitted by regression equations. Based on the obtained models and the selected desirability function, the nanoparticles were optimized to maximize Y1 and minimize Y2. These optimal conditions were achieved using 3% (w/v) PCL, 1% (w/v) PVA, and an AP/OP ratio of 1.7, with predicted values of 89.1% for Y1 and 280 nm for Y2. Another batch was produced under the same optimal conditions. The entrapment efficiency of this new batch was measured at 81.6% (Y1) and the particles had a mean size of 247 nm (Y2) and a polydispersity index of 0.062 (Y3). Conclusion This investigation obtained UT-loaded nanoparticle formulations with desired characteristics. The BBD approach was a useful tool for nanoparticle development and optimization, and

  14. UPA-sensitive ACPP-conjugated nanoparticles for multi-targeting therapy of brain glioma.

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    Zhang, Bo; Zhang, Yujie; Liao, Ziwei; Jiang, Ting; Zhao, Jingjing; Tuo, Yanyan; She, Xiaojian; Shen, Shun; Chen, Jun; Zhang, Qizhi; Jiang, Xinguo; Hu, Yu; Pang, Zhiqing

    2015-01-01

    Now it is well evidenced that tumor growth is a comprehensive result of multiple pathways, and glioma parenchyma cells and stroma cells are closely associated and mutually compensatory. Therefore, drug delivery strategies targeting both of them simultaneously might obtain more promising therapeutic benefits. In the present study, we developed a multi-targeting drug delivery system modified with uPA-activated cell-penetrating peptide (ACPP) for the treatment of brain glioma (ANP). In vitro experiments demonstrated nanoparticles (NP) decorated with cell-penetrating peptide (CPP) or ACPP could significantly improve nanoparticles uptake by C6 glioma cells and nanoparticles penetration into glioma spheroids as compared with traditional NP and thus enhanced the therapeutic effects of its payload when paclitaxel (PTX) was loaded. In vivo imaging experiment revealed that ANP accumulated more specifically in brain glioma site than NP decorated with or without CPP. Brain slides further showed that ACPP contributed to more nanoparticles accumulation in glioma site, and ANP could co-localize not only with glioma parenchyma cells, but also with stroma cells including neo-vascular cells and tumor associated macrophages. The pharmacodynamics results demonstrated ACPP could significantly improve the therapeutic benefits of nanoparticles by significantly prolonging the survival time of glioma bearing mice. In conclusion, the results suggested that nanoparticles modified with uPA-sensitive ACPP could reach multiple types of cells in glioma tissues and provide a novel strategy for glioma targeted therapy.

  15. Application of quality by design approach to optimize process and formulation parameters of rizatriptan loaded chitosan nanoparticles

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    Ajinath Eknath Shirsat

    2015-01-01

    Full Text Available The purpose of present study was to optimize rizatriptan (RZT chitosan (CS nanoparticles using ionic gelation method by application of quality by design (QbD approach. Based on risk assessment, effect of three variables, that is CS %, tripolyphosphate % and stirring speed were studied on critical quality attributes (CQAs; particle size and entrapment efficiency. Central composite design (CCD was implemented for design of experimentation with 20 runs. RZT CS nanoparticles were characterized for particle size, polydispersity index, entrapment efficiency, in-vitro release study, differential scanning calorimetric, X-ray diffraction, scanning electron microscopy (SEM. Based on QbD approach, design space (DS was optimized with a combination of selected variables with entrapment efficiency > 50% w/w and a particle size between 400 and 600 nm. Validation of model was performed with 3 representative formulations from DS for which standard error of − 0.70-3.29 was observed between experimental and predicted values. In-vitro drug release followed initial burst release 20.26 ± 2.34% in 3-4 h with sustained drug release of 98.43 ± 2.45% in 60 h. Lower magnitude of standard error for CQAs confirms the validation of selected CCD model for optimization of RZT CS nanoparticles. In-vitro drug release followed dual mechanism via, diffusion and polymer erosion. RZT CS nanoparticles were prepared successfully using QbD approach with the understanding of the high risk process and formulation parameters involved and optimized DS with a multifactorial combination of critical parameters to obtain predetermined RZT loaded CS nanoparticle specifications.

  16. Antimicrobial and cell viability measurement of bovine serum albumin capped silver nanoparticles (Ag/BSA) loaded collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film.

    Science.gov (United States)

    Bakare, Rotimi; Hawthrone, Samantha; Vails, Carmen; Gugssa, Ayele; Karim, Alamgir; Stubbs, John; Raghavan, Dharmaraj

    2016-03-01

    Bacterial infection of orthopedic devices has been a major concern in joint replacement procedures. Therefore, this study is aimed at formulating collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film loaded with bovine serum albumin capped silver nanoparticles (Ag/BSA NPs) to inhibit bacterial growth while retaining/promoting osteoblast cells viability. The nanoparticles loaded collagen immobilized PHBV film was characterized for its composition by X-ray Photoelectron Spectroscopy and Anodic Stripping Voltammetry. The extent of loading of Ag/BSA NPs on collagen immobilized PHBV film was found to depend on the chemistry of the functionalized PHBV film and the concentration of Ag/BSA NPs solution used for loading nanoparticles. Our results showed that more Ag/BSA NPs were loaded on higher molecular weight collagen immobilized PHEMA-g-PHBV film. Maximum loading of Ag/BSA NPs on collagen immobilized PHBV film was observed when 16ppm solution was used for adsorption studies. Colony forming unit and optical density measurements showed broad antimicrobial activity towards Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa at significantly lower concentration i.e., 0.19 and 0.31μg/disc, compared to gentamicin and sulfamethoxazole trimethoprim while MTT assay showed that released nanoparticles from Ag/BSA NPs loaded collagen immobilized PHBV film has no impact on MCTC3-E1 cells viability. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: preparation, cellular uptake, tissue distribution, and anticancer activity

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    Duan YR

    2012-07-01

    Full Text Available Peihao Yin,1,* Yan Wang,1,* YanYan Qiu,1 LiLi Hou,1 Xuan Liu,1 Jianmin Qin,1 Yourong Duan,2 Peifeng Liu,2 Ming Qiu,3 Qi Li11Department of Clinical Oncology, Putuo Hospital and Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Shanghai Cancer Institute, Jiaotong University, Shanghai, China; 3Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China *These authors contributed equally to this workBackground: Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs made of methoxy polyethylene glycol (mPEG, polylactic-co-glycolic acid (PLGA, poly-L-lysine (PLL, and cyclic arginine-glycine-aspartic acid (cRGD loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs, in SW620 colon cancer-bearing mice.Methods: BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested.Results: BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In the SW620

  18. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats

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    Yang X

    2012-04-01

    Full Text Available Xinxin Yang1*, Ruiyuan Zheng2*, Yunpeng Cai2, Meiling Liao2, Weien Yuan1,2, Zhenguo Liu11Department of Neurology, Xinhua Hospital (affiliated to Shanghai Jiaotong University School of Medicine, 2School of Pharmacy, Shanghai Jiaotong University, Shanghai, People's Republic of China*Xinxin Yang and Ruiyuan Zheng contributed equally to this workBackground: Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood.Methods: In this study, we prepared levodopa methyl ester (LDME/benserazide-loaded nanoparticles, which can release LDME and benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus benserazide or the same dose of LDME/benserazide-loaded nanoparticles. Apomorphine-induced rotations and abnormal involuntary movements (AIMs were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay.Results: Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus benserazide or LDME/benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20

  19. Formulation and in-vitro evaluation of pantoprazole loaded pH-sensitive polymeric nanoparticles

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    Ahmed Mohammed Nasef

    2017-12-01

    Our results suggested that nanoprecipitation method is effective to produce pH-sensitive polymeric nanoparticles, which can be used as a delivery system for acid labile drug (Pantoprazole to avoid its degradation in acidic medium of the stomach.

  20. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.