Determination of the Optimum Conditions for Production of Chitosan Nanoparticles

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A. Dustgani

2007-12-01

Full Text Available Bioedegradable nanoparticles are intensively investigated for their potential applications in drug delivery systems. Being a biocompatible and biodegradable polymer, chitosan holds great promise for use in this area. This investigation was concerned with determination and optimization of the effective parameters involved in the production of chitosan nanoparticles using ionic gelation method. Studied variables were concentration and pH of the chitosan solution, the ratio of chitosan to sodium tripolyphosphate therein and the molecular weight of chitosan. For this purpose, Taguchistatistical method was used for design of experiments in three levels. The size of chitosan nanoparticle was determined using laser light scattering. The experimental results showed that concentration of chitosan solution was the most important parameter and chitosan molecular weight the least effective parameter. The optimum conditions for preparation of nanoparticles were found to be 1 mg/mL chitosan solution with pH=5, chitosan to sodium tripolyphosphate ratio of 3 and chitosan molecular weight of 200,000 daltons. The average nanoparticle size at optimum conditions was found to be about 150 nm.

Chitosan Based Self-Assembled Nanoparticles in Drug Delivery

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Javier Pérez Quiñones

2018-02-01

Full Text Available Chitosan is a cationic polysaccharide that is usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine. It is biocompatible, biodegradable, mucoadhesive, and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures, and illustrates the state of the art of their application in drug delivery.

Surface modification of protein enhances encapsulation in chitosan nanoparticles

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Koyani, Rina D.; Andrade, Mariana; Quester, Katrin; Gaytán, Paul; Huerta-Saquero, Alejandro; Vazquez-Duhalt, Rafael

2018-04-01

Chitosan nanoparticles have a huge potential as nanocarriers for environmental and biomedical purposes. Protein encapsulation in nano-sized chitosan provides protection against inactivation, proteolysis, and other alterations due to environmental conditions, as well as the possibility to be targeted to specific tissues by ligand functionalization. In this work, we demonstrate that the chemical modification of the protein surface enhances the protein loading in chitosan nanocarriers. Encapsulation of green fluorescent protein and the cytochrome P450 was studied. The increase of electrostatic interactions between the free amino groups of chitosan and the increased number of free carboxylic groups in the protein surface enhance the protein loading, protein retention, and, thus, the enzymatic activity of chitosan nanoparticles. The chemical modification of protein surface with malonic acid moieties reduced drastically the protein isoelectric point increasing the protein interaction with the polycationic biomaterial and chitosan. The chemical modification of protein does not alter the morphology of chitosan nanoparticles that showed an average diameter of 18 nm, spheroidal in shape, and smooth surfaced. The strategy of chemical modification of protein surface, shown here, is a simple and efficient technique to enhance the protein loading in chitosan nanoparticles. This technique could be used for other nanoparticles based on polycationic or polyanionic materials. The increase of protein loading improves, doubtless, the performance of protein-loaded chitosan nanoparticles for biotechnological and biomedical applications.

In Situ Mineralization of Magnetite Nanoparticles in Chitosan Hydrogel

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Wang, Yongliang; Li, Baoqiang; Zhou, Yu; Jia, Dechang

2009-09-01

Based on chelation effect between iron ions and amino groups of chitosan, in situ mineralization of magnetite nanoparticles in chitosan hydrogel under ambient conditions was proposed. The chelation effect between iron ions and amino groups in CS-Fe complex, which led to that chitosan hydrogel exerted a crucial control on the magnetite mineralization, was proved by X-ray photoelectron spectrum. The composition, morphology and size of the mineralized magnetite nanoparticles were characterized by X-ray diffraction, Raman spectroscopy, transmission electron microscopy and thermal gravity. The mineralized nanoparticles were nonstoichiometric magnetite with a unit formula of Fe2.85O4 and coated by a thin layer of chitosan. The mineralized magnetite nanoparticles with mean diameter of 13 nm dispersed in chitosan hydrogel uniformly. Magnetization measurement indicated that superparamagnetism behavior was exhibited. These magnetite nanoparticles mineralized in chitosan hydrogel have potential applications in the field of biotechnology. Moreover, this method can also be used to synthesize other kinds of inorganic nanoparticles, such as ZnO, Fe2O3 and hydroxyapatite.

In Situ Mineralization of Magnetite Nanoparticles in Chitosan Hydrogel

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Wang Yongliang

2009-01-01

Full Text Available Abstract Based on chelation effect between iron ions and amino groups of chitosan, in situ mineralization of magnetite nanoparticles in chitosan hydrogel under ambient conditions was proposed. The chelation effect between iron ions and amino groups in CS–Fe complex, which led to that chitosan hydrogel exerted a crucial control on the magnetite mineralization, was proved by X-ray photoelectron spectrum. The composition, morphology and size of the mineralized magnetite nanoparticles were characterized by X-ray diffraction, Raman spectroscopy, transmission electron microscopy and thermal gravity. The mineralized nanoparticles were nonstoichiometric magnetite with a unit formula of Fe2.85O4and coated by a thin layer of chitosan. The mineralized magnetite nanoparticles with mean diameter of 13 nm dispersed in chitosan hydrogel uniformly. Magnetization measurement indicated that superparamagnetism behavior was exhibited. These magnetite nanoparticles mineralized in chitosan hydrogel have potential applications in the field of biotechnology. Moreover, this method can also be used to synthesize other kinds of inorganic nanoparticles, such as ZnO, Fe2O3and hydroxyapatite.

Reverse Transfection Using Gold Nanoparticles

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Yamada, Shigeru; Fujita, Satoshi; Uchimura, Eiichiro; Miyake, Masato; Miyake, Jun

Reverse transfection from a solid surface has the potential to deliver genes into various types of cell and tissue more effectively than conventional methods of transfection. We present a method for reverse transfection using a gold colloid (GC) as a nanoscaffold by generating nanoclusters of the DNA/reagentcomplex on a glass surface, which could then be used for the regulation of the particle size of the complex and delivery of DNA into nuclei. With this method, we have found that the conjugation of gold nanoparticles (20 nm in particle size) to the pEGFP-N1/Jet-PEI complex resulted in an increase in the intensity of fluorescence of enhanced green fluorescent protein (EGFP) (based on the efficiency of transfection) from human mesenchymal stem cells (hMSCs), as compared with the control without GC. In this manner, we constructed a method for reverse transfection using GC to deliver genes into the cells effectively.

Gold nanoparticles stabilized by chitosan

International Nuclear Information System (INIS)

Geraldes, Adriana N.; Oliveira, Maria Jose A.; Silva, Andressa A. da; Leal, Jessica; Batista, Jorge G.S.; Lugao, Ademar B.

2015-01-01

In our laboratory has been growing the interest in studying gold nanoparticles and for this reason, the aim of this work is report the first results of the effect of chitosan as stabilizer in gold nanoparticle formulation. AuNPs were synthesized by reducing hydrogen tetrachloroaurate (HAuCl 4 ) using NaBH 4 or gamma irradiation (25kGy) as reduction agent. The chitosan (3 mol L -1 ) was added at 0.5; 1.0 and 1.5 mL. The gold nanoparticles were characterized by UV-Vis absorption spectroscopy, X-ray diffraction (XRD) and Transmission electron microscopy (TEM). Their physical stability was determined using a UV-Vis spectrophotometer over one week during storage at room temperature. Absorption measurements indicated that the plasmon resonance wavelength appears at a wavelength around 530 nm. Has been observed that Chitosan in such quantities were not effective in stabilizing the AuNPs. (author)

Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model

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Hu, Yu-Lan; Qi, Wang; Han, Feng; Shao, Jian-Zhong; Gao, Jian-Qing

2011-01-01

Background Although there are a number of reports regarding the toxicity evaluation of inorganic nanoparticles, knowledge on biodegradable nanomaterials, which have always been considered safe, is still limited. For example, the toxicity of chitosan nanoparticles, one of the most widely used drug/gene delivery vehicles, is largely unknown. In the present study, the zebrafish model was used for a safety evaluation of this nanocarrier. Methods Chitosan nanoparticles with two particle sizes were prepared by ionic cross-linking of chitosan with sodium tripolyphosphate. Chitosan nanoparticles of different concentrations were incubated with zebrafish embryos, and ZnO nanoparticles were used as the positive control. Results Embryo exposure to chitosan nanoparticles and ZnO nanoparticles resulted in a decreased hatching rate and increased mortality, which was concentration-dependent. Chitosan nanoparticles at a size of 200 nm caused malformations, including a bent spine, pericardial edema, and an opaque yolk in zebrafish embryos. Furthermore, embryos exposed to chitosan nanoparticles showed an increased rate of cell death, high expression of reactive oxygen species, as well as overexpression of heat shock protein 70, indicating that chitosan nanoparticles can cause physiological stress in zebrafish. The results also suggest that the toxicity of biodegradable nanocarriers such as chitosan nanoparticles must be addressed, especially considering the in vivo distribution of these nanoscaled particles. Conclusion Our results add new insights into the potential toxicity of nanoparticles produced by biodegradable materials, and may help us to understand better the nanotoxicity of drug delivery carriers. PMID:22267920

Advances in preparation and characterization of chitosan nanoparticles for therapeutics.

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Chandra Hembram, Krushna; Prabha, Shashi; Chandra, Ramesh; Ahmed, Bahar; Nimesh, Surendra

2016-01-01

Polymers have been largely explored for the preparation of nanoparticles due to ease of preparation and modification, large gene/drug loading capacity, and biocompatibility. Various methods have been adapted for the preparation and characterization of chitosan nanoparticles. Focus on the different methods of preparation and characterization of chitosan nanoparticles. Detailed literature survey has been done for the studies reporting various methods of preparation and characterization of chitosan nanoparticles. Published database suggests of several methods which have been developed for the preparation and characterization of chitosan nanoparticles as per the application.

Functional gene silencing mediated by chitosan/siRNA nanocomplexes

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Ji, A M; Su, D; Che, O; Li, W S; Sun, L; Zhang, Z Y; Xu, F [Department of Pharmaceutical Science, Zhujiang Hospital, Southern Medical University, Guangzhou 510282 (China); Yang, B, E-mail: andrewfxu1998@gmail.co [Department of Chemistry, Indiana University-Bloomington, Bloomington, IN 47405 (United States)

2009-10-07

Chitosan/siRNA nanoparticles to knock down FHL2 gene expression were reported in this work. The physicochemical properties such as particle size, surface charge, morphology and complex stability of chitosan nanoparticle-incorporated siRNA were evaluated. Nanoparticles which were formulated with chitosan/siRNA exhibited irregular, lamellar and dendritic structures with a hydrodynamic radius size of about 148 nm and net positive charges with zeta-potential value of 58.5 mV. The knockdown effect of the chitosan/siRNA nanoparticles on gene expression in FHL2 over-expressed human colorectal cancer Lovo cells was investigated. The result showed that FHL2 siRNA formulated within chitosan nanoparticles could knock down about 69.6% FHL2 gene expression, which is very similar to the 68.8% reduced gene expression when siRNA was transfected with liposome Lipofectamine. Western analysis further showed significant FHL-2 protein expression reduced by the chitosan/siRNA nanoparticles. The results also showed that blocking FHL2 expression by siRNA could also inhibit the growth and proliferation of human colorectal cancer Lovo cells. The current results demonstrated that chitosan-based siRNA nanoparticles were a very efficient delivery system for siRNA in vivo as previously reported.

Functional gene silencing mediated by chitosan/siRNA nanocomplexes

International Nuclear Information System (INIS)

Ji, A M; Su, D; Che, O; Li, W S; Sun, L; Zhang, Z Y; Xu, F; Yang, B

2009-01-01

Chitosan/siRNA nanoparticles to knock down FHL2 gene expression were reported in this work. The physicochemical properties such as particle size, surface charge, morphology and complex stability of chitosan nanoparticle-incorporated siRNA were evaluated. Nanoparticles which were formulated with chitosan/siRNA exhibited irregular, lamellar and dendritic structures with a hydrodynamic radius size of about 148 nm and net positive charges with zeta-potential value of 58.5 mV. The knockdown effect of the chitosan/siRNA nanoparticles on gene expression in FHL2 over-expressed human colorectal cancer Lovo cells was investigated. The result showed that FHL2 siRNA formulated within chitosan nanoparticles could knock down about 69.6% FHL2 gene expression, which is very similar to the 68.8% reduced gene expression when siRNA was transfected with liposome Lipofectamine. Western analysis further showed significant FHL-2 protein expression reduced by the chitosan/siRNA nanoparticles. The results also showed that blocking FHL2 expression by siRNA could also inhibit the growth and proliferation of human colorectal cancer Lovo cells. The current results demonstrated that chitosan-based siRNA nanoparticles were a very efficient delivery system for siRNA in vivo as previously reported.

Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection

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Wang Z

2016-05-01

Full Text Available Zhongshan Wang,1 Guangsheng Wu,2,3 Mengying Wei,4 Qian Liu,1 Jian Zhou,1 Tian Qin,1 Xiaoke Feng,1 Huan Liu,1 Zhihong Feng,1 Yimin Zhao1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, 2State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi’an, 3Qingdao First Sanatorium, Jinan Military Region, Qingdao, Shandong Province, 4Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, People’s Republic of China Abstract: Cell sheet engineering has emerged as a novel approach to effectively deliver seeding cells for tissue regeneration, and developing human bone marrow mesenchymal stem cell (hBMMSC sheets with high osteogenic ability is a constant requirement from clinics for faster and higher-quality bone formation. In this work, we fabricated biocompatible and safe chitosan (CS/hyaluronic acid (HA nanoparticles (NPs to deliver microRNA-21 (miR-21, which has been proved to accelerate osteogenesis in hBMMSCs; then, the CS/HA/miR-21 NPs were cross-linked onto the surfaces of culture plates with 0.2% gel solution to fabricate miR-21-functionalized culture plates for reverse transfection. hBMMSC sheets were induced continuously for 14 days using a vitamin C-rich method on the miR-21-functionalized culture plates. For the characterization of CS/HA/miR-21 NPs, the particle size, zeta potential, surface morphology, and gel retardation were sequentially investigated. Then, the biological effects of hBMMSC sheets on the miR-21-functionalized culture plates were evaluated. The assay results demonstrated that the hBMMSC sheets could be successfully induced via the novel

Chitosan nanoparticles as a modified diclofenac drug release system

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Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

2017-08-01

This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model

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Hu YL

2011-12-01

Full Text Available Yu-Lan Hu1, Wang Qi1, Feng Han2, Jian-Zhong Shao3, Jian-Qing Gao11Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, 3College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, People's Republic of ChinaBackground: Although there are a number of reports regarding the toxicity evaluation of inorganic nanoparticles, knowledge on biodegradable nanomaterials, which have always been considered safe, is still limited. For example, the toxicity of chitosan nanoparticles, one of the most widely used drug/gene delivery vehicles, is largely unknown. In the present study, the zebrafish model was used for a safety evaluation of this nanocarrier.Methods: Chitosan nanoparticles with two particle sizes were prepared by ionic cross-linking of chitosan with sodium tripolyphosphate. Chitosan nanoparticles of different concentrations were incubated with zebrafish embryos, and ZnO nanoparticles were used as the positive control.Results: Embryo exposure to chitosan nanoparticles and ZnO nanoparticles resulted in a decreased hatching rate and increased mortality, which was concentration-dependent. Chitosan nanoparticles at a size of 200 nm caused malformations, including a bent spine, pericardial edema, and an opaque yolk in zebrafish embryos. Furthermore, embryos exposed to chitosan nanoparticles showed an increased rate of cell death, high expression of reactive oxygen species, as well as overexpression of heat shock protein 70, indicating that chitosan nanoparticles can cause physiological stress in zebrafish. The results also suggest that the toxicity of biodegradable nanocarriers such as chitosan nanoparticles must be addressed, especially considering the in vivo distribution of these nanoscaled particles.Conclusion: Our results add new insights into the potential toxicity of nanoparticles produced by

Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

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Yan, Chen; Jie, Leng; Yongqi, Wang [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Weiming, Xiao [Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Juqun, Xi [Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China); Yanbing, Ding [Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Li, Qian [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Xingyuan, Pan [Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China); Mingchun, Ji [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Weijuan, Gong, E-mail: wjgong@yzu.edu.cn [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China); Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009 (China)

2015-07-31

Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.

Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

International Nuclear Information System (INIS)

Yan, Chen; Jie, Leng; Yongqi, Wang; Weiming, Xiao; Juqun, Xi; Yanbing, Ding; Li, Qian; Xingyuan, Pan; Mingchun, Ji; Weijuan, Gong

2015-01-01

Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8 + T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle

Adherence of paclitaxel drug in magnetite chitosan nanoparticles

International Nuclear Information System (INIS)

Escobar Zapata, Edna V.; Martínez Pérez, Carlos A.; Rodríguez González, Claudia A.; Castro Carmona, Javier S.; Quevedo Lopez, Manuel A.; García-Casillas, Perla E.

2012-01-01

Highlights: ► Chitosan silica magnetite adsorbs antineoplastic drug. ► Silica coating improve the drug adherence. - Abstract: Cancer treatment is a big challenge in medicine where chemotherapies and radiotherapies are aggressive and poorly effective having side effects as delirium, fatigue, insomnia, nausea and vomiting which are common problems for cancer patients. For this reason, during the last two decades, many researchers have developed several techniques to improve the current therapies; one of them is the functionalization of magnetic nanoparticles for drug delivery. In this work, magnetic nanoparticles with an average crystallite size 21.8 nm were covered in a core/shell type; magnetite/silica, magnetite/chitosan, and a double shell magnetite/silica/chitosan were developed for attaching an antineoplastic drug. The mechanism for the functionalization of the nanoparticles with a single and double shell was studied with Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adherence of an antineoplastic drug, paclitaxel, onto functionalized nanoparticles was analyzed with a UV–Visible spectroscopy at a wavelength of 253 nm. It was found that the adherence of the drug is improved up to 18% when magnetite nanoparticles are coated with a single chitosan shell, and when the nanoparticles are coated with a silica/chitosan shell the adherence increases up to 29%.

Immunological evaluation of chitosan nanoparticles loaded with tetanus toxoid.

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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).

Synthesis and optimization of chitosan nanoparticles: Potential applications in nanomedicine and biomedical engineering.

Science.gov (United States)

Ghadi, Arezou; Mahjoub, Soleiman; Tabandeh, Fatemeh; Talebnia, Farid

2014-01-01

Chitosan nanoparticles have become of great interest for nanomedicine, biomedical engineering and development of new therapeutic drug release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity. The aim of the present study was to synthesis and optimize of the chitosan nanoparticles for industrial and biomedical applications. Fe3O4 was synthesized and optimized as magnetic core nanoparticles and then chitosan covered this magnetic core. The size and morphology of the nano-magnetic chitosan was analyzed by scanning electron microscope (SEM). Topography and size distribution of the nanoparticles were shown with two-dimensional and three-dimensional images of atomic force microscopy (AFM). The nanoparticles were analyzed using transmission electron microscopy (TEM). The chitosan nanoparticles prepared in the experiment exhibited white powder shape. The SEM micrographs of the nano-magnetic chitosan showed that they were approximately uniform spheres. The unmodified chitosan nanoparticles composed of clusters of nanoparticles with sizes ranging from 10 nm to 80 nm. AFM provides a three-dimensional surface profile. The TEM image showed physical aggregation of the chitosan nanoparticles. The results show that a novel chitosan nanoparticle was successfully synthesized and characterized. It seems that this nanoparticle like the other chitosan nano particles has potential applications for nanomedicine, biomedical engineering, industrial and pharmaceutical fields.

Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery

DEFF Research Database (Denmark)

Gordon, Sarah; Saupe, Anne; McBurney, Warren

2008-01-01

In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised...... of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with ... released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo....

Adherence of paclitaxel drug in magnetite chitosan nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Escobar Zapata, Edna V.; Martinez Perez, Carlos A.; Rodriguez Gonzalez, Claudia A.; Castro Carmona, Javier S. [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico); Quevedo Lopez, Manuel A. [Departamento de Polimeros y Materiales, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora (Mexico); Garcia-Casillas, Perla E., E-mail: pegarcia@uacj.mx [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico)

2012-09-25

Highlights: Black-Right-Pointing-Pointer Chitosan silica magnetite adsorbs antineoplastic drug. Black-Right-Pointing-Pointer Silica coating improve the drug adherence. - Abstract: Cancer treatment is a big challenge in medicine where chemotherapies and radiotherapies are aggressive and poorly effective having side effects as delirium, fatigue, insomnia, nausea and vomiting which are common problems for cancer patients. For this reason, during the last two decades, many researchers have developed several techniques to improve the current therapies; one of them is the functionalization of magnetic nanoparticles for drug delivery. In this work, magnetic nanoparticles with an average crystallite size 21.8 nm were covered in a core/shell type; magnetite/silica, magnetite/chitosan, and a double shell magnetite/silica/chitosan were developed for attaching an antineoplastic drug. The mechanism for the functionalization of the nanoparticles with a single and double shell was studied with Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adherence of an antineoplastic drug, paclitaxel, onto functionalized nanoparticles was analyzed with a UV-Visible spectroscopy at a wavelength of 253 nm. It was found that the adherence of the drug is improved up to 18% when magnetite nanoparticles are coated with a single chitosan shell, and when the nanoparticles are coated with a silica/chitosan shell the adherence increases up to 29%.

Evaluation of Hemagglutination Activity of Chitosan Nanoparticles Using Human Erythrocytes

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Jefferson Muniz de Lima

2015-01-01

Full Text Available Chitosan is a polysaccharide composed of randomly distributed chains of β-(1-4 D-glucosamine and N-acetyl-D-glucosamine. This compound is obtained by partial or total deacetylation of chitin in acidic solution. The chitosan-based hemostatic agents have been gaining much attention in the management of bleeding. The aim of this study was to evaluate in vitro hemagglutination activity of chitosan nanoparticles using human erythrocytes. The preparation of nanoparticles was achieved by ionotropic gelification technique followed by neutralization with NaOH 1 mol/L−1. The hemagglutination activity was performed on a solution of 2% erythrocytes (pH 7.4 on PBS collected from five healthy volunteers. The hemolysis determination was made by spectrophotometric analysis. Chitosan nanoparticle solutions without NaOH addition changed the reddish colour of the wells into brown, suggesting an oxidative reaction of hemoglobin and possible cell lysis. All neutralized solutions of chitosan nanoparticles presented positive haemagglutination, without any change in reaction color. Chitosan nanoparticles presented hemolytic activity ranging from 186.20 to 223.12%, while neutralized solutions ranged from 2.56 to 72.54%, comparing to distilled water. Results highlight the need for development of new routes of synthesis of chitosan nanoparticles within human physiologic pH.

Immobilization of gold nanoparticles on cell culture surfaces for safe and enhanced gold nanoparticle-mediated laser transfection

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Kalies, Stefan; Heinemann, Dag; Schomaker, Markus; Gentemann, Lara; Meyer, Heiko; Ripken, Tammo

2014-01-01

Abstract. In comparison to standard transfection methods, gold nanoparticle-mediated laser transfection has proven to be a versatile alternative. This is based on its minor influence on cell viability and its high efficiency, especially for the delivery of small molecules like small interfering RNA. However, in order to transfer it to routine usage, a safety aspect is of major concern: The avoidance of nanoparticle uptake by the cells is desired. The immobilization of the gold nanoparticles on cell culture surfaces can address this issue. In this study, we achieved this by silanization of the appropriate surfaces and the binding of gold nanoparticles to them. Comparable perforation efficiencies to the previous approaches of gold nanoparticle-mediated laser transfection with free gold nanoparticles are demonstrated. The uptake of the immobilized particles by the cells is unlikely. Consequently, these investigations offer the possibility of bringing gold nanoparticle-mediated laser transfection closer to routine usage. PMID:25069006

One-Step Method for Preparation of Magnetic Nanoparticles Coated with Chitosan

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Karla M. Gregorio-Jauregui

2012-01-01

Full Text Available Preparation of magnetic nanoparticles coated with chitosan in one step by the coprecipitation method in the presence of different chitosan concentrations is reported here. Obtaining of magnetic superparamagnetic nanoparticles was confirmed by X-ray diffraction and magnetic measurements. Scanning transmission electron microscopy allowed to identify spheroidal nanoparticles with around 10-11 nm in average diameter. Characterization of the products by Fourier transform infrared spectroscopy demonstrated that composite chitosan-magnetic nanoparticles were obtained. Chitosan content in obtained nanocomposites was estimated by thermogravimetric analysis. The nanocomposites were tested in Pb2+ removal from a PbCl2 aqueous solution, showing a removal efficacy up to 53.6%. This work provides a simple method for chitosan-coated nanoparticles obtaining, which could be useful for heavy metal ions removal from water.

Copper nanoparticles synthesis by gamma irradiation in chitosan aqueous system

International Nuclear Information System (INIS)

Shahrul Izwan Ahmad; Md Soot Ahmad; Shahidan Radiman

2009-01-01

A study on effect of chitosan concentration on the copper nanoparticles synthesis using gamma irradiation as source of reducing agent has been done at total absorbed dose of 50 kGy. The addition of ethanol is vital as scavenger of oxidation radical that eliminate the function of reducing agent produced by radiolysis process of gamma ray in water system. Transmission electron microscopy observations show the formation of copper nanoparticles embedded in chitosan matrix. As the concentration of chitosan increase the solution become darker and nanoparticles produced are densely, in order form with polydisperse size. While at the low concentration of chitosan, the color of solution become more reddish and the particles produced are monodisperse in size with regular shape and more orderly. The phase of pure copper nanoparticles embedded in the chitosan matrix was confirmed by X-ray diffraction. (Author)

Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles

Science.gov (United States)

Taner, Gökçe; Yeşilöz, Recep; Özkan Vardar, Deniz; Şenyiğit, Taner; Özer, Özgen; Degen, Gisela H.; Başaran, Nurşen

2014-02-01

Nanoparticles-based drug targeting delivery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nanoparticles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of lecithin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration.

The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

Science.gov (United States)

Wang, Yun; Lin, Fu-xing; Zhao, Yu; Wang, Mo-zhen; Ge, Xue-wu; Gong, Zheng-xing; Bao, Dan-dan; Gu, Yu-fang

2014-01-01

Novel submicron core-shell-structured chitosan-based composite particles encapsulated with enhanced green fluorescent protein plasmids (pEGFP) were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS) and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC). pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. PMID:25364253

The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

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Wang Y

2014-10-01

Full Text Available Yun Wang,1 Fu-xing Lin,2 Yu Zhao,1 Mo-zhen Wang,2 Xue-wu Ge,2 Zheng-xing Gong,1 Dan-dan Bao,1 Yu-fang Gu1 1Department of Plastic Surgery, First Affiliated Hospital of Anhui Medical University, 2CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China Abstract: Novel submicron core-shell-structured chitosan-based composite particles ­encapsulated with enhanced green fluorescent protein plasmids (pEGFP were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC. pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. Keywords: gene therapy, gene transfection, hydroxybutyl chitosan, thiolated N-alkylated chitosan, pEGFP, complex coacervation

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.

Transfection Agent Induced Nanoparticle Cell Loading

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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.

Ascorbic acid prevents cellular uptake and improves biocompatibility of chitosan nanoparticles.

Science.gov (United States)

Elshoky, Hisham A; Salaheldin, Taher A; Ali, Maha A; Gaber, Mohamed H

2018-04-11

Chitosan nanoparticles have many applications, such as gene and drug delivery, due to their biocompatibility. Chitosan nanoparticles are currently produced by dissolution in acetic acid that affects the biocompatibility at acidic pH. Here, we synthesized and characterized chitosan (CS) and ascorbate chitosan (AsCS) nanoparticles and investigated their cytotoxic effects, internalization, and distribution in the human colon carcinoma cell line using confocal laser scanning microscopy (CLSM). The CS and AsCS nanoparticles were spherical with average particle sizes of 44±8.4nm and 87±13.6nm, respectively. CS nanoparticles were taken up by the cells and showed dose-dependent cytotoxicity. By contrast, AsCS nanoparticles were not internalized and showed no cytotoxicity. Therefore, AsCS nanoparticles are more biocompatible than CS nanoparticles and may be more suitable for extracellular drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Chitosan magnetic nanoparticles for drug delivery systems.

Science.gov (United States)

Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

2017-06-01

The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells.

Science.gov (United States)

Talaei, Fatemeh; Azizi, Ebrahim; Dinarvand, Rassoul; Atyabi, Fatemeh

2011-01-01

Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo.

Core shell methyl methacrylate chitosan nanoparticles: In vitro mucoadhesion and complement activation

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F Atyabi

2011-10-01

Full Text Available Background and the purpose of the study: Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. Methods: Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione (GSH to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum (HS by measurement of the hemolytic capacity of the complement system after contact with nanoparticles.   Results:   The FT-IR and 1HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate (MMA homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process. Major conclusion: It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan.

Non-monotonic wetting behavior of chitosan films induced by silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Praxedes, A.P.P.; Webler, G.D.; Souza, S.T. [Instituto de Física, Universidade Federal de Alagoas, 57072-970 Maceió, AL (Brazil); Ribeiro, A.S. [Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, 57072-970 Maceió, AL (Brazil); Fonseca, E.J.S. [Instituto de Física, Universidade Federal de Alagoas, 57072-970 Maceió, AL (Brazil); Oliveira, I.N. de, E-mail: italo@fis.ufal.br [Instituto de Física, Universidade Federal de Alagoas, 57072-970 Maceió, AL (Brazil)

2016-05-01

Highlights: • The addition of silver nanoparticles modifies the morphology of chitosan films. • Metallic nanoparticles can be used to control wetting properties of chitosan films. • The contact angle shows a non-monotonic dependence on the silver concentration. - Abstract: The present work is devoted to the study of structural and wetting properties of chitosan-based films containing silver nanoparticles. In particular, the effects of silver concentration on the morphology of chitosan films are characterized by different techniques, such as atomic force microscopy (AFM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). By means of dynamic contact angle measurements, we study the modification on surface properties of chitosan-based films due to the addition of silver nanoparticles. The results are analyzed in the light of molecular-kinetic theory which describes the wetting phenomena in terms of statistical dynamics for the displacement of liquid molecules in a solid substrate. Our results show that the wetting properties of chitosan-based films are high sensitive to the fraction of silver nanoparticles, with the equilibrium contact angle exhibiting a non-monotonic behavior.

Preparation and Comparison of Chitosan Nanoparticles with Different Degrees of Glutathione Thiolation

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R Dinarvand

2011-12-01

Full Text Available Background: Chitosan has gained considerable attentions as a biocompatible carrier to improve delivery of active agents. Application of this vehicle in the form of nanoparticle could profit advantages of nanotechnology to increase efficacy of active agents. The purpose of this study was to provide detailed information about chitosan-glutathione (Cht-GSHnanoparticles which are gaining popularity because of their high mucoadhesive and extended drug release properties. Methods: Depolymerization of chitosan was carried out using sodium nitrite method.Glutathione was covalently attached to chitosan and the solubility of the resulting conjugates was evaluated. Nanoparticles were prepared by ionic gelation method and then the effect of glutathione immobilization on properties of nanoparticles was investigated. Results: Thiolation efficiency was higher in lower molecular weight chitosan polymers compared to unmodified chitosan nanoparticles. Cht-GSH conjugates of the same molecular weight but with different degrees of thiolation had the same hydrodynamic diameter (995± nm and surface charge (102± mV as unmodified chitosan, but comprised of a denser network structure and lower concentration. Cht-GSH nanoparticles also exhibited greater mucoadhesive strength which was less affected by ionic strength and pH of the environment. Conclusion:Thiolation improves the solubility of chitosan without any significant changes in size and charge of nanoparticles, but affects the nanogel structure.

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

Directory of Open Access Journals (Sweden)

Talaei F

2011-09-01

Full Text Available Fatemeh Talaei1, Ebrahim Azizi2, Rassoul Dinarvand3, Fatemeh Atyabi31Novel Drug Delivery Systems Lab, 2Molecular Research Lab, Department of Pharmacology and Toxicology, 3Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan and NAP-C (N-acetyl penicillamine-chitosan in anticancer drug delivery targeting epidermal growth factor receptor (EGFR. Doxorubicin (DOX and antisense oligonucleotide (ASOND-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo

Biological evaluation of silver nanoparticles incorporated into chitosan-based membranes

NARCIS (Netherlands)

Shao, J.; Yu, N.; Kolwijck, E.; Wang, B.; Tan, K.W.; Jansen, J.A.; Walboomers, X.F.; Yang, F.

2017-01-01

AIM: To evaluate the antibacterial potential and biological performance of silver nanoparticles in chitosan-based membranes. MATERIALS & METHODS: Electrospun chitosan/poly(ethylene oxide) membranes with different amounts of silver nanoparticles were evaluated for antibacterial properties and

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.

Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast cells

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Shi S

2012-10-01

Full Text Available Si-Feng Shi,1 Jing-Fu Jia,2 Xiao-Kui Guo,3 Ya-Ping Zhao,2 De-Sheng Chen,1 Yong-Yuan Guo,1 Tao Cheng,1 Xian-Long Zhang11Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital, School of Medicine, 2School of Chemistry and Chemical Technology, 3Department of Medical Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University Shanghai, ChinaBackground: Bone disorders (including osteoporosis, loosening of a prosthesis, and bone infections are of great concern to the medical community and are difficult to cure. Therapies are available to treat such diseases, but all have drawbacks and are not specifically targeted to the site of disease. Chitosan is widely used in the biomedical community, including for orthopedic applications. The aim of the present study was to coat chitosan onto iron oxide nanoparticles and to determine its effect on the proliferation and differentiation of osteoblasts.Methods: Nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, x-ray diffraction, zeta potential, and vibrating sample magnetometry. Uptake of nanoparticles by osteoblasts was studied by transmission electron microscopy and Prussian blue staining. Viability and proliferation of osteoblasts were measured in the presence of uncoated iron oxide magnetic nanoparticles or those coated with chitosan. Lactate dehydrogenase, alkaline phosphatase, total protein synthesis, and extracellular calcium deposition was studied in the presence of the nanoparticles.Results: Chitosan-coated iron oxide nanoparticles enhanced osteoblast proliferation, decreased cell membrane damage, and promoted cell differentiation, as indicated by an increase in alkaline phosphatase and extracellular calcium deposition. Chitosan-coated iron oxide nanoparticles showed good compatibility with osteoblasts.Conclusion: Further research is necessary to optimize magnetic nanoparticles for the treatment of bone disease

Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

Science.gov (United States)

Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

2015-01-01

Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

Synthesis and in vitro antifungal efficacy of oleoyl-chitosan nanoparticles against plant pathogenic fungi.

Science.gov (United States)

Xing, Ke; Shen, Xiaoqiang; Zhu, Xiao; Ju, Xiuyun; Miao, Xiangmin; Tian, Jun; Feng, Zhaozhong; Peng, Xue; Jiang, Jihong; Qin, Sheng

2016-01-01

An antifungal dispersion system was prepared by oleoyl-chitosan (O-chitosan) nanoparticles, and the antifungal activity against several plant pathogenic fungi was investigated. Under scanning electron microscopy, the nanoparticles formulation appeared to be uniform with almost spherical shape. The particle size of nanoparticles was around 296.962 nm. Transmission electron microscopy observation showed that nanoparticles could be well distributed in potato dextrose agar medium. Mycelium growth experiment demonstrated that Nigrospora sphaerica, Botryosphaeria dothidea, Nigrospora oryzae and Alternaria tenuissima were chitosan-sensitive, while Gibberella zeae and Fusarium culmorum were chitosan-resistant. The antifungal index was increased as the concentration of nanoparticles increased for chitosan-sensitive fungi. Fatty acid analyses revealed that plasma membranes of chitosan-sensitive fungi were shown to have lower levels of unsaturated fatty acid than chitosan-resistant fungi. Phylogenetic analysis based on ITS gene sequences indicated that two chitosan-resistant fungi had a near phylogenetic relationship. Results showed that O-chitosan nanoparticles could be a useful alternative for controlling pathogenic fungi in agriculture. Copyright © 2015 Elsevier B.V. All rights reserved.

Chitosan-coupled solid lipid nanoparticles: Tuning nanostructure and mucoadhesion.

Science.gov (United States)

Sandri, Giuseppina; Motta, Simona; Bonferoni, Maria Cristina; Brocca, Paola; Rossi, Silvia; Ferrari, Franca; Rondelli, Valeria; Cantù, Laura; Caramella, Carla; Del Favero, Elena

2017-01-01

Solid Lipid Nanoparticles (SLNs) composed of biodegradable physiological lipids have been widely proposed as efficient drug delivery systems, also for ophthalmic administration. Recently, chitosan-associated-SLNs have been developed to further improve the residence time of these colloidal systems in the precorneal area by means of mucoadhesive interaction. In the present study, a one-step preparation protocol was used aiming both at scale-up ease and at stronger coupling between chitosan and SLNs. The resulting particles were chitosan associated-SLNs (CS-SLNs). These nanoparticles were characterized, as compared to both the chitosan-free and the usual chitosan-coated ones, by applying a multi-technique approach: light, neutron and X-ray scattering, Zeta-potential, AFM, calorimetry. It was assessed that, while keeping the features of nano-size and surface-charge required for an efficient vector, these new nanoparticles display a strong and intimate interaction between chitosan and SLNs, far more settled than the usual simple coverage. Moreover, this one-step preparation method allows to obtain a strong and intimate interaction between chitosan and SLNs, firmer than the usual simple coating. This confers to the CS-SLNs an improved mucoadhesion, opening the way for a high-performing ophthalmic formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Poly-ϵ-caprolactone/chitosan nanoparticles provide strong adjuvant effect for hepatitis B antigen.

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Jesus, Sandra; Soares, Edna; Borchard, Gerrit; Borges, Olga

2017-10-01

This work aims to investigate the adjuvant effect of poly-ϵ-caprolactone/chitosan nanoparticles (NPs) for hepatitis B surface antigen (HBsAg) and the plasmid DNA encoding HBsAg (pRC/CMV-HBs). Both antigens were adsorbed onto preformed NPs. Vaccination studies were performed in C57BL/6 mice. Transfection efficiency was investigated in A549 cell line. HBsAg-adsorbed NPs generated strong anti-HBsAg IgG titers, mainly of IgG1 isotype, and induced antigen-specific IFN-γ and IL-17 secretion by spleen cells. The addition of pRC/CMV-HBs to the HBsAg-adsorbed NPs inhibited IL-17 secretion but had minor effect on IFN-γ levels. Lastly, pRC/CMV-HBs-loaded NPs generated a weak serum antibody response. Poly-ϵ-caprolactone/chitosan NPs provide a strong humoral adjuvant effect for HBsAg and induce a Th1/Th17-mediated cellular immune responses worth explore for hepatitis B virus vaccination.

Design, characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin.

Science.gov (United States)

Mortazavian, Elaheh; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza

2014-05-01

The purpose of this study is to optimize and characterize of chitosan buccal film for delivery of insulin nanoparticles that were prepared from thiolated dimethyl ethyl chitosan (DMEC-Cys). Insulin nanoparticles composed of chitosan and dimethyl ethyl chitosan (DMEC) were also prepared as control groups. The release of insulin from nanoparticles was studied in vitro in phosphate buffer solution (PBS) pH 7.4. Optimization of chitosan buccal films has been carried out by central composite design (CCD) response surface methodology. Independent variables were different amounts of chitosan and glycerol as mucoadhesive polymer and plasticizer, respectively. Tensile strength and bioadhesion force were considered as dependent variables. Ex vivo study was performed on excised rabbit buccal mucosa. Optimized insulin nanoparticles were obtained with acceptable physicochemical properties. In vitro release profile of insulin nanoparticles revealed that the highest solubility of nanoparticles in aqueous media is related to DMEC-Cys nanoparticles. CCD showed that optimized buccal film containing 4% chitosan and 10% glycerol has 5.81 kg/mm(2) tensile strength and 2.47 N bioadhesion forces. Results of ex vivo study demonstrated that permeation of insulin nanoparticles through rabbit buccal mucosa is 17.1, 67.89 and 97.18% for chitosan, DMEC and DMEC-Cys nanoparticles, respectively. Thus, this study suggests that DMEC-Cys can act as a potential enhancer for buccal delivery of insulin.

Synthesis, characterization and antibacterial study on the chitosan-functionalized Ag nanoparticles.

Science.gov (United States)

Biao, Linhai; Tan, Shengnan; Wang, Yuanlin; Guo, Ximin; Fu, Yujie; Xu, Fengjie; Zu, Yuangang; Liu, Zhiguo

2017-07-01

This study provided a facile, one-step hydrothermal method to synthesize stable Ag colloid in aqueous solution by utilizing chitosan as both reductant and stabilizer. The formation of chitosan-functionalized Ag nanoparticles was verified by UV-Vis, FTIR, TEM, AFM and XRD measurements. FTIR results revealed that the primary amine groups and amide groups of chitosan have specific interactions with the surface of Ag nanoparticles. The average diameter of the Ag nanoparticles is 10.0±5.4nm as determined by TEM. Ag nanoparticles are highly crystalline as revealed by HR-TEM and XRD measurements. The size and shape of Ag nanoparticles are also found to depend on the pH condition in the synthesis. Ag nanoparticles were the main products at pH5.0 whereas large Ag nanotriangle and truncated triangular nanoplate were dominant at pH4.0 in the synthesis. Due to its monodispersity and good stability, the chitosan-functionalized Ag colloid synthesized at pH5.0 was further tested for its antibacterial activities against gram-positive bacteria, gram-negative bacteria and fungus. The results of zone of inhibition, inhibition ratio and SEM characterization revealed that chitosan-functionalized Ag nanoparticles have great bactericidal efficiency against both bacteria and fungus. Copyright © 2017 Elsevier B.V. All rights reserved.

Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma.

Science.gov (United States)

Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

2017-09-01

Rationale of this study was framed to investigate the protective effect and anti-cancer property of nanoparticles based on chitosan isolated from squid, Sepioteuthis lessoniana, on hepatic cells in N-Nitrosodiethylamine-induced hepatocellular carcinoma in rats. The results conferred that the chitosan nanoparticle supplementation had a protective effect on liver cells by reducing the levels of marker enzymes and bilirubin and thus increasing the albumin levels. The level of reduced glutathione, ascorbic acid and α-tocopherol significantly increased in both post- and pre-treatment with chitosan nanoparticles. The levels of antioxidant enzymes were enhanced and lipid peroxidation products were diminished while treating nitrosodiethylamine-induced hepatocellular carcinoma with chitosan nanoparticles. Supplementation of chitosan nanoparticles had potent anti-hyperlipidemic property that was evidenced by monitoring the serum lipid levels and its components. Animals pre-treated with chitosan nanoparticles along with nitrosodiethylamine showed a significant reduction in the total cholesterol and triglycerides levels with increase in the levels of phospholipids and free fatty acids. Chitosan nanoparticles treated rats showed significant increment in high-density lipoprotein cholesterol and reduction in low-density lipoprotein and very low-density lipoprotein cholesterol when compared with levels in nitrosodiethylamine-induced hepatocellular carcinoma. Nitrosodiethylamine-induced carcinoma changes on circulation and hepatic antioxidant defense mechanism were regulated by chitosan nanoparticles, concluding that the chitosan nanoparticles have a potent protective effect on liver cells which might be due to its robust antioxidant and anti-lipidemic property. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chitosan nanoparticles enhances the anti-quorum sensing activity of kaempferol.

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Ilk, Sedef; Sağlam, Necdet; Özgen, Mustafa; Korkusuz, Feza

2017-01-01

Quorum sensing (QS) is a cell density dependent expression of species in bacteria mediated by compounds called autoinducers (AI). Several processes responsible for successful establishment of bacterial infection are mediated by QS. Inhibition of QS is therefore being considered as a new target for antimicrobial chemotherapy. Flavonoid compounds are strong antioxidant and antimicrobial agents but their applications are limited due to their poor dissolution and bioavailability. Our objective was to investigate the effect of kaempferol loaded chitosan nanoparticles on modulating QS mediated by AI in model bioassay test systems. For this purpose, kaempferol loaded nanoparticles were synthesized and characterized in terms of hydrodynamic diameter, hydrogen bonding, amorphous transformation and antioxidant activity. QS inhibition in time dependent manner of nanoparticles was measured in violacein pigment producing using the biosensor strain Chromobacterium violaceum CV026 mediated by AI known as acylated homoserine lactone (AHL). Our results indicated that the average kaempferol loaded chitosan/TPP nanoparticle size and zeta potential were 192.27±13.6nm and +35mV, respectively. The loading and encapsulation efficiency of kaempferol into chitosan/TPP nanoparticles presented higher values between 78 and 93%. Kaempferol loaded chitosan/TPP nanoparticle during the 30 storage days significantly inhibited the production of violacein pigment in Chromobacterium violaceum CV026. The observation that kaempferol encapsulated chitosan nanoparticles can inhibit QS related processes opens up an exciting new strategy for antimicrobial chemotherapy as stable QS-based anti-biofilm agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Inorganic nanoparticles for transfection of mammalian cells and removal of viruses from aqueous solutions.

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Link, Nils; Brunner, Tobias J; Dreesen, Imke A J; Stark, Wendelin J; Fussenegger, Martin

2007-12-01

Owing to their small size, synthetic nanoparticles show unprecedented biophysical and biochemical properties which may foster novel advances in life-science research. Using flame-spray synthesis technology we have produced non-coated aluminum-, calcium-, cerium-, and zirconium-derived inorganic metal oxide nanoparticles which not only exhibit high affinity for nucleic acids, but can sequester such compounds from aqueous solution. This non-covalent DNA-binding capacity was successfully used to transiently transfect a variety of mammalian cells including human, reaching transfection efficiencies which compared favorably with classic calcium phosphate precipitation (CaP) procedures and lipofection. In this straightforward protocol, transfection was enabled by simply mixing nanoparticles with DNA in solution prior to addition to the target cell population. Transiently transfected cells showed higher production levels of the human secreted glycoprotein SEAP compared to isogenic populations transfected with established technologies. Inorganic metal oxide nanoparticles also showed a high binding capacity to human-pathogenic viruses including adenovirus, adeno-associated virus and human immunodeficiency virus type 1 and were able to clear these pathogens from aqueous solutions. The DNA transfection and viral clearance capacities of inorganic metal oxide nanoparticles may provide cost-effective biopharmaceutical manufacturing and water treatment in developing countries.

Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: Ibuprofen

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Hassani Najafabadi, Alireza [Department of Chemistry, Amirkabir University of Technology, P.O. Box 1587-4413, Tehran (Iran, Islamic Republic of); Abdouss, Majid, E-mail: phdabdouss44@aut.ac.ir [Department of Chemistry, Amirkabir University of Technology, P.O. Box 1587-4413, Tehran (Iran, Islamic Republic of); Faghihi, Shahab [Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of)

2014-08-01

Current methods for preparation of PEGylated chitosan have limitations such as harsh de protecting step and several purification cycles. In the present study, a facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan under mild condition is introduced to improve water solubility of chitosan and control the release of poor water soluble drugs. The method consists of chitosan modification by grafting the C6 position of chitosan to mPEG which is confirmed by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance ({sup 1}HNMR) analyses. The amine groups at the C2 position of chitosan are protected using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and {sup 1}HNMR. The synthesized polymer is then employed to prepare nanoparticles which are characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for their size and morphology. The nanoparticles are used for encapsulation of ibuprofen followed by in vitro release investigation in gastrointestinal and simulated biological fluids. The chitosan nanoparticles are used as control. The PEGylated nanoparticles show a particle size of 80 nm with spherical morphology. The results clearly show that drug release from PEGylated chitosan nanoparticles is remarkably slower than chitosan. In addition, drug encapsulation and encapsulation efficiency in PEGylated nanoparticles are dependent on the amount of drug added to the formulation being significantly higher than chitosan nanoparticles. This study provides an efficient, novel, and facile method for preparing a nano carrier system for delivery of water insoluble drugs. - Highlights: • A facile novel method for conjugating methoxy polyethylene glycol (mPEG) to chitosan is introduced. • Fabricated PEG

Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: Ibuprofen

International Nuclear Information System (INIS)

Hassani Najafabadi, Alireza; Abdouss, Majid; Faghihi, Shahab

2014-01-01

Current methods for preparation of PEGylated chitosan have limitations such as harsh de protecting step and several purification cycles. In the present study, a facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan under mild condition is introduced to improve water solubility of chitosan and control the release of poor water soluble drugs. The method consists of chitosan modification by grafting the C6 position of chitosan to mPEG which is confirmed by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance ( 1 HNMR) analyses. The amine groups at the C2 position of chitosan are protected using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and 1 HNMR. The synthesized polymer is then employed to prepare nanoparticles which are characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for their size and morphology. The nanoparticles are used for encapsulation of ibuprofen followed by in vitro release investigation in gastrointestinal and simulated biological fluids. The chitosan nanoparticles are used as control. The PEGylated nanoparticles show a particle size of 80 nm with spherical morphology. The results clearly show that drug release from PEGylated chitosan nanoparticles is remarkably slower than chitosan. In addition, drug encapsulation and encapsulation efficiency in PEGylated nanoparticles are dependent on the amount of drug added to the formulation being significantly higher than chitosan nanoparticles. This study provides an efficient, novel, and facile method for preparing a nano carrier system for delivery of water insoluble drugs. - Highlights: • A facile novel method for conjugating methoxy polyethylene glycol (mPEG) to chitosan is introduced. • Fabricated PEG-grafted chitosan

Development of chitosan-nanoparticle film based materials for controlled quality of minced beef during refrigerated storage

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Erdawati

2010-10-01

Chitosan nanoparticles were prepared based on the ionic gelation of chitosan with tripolyphosphate anions. The physicochemical properties of the chitosan nanoparticles were determined by FTIR analysis, XRD pattern and TEM. The effects of chitosan nanoparticles treatment on the shelf-life extension of minced beef stored at 20±1° C were studied, including chemical and microbiological,. Results indicated that chitosan nanoparticle treatment reduced the total microbial load of fresh minced beef about 10-fold (from 3.2×104 CFU/g to 5.4×102 CFU/g) before storage and the microbial flora was different with that of raw samples. The wide-spectrum antibacterial property of chitosan against bacteria isolated from minced beef was confirmed, and chitosan concentration of 400 ppm was eventually determined for application in minced beef. Based on microbiological analysis, biochemical indices determination and sensory evaluation, shelf-lives of 2-3 days for control, 4-5 days for nanoparticle chitosan treatment samples, were observed, indicating that chitosan nanoparticle have a great potential for minced beef preservation.

Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

International Nuclear Information System (INIS)

Ahmad, Tanveer; Bae, Hongsub; Iqbal, Yousaf; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun; Sohn, Derac

2015-01-01

We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe 2 O 4 ) nanoparticles as both T 1 and T 2 contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T 1 and T 2 relaxivities were 0.858±0.04 and 1.71±0.03 mM −1 s −1 , respectively. In animal experimentation, both a 25% signal enhancement in the T 1 -weighted mage and a 71% signal loss in the T 2 -weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T 1 and T 2 contrast agents in MRI. We note that the applicability of our nanoparticles as both T 1 and T 2 contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe 2 O 4 ) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T 1 and T 2 contrast agents for MRI by measuring T 1 and T 2 relaxation times as a function of iron concentration. • Both T 1 and T 2 effects were also observed in animal experimentation

Mucosal delivery of liposome-chitosan nanoparticle complexes.

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Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

2009-01-01

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

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

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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.

Delivery of proteins to mammalian cells via gold nanoparticle mediated laser transfection

International Nuclear Information System (INIS)

Heinemann, D; Kalies, S; Schomaker, M; Ertmer, W; Meyer, H; Ripken, T; Murua Escobar, H

2014-01-01

Nanoparticle laser interactions are in widespread use in cell manipulation. In particular, molecular medicine needs techniques for the directed delivery of molecules into mammalian cells. Proteins are the final mediator of most cellular cascades. However, despite several methodical approaches, the efficient delivery of proteins to cells remains challenging. This paper presents a new protein transfection technique via laser scanning of cells previously incubated with gold nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles cause a transient permeabilization of the cellular membrane, allowing proteins to enter the cell. Applying this technique, it was possible to deliver green fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a high level of cell viability. Furthermore, a functional delivery of Caspase 3, an apoptosis mediating protein, was demonstrated and evaluated in several cellular assays. Compared to conventional protein transfection techniques such as microinjection, the methodical approach presented here enables high-throughput transfection of about 10 000 cells per second. Moreover, a well-defined point in time of delivery is guaranteed by gold nanoparticle mediated laser transfection, allowing the detailed temporal analysis of cellular pathways and protein trafficking. (papers)

Preparation and Optimization of Labeled Chitosan Nanoparticles and Evaluation of their Release from Transdermal Drug Delivery System

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Mohsen Sadeghi

2015-09-01

Full Text Available Biocompatible nanoparticles are widely used in biomedical engineering. In this study, chitosan nanoparticles were prepared using ionic gelation method in view of two determining factors namely method of adding chitosan into the tripolyphosphate (TPP solution and thermal shock application. With regard to the concentration of chitosan and TPP solutions as two variables, the mean particle size of chitosan nanoparticles and their preparation yield were optimized using response surface method. According to previous studies and some preliminary experiments, the chitosan and TPP solution concentration ranges were determined to be 0.5-2.5 mg/mL and 0.25-1.25 mg/mL, respectively. The optimum values of 1.25 mg/mL and 0.6 mg/mL were obtained for chitosan and TPP solution concentrations in the order given. The optimized response value for the chitosan nanoparticles size was found to be 54 nm and preparation yield was 62%. The Zeta potential of resulting spherical nanoparticles was around 31 mV. Chitosan-fluorescein isothiocyanate (FITC polymer was prepared based on the reaction between isothiocyanate functional group of FITC and primary amine functional group of chitosan. FTIR analysis was performed to demonstrate the presence of new bond formation. Labeled chitosan nanoparticles were prepared in the optimized condition using chitosan-FITC polymer. The release behavior of the labeled chitosan nanoparticles from transdermal patches was evaluated. The mean size of chitosan-FITC nanoparticles was determined to be 70 nm. Finally, it was shown that the chitosan nanoparticles were not able to release from acrylic adhesive film without using a method to speed up their diffusion.

Effect of chitosan and thiolated chitosan coating on the inhibition behaviour of PIBCA nanoparticles against intestinal metallopeptidases

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Bravo-Osuna, Irene; Vauthier, Christine; Farabollini, Alessandra; Millotti, Gioconda; Ponchel, Gilles, E-mail: gilles.ponchel@u-psud.f [UMR CNRS 8612, Universite Paris Sud, Laboratoire de Physicochimie, Faculte de Pharmacie, Pharmacotechnie et Biopharmacie (France)

2008-12-15

Surface modified nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) cores surrounded by a chitosan and thiolated chitosan gel layer were prepared and characterized in previous works. The presence of such biopolymers on the nanoparticle surface conferred those nanosystems interesting characteristics that might partially overcome the gastrointestinal enzymatic barrier, improving the oral administration of pharmacologically active peptides. In the present work, the antiprotease behaviour of this family of core-shell nanoparticles was in vitro tested against two model metallopeptidases present in the gastrointestinal tract (GIT): Carboxypeptidase A -CP A- (luminal protease) and Leucine Aminopeptidase M -LAP M- (membrane protease). As previous step, the zinc-binding capacity of these nanoparticles was evaluated. Interestingly, an improvement of both the zinc-binding capacity and the antiprotease effect of chitosan was observed when the biopolymers (chitosan and thiolated chitosan) were used as coating component of the core-shell nanoparticles, in comparison with their behaviour in solution, thanks to the different biopolymer chains rearrangement. The presence of amino, hydroxyl and thiol groups on the nanoparticle surface promoted zinc binding and hence the inhibition of the metallopeptidases analysed. On the contrary, the occurrence of a cross-linked structure in the gel layer surrounding the PIBCA cores of thiolated formulations, due to the formation of interchain and intrachain disulphide bonds, partially limited the inhibition of the proteases. The low accessibility of cations to the active groups of the cross-linked polymeric shell was postulated as a possible explanation of this behaviour. Results obtained in this work make this family of surface-modified nanocarriers promising candidates for the successfull administration of pharmacologically active peptides and proteins by the oral route.

Incorporating pTGF-β1/calcium phosphate nanoparticles with fibronectin into 3-dimensional collagen/chitosan scaffolds: Efficient, sustained gene delivery to stem cells for chondrogenic differentiation

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X Cao

2012-02-01

Full Text Available The objective of this study was to prepare a 3-dimensional nanoparticle gene delivery system (3D-NGDS based on collagen/chitosan scaffolds, in which plasmid transforming growth factor beta 1 (TGF-β1/calcium phosphate nanoparticles mixed with fibronectin (FN were used to transfect mesenchymal stem cells (MSCs. Scanning electron microscopy was used to characterise the microstructure of 3-dimensional collagen/chitosan scaffolds. An analysis performed to quantify the TGF-b1 concentrations in MSC cultures revealed that the MSCs transfected with the 3D-NGDS showed remarkably high levels of TGF-b1 over long periods, retaining a concentration of TGF-b1 of approximately 10 ng/mL within two weeks, with the highest level (12.6 ng/mL being observed on the 6th day. An immunohistochemistry analysis for collagen type II revealed that much higher production of collagen II from the 9th to 15th day was observed in the 3D-NGDS-transfected MSCs than that in MSCs transfected by the Lipofectamine 2000 method. The glycosaminoglycan content of the 3D-NGDS was comparable to those treated with TGF-β1 as well as TGF-β1 plus dexamethasone, and was significantly higher than those treated with free plasmid and Lipofectamine 2000. A remarkable type I collagen expression inhibition of the 3D-NGDS at day 21 was observed via ELISA. These results suggested that transfection with the 3D-NGDS could successfully induce MSC chondrogenic differentiation in vitro without dexamethasone. In summary, the 3D-NGDS could be developed into a promising alternative method to transfer exogenous nucleic acid to MSCs in clinical trials.

ANTIMICROBIAL ACTIVITY OF Ag+, Cu2+, Zn2+, Mg2+ IONS DOPED CHITOSAN NANOPARTICLES

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Sukhodub LB

2015-04-01

Full Text Available Modification by polymers and inorganic ions of the bioactive materials for orthopedic implants with the purpose of initiating controlled reactions in tissues that surround the implant, is one of the modern approaches in medical materials. A key feature of functional polymers is their ability to form complexes with various metal ions in solution. Chitosan is natural biopolymer with pronounced affinity to transition metal ions. Some researches prove the higher antimicrobial activity of Chitosan-metal complexes compared with pure Chitosan. The purpose of this work was the study of antimicrobial activity of Chitosan nanoparticles modified by metal ions Ag+, Cu2+, Zn2+, Mg2+ against reference strains S. aureus 25923 ATSS, E. coli ATCC 25922, C. albicans ATCC 885653 for their further use as components of the composite biomaterials for medical purpose.Chitosan nanoparticles suspension was prepared by known method based on the ionotropic gelation between chitosan and sodium tripolyphosphate.To obtain Chitosan-metal nanoparticles to the Chitosan suspension were added the corresponding metal ions aqueous solutions in quantity to match the concentration of metal ions of 200 ppm . Antibacterial activities of Ag+, Cu2+, Zn2+, Mg2+ ions doped Chitosan nanoparticles, pure Chitosan nanoparticles, metal ions and 1% (v/v acetic acid solution (it was used as solvent for Chitosan against bacteria were evaluated by determination of minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC in vitro. Muller– Hinton (MH broth and MH agar (Russia were used as growth media. The bacteria suspension for further use was prepared with concentration that corresponded 0,5units by McFarland scale. The MIC was determined by a broth dilution method. The results were read after 24 hours of experimental tubes incubation at 37 oC as equivalent to the concentration of the tube without visible growth. To evaluate MBC, a sample of 0,1 ml was transferred from

Chitosan-based nanoparticles for rosmarinic acid ocular delivery--In vitro tests.

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da Silva, Sara Baptista; Ferreira, Domingos; Pintado, Manuela; Sarmento, Bruno

2016-03-01

In this study, chitosan nanoparticles were used to encapsulate antioxidant rosmarinic acid, Salvia officinalis (sage) and Satureja montana (savory) extracts as rosmarinic acid natural vehicles. The nanoparticles were prepared by ionic gelation using chitosan and sodium tripolyphosphate (TPP) in a mass ratio of 7:1, at pH 5.8. Particle size distribution analysis and transmission electron microscopy (TEM) confirmed the size ranging from 200 to 300 nm, while surface charge of nanoparticles ranged from 20 to 30 mV. Nanoparticles demonstrate to be safe without relevant cytotoxicity against retina pigment epithelium (ARPE-19) and human cornea cell line (HCE-T). The permeability study in HCE monolayer cell line showed an apparent permeability coefficient Papp of 3.41±0.99×10(-5) and 3.24±0.79×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. In ARPE-19 monolayer cell line the Papp was 3.39±0.18×10(-5) and 3.60±0.05×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. Considering the mucin interaction method, nanoparticles indicate mucoadhesive proprieties suggesting an increased retention time over the ocular mucosa after instillation. These nanoparticles may be promising drug delivery systems for ocular application in oxidative eye conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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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

5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

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R. Seda Tığlı Aydın

2012-01-01

Full Text Available Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nm and 243.1±17.9 nm particle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1–60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments.

An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery

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Munawar A. Mohammed

2017-11-01

Full Text Available The focus of this review is to provide an overview of the chitosan based nanoparticles for various non-parenteral applications and also to put a spotlight on current research including sustained release and mucoadhesive chitosan dosage forms. Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary use and approved for wound dressing applications. Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration. Chitosan has chemical functional groups that can be modified to achieve specific goals, making it a polymer with a tremendous range of potential applications. Nanoparticles (NP prepared with chitosan and chitosan derivatives typically possess a positive surface charge and mucoadhesive properties such that can adhere to mucus membranes and release the drug payload in a sustained release manner. Chitosan-based NP have various applications in non-parenteral drug delivery for the treatment of cancer, gastrointestinal diseases, pulmonary diseases, drug delivery to the brain and ocular infections which will be exemplified in this review. Chitosan shows low toxicity both in vitro and some in vivo models. This review explores recent research on chitosan based NP for non-parenteral drug delivery, chitosan properties, modification, toxicity, pharmacokinetics and preclinical studies.

Synthesis and Characterization of New Thiolated Chitosan Nanoparticles Obtained by Ionic Gelation Method

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Reynaldo Esquivel

2015-01-01

Full Text Available We derivatized low molecular weight chitosan (LMWC with 3-mercaptopropanoic acid (3-MPA by a coupling reaction. The chemical modification of LMWC was characterized by Fourier transform infrared spectroscopy (FT-IR and nuclear magnetic resonance, 1HNMR. We researched the influence of 3-MPA on the nanoparticles formation by ionic gelation method using sodium tripolyphosphate (TPP as cross-linker reagent. In order to optimize the nanoparticles formation, we studied the effect of the pH solution and molar ratio on nanoparticles stability. Analyses of particle size, morphology, and surface charge were determined by dynamic light scattering, Atomic Force Microscopy, and zeta potential, respectively. It was found that formation of semispherical and stable nanoparticles was improved due to the chemical modification of chitosan. Optimized semispherical nanoparticles of thiolated chitosan were synthesized with the parameters (pH 4.7, molar ratios 1 : 106. Additionally, we reported the thermodynamic profile of the nanoparticles formation determined by isothermal titration calorimetry (ITC. The aggregation process achieved to form nanoparticles of thiolated and nonmodified chitosan consisted of two stages, considering one binding site model. Gibbs free energy (ΔG and binding constant (Ka describe the aggregation process of thiolated chitosan/TPP, which is an initial reaction and followed by an endothermic stage. These results are promising for the possible application of these nanoparticles as nanocarriers and delivery systems.

Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

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Ahmad, Tanveer [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, Abdul Wali Khan University, Mardan (Pakistan); Bae, Hongsub; Iqbal, Yousaf [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Rhee, Ilsu, E-mail: ilrhee@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hong, Sungwook [Division of Science Education, Daegu University, Gyeongsan 712-714 (Korea, Republic of); Chang, Yongmin; Lee, Jaejun [Department of Diagnostic Radiology, College of Medicine, Kyungpook National University and Hospital, Daegu 700-721 (Korea, Republic of); Sohn, Derac [Department of Physics, Hannam University, Daejon (Korea, Republic of)

2015-05-01

We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe{sub 2}O{sub 4}) nanoparticles as both T{sub 1} and T{sub 2} contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T{sub 1} and T{sub 2} relaxivities were 0.858±0.04 and 1.71±0.03 mM{sup −1} s{sup −1}, respectively. In animal experimentation, both a 25% signal enhancement in the T{sub 1}-weighted mage and a 71% signal loss in the T{sub 2}-weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T{sub 1} and T{sub 2} contrast agents in MRI. We note that the applicability of our nanoparticles as both T{sub 1} and T{sub 2} contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe{sub 2}O{sub 4}) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T{sub 1} and T{sub 2} contrast agents for MRI by measuring T{sub 1} and T{sub 2} relaxation times as a function of iron concentration. • Both T{sub 1} and T{sub 2} effects were also observed in animal experimentation.

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

Science.gov (United States)

Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Oral Vaccination Based on DNA-Chitosan Nanoparticles against Schistosoma mansoni Infection

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Carolina R. Oliveira

2012-01-01

Full Text Available The development of a vaccine would be essential for the control of schistosomiasis, which is recognized as the most important human helminth infection in terms of morbidity and mortality. A new approach of oral vaccination with DNA-chitosan nanoparticles appears interesting because of their great stability and the ease of target accessibility, besides chitosan immunostimulatory properties. Here we described that chitosan nanoparticles loaded with plasmid DNA encoding Rho1-GTPase protein of Schistosoma mansoni, prepared at different molar ratios of primary amines to DNA phosphate anion (N/P, were able to complex electrostatically with DNA and condense it into positively charged nanostructures. Nanoparticles were able to maintain zeta potential and size characteristics in media that simulate gastric (SGF and intestinal fluids (SIF. Further in vivo studies showed that oral immunization was not able to induce high levels of specific antibodies but induced high levels of the modulatory cytokine IL-10. This resulted in a significative reduce of liver pathology, although it could not protect mice of infection challenge with S. mansoni worms. Mice immunized only with chitosan nanoparticles presented 47% of protection against parasite infection, suggesting an important role of chitosan in inducing a protective immune response against schistosomiasis, which will be more explored in further studies.

Preparing and Characterizing Chitosan Nanoparticles Containing Hemiscorpius lepturus Scorpion Venom as an Antigen Delivery System

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Mohammadpour Dounighi, N.

2012-11-01

Full Text Available In recent years, chitosan nanoparticles have been studied widely for protein delivery. In this study, Hemiscorpius lepturus (HL venom was encapsulated in chitosan nanoparticles. The aim of the present work was to carry out a systematic study for preparing biocompatible and biodegradable nanoparticles for loading HL scorpion venom and to evaluate their potential as an antigen delivery system. In this study, HL venom loaded chitosan nanoparticles fabricated by ionic gelation of chitosan and tripolyphosphate and the factors which may be influenced in the preparation of nanoparticles were analyzed. Also, their physicochemical properties and in vitro release behavior were studied. The optimum encapsulation efficiency and capacity were observed when the chitosan concentration and HL venom were 2mg/ml and 500µg/ml, respectively. The HL venom loaded nanoparticles were in the size range of 130-160nm (polydispersity index values of 0.423 and exhibited the positive zeta potential. Transmission electron microscope imaging showed spherical and smooth surface of nanoparticles. The profiles of the release exhibited a burst releases about 50% in the first 4 hr and then slowed down at a constant rate. The obtained results suggested that the chitosan nanoparticles prepared in this work had the potential for antigen delivery.

Improvement of interaction between PVA and chitosan via magnetite nanoparticles for drug delivery application.

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Shagholani, Hamidreza; Ghoreishi, Sayed Mehdi; Mousazadeh, Mohammad

2015-01-01

Magnetite nanoparticles were synthesized by coprecipitation under ultrasonication followed by coating with chitosan. Polyvinyl alcohol (PVA) is then combined with the chitosan that coated the magnetite nanoparticles. The combination occurs by hydrogen binding and ionic cross-linking of the amino and hydroxyl groups of chitosan and PVA respectively. The magnetite nanoparticles have an average size of 10.62 nm that was confirmed by TEM. The VSM measurements showed that nanoparticles were superparamagnetic. The coatings on the core nanoparticles were estimated by AAS and the attachments of coating to the nanoparticles were confirmed by FT-IR analysis. Physicochemical properties of nanoparticles were measured by DLS and zeta potential. Naked magnetite, chitosan and PVA coating have zeta potential of +36.4, +48.1 and -12.5 mV respectively. The unspecific adsorption and interaction between nanoparticles and bovine serum albumin (BSA) were investigated systematically by UV-vis spectroscopy method. The nanoparticles that were modified by PVA present low protein adsorption, which makes them a practical choice for preventing opsonization in clinical application and drug delivery. Copyright © 2015. Published by Elsevier B.V.

Attenuated effects of chitosan-capped gold nanoparticles on LPS-induced toxicity in laboratory rats

International Nuclear Information System (INIS)

Stefan, Marius; Melnig, Viorel; Pricop, Daniela; Neagu, Anca; Mihasan, Marius; Tartau, Liliana; Hritcu, Lucian

2013-01-01

The impact of nanoparticles in medicine and biology has increased rapidly in recent years. Gold nanoparticles (AuNP) have advantageous properties such as chemical stability, high electron density and affinity to biomolecules. However, the effects of AuNP on human body after repeated administration are still unclear. Therefore, the purpose of the present study was to evaluate the effects of gold-11.68 nm (AuNP1, 9.8 μg) and gold-22.22 nm (AuNP2, 19.7 μg) nanoparticles capped with chitosan on brain and liver tissue reactivity in male Wistar rats exposed to lipopolysaccharide (LPS from Escherichia coli serotype 0111:B4, 250 μg) upon 8 daily sessions of intraperitoneal administration. Our results suggest that the smaller size of chitosan-capped AuNP shows the protective effects against LPS-induced toxicity, suggesting a very high potential for biomedical applications. - Highlights: ► Smaller size of chitosan-capped gold nanoparticles acts against LPS-induced toxicity. ► Larger size of chitosan-capped gold nanoparticles agglomerated inside neurons and induced toxicity in combination with LPS. ► Chitosan has excellent biocompatible proprieties. ► Smaller size of chitosan-capped gold nanoparticles demonstrates great potential in biomedical applications.

miRNA-218-loaded carboxymethyl chitosan - Tocopherol nanoparticle to suppress the proliferation of gastrointestinal stromal tumor growth

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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.

Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

DEFF Research Database (Denmark)

Martirosyan, Alina; Olesen, Morten Jarlstad; Howard, Kenneth A.

2014-01-01

of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties...... of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA....

Acceleration of gene transfection efficiency in neuroblastoma cells through polyethyleneimine/poly(methyl methacrylate core-shell magnetic nanoparticles

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Tencomnao T

2012-06-01

Full Text Available Tewin Tencomnao,1,* Kewalin Klangthong,2,* Nuttaporn Pimpha,3 Saowaluk Chaleawlert-umpon,3 Somsak Saesoo,3 Noppawan Woramongkolchai,3 Nattika Saengkrit,31Center for Excellence in Omics-Nano Medical Technology Development Project, 2Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 3National Nanotechnology Center, National Science and Technology Development Agency, Pathumthani, Thailand*Both authors contributed equally to this workBackground: The purpose of this study was to demonstrate the potential of magnetic poly(methyl methacrylate (PMMA core/polyethyleneimine (PEI shell (mag-PEI nanoparticles, which possess high saturation magnetization for gene delivery. By using mag-PEI nanoparticles as a gene carrier, this study focused on evaluation of transfection efficiency under magnetic induction. The potential role of this newly synthesized nanosphere for therapeutic delivery of the tryptophan hydroxylase-2 (TPH-2 gene was also investigated in cultured neuronal LAN-5 cells.Methods: The mag-PEI nanoparticles were prepared by one-step emulsifier-free emulsion polymerization, generating highly loaded and monodispersed magnetic polymeric nanoparticles bearing an amine group. The physicochemical properties of the mag-PEI nanoparticles and DNA-bound mag-PEI nanoparticles were investigated using the gel retardation assay, atomic force microscopy, and zeta size measurements. The gene transfection efficiencies of mag-PEI nanoparticles were evaluated at different transfection times. Confocal laser scanning microscopy confirmed intracellular uptake of the magnetoplex. The optimal conditions for transfection of TPH-2 were selected for therapeutic gene transfection. We isolated the TPH-2 gene from the total RNA of the human medulla oblongata and cloned it into an expression vector. The plasmid containing TPH-2 was subsequently bound onto the

Hyaluronic acid-coated chitosan nanoparticles: molecular weight-dependent effects on morphology and hyaluronic acid presentation.

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Almalik, Abdulaziz; Donno, Roberto; Cadman, Christopher J; Cellesi, Francesco; Day, Philip J; Tirelli, Nicola

2013-12-28

Chitosan nanoparticles are popular carriers for the delivery of macromolecular payloads, e.g. nucleic acids. In this study, nanoparticles were prepared via complexation with triphosphate (TPP) anions and were successively coated with hyaluronic acid (HA). Key variables of the preparative process (e.g. chitosan and HA molecular weight) were optimised in view of the maximisation of loading with DNA, of the Zeta potential and of the dimensional stability, and the resulting particles showed excellent storage stability. We have focused on the influence of chitosan molecular weight on nanoparticle properties. Larger molecular weight increased their porosity (=decreased cross-link density), and this caused also larger dimensional changes in response to variations in osmotic pressure or upon drying. The dependency of nanoparticle porosity on chitosan molecular weight had a profound effect on the adsorption of HA on the nanoparticles; HA was apparently able to penetrate deeply into the more porous high molecular weight (684 kDa) chitosan nanoparticles, while it formed a corona around those composed of more densely cross-linked low molecular weight (25 kDa) chitosan. Atomic Force Microscopy (AFM) allowed not only to highlight the presence of this corona, but also to estimate its apparent thickness to about 20-30 nm (in a dry state). The different morphology has a significant effect on the way HA is presented to biomolecules, and this has specific relevance in relation to interactions with HA receptors (e.g. CD44) that influence kinetics and mechanism of nanoparticle uptake. Finally, it is worth to mention that chitosan molecular weight did not appear to greatly affect the efficiency of nanoparticle loading with DNA, but significantly influenced its chitosanase-triggered release, with high molecular chitosan nanoparticles seemingly more prone to degradation by this enzyme. © 2013.

Chitosan nanoparticles affect acid tolerance response in adhered cells of strpetococcus mutans

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Neilands, Julia; Sutherland, Duncan S; Resin, Anton

2011-01-01

In this study we evaluated the effect of chitosan nanoparticles on the acid tolerance response (ATR) of adhered Streptococcus mutans. An ATR was induced by exposing S. mutans to pH 5.5 for 2 h and confirmed by exposing the acid-adapted cells to pH 3.5 for 30 min, with the majority of cells...... appearing viable according to the LIVE/DEAD (R) technique. However, when chitosan nanoparticles were present during the exposure to pH 5.5, no ATR occurred as most cells appeared dead after the pH 3.5 shock. We conclude that the chitosan nanoparticles tested had the ability to hinder ATR induction...

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

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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

Characterization and Biocompatibility of Chitosan Gels with Silver and Gold Nanoparticles

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C. Sámano-Valencia

2014-01-01

Full Text Available The presence of bacterial resistance to antibiotics is a very important issue and the search of new alternatives is necessary. In this work, a combination of chitosan gel with silver or gold nanoparticles was prepared and characterized using thermal, rheology, bactericide, and biocompatibility analyses. ESEM images were also taken to visualize the incorporation of the nanoparticles into the gel matrix. Thermal analysis showed a better thermal stability in the chitosan-gold nanoparticles gels compared to the chitosan-silver nanoparticles gels. Rheology analyses showed that the viscosity of the gels decreased when velocity increased and there were differences in viscosity when silver and gold nanoparticles concentrations change. ESEM images showed the presence of agglomerates of silver and gold nanoparticles into the gel matrix with a good distribution; in some cases the formation of microstructures was found. Bactericide results show that these materials present an antibacterial activity against S. aureus, S. mutans, and E. coli. The biocompatibility test showed neither negative reaction nor wound healing delay after the application of the gels in an in vivo test. The gels with silver and gold nanoparticles could be used to treat wound infections in oral or skin applications.

Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

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Dag Heinemann

Full Text Available Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

Science.gov (United States)

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Murua Escobar, Hugo; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

Gold Nanoparticle Mediated Laser Transfection for Efficient siRNA Mediated Gene Knock Down

Science.gov (United States)

Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Escobar, Hugo Murua; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

2013-01-01

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types. PMID:23536802

Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: ibuprofen.

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Hassani Najafabadi, Alireza; Abdouss, Majid; Faghihi, Shahab

2014-08-01

Current methods for preparation of PEGylated chitosan have limitations such as harsh de protecting step and several purification cycles. In the present study, a facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan under mild condition is introduced to improve water solubility of chitosan and control the release of poor water soluble drugs. The method consists of chitosan modification by grafting the C6 position of chitosan to mPEG which is confirmed by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance ((1)HNMR) analyses. The amine groups at the C2 position of chitosan are protected using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and (1)HNMR. The synthesized polymer is then employed to prepare nanoparticles which are characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for their size and morphology. The nanoparticles are used for encapsulation of ibuprofen followed by in vitro release investigation in gastrointestinal and simulated biological fluids. The chitosan nanoparticles are used as control. The PEGylated nanoparticles show a particle size of 80 nm with spherical morphology. The results clearly show that drug release from PEGylated chitosan nanoparticles is remarkably slower than chitosan. In addition, drug encapsulation and encapsulation efficiency in PEGylated nanoparticles are dependent on the amount of drug added to the formulation being significantly higher than chitosan nanoparticles. This study provides an efficient, novel, and facile method for preparing a nano carrier system for delivery of water insoluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Collagen-chitosan scaffold modified with Au and Ag nanoparticles: Synthesis and structure

International Nuclear Information System (INIS)

Rubina, M.S.; Kamitov, E.E.; Zubavichus, Ya. V.; Peters, G.S.; Naumkin, A.V.; Suzer, S.; Vasil’kov, A.Yu.

2016-01-01

Graphical abstract: - Highlights: • Biocompatible collagen-chitosan scaffolds were modified by Au and Ag nanoparticles via the metal-vapor synthesis. • Structural and morphological parameters of the nanocomposites were assessed using a set of modern instrumental techniques, including electron microscopy, X-ray diffraction, small-angle X-ray scattering, EXAFS, XPS. • Potential application of the nanocomposites are envisaged. - Abstract: Nowadays, the dermal biomimetic scaffolds are widely used in regenerative medicine. Collagen-chitosan scaffold one of these materials possesses antibacterial activity, good compatibility with living tissues and has been already used as a wound-healing material. In this article, collagen-chitosan scaffolds modified with Ag and Au nanoparticles have been synthesized using novel method - the metal-vapor synthesis. The nanocomposite materials are characterized by XPS, TEM, SEM and synchrotron radiation-based X-ray techniques. According to XRD data, the mean size of the nanoparticles (NPs) is 10.5 nm and 20.2 nm in Au-Collagen-Chitosan (Au-CollCh) and Ag-Collagen-Chitosan (Ag-CollCh) scaffolds, respectively in fair agreement with the TEM data. SAXS analysis of the composites reveals an asymmetric size distribution peaked at 10 nm for Au-CollCh and 25 nm for Ag-CollCh indicative of particle's aggregation. According to SEM data, the metal-carrying scaffolds have layered structure and the nanoparticles are rather uniformly distributed on the surface material. XPS data indicate that the metallic nanoparticles are in their unoxidized/neutral states and dominantly stabilized within the chitosan-rich domains.

Collagen-chitosan scaffold modified with Au and Ag nanoparticles: Synthesis and structure

Energy Technology Data Exchange (ETDEWEB)

Rubina, M.S.; Kamitov, E.E. [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991 Russian Federation (Russian Federation); Zubavichus, Ya. V.; Peters, G.S. [National Research center «Kurchatov Institute», Moscow, 123182 Russian Federation (Russian Federation); Naumkin, A.V. [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991 Russian Federation (Russian Federation); Suzer, S. [Department of Chemistry, Bilkent University, Ankara, 06800 Turkey (Turkey); Vasil’kov, A.Yu., E-mail: alexandervasilkov@yandex.ru [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, 119991 Russian Federation (Russian Federation)

2016-03-15

Graphical abstract: - Highlights: • Biocompatible collagen-chitosan scaffolds were modified by Au and Ag nanoparticles via the metal-vapor synthesis. • Structural and morphological parameters of the nanocomposites were assessed using a set of modern instrumental techniques, including electron microscopy, X-ray diffraction, small-angle X-ray scattering, EXAFS, XPS. • Potential application of the nanocomposites are envisaged. - Abstract: Nowadays, the dermal biomimetic scaffolds are widely used in regenerative medicine. Collagen-chitosan scaffold one of these materials possesses antibacterial activity, good compatibility with living tissues and has been already used as a wound-healing material. In this article, collagen-chitosan scaffolds modified with Ag and Au nanoparticles have been synthesized using novel method - the metal-vapor synthesis. The nanocomposite materials are characterized by XPS, TEM, SEM and synchrotron radiation-based X-ray techniques. According to XRD data, the mean size of the nanoparticles (NPs) is 10.5 nm and 20.2 nm in Au-Collagen-Chitosan (Au-CollCh) and Ag-Collagen-Chitosan (Ag-CollCh) scaffolds, respectively in fair agreement with the TEM data. SAXS analysis of the composites reveals an asymmetric size distribution peaked at 10 nm for Au-CollCh and 25 nm for Ag-CollCh indicative of particle's aggregation. According to SEM data, the metal-carrying scaffolds have layered structure and the nanoparticles are rather uniformly distributed on the surface material. XPS data indicate that the metallic nanoparticles are in their unoxidized/neutral states and dominantly stabilized within the chitosan-rich domains.

Synthesis, characterization and antibacterial activity of hybrid chitosan-cerium oxide nanoparticles: As a bionanomaterials.

Science.gov (United States)

Senthilkumar, R P; Bhuvaneshwari, V; Ranjithkumar, R; Sathiyavimal, S; Malayaman, V; Chandarshekar, B

2017-11-01

The hybrid chitosan cerium oxide nanoparticles were prepared for the first time by green chemistry approach using plant leaf extract. The intense peak observed around 292nm in the UV-vis spectrum indicate the formation of cerium oxide nanoparticles. The XRD pattern revealed that the hybrid chitosan-cerium oxide nanoparticles have a polycrystalline structure with cubic fluorite phase. The FTIR spectrum of prepared samples showed the formation of Ce-O bonds and chitosan main chains COC and CO. The FESEM image of hybrid chitosan cerium oxide nanoparticles revealed that the particles are spherical in shape with grains size varying from 23.12nm to 89.91nm. EDAX analysis confirmed the presence of Ce, O, C and N elements in the prepared sample. TEM images showed that the prepared hybrid chitosan-cerium oxide nanoparticles are predominantly uniform in size and most of the particles are spherical in shape with less agglomeration and the particles size varies from 3.61nm to 24.40nm. The prepared chitosan cerium oxide nanoparticles of 50μL concentration showed good antibacterial properties against test pathogens, which was confirmed by the FESEM analysis. The prepared small particle size facilitate that these hybrid ChiCO 2 NPs could effectively be used in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia.

Science.gov (United States)

Kim, Dong-Hyun; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Lee, Yong-Keun

2009-01-01

The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia. 2008 Wiley Periodicals, Inc.

Chitosan-coated magnetic nanoparticles prepared in one step by reverse microemulsion precipitation.

Science.gov (United States)

López, Raúl G; Pineda, María G; Hurtado, Gilberto; León, Ramón Díaz de; Fernández, Salvador; Saade, Hened; Bueno, Darío

2013-09-27

Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70 °C and 80 °C in a one-step method, which comprises precipitation in reverse microemulsion in the presence of low chitosan concentration in the aqueous phase. X-ray diffractometry showed that CMNP obtained at both temperatures contain a mixture of magnetite and maghemite nanoparticles with ≈4.5 nm in average diameter, determined by electron microscopy, which suggests that precipitation temperature does not affect the particle size. The chitosan coating on nanoparticles was inferred from Fourier transform infrared spectrometry measurements; furthermore, the carbon concentration in the nanoparticles allowed an estimation of chitosan content in CMNP of 6%-7%. CMNP exhibit a superparamagnetic behavior with relatively high final magnetization values (≈49-53 emu/g) at 20 kOe and room temperature, probably due to a higher magnetite content in the mixture of magnetic nanoparticles. In addition, a slight direct effect of precipitation temperature on magnetization was identified, which was ascribed to a possible higher degree of nanoparticles crystallinity as temperature at which they are obtained increases. Tested for Pb2+ removal from a Pb(NO3)2 aqueous solution, CMNP showed a recovery efficacy of 100%, which makes them attractive for using in heavy metals ion removal from waste water.

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.

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

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

The impact of arginine-modified chitosan-DNA nanoparticles on the function of macrophages

Energy Technology Data Exchange (ETDEWEB)

Liu Lanxia; Bai Yuanyuan; Song Chunni; Zhu Dunwan; Song Liping; Zhang Hailing; Dong Xia; Leng Xigang, E-mail: lengxg@bme.org.c [Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Laboratory of Bioengineering (China)

2010-06-15

It has been demonstrated that incorporation of arginine moieties into chitosan significantly elevates the transgenic efficacy of the chitosan. However, little is known about the impact of arginine-modified chitosan on the function of macrophages, which play a vitally important role in the inflammatory response of the body to foreign substances, especially particulate substances. This study was designed to investigate the impact of arginine-modified chitosan/DNA nanoparticles on the function of the murine macrophage through observation of phagocytic activity and production of pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-10, IL-12, and TNF-{alpha}). Results showed that both chitosan/DNA nanoparticles and arginine-modified chitosan/DNA nanoparticles, containing 20 {mu}g/mL DNA, were internalized by almost all the macrophages in contact. This led to no significant changes, compared to the non-exposure group, in production of cytokines and phagocytic activity of the macrophages 24 h post co-incubation, whereas exposure to LPS induced obviously elevated cytokine production and phagocytic activity, suggesting that incorporation of arginine moieties into chitosan does not have a negative impact on the function of the macrophages.

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

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.

Development of Cy5.5-Labeled Hydrophobically Modified Glycol Chitosan Nanoparticles for Protein Delivery

Science.gov (United States)

Chin, Amanda

Therapeutic proteins are often highly susceptible to enzymatic degradation, thus restricting their in vivo stability. To overcome this limitation, delivery systems designed to promote uptake and reduce degradation kinetics have undergone a rapid shift from macro-scale systems to nanomaterial based carriers. Many of these nanomaterials, however, elicit immune responses and may have cytotoxic effects both in vitro and in vivo. The naturally derived polysaccharide chitosan has emerged as a promising biodegradable material and has been utilized for many biomedical applications; nevertheless, its function is often constrained by poor solubility. Glycol chitosan, a derivative of chitosan, can be hydrophobically modified to impart amphiphilic properties that enable the self-assembly into nanoparticles in aqueous media at neutral pH. This nanoparticle system has shown initial success as a therapeutic agent in several model cell culture systems, but little is known about its stability against enzymatic degradation. Therefore, the goal of this research was to investigate the resistance of hydrophobically modified glycol chitosan against enzyme-catalyzed degradation using an in vivo simulated system containing lysozyme. To synthesize the nanoparticles, hydrophobic cholanic acid was first covalently conjugated to glycol chitosan using of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Conjugates were purified by dialysis, lyophilized, and ultra-sonicated to form nanoparticles. Fourier transform infrared (FT-IR) spectroscopy confirmed the binding of 5beta-cholanic acid to the glycol chitosan. Particle size and stability over time were determined with dynamic light scattering (DLS), and particle morphology was evaluated by transmission electron microscopy (TEM). The average diameter of the nanoparticles was approximately 200 nm, which remained stable at 4°C for up to 10 days. Additionally, a near infrared fluorescent (NIRF) dye

Synthesis and Optimization of Chitosan Nanoparticles of Shrimp shell as Adsorbent of Pb2+ Ions

Directory of Open Access Journals (Sweden)

Sulistyani Sulistyani

2017-11-01

Full Text Available Synthesis and optimization of chitosan nanoparticles from shrimp shell as an adsorbent of Pb2+ ions has been done. Chitosan is obtained through several stages, namely deproteinase, demineralization and deacetylation. Deproteinase by using 2 N NaOH solution (a ratio of 1:6 w/v while stirring at 90 °C for 1 hour. Demineralization by using 1 N HCl solution (a ratio of 1:12 w/v while stirring at room temperature for 1 hour. Deacetylation by using 50% NaOH solution (a ratio of 1:10 w/v at 120 °C for 3 hours. Chitosan nanoparticles are obtained by adding a solution of 1% CH3COOH and a few drops of NH3 concentrated at 90 °C to form a white gel is then washed to pH neutral and dried. Characterization of chitosan include analysis of degree of deacetylation by using FTIR and analysis of particle size by using Particle Size Analyzer (PSA. Chitosan nanoparticles was then applied as an adsorbent of lead. Optimization of chitosan as an adsorbent include contact time and pH. Concentration of lead is determined using Atomic Absorption Spectroscopy (AAS. The results showed chitosan synthesis product has a size of ~600 nm, so that it can be expressed as nanoparticles with a degree of deacetylation of 62.69%. Chitosan nanoparticles as adsorbent optimum at pH 3 and a contact time of 2 hours with an adsorption capacity of 13,25 mg/g .

Chitosan doped with nanoparticles of copper, nickel and cobalt.

Science.gov (United States)

Cárdenas-Triviño, Galo; Elgueta, Carolina; Vergara, Luis; Ojeda, Javier; Valenzuela, Ariel; Cruzat, Christian

2017-11-01

Metal colloids in 2 propanol using nanoparticles (NPs) of copper, nickel and cobalt were prepared by Chemical Liquid Deposition (CLD) method. The resulting colloidal dispersions were characterized by Transmission Electron Microscopy (TEM). The colloids were supported in chitosan. Then, microbiological assays were performed using E. coli and S. aureus in order to determine the bactericide/bacteriostatic activity of nanoparticles (NPs) trapped or chelated with chitosan. Finally, the toxicity of the metal colloids Cu, Ni and Co was tested. Bio-assays were conducted in three different animal species. First of all on earth warms (Eisenia foetida) to evaluate the toxicity and the biocompatibility of chitosan in lactic acid (1% and 0.5%). Secondly bio-assay done in fishes (rainbow trout), the liver toxicity of NPs in vivo was evaluated. Finally, a bio-assay was conducted in Sprange-Dawley rats of 100g weight, which were injected intraperitoneally with different solutions of chitosan metal colloids. Then, the minimum and maximum concentration were determined for copper, nickel and cobalt. The purpose of the use of chitosan was acting as a carrier for some magnetic NPs, which toxicity would allow to obtain new polymeric materials with potential applications as magnet future drugs carrier. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and Optimization of Insulin-Chitosan Nanoparticles

African Journals Online (AJOL)

to optimize formulation. Properties such as particle shape, size, zeta potential and release behavior ... the positively charged chitosan nanoparticles had strong electrostatic ... dropping 3 ml of TPP reserve liquid quickly into the system at 40 ºC ...

Preparation, characterization and adsorption properties of chitosan nanoparticles for eosin Y as a model anionic dye

International Nuclear Information System (INIS)

Du Wenli; Xu Zirong; Han Xinyan; Xu Yinglei; Miao Zhiguo

2008-01-01

The present study dealt with the adsorption of eosin Y, as a model anionic dye, from aqueous solution using chitosan nanoparticles prepared by the ionic gelation between chitosan and tripolyphosphate. The nanoparticles were characterized by atomic force microscopy (AFM), size and zeta potential analysis. A batch system was applied to study the adsorption of eosin Y from aqueous solution by chitosan nanoparticles. The results showed that the adsorption of eosin Y on chitosan nanoparticles was affected by contact time, eosin Y concentration, pH and temperature. Experimental data followed Langmuir isotherm model and the adsorption capacity was found to be 3.333 g/g. The adsorption process was endothermic in nature with an enthalpy change (ΔH) of 16.7 kJ/mol at 20-50 deg. C. The optimum pH value for eosin Y removal was found to be 2-6. The dye was desorbed from the chitosan nanoparticles by increasing the pH of the solution

Preparation, characterization and adsorption properties of chitosan nanoparticles for eosin Y as a model anionic dye

Energy Technology Data Exchange (ETDEWEB)

Du Wenli [Institute of Feed Science, College of Animal Science, Zhejiang University, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou 310029 (China)], E-mail: wenlidu@126.com; Xu Zirong; Han Xinyan; Xu Yinglei; Miao Zhiguo [Institute of Feed Science, College of Animal Science, Zhejiang University, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou 310029 (China)

2008-05-01

The present study dealt with the adsorption of eosin Y, as a model anionic dye, from aqueous solution using chitosan nanoparticles prepared by the ionic gelation between chitosan and tripolyphosphate. The nanoparticles were characterized by atomic force microscopy (AFM), size and zeta potential analysis. A batch system was applied to study the adsorption of eosin Y from aqueous solution by chitosan nanoparticles. The results showed that the adsorption of eosin Y on chitosan nanoparticles was affected by contact time, eosin Y concentration, pH and temperature. Experimental data followed Langmuir isotherm model and the adsorption capacity was found to be 3.333 g/g. The adsorption process was endothermic in nature with an enthalpy change ({delta}H) of 16.7 kJ/mol at 20-50 deg. C. The optimum pH value for eosin Y removal was found to be 2-6. The dye was desorbed from the chitosan nanoparticles by increasing the pH of the solution.

Functional enhancement of chitosan and nanoparticles in cell culture, tissue engineering, and pharmaceutical applications

Directory of Open Access Journals (Sweden)

Wenjuan eGao

2012-08-01

Full Text Available Abstract: As a biomaterial, chitosan has been widely used in tissue engineering, wound healing, drug delivery, and other biomedical applications. It can be formulated in a variety of forms, such as powder, film, sphere, gel and fiber. These features make chitosan an almost ideal biomaterial in cell culture applications, and cell cultures arguably constitute the most practical way to evaluate biocompatibility and biotoxicity. The advantages of cell cultures are that they can be performed under totally controlled environments, allow high throughput functional screening, and are less costly, as compared to other assessment methods. Chitosan can also be modified into multilayer composite by combining with other polymers and moieties to alter the properties of chitosan for particular biomedical applications. This review briefly depicts and discusses applications of chitosan and nanoparticles in cell culture, in particular, the effects of chitosan and nanoparticles on cell adhesion, cell survival, and the underlying molecular mechanisms: both stimulatory and inhibitory influences are discussed. Our aim is to update the current status of how nanoparticles can be utilized to modify the properties of chitosan to advance the art of tissue engineering by using cell cultures.

Preparation and protection of silver nanoparticles with chitosan derivative

International Nuclear Information System (INIS)

Nguyen Thi Kim Cuc; Cao Van Du; Nguyen Cuu Khoa; Tran Ngoc Quyen

2013-01-01

In this paper, nano silver solution is prepared and stabilized by chitosan dihydroxyphenyl acetamide (CDHPA). Chitosan is a natural carbohydrate polymer deriving from chitin that has biodegradable, biocompatible, antibacterial and antifungal properties, so when conjugation of the polymer and silver nanoparticles could be expected to increase bactericidal features of the obtained product. The chemical and physical methods were used to characterize the chitosan derivative such as transmission spectrum (UV-Vis), IR spectrum, nuclear magnetic resonance (1H-NMR). Morphology of the obtained nano silver particles were observed by transmission electron microscopy (TEM). (author)

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.

An Insight into the Interactions between a-Tocopherol and Chitosan in Ultrasound-Prepared Nanoparticles

International Nuclear Information System (INIS)

Naghibzadeh, M.; Amani, A.; Esmaeilzadeh, E.; Amini, M.; Mottaghi-Dastjerdi, N.; Faramarzi, M.A.; Faramarzi, M.A.

2010-01-01

The aim of this study was to investigate the interactions between a-tocopherol and chitosan molecules prepared subsequent to preparation of a-tocopherol-loaded chitosan nanoparticles using ultrasonication. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) analyses showed semi spherical particles with an average size of approximately 350 nm. Also from reconstitution test, a-tocopherol was suggested as stabilizing agent during lyophilization/reconstitution process. The zeta potentials of chitosan and a-tocopherol nanoparticles were larger than ±30 mV, representing suitable stability. Data obtained from FTIR showed possibility of chemical interaction between chitosan and a-tocopherol. Furthermore, the results from FTIR, NMR, and XRD spectroscopy confirmed electrostatic interactions between the two molecules. Overall, this procedure could be considered as a facile method to prepare a-tocopherol-loaded nanoparticles.

Synthesis, characterization and cytotoxicity of S-nitroso-mercaptosuccinic acid-containing alginate/chitosan nanoparticles

Science.gov (United States)

Seabra, Amedea B.; Fabbri, Giulia K.; Pelegrino, Milena T.; Silva, Letícia C.; Rodrigues, Tiago

2017-06-01

Nitric oxide (NO) is an endogenous free radical, which plays key roles in several biological processes including vasodilation, neurotransmission, inhibition of platelet adhesion, cytotoxicity against pathogens, wound healing, and defense against cancer. Due to the relative instability of NO in vivo (half-life of ca. 0.5 seconds), there is an increasing interest in the development of low molecular weight NO donors, such as S-nitrosothiols (RSNOs), which are able to prolong and preserve the biological activities of NO in vivo. In order to enhance the sustained NO release in several biomedical applications, RSNOs have been successfully allied to nanomaterials. In this context, this work describes the synthesis and characterization of the NO donor S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), which belongs to the class of RSNOs, and its incorporation in polymeric biodegradable nanoparticles composed by alginate/chitosan. First, chitosan nanoparticles were obtained by gelation process with sodium tripolyphosphate (TPP), followed by the addition of the alginate layer, to enhance the nanoparticle protection. The obtained nanoparticles presented a hydrodynamic diameter of 343 ± 38 nm, polydispersity index (PDI) of 0.36 ± 0.1, and zeta potential of - 30.3 ± 0.4 mV, indicating their thermal stability in aqueous suspension. The negative zeta potential value was assigned to the presence of alginate chains on the surface of chitosan/TPP nanoparticles. The encapsulation efficiency of the NO donor into the polymeric nanoparticles was found to be 98 ± 0.2%. The high encapsulation efficiency value was attributed to the positive interactions between the NO donor and the polymeric content of the nanoparticles. Kinetics of NO release from the nanoparticles revealed a spontaneous and sustained release of therapeutic amounts of NO, for several hours under physiological temperature. The incubation of NO-releasing alginate/chitosan nanoparticles with human hepatocellular carcinoma

Radiation synthesis of chitosan stabilized gold nanoparticles comparison between e− beam and γ irradiation

International Nuclear Information System (INIS)

Vo, Khoa Dang Nguyen; Kowandy, Christelle; Dupont, Laurent; Coqueret, Xavier; Hien, Nguyen Quoc

2014-01-01

Gold nanoparticles were synthesized via radiolytic reduction of Au(III) salts induced by e − beam or γ-irradiation, using chitosan as a stabilizer. The effect of irradiation dose, chitosan concentration and the conditioning of HAuCl 4 –chitosan solutions were studied. UV–visible absorption measurements reveal that the size of Au clusters formed immediately after irradiation is correlated with the extent of chitosan scission chain of chitosan and fall with the increase of dose absorbed. This effect is more pronounced with solution conditioned under Argon (Ar). Au clusters coalesce to form stable nanoparticles after two weeks. - Highlights: • This paper underlines the potential of ionizing radiations in the synthesis of AuNps. • The size of the nanoparticles, and their stability are controlled by the ratio [GLA]/[Au(III)] • This paper compares results obtained with e − beam and γ irradiation for the AuNps synthesis. • This paper points the influence of dose rate on the size of preformed Au clusters

Chitosan nanoparticle-based neuronal membrane sealing and neuroprotection following acrolein-induced cell injury

Directory of Open Access Journals (Sweden)

Shi Riyi

2010-01-01

Full Text Available Abstract Background The highly reactive aldehyde acrolein is a very potent endogenous toxin with a long half-life. Acrolein is produced within cells after insult, and is a central player in slow and progressive "secondary injury" cascades. Indeed, acrolein-biomolecule complexes formed by cross-linking with proteins and DNA are associated with a number of pathologies, especially central nervous system (CNS trauma and neurodegenerative diseases. Hydralazine is capable of inhibiting or reducing acrolein-induced damage. However, since hydralazine's principle activity is to reduce blood pressure as a common anti-hypertension drug, the possible problems encountered when applied to hypotensive trauma victims have led us to explore alternative approaches. This study aims to evaluate such an alternative - a chitosan nanoparticle-based therapeutic system. Results Hydralazine-loaded chitosan nanoparticles were prepared using different types of polyanions and characterized for particle size, morphology, zeta potential value, and the efficiency of hydralazine entrapment and release. Hydralazine-loaded chitosan nanoparticles ranged in size from 300 nm to 350 nm in diameter, and with a tunable, or adjustable, surface charge. Conclusions We evaluated the utility of chitosan nanoparticles with an in-vitro model of acrolein-mediated cell injury using PC -12 cells. The particles effectively, and statistically, reduced damage to membrane integrity, secondary oxidative stress, and lipid peroxidation. This study suggests that a chitosan nanoparticle-based therapy to interfere with "secondary" injury may be possible.

Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Jahanbin, Tania [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Sauriat-Dorizon, Hélène [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France); Spearman, Peter [Faculty of Science, Engineering and Computing, University of Kingston, Penrhyn Road Kingston upon Thames Surrey KT1 2EE, London (United Kingdom); Benderbous, Soraya, E-mail: soraya.benderbous@univ-tlse3.fr [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Korri-Youssoufi, Hafsa, E-mail: hafsa.korri-youssoufi@u-psud.fr [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France)

2015-07-01

A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles has been developed. The chitosan nanoparticles were synthesized following an ionic gelation method and the conditions optimized to generate small nanoparticles (CNs) with a narrow size distribution of 35–65 nm. The gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP) has been examined by UV–visible, Fourier transform infrared spectroscopies (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the successful association of Gd(TPyP) without any structural distortion throughout the chitosan nanoparticles. The potential of Gd(TPyP)-CNs as MRI contrast agent has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities of Gd(TPyP)-CNs obtained from T{sub 1}-weighted images, increased with Gd concentration and attained an optimum r{sub 1} of 38.35 mM{sup −1} s{sup −1}, which is 12-fold higher compared to commercial Gd-DOTA (~ 4 mM{sup −1} s{sup −1} at 3T). The combination of such strong MRI contrast with the known properties of porphyrins in photodynamic therapy and biocompatibility of chitosan, presents a new perspective in using these compounds in cancer theranostics. - Highlights: • Synthesis of chitosan nanoparticles with small size • Study of loading properties with gadolinium porphyrins • In vitro properties of the conjugated complex as contrast agent for MRI imaging • Comparison of MRI properties with commercial contrast agent Gd-DOTA.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

Science.gov (United States)

Özcan, İpek; Azizoğlu, Erkan; Şenyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders. PMID:23390364

Efficient gene delivery using chitosan-polyethylenimine hybrid systems

Energy Technology Data Exchange (ETDEWEB)

Jiang, Hu-Lin; Kim, Tae-Hee; Kim, You-Kyoung; Park, In-Young; Cho, Chong-Su [Department of Agricultural Bioechnology, Seoul National University, Seoul 151-921 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of)], E-mail: chocs@plaza.snu.ac.kr

2008-06-01

Chitosan and chitosan derivatives have been investigated as non-viral vectors because they have several advantages, such as biocompatibility, biodegradability, low cytotoxicity and low immunogenicity. However, low transfection efficiency and low cell specificity must be solved for their use in clinical trials. In this paper, chitosan-polyethylenimine (PEI) hybrid systems such as chitosan/PEI blend and chitosan-graft-PEI are described for efficient gene delivery because the PEI has high transfection efficiency owing to a proton sponge effect and chitosan has biocompatibility. Also, hepatocyte specificity of the galactosylated chitosan is explained after combination with PEI.

Efficient gene delivery using chitosan-polyethylenimine hybrid systems

International Nuclear Information System (INIS)

Jiang, Hu-Lin; Kim, Tae-Hee; Kim, You-Kyoung; Park, In-Young; Cho, Chong-Su; Cho, Myung-Haing

2008-01-01

Chitosan and chitosan derivatives have been investigated as non-viral vectors because they have several advantages, such as biocompatibility, biodegradability, low cytotoxicity and low immunogenicity. However, low transfection efficiency and low cell specificity must be solved for their use in clinical trials. In this paper, chitosan-polyethylenimine (PEI) hybrid systems such as chitosan/PEI blend and chitosan-graft-PEI are described for efficient gene delivery because the PEI has high transfection efficiency owing to a proton sponge effect and chitosan has biocompatibility. Also, hepatocyte specificity of the galactosylated chitosan is explained after combination with PEI

Mucoadhesive nanoparticles made of thiolated quaternary chitosan crosslinked with hyaluronan.

Science.gov (United States)

Zambito, Ylenia; Felice, Francesca; Fabiano, Angela; Di Stefano, Rossella; Di Colo, Giacomo

2013-01-30

Mucoadhesive polymeric nanoparticles intended for drug transport across the gastrointestinal mucosa were prepared from quaternary ammonium-chitosan conjugates synthesised from reduced-MW chitosan (32 kDa). Conjugates contained pendant moieties of 2-4 adjacent diethyl-dimethylene-ammonium groups substituted on repeating units (26-55%). Conjugates were thiolated via amide bonds with thioglycolic acid to yield products with thiol content in the 35-87 μmol/g range. Nanoparticles with mean size in the 270-370 nm range and positive zeta-potential (+3.7 to +12.5 mV) resulted from ionotropic gelation of the thiolated conjugates with de-polymerised hyaluronic acid (470 kDa). The nanoparticles were fairly stable in size and thiol content and showed a significant mucoadhesivity, matching and even exceeding that of the constituent polymers. Nanoparticles were internalised by endothelial progenitor cells in direct relation to their surface charge intensity. Nanoparticle uptake significantly improved cell viability and resistance to oxidation. The lyophilised nanoparticles were re-dispersible and could make a manageable formulation for oral use. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of chitosan and chitosan nanoparticles on the performance and charge recombination of water-based gel electrolyte in dye sensitized solar cells.

Science.gov (United States)

Khalili, Malihe; Abedi, Mohammad; Amoli, Hossein Salar; Mozaffari, Seyed Ahmad

2017-11-01

In commercialization of liquid dye-sensitized solar cells (DSSCs), whose leakage, evaporation and toxicity of organic solvents are limiting factors, replacement of organic solvents with water-based gel electrolyte is recommended. This work reports on utilizing and comparison of chitosan and chitosan nanoparticle as different gelling agents in preparation of water-based gel electrolyte in fabrication of dye sensitized solar cells. All photovoltaic parameters such as open circuit voltage (V oc ), fill factor (FF), short circuit current density (J sc ) and conversion efficiency (η) were measured. For further characterization, electrochemical impedance spectroscopy (EIS) was used to study the charge transfer at Pt/electrolyte interface and charge recombination and electron transport at TiO 2 /dye/electrolyte interface. Significant improvements in conversion efficiency and short circuit current density of DSSCs fabricated by chitosan nanoparticle were observed that can be attributed to the higher mobility of I 3 - due to the lower viscosity and smaller size of chitosan nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chitosan-Coated Magnetic Nanoparticles Prepared in One Step by Reverse Microemulsion Precipitation

OpenAIRE

Hened Saade; Salvador Fernández; Ramón Díaz de León; Gilberto Hurtado; María G. Pineda; Raúl G. López; Darío Bueno

2013-01-01

Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70 ?C and 80 ?C in a one-step method, which comprises precipitation in reverse microemulsion in the presence of low chitosan concentration in the aqueous phase. X-ray diffractometry showed that CMNP obtained at both temperatures contain a mixture of magnetite and maghemite nanoparticles with ?4.5 nm in average diameter, determined by electron microscopy, which suggests that precipitation temperature does not affect the particle si...

Chitosan nanoparticles as drug delivery carriers for biomedical engineering

International Nuclear Information System (INIS)

Shi, L.E.S.; Chen, M.; XINF, L.Y.; Guo, X.F.; Zhao, L.M.

2011-01-01

Chitosan is a rather abundant material, which has been widely used in food industrial and bioengineering aspects, including in encapsulating active food ingredients, in enzyme immobilization, and as a carrier for drug delivery, due to its significant biological and chemical properties such as biodegradable, biocompatible, bioactive and polycationic. This review discussed preparation and applications of chitosan nanoparticles in the biomedical engineering field, namely as a drug delivery carrier for biopharmaceuticals. (author)

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.

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

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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.

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.

Formulation, characterization, and expression of a recombinant MOMP Chlamydia trachomatis DNA vaccine encapsulated in chitosan nanoparticles

Directory of Open Access Journals (Sweden)

Cambridge CD

2013-05-01

Full Text Available Chino D Cambridge, Shree R Singh, Alain B Waffo, Stacie J Fairley, Vida A DennisCenter for NanoBiotechnology Research (CNBR, Alabama State University, Montgomery, AL, USAAbstract: Chlamydia trachomatis is a bacterial sexually transmitted infection affecting millions of people worldwide. Previous vaccination attempts have employed the recombinant major outer membrane protein (MOMP of C. trachomatis nonetheless, with limited success, perhaps, due to stability, degradation, and delivery issues. In this study we cloned C. trachomatis recombinant MOMP DNA (DMOMP and encapsulated it in chitosan nanoparticles (DMCNP using the complex coacervation technique. Physiochemical characterizations of DMCNP included transmission and scanning electron microcopy, Fourier transform infrared and ultraviolet-visible spectroscopy, and zeta potential. Encapsulated DMOMP was 167–250 nm, with a uniform spherical shape and homogenous morphology, and an encapsulation efficiency > 90%. A slow release pattern of encapsulated DMOMP, especially in acidic solution, was observed over 7 days. The zeta potential of DMCNP was ~8.80 mV, which indicated that it was highly stable. Toxicity studies of DMCNP (25–400 µg/mL to Cos-7 cells using the MTT assay revealed minimal toxicity over 24–72 hours with >90% viable cells. Ultra-violet visible (UV-vis spectra indicated encapsulated DMOMP protection by chitosan, whereas agarose gel electrophoresis verified its protection from enzymatic degradation. Expression of MOMP protein in DMCNP-transfected Cos-7 cells was demonstrated via Western blotting and immunofluorescence microscopy. Significantly, intramuscular injection of BALB/c mice with DMCNP confirmed the delivery of encapsulated DMOMP, and expression of the MOMP gene transcript in thigh muscles and spleens. Our data show that encapsulation of DMOMP in biodegradable chitosan nanoparticles imparts stability and protection from enzymatic digestion, and enhances delivery and

Controlled fabrication of gold nanoparticles biomediated by glucose oxidase immobilized on chitosan layer-by-layer films

International Nuclear Information System (INIS)

Caseli, Luciano; Santos, David S. dos; Aroca, Ricardo F.; Oliveira, Osvaldo N.

2009-01-01

The control of size and shape of metallic nanoparticles is a fundamental goal in nanochemistry, and crucial for applications exploiting nanoscale properties of materials. We present here an approach to the synthesis of gold nanoparticles mediated by glucose oxidase (GOD) immobilized on solid substrates using the Layer-by-Layer (LbL) technique. The LbL films contained four alternated layers of chitosan and poly(styrene sulfonate) (PSS), with GOD in the uppermost bilayer adsorbed on a fifth chitosan layer: (chitosan/PSS) 4 /(chitosan/GOD). The films were inserted into a solution containing gold salt and glucose, at various pHs. Optimum conditions were achieved at pH 9, producing gold nanoparticles of ca. 30 nm according to transmission electron microscopy. A comparative study with the enzyme in solution demonstrated that the synthesis of gold nanoparticles is more efficient using immobilized GOD.

Preparation and characterization of β-cyclodextrin grafted N-maleoyl chitosan nanoparticles for drug delivery

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Xinyu Hou

2017-11-01

Full Text Available β-cyclodextrin (CD grafted N-maleoyl chitosan (CD-g-NMCS with two different degrees of substitution (DS of N-maleoyl (DS = 21.2% and 30.5% were synthesized from maleic anhydride and chitosan bearing pendant cyclodextrin (CD-g-CS. CD-g-NMCS based nanoparticles were prepared via an ionic gelation method together with chitosan and CD-g-CS nanoparticles. The size and zeta potential of prepared CD-g-NMCS nanoparticles were 179.2~274.0 nm and 36.2~42.4 mV, respectively. In vitro stability test indicated that CD-g-NMCS nanoparticles were more stable in phosphate-buffered saline compared with chitosan nanoparticles. Moreover, a poorly water-soluble drug, ketoprofen (KTP, was selected as a model drug to study the obtained nanoparticle's potentials as drug delivery carriers. The drug loading efficiency of CD-g-NMCS20 nanoparticles were 14.8% for KTP. MTT assay showed that KTP loaded CD-g-NMCS nanoparticles were safe drug carriers. Notably, in vitro drug release studies showed that KTP was released in a sustained-release manner for the nanoparticles. The pharmacokinetic of drug loaded CD-g-NMCS20 nanoparticles were evaluated in rats after intravenous administration. The results of studies revealed that, compared with free KTP, KTP loaded CD-g-NMCS20 nanoparticles exhibited a significant increase in AUC0→24h and mean residence time by 6.6-fold and 2.9-fold, respectively. Therefore, CD-g-NMCS nanoparticles could be used as a novel promising nanoparticle-based drug delivery system for sustained release of poorly water-soluble drugs. The carboxylic acid groups of the CD-g-NMCS molecule provide convenient sites for further structural modifications including introduction of tissue- or disease- specific targeting groups.

Iontophoresis on minoxidil sulphate-loaded chitosan nanoparticles accelerates drug release, decreasing their targeting effect to hair follicles

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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.

Amphotericin-B entrapped lecithin/chitosan nanoparticles for prolonged ocular application.

Science.gov (United States)

Chhonker, Yashpal S; Prasad, Yarra Durga; Chandasana, Hardik; Vishvkarma, Akhilesh; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

2015-01-01

Fungal keratitis is the major cause of vision loss worldwide. Amphotericin-B is considered as the drug of choice for fungal infections. However, its use in ophthalmic drug delivery is limited by the low precorneal residence at ocular surface as a result of blinking reflex, tear turnover and nasopharyngeal drainage. We report Amphotericin-B loaded lecithin/chitosan nanoparticles for prolonged ocular application. The prepared nanoparticles were in the size range of 161.9-230.5 nm, entrapment efficiency of 70-75%, theoretical drug loading of 5.71% with positive zeta potential of 26.6-38.3 mV. As demonstrated by antifungal susceptibility against Candida albicans and Aspergillus fumigatus, nanoparticles were more effective than marketed formulation. They exhibited pronounced mucoadhesive properties. In-vivo pharmacokinetic studies in New Zealand albino rabbit eyes indicated improved bioavailablity (∼ 2.04 fold) and precorneal residence time (∼ 3.36 fold) by nanoparticles prepared from low molecular weight chitosan as compared with marketed formulation. Copyright © 2014. Published by Elsevier B.V.

Characterization of physicochemical and colloidal properties of hydrogel chitosan-coated iron-oxide nanoparticles for cancer therapy

International Nuclear Information System (INIS)

Catalano, E; Di Benedetto, A

2017-01-01

Superparamagnetic iron oxide nanoparticles have recently been investigated for their potential to kill cancer cells with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe 3 O 4 magnetic nanoparticles were synthesized to induce magnetic hyperthermia, and targeted delivering of chemotherapeutics in the cancer microenvironment. The characteristic properties of synthesized bare and CS-MNPs were analyzed by various analytical methods: X-ray diffraction, Fourier transformed infrared spectroscopy, Scanning electron microscopy and Thermo-gravimetric analysis/differential thermal analysis. Magnetic nanoparticles were successfully synthesized using the co-precipitation method. This synthesis technique resulted in nanoparticles with an average particle size of 16 nm. The pure obtained nanoparticles were then successfully encapsulated with 4-nm-thick chitosan coating. The formation of chitosan on the surface of nanoparticles was confirmed by physicochemical analyses. Heating experiments at safe magnetic field (f = 100 kHz, H =10-20 kA m -1 ) revealed that the maximum achieved temperature of water stable chitosan-coated nanoparticles (50 mg ml -1 ) is fully in agreement with cancer therapy and biomedical applications. (paper)

Characterization of physicochemical and colloidal properties of hydrogel chitosan-coated iron-oxide nanoparticles for cancer therapy

Science.gov (United States)

Catalano, E.; Di Benedetto, A.

2017-05-01

Superparamagnetic iron oxide nanoparticles have recently been investigated for their potential to kill cancer cells with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe3O4 magnetic nanoparticles were synthesized to induce magnetic hyperthermia, and targeted delivering of chemotherapeutics in the cancer microenvironment. The characteristic properties of synthesized bare and CS-MNPs were analyzed by various analytical methods: X-ray diffraction, Fourier transformed infrared spectroscopy, Scanning electron microscopy and Thermo-gravimetric analysis/differential thermal analysis. Magnetic nanoparticles were successfully synthesized using the co-precipitation method. This synthesis technique resulted in nanoparticles with an average particle size of 16 nm. The pure obtained nanoparticles were then successfully encapsulated with 4-nm-thick chitosan coating. The formation of chitosan on the surface of nanoparticles was confirmed by physicochemical analyses. Heating experiments at safe magnetic field (f = 100 kHz, H =10-20 kA m-1) revealed that the maximum achieved temperature of water stable chitosan-coated nanoparticles (50 mg ml-1) is fully in agreement with cancer therapy and biomedical applications.

Chitosan and carboxymethyl-chitosan capping ligands: Effects on the nucleation and growth of hydroxyapatite nanoparticles for producing biocomposite membranes

Energy Technology Data Exchange (ETDEWEB)

Dumont, Vitor C.; Mansur, Alexandra A.P.; Carvalho, Sandhra M.; Medeiros Borsagli, Fernanda G.L.; Pereira, Marivalda M.; Mansur, Herman S., E-mail: hmansur@demet.ufmg.br

2016-02-01

Synthetic biomaterials based on calcium phosphates (CaP) have been widely studied for bone tissue reconstruction therapies, but no definitive solution that fulfills all of the required properties has been identified. Thus, this study reports the synthesis of composite membranes based on nanohydroxyapatite particles (nHA) embedded in chitosan (CHI) and O-carboxymethyl chitosan (CMC) matrices produced using a one-step co-precipitation method in water media. Biopolymers were used as capping ligands for simultaneously controlling the nucleation and growth of the nHA particles during the precipitation process and also to form the polymeric network of the biocomposites. The bionanocomposites were extensively characterized using light microscopy (LM), scanning and transmission electron microscopy (SEM/TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), atomic force microscopy (AFM), X-ray micro-CT analysis (μCT), and MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) cell proliferation assays for cell cytotoxicity. The results demonstrated that the ligands used during the synthesis highly affected the composites produced, primarily due the changes in the mechanisms and kinetics of nucleation and growth of the HA particles at the nanoscale level. The SEM images revealed that the use of carboxyl-functionalized chitosan (CMC) ligands significantly reduced the average size of the HA nanoparticles and caused the formation of a narrower size distribution (90 ± 20 nm) compared to the HA nanoparticles produced with chitosan ligands (220 ± 50 nm). The same trend was verified by the AFM analysis, where the nHA particles were formed evenly dispersed in the polymer matrix. However, the CMC-based composites were more homogeneously distributed, which was endorsed by the images collected via X-ray micro-CT. The FTIR spectra and the XRD analysis indicated that nanosized hydroxyapatite was the

Paraquat-loaded alginate/chitosan nanoparticles: Preparation, characterization and soil sorption studies

Energy Technology Data Exchange (ETDEWEB)

Santos Silva, Mariana dos; Sgarbi Cocenza, Daniela [Department of Environmental Engineering, Sao Paulo State University - UNESP, Avenida Tres de Marco, No. 511, CEP 18087-180, Sorocaba, SP (Brazil); Grillo, Renato; Silva de Melo, Nathalie Ferreira [Department of Environmental Engineering, Sao Paulo State University - UNESP, Avenida Tres de Marco, No. 511, CEP 18087-180, Sorocaba, SP (Brazil); Department of Biochemistry, Institute of Biology, State University of Campinas - UNICAMP, Campinas, SP (Brazil); Tonello, Paulo Sergio [Department of Environmental Engineering, Sao Paulo State University - UNESP, Avenida Tres de Marco, No. 511, CEP 18087-180, Sorocaba, SP (Brazil); Camargo de Oliveira, Luciana [Department of Chemistry, UFSCAr, Campus Sorocaba, SP (Brazil); Lopes Cassimiro, Douglas [Institute of Chemistry, Sao Paulo State University - UNESP, Araraquara, SP (Brazil); Rosa, Andre Henrique [Department of Environmental Engineering, Sao Paulo State University - UNESP, Avenida Tres de Marco, No. 511, CEP 18087-180, Sorocaba, SP (Brazil); Fernandes Fraceto, Leonardo, E-mail: leonardo@sorocaba.unesp.br [Department of Environmental Engineering, Sao Paulo State University - UNESP, Avenida Tres de Marco, No. 511, CEP 18087-180, Sorocaba, SP (Brazil); Department of Biochemistry, Institute of Biology, State University of Campinas - UNICAMP, Campinas, SP (Brazil)

2011-06-15

Agrochemicals are amongst the contaminants most widely encountered in surface and subterranean hydrological systems. They comprise a variety of molecules, with properties that confer differing degrees of persistence and mobility in the environment, as well as different toxic, carcinogenic, mutagenic and teratogenic potentials, which can affect non-target organisms including man. In this work, alginate/chitosan nanoparticles were prepared as a carrier system for the herbicide paraquat. The preparation and physico-chemical characterization of the nanoparticles was followed by evaluation of zeta potential, pH, size and polydispersion. The techniques employed included transmission electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. The formulation presented a size distribution of 635 {+-} 12 nm, polydispersion of 0.518, zeta potential of -22.8 {+-} 2.3 mV and association efficiency of 74.2%. There were significant differences between the release profiles of free paraquat and the herbicide associated with the alginate/chitosan nanoparticles. Tests showed that soil sorption of paraquat, either free or associated with the nanoparticles, was dependent on the quantity of organic matter present. The results presented in this work show that association of paraquat with alginate/chitosan nanoparticles alters the release profile of the herbicide, as well as its interaction with the soil, indicating that this system could be an effective means of reducing negative impacts caused by paraquat.

Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

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Yousefpour P

2011-09-01

Full Text Available Parisa Yousefpour1, Fatemeh Atyabi2, Ebrahim Vasheghani-Farahani3, Ali-Akbar Mousavi Movahedi1, Rassoul Dinarvand21Department of Biotechnology, Faculty of Science, University of Tehran, 2Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 3Biotechnology Group, Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, Tehran, IranBackground: Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action.Methods: Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX nanoparticles (particle size, 200 nm via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles.Results: CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb contained 47 µg/mg doxorubicin and 33.5 µg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and

Self-assembled nanoparticles of modified-chitosan conjugates for the sustained release of dl-α-tocopherol

DEFF Research Database (Denmark)

Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen

2013-01-01

Synthetic O6-succinylated chitosan and commercial glycol chitosan were covalently linked to dl-α-tocopheryl monoesters for controlled release of vitamin E. These conjugates formed self-assembled nanoparticles in aqueous solution with 254–496 nm mean diameters and dl-α-tocopherol contents between 27...... and 39% (w/w). The particles appeared as 40–75 nm almost spherical nanoparticles when studied by scanning and transmission electron microscopy upon drying. Drug linking to chitosan matrix was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning...... calorimetry and wide-angle X-ray diffraction. In vitro tocopherol release studies performed in water at acid pH indicated a drug release dependence on drug content, hydrated particle sizes and employed chitosan derivative. Almost constant release rates were observed the first 7 h. The obtained nanoparticles...

Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.

Science.gov (United States)

Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

Energy Technology Data Exchange (ETDEWEB)

Kong, Zwe-Ling, E-mail: kongzl@mail.ntou.edu.tw; Chang, Jenq-Sheng; Chang, Ke Liang B. [National Taiwan Ocean University, Department of Food Science (China)

2013-09-15

Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

Science.gov (United States)

Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

2013-09-01

Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

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

Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

International Nuclear Information System (INIS)

Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

2009-01-01

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Effect of tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue

Science.gov (United States)

Sukmawati, Anita; Utami, Wahyu; Yuliani, Ratna; Da'i, Muhammad; Nafarin, Akhmad

2018-02-01

Delivery of anticancer is facing several problems including unspecific delivery of active substance to the targeted cell. The conjugation between chitosan and folate (chitosan-FA) was used for nanoparticle preparation containing combination of doxorubicin (DOX) and curcumin analogue, 2,5-bis-(4-hydroxi,3,5-dimethyl)-benzylidincylopentanone, as active substances. The purpose of this research is investigating formulation aspect for chitosan-FA nanoparticle by addition various tween 80 to achieve desired nano-size particle. The ionic gelation method was used for nanoparticle preparation using 0.05% w/v chitosan-FA with addition of 0.1 and 0.5% v/v of tween 80. The result showed that the high concentration of tween 80 during nanoparticle preparation lead to formation of smaller size particle. The 111.8 ±4.11 nm particle size was revealed by addition of 0.5% v/v tween 80 during chitosan-FA nanoparticle preparation loaded with active substances.

Radiation-induced degradation of carboxymethylated chitosan and its application in preparation of ionic liquids and silver nanoparticles

International Nuclear Information System (INIS)

Zhai Maolin; Huang Ling; Peng Jing; Li Jiuqiang; Wei Genshuan

2006-01-01

of [emim]CM-chitosan ionic liquids with different molecular weights ranging from 1.1x10 -2 to 2.6 x 10 -2 S·cm -1 at 30 degree C. It can be expected that this new kind of ionic liquids will have important application in electrochemistry. Considering the reductive ability of CM-chitosan, silver nanoparticles were synthesized by a convenient and green method in CM-chitosan dilute aqueous solution with UV lights. Both the concentrations of silver nitrate and CM-chitosan, which acted as reduction agent and stabilization agent, have effect on the conformation of silver nanoparticles. Uv-vis spectra and transmission electron microscopy (TEM) images revealed the formation of silver nanoparticles inside and outside the polysaccharide templates within 20 min of UV irradiation. Dynamic light scattering (DLS) measurements showed that the silver nanoparticles were in an average diameter of 8 nm with narrow size distributions. The silver nanoparticles can be dispersed stably in alkaline CM-chitosan solution for a long time, and morphology of the silver/CM-chitosan composites was branched-like under TEM and polarized optical microscopy (POM) observations. (authors)

Gold nanoparticles stabilized by chitosan; Sintese de nanoparticulas de ouro estabilizadas por quitosana

Energy Technology Data Exchange (ETDEWEB)

Geraldes, Adriana N.; Oliveira, Maria Jose A.; Silva, Andressa A. da; Leal, Jessica; Batista, Jorge G.S.; Lugao, Ademar B., E-mail: drinager@ig.com.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2015-07-01

In our laboratory has been growing the interest in studying gold nanoparticles and for this reason, the aim of this work is report the first results of the effect of chitosan as stabilizer in gold nanoparticle formulation. AuNPs were synthesized by reducing hydrogen tetrachloroaurate (HAuCl{sub 4}) using NaBH{sub 4} or gamma irradiation (25kGy) as reduction agent. The chitosan (3 mol L{sup -1}) was added at 0.5; 1.0 and 1.5 mL. The gold nanoparticles were characterized by UV-Vis absorption spectroscopy, X-ray diffraction (XRD) and Transmission electron microscopy (TEM). Their physical stability was determined using a UV-Vis spectrophotometer over one week during storage at room temperature. Absorption measurements indicated that the plasmon resonance wavelength appears at a wavelength around 530 nm. Has been observed that Chitosan in such quantities were not effective in stabilizing the AuNPs. (author)

About the Sterilization of Chitosan Hydrogel Nanoparticles.

Directory of Open Access Journals (Sweden)

Raquel Galante

Full Text Available In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation, a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP hydrogel nanoparticles (CS-HNP, with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol. Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.

About the Sterilization of Chitosan Hydrogel Nanoparticles.

Science.gov (United States)

Galante, Raquel; Rediguieri, Carolina F; Kikuchi, Irene Satiko; Vasquez, Pablo A S; Colaço, Rogério; Serro, Ana Paula; Pinto, Terezinha J A

2016-01-01

In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

Directory of Open Access Journals (Sweden)

Özcan İ

2013-01-01

Full Text Available İpek Özcan, Erkan Azizoğlu, Taner Şenyiğit, Mine Özyazıcı, Özgen ÖzerEge University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Bornova, Izmir, TurkeyAbstract: The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%, were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01% was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.Keywords: skin permeation, anti-inflammatory activity, skin blanching, TEWL

Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles

DEFF Research Database (Denmark)

Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent

2015-01-01

chitosan-poly(ethylene imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by αvβ3-targeted versus non-targeted nanoparticles was quantified in the human non-small cell lung carcinoma cell line H1299 expressing enhanced green fluorescent protein (EGFP) using a stem-loop reverse...... that these nanoparticles might end up in late endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus, the silencing efficiency of the chitosan-based nanoparticles is strongly dependent on the uptake and the intracellular trafficking in H1299 EGFP cells, which is critical information towards...

Synthesis and characterization of thiolated carboxymethyl chitosan-graft-cyclodextrin nanoparticles as a drug delivery vehicle for albendazole.

Science.gov (United States)

Alamdarnejad, Ghazaleh; Sharif, Alireza; Taranejoo, Shahrouz; Janmaleki, Mohsen; Kalaee, Mohammad Reza; Dadgar, Mohsen; Khakpour, Mazyar

2013-08-01

A new strategy for the synthesis of thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles by an ionic-gelation method is presented. The synthetic approach was based on the utilization of 1,6-hexamethylene diisocyanate during cyclodextrin grafting onto carboxymethyl chitosan. The use of the 1,6-hexamethylene diisocyanate resulted in reactions between cyclodextrin and active sites at the C6-position of chitosan, and preserved amino groups of chitosan for subsequent reactions with thioglycolic acid, as the thiolating agent, and tripolyphosphate, as the gelling counterion. Various methods such as scanning electron microscopy, rheology and in vitro release studies were employed to exhibit significant features of the nanoparticles for mucosal albendazole delivery applications. It was found that the thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles prepared using an aqueous solution containing 1 wt% of tripolyphosphate and having 115.65 (μmol/g polymer) of grafted thiol groups show both the highest mucoadhesive properties and the highest albendazole entrapment efficiency. The latter was confirmed theoretically by calculating the enthalpy of mixing of albendazole in the above thiolated chitosan polymer.

tRNA conjugation with chitosan nanoparticles: An AFM imaging study.

Science.gov (United States)

Agudelo, D; Kreplak, L; Tajmir-Riahi, H A

2016-04-01

The conjugation of tRNA with chitosan nanoparticles of different sizes 15,100 and 200 kDa was investigated in aqueous solution using multiple spectroscopic methods and atomic force microscopy (AFM). Structural analysis showed that chitosan binds tRNA via G-C and A-U base pairs as well as backbone PO2 group, through electrostatic, hydrophilic and H-bonding contacts with overall binding constants of KCh-15-tRNA=4.1 (±0.60)×10(3)M(-1), KCh-100-tRNA=5.7 (±0.8)×10(3)M(-1) and KCh-200-tRNA=1.2 (±0.3)×10(4)M(-1). As chitosan size increases more stable polymer-tRNA conjugate is formed. AFM images showed major tRNA aggregation and particle formation occurred as chitosan concentration increased. Even though chitosan induced major biopolymer structural changes, tRNA remains in A-family structure. Copyright © 2015 Elsevier B.V. All rights reserved.

Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA

NARCIS (Netherlands)

Olbrich, C; Bakowsky, U; Muller, RH; Kneuer, C

2001-01-01

The suitability of cationically modified solid-lipid nanoparticles (SLN) as a novel transfection agent was investigated. SLN were produced by hot homogenisation using either Compritol ATO 888 or paraffin as matrix lipid, a mixture of Tween 80 and Span 85 as tenside and either EQ1

Self-assembled nanoparticles of glycol chitosan – Ergocalciferol succinate conjugate, for controlled release

DEFF Research Database (Denmark)

Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen

2012-01-01

Glycol chitosan was linked to vitamin D2 hemisuccinate (ergocalciferol hemisuccinate) for controlled release through water-soluble carbodiimide activation. The resulting conjugate formed self-assembled nanoparticles in aqueous solution with particle size of 279 nm and ergocalciferol hemisuccinate...... content of 8.4% (w/w). Almost spherical 50–90 nm nanoparticles were observed by scanning and transmission electron microscopy upon drying. Drug linking to glycol chitosan was confirmed by FTIR spectroscopy and proton NMR. Particles were also characterized by differential scanning calorimetry and wide...

Experimental and model study of the formation of chitosan-tripolyphosphate-siRNA nanoparticles

DEFF Research Database (Denmark)

Schrøder, Tine Daa; Olsen, Lars Folke; Long, Yi

2014-01-01

Chitosan-tripolyphosphate (TPP) nanoparticles have received great interest as a drug delivery system due to the simple and mild procedure of ionic gelation and the biocompatibility of chitosan. We have studied the formation of chitosan nano- and microparticles through ionic gelation with TPP...... in the absence and presence of NaCl, by measuring the kinetics of formation, particle size, and zeta potential. Depending on the experimental conditions (concentrations of chitosan and TPP and the presence or absence of NaCl), particle formation displays an exponential or a sigmoidal time dependency. In order...

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

Science.gov (United States)

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-08-24

Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

Directory of Open Access Journals (Sweden)

Mohapatra Shyam S

2006-08-01

Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

Receptor-mediated gene delivery using chemically modified chitosan

International Nuclear Information System (INIS)

Kim, T H; Jiang, H L; Nah, J W; Cho, M H; Akaike, T; Cho, C S

2007-01-01

Chitosan has been investigated as a non-viral vector because it has several advantages such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, the low specificity and low transfection efficiency of chitosan need to be solved prior to clinical application. In this paper, we focused on the galactose or mannose ligand modification of chitosan for enhancement of cell specificity and transfection efficiency via receptor-mediated endocytosis in vitro and in vivo

Chitosan/bioactive glass nanoparticle composite membranes for periodontal regeneration

NARCIS (Netherlands)

Mota, J.; Yu, N.; Caridade, S.G.; Luz, G.M.; Gomes, M.E.R.; Reis, R.L.; Jansen, J.A.; Walboomers, X.F.; Mano, J.F.

2012-01-01

Barrier membranes are used in periodontal applications with the aim of supporting periodontal regeneration by physically blocking migration of epithelial cells. The present work proposes a combination of chitosan (CHT) with bioactive glass nanoparticles (BG-NPs) in order to produce a novel guided

Hypoxia-inducible bidirectional shRNA expression vector delivery using PEI/chitosan-TBA copolymers for colorectal Cancer gene therapy.

Science.gov (United States)

Javan, Bita; Atyabi, Fatemeh; Shahbazi, Majid

2018-04-12

This investigation was conducted to construct a hypoxia/colorectal dual-specific bidirectional short hairpin RNA (shRNA) expression vector and to transfect it into the colon cancer cell line HT-29 with PEI/chitosan-TBA nanoparticles for the simultaneous knock down of β-catenin and Bcl-2 under hypoxia. To construct a pRNA-bipHRE-CEA vector, the carcinoma embryonic antigen (CEA) promoter designed in two directions and the vascular endothelial growth factor (VEGF) enhancer were inserted between two promoters for hypoxic cancer specific gene expression. To confirm the therapeutic effect of the dual-specific vector, β-catenin and Bcl-2 shRNAs were inserted downstream of each promoter. The physicochemical properties, the cytotoxicity, and the transfection efficiency of these PEI/chitosan-TBA nanoparticles were investigated. In addition, the antitumor effects of the designed vector on the expression of β-catenin and Bcl-2, cell cycle distribution, and apoptosis were investigated in vitro. The silencing effect of the hypoxia-response shRNA expression vector was relatively low (18%-25%) under normoxia, whereas it was significantly increased to approximately 50%-60% in the HT-29 cell line. Moreover, the cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing under hypoxia. Furthermore, MTS assay, fluorescence microscopy images, and flow cytometry analyses confirmed that the PEI/chitosan-TBA blend system provided effective transfection with low cytotoxicity. This novel hypoxia-responsive shRNA expression vector may be useful for RNA interference (RNAi)-based cancer gene therapy in hypoxic colorectal tumors. Moreover, the PEI/chitosan-TBA copolymer might be a promising gene carrier for use in gene transfer in vivo. Copyright © 2017. Published by Elsevier Inc.

Curcumin drug delivery by vanillin-chitosan coated with calcium ferrite hybrid nanoparticles as carrier.

Science.gov (United States)

Kamaraj, Sriram; Palanisamy, Uma Maheswari; Kadhar Mohamed, Meera Sheriffa Begum; Gangasalam, Arthanareeswaran; Maria, Gover Antoniraj; Kandasamy, Ruckmani

2018-04-30

The aim of the present investigation is the development, optimization and characterization of curcumin-loaded hybrid nanoparticles of vanillin-chitosan coated with super paramagnetic calcium ferrite. The functionally modified vanillin-chitosan was prepared by the Schiff base reaction to enhance the hydrophobic drug encapsulation efficiency. Calcium ferrite (CFNP) nano particles were added to the vanillin modified chitosan to improve the biocompatibility. The vanillin-chitosan-CFNP, hybrid nanoparticle carrier was obtained by ionic gelation method. Characterizations of the hybrid materials were performed by XRD, FTIR, 1 H NMR, TGA, AFM and SEM techniques to ensure the modifications on the chitosan material. Taguchi method was applied to optimize the drug (curcumin) encapsulation efficiency by varying the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP (sodium tripolyphospate) to chitosan-vanillin ratios. The maximum encapsulation efficiency was obtained as 98.3% under the conditions of 0.1, 0.75 and 1.0 for the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP to chitosan-vanillin ratios, respectively. The curcumin release was performed at various pH, initial drug loading concentrations and magnetic fields. The drug release mechanism was predicted by fitting the experimental kinetic data with various drug release models. The drug release profiles showed the best fit with Higuchi model under the most of conditions. The drug release mechanism followed both non-Fickian diffusion and case II transport mechanism for chitosan, however the non-Fickian diffusion mechanism was followed for the vanillin modified chitosan. The biocompatibility of the hybrid material was tested using L929 fibroblast cells. The cytotoxicity test was performed against MCF-7 breast cancer cell line to check the anticancer property of the hybrid nano carrier with the curcumin drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Fabrication of chitosan-silver nanoparticle hybrid 3D porous structure as a SERS substrate for biomedical applications

Science.gov (United States)

Jung, Gyeong-Bok; Kim, Ji-Hye; Burm, Jin Sik; Park, Hun-Kuk

2013-05-01

We propose a simple, low-cost, large-area, and functional surface enhanced Raman scattering (SERS) substrate for biomedical applications. The SERS substrate with chitosan-silver nanoparticles (chitosan-Ag NPs) hybrid 3D porous structure was fabricated simply by a one-step method. The chitosan was used as a template for the Ag NPs deposition. SERS enhancement by the chitosan-Ag NPs substrate was experimentally verified using rhodamine B as an analyte. Thiolated single stranded DNA was also measured for atopic dermatitis genetic markers (chemokines CCL17) at a low concentration of 5 pM. We successfully designed a novel SERS substrate with silver nanoparticle hybridized 3D porous chitosan that has the potential to become a highly sensitive and selective tool for biomedical applications.

Potentiometric urea biosensor utilizing nanobiocomposite of chitosan-iron oxide magnetic nanoparticles

International Nuclear Information System (INIS)

Ali, A; Israr, M Q; Sadaf, J R; Nur, O; Willander, M; AlSalhi, M S; Atif, M; Ansari, Anees A; Ahmed, E

2013-01-01

The iron oxide (Fe 3 O 4 ) magnetic nanoparticles have been fabricated through a simple, cheap and reproducible approach. Scanning electron microscope, x-rays powder diffraction of the fabricated nanoparticles. Furthermore, the fabrication of potentiometric urea biosensor is carried out through drop casting the initially prepared isopropanol and chitosan solution, containing Fe 3 O 4 nanoparticles, on the glass fiber filter with a diameter of 2 cm and a copper wire (of thickness −500 μm) has been utilized to extract the voltage signal from the functionalized nanoparticles. The functionalization of surface of the Fe 3 O 4 nanoparticles is obtained by the electrostatically immobilization of urease onto the nanobiocomposite of the chitosan- Fe 3 O 4 in order to enhance the sensitivity, specificity, stability and reusability of urea biosensor. Electrochemical detection procedure has been adopted to measure the potentiometric response over the wide logarithmic concentration range of the 0.1 mM to 80 mM. The Fe 3 O 4 nanoparticles based urea biosensor depicts good sensitivity with ∼42 mV per decade at room temperature. Durability of the biosensor could be considerably enhanced by applying a thin layer of the nafion. In addition, the reasonably stable output response of the biosensor has been found to be around 12 sec.

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.

Design of peptide-conjugated glycol chitosan nanoparticles for near infrared fluorescent (NIRF) in vivo imaging of bladder tumors

Science.gov (United States)

Key, Jaehong; Dhawan, Deepika; Knapp, Deborah W.; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Leary, James F.

2012-03-01

Enhanced permeability and retention (EPR) effects for tumor treatment have been utilized as a representative strategy to accumulate untargeted nanoparticles in the blood vessels around tumors. However, the EPR effect itself was not sufficient for the nanoparticles to penetrate into cancer cells. For the improvement of diagnosis and treatment of cancer using nanoparticles, many more nanoparticles need to specifically enter cancer cells. Otherwise, can leave the tumor area and not contribute to treatment. In order to enhance the internalization process, specific ligands on nanoparticles can help their specific internalization in cancer cells by receptor-mediated endocytosis. We previously developed glycol chitosan based nanoparticles that suggested a promising possibility for in vivo tumor imaging using the EPR effect. The glycol chitosan nanoparticles showed a long circulation time beyond 1 day and they were accumulated predominantly in tumor. In this study, we evaluated two peptides for specific targeting and better internalization into urinary bladder cancer cells. We conjugated the peptides on to the glycol chitosan nanoparticles; the peptide-conjugated nanoparticles were also labeling with near infrared fluorescent (NIRF) dye, Cy5.5, to visualize them by optical imaging in vivo. Importantly real-time NIRF imaging can also be used for fluorescence (NIRF)-guided surgery of tumors beyond normal optical penetration depths. The peptide conjugated glycol chitosan nanoparticles were characterized with respect to size, stability and zeta-potential and compared with previous nanoparticles without ligands in terms of their internalization into bladder cancer cells. This study demonstrated the possibility of our nanoparticles for tumor imaging and emphasized the importance of specific targeting peptides.

Insight on the formation of chitosan nanoparticles through ionotropic gelation with tripolyphosphate.

Science.gov (United States)

Koukaras, Emmanuel N; Papadimitriou, Sofia A; Bikiaris, Dimitrios N; Froudakis, George E

2012-10-01

This work reports details pertaining to the formation of chitosan nanoparticles that we prepare by the ionic gelation method. The molecular interactions of the ionic cross-linking of chitosan with tripolyphosphate have been investigated and elucidated by means of all-electron density functional theory. Solvent effects have been taken into account using implicit models. We have identified primary-interaction ionic cross-linking configurations that we define as H-link, T-link, and M-link, and we have quantified the corresponding interaction energies. H-links, which display high interaction energies and are also spatially broadly accessible, are the most probable cross-linking configurations. At close range, proton transfer has been identified, with maximum interaction energies ranging from 12.3 up to 68.3 kcal/mol depending on the protonation of the tripolyphosphate polyanion and the relative coordination of chitosan with tripolyphosphate. On the basis of our results for the linking types (interaction energies and torsion bias), we propose a simple mechanism for their impact on the chitosan/TPP nanoparticle formation process. We introduce the β ratio, which is derived from the commonly used α ratio but is more fundamental since it additionally takes into account structural details of the oligomers.

Transformation of thiolated chitosan-templated gold nanoparticles to huge microcubes

International Nuclear Information System (INIS)

Sun, Yudie; Liu, Honglin; Yang, Liangbao; Sun, Bai; Liu, Jinhuai

2014-01-01

Graphical abstract: - Highlights: • Mercapto groups were grafted to chitosan molecule by a reactive amine reduction. • Functional polymer with well-defined monomer units controls AuNPs assembly. • Assembled morphologies depend on the ratio of AuNPs to thiolate groups. • Microcubes with side length of ∼20 μm was synthesized through a dialysis step. • A edge-to-middle growth mechanism of gold microcubes was observed. - Abstract: The L-cysteine molecules were successfully grafted to the 2-amino group of chitosan by a reactive amine reduction, and the as-synthesized thiolated chitosan (TC) molecules were used as the templates to direct the self-assembly of gold nanoparticles and induce the transformation of these assemblies to gold microcubes through a deep-going dialysis. We found that the ratio of gold nanoparticles to TC molecules could greatly affect the shape of the assembled clusters. Different stages of these clusters and microstructures during the dialysis process were characterized by scanning electron microscope (SEM), and the microcubes with average side length of about 20 μm were successfully synthesized. According to the morphology evolution of the assembly, it could be concluded that the microcubes were formed from external to internal. The SERS area mapping images of microcubes and some clusters were also collected to study the formation mechanism of gold microcubes. Our work demonstrates a simple and highly effective way to assemble gold nanoparticles into microcubes with unique properties

Transformation of thiolated chitosan-templated gold nanoparticles to huge microcubes

Energy Technology Data Exchange (ETDEWEB)

Sun, Yudie [School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026 (China); Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei 230031 (China); Liu, Honglin, E-mail: hlliu@iim.ac.cn [Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei 230031 (China); Yang, Liangbao, E-mail: lbyang@iim.ac.cn [Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei 230031 (China); Sun, Bai; Liu, Jinhuai [Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei 230031 (China)

2014-05-01

Graphical abstract: - Highlights: • Mercapto groups were grafted to chitosan molecule by a reactive amine reduction. • Functional polymer with well-defined monomer units controls AuNPs assembly. • Assembled morphologies depend on the ratio of AuNPs to thiolate groups. • Microcubes with side length of ∼20 μm was synthesized through a dialysis step. • A edge-to-middle growth mechanism of gold microcubes was observed. - Abstract: The L-cysteine molecules were successfully grafted to the 2-amino group of chitosan by a reactive amine reduction, and the as-synthesized thiolated chitosan (TC) molecules were used as the templates to direct the self-assembly of gold nanoparticles and induce the transformation of these assemblies to gold microcubes through a deep-going dialysis. We found that the ratio of gold nanoparticles to TC molecules could greatly affect the shape of the assembled clusters. Different stages of these clusters and microstructures during the dialysis process were characterized by scanning electron microscope (SEM), and the microcubes with average side length of about 20 μm were successfully synthesized. According to the morphology evolution of the assembly, it could be concluded that the microcubes were formed from external to internal. The SERS area mapping images of microcubes and some clusters were also collected to study the formation mechanism of gold microcubes. Our work demonstrates a simple and highly effective way to assemble gold nanoparticles into microcubes with unique properties.

Preparation of chitosan-stabilized Fe{sup 0} nanoparticles for removal of hexavalent chromium in water

Energy Technology Data Exchange (ETDEWEB)

Geng, Bing [Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Jin, Zhaohui, E-mail: jinzh@nankai.edu.cn [Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China); Li, Tielong; Qi, Xinhua [Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, College of Environmental Science and Engineering, Nankai University, Tianjin 300071 (China)

2009-09-01

Chitosan-stabilized Fe{sup 0} nanoparticles (CTO-Fe{sup 0}) and Fe{sup 0} nanoparticles synthesized in ethanol-water mixed system (EW-Fe{sup 0}) were tested for reduction of Cr(VI) in water. Fourier transform infrared (FTIR) study suggested that nitrogen and oxygen atoms are the binding sites for chitosan on iron which was accountable for the stability of Fe{sup 0} nanoparticles. While the EW-Fe{sup 0} ignites spontaneously when exposed to air, the CTO-Fe{sup 0} was still in zero valence state after exposure to air over 2-month period as shown by X-ray powder diffraction patterns. Batch experiments demonstrated that the maximum Cr(VI) reduction rates for CTO-Fe{sup 0} was about 3 times higher than EW-Fe{sup 0}. Characterizations with high-resolution X-ray photoelectron spectroscopy (HR-XPS) revealed that Cr(VI) was reduced to Cr(III) and Fe(III) was the only component present on the Fe{sup 0} nanoparticles surface. Additionally, chitosan can inhibited the formation of Fe(III)-Cr(III) precipitation due to its high ability to chelate Fe(III) which resulted in k{sub obs} for CTO-Fe{sup 0} was about 1-3 times higher than EW-Fe{sup 0}. Due to the fast reaction kinetics and good stability against oxidation in air, the chitosan-stabilized Fe{sup 0} nanoparticles have the potential to become an effective agent for in situ subsurface environment remediation.

Uranium removal by chitosan impregnated with magnetite nanoparticles: adsorption and desorption

International Nuclear Information System (INIS)

Stopa, Luiz Claudio Barbosa; Yamaura, Mitiko

2009-01-01

A magnetic biosorbent composed of nanoparticles of magnetite covered with chitosan, denominated magnetic chitosan, was prepared. The magnetic chitosan has showed a magnetic response of intense attraction in the presence of a magnetic field without however to become magnetic, a typical behavior of superparamagnetic material. Its adsorption performance was evaluated by the adsorption isotherm models of Langmuir and Freundlich for uranium ions and the desorption behavior using carbonate and oxalate ions was investigated. The adsorption equilibrium data fitted well to the Langmuir model, being the maximum adsorption capacity equal 42 mg g -1 . In the desorption studies, 94% of recovered UO 2 2+ with carbonate ion were verified under the conditions studied. The chitosan, available as a byproduct of marine food processing, is environmentally safe and can be a low cost adsorbent for U removal from waterwaste. The magnetic chitosan as adsorbent of U to treat radioactive waterwaste is a sustainable technology. (author)

Covalently bound DNA on naked iron oxide nanoparticles: Intelligent colloidal nano-vector for cell transfection.

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Magro, Massimiliano; Martinello, Tiziana; Bonaiuto, Emanuela; Gomiero, Chiara; Baratella, Davide; Zoppellaro, Giorgio; Cozza, Giorgio; Patruno, Marco; Zboril, Radek; Vianello, Fabio

2017-11-01

Conversely to common coated iron oxide nanoparticles, novel naked surface active maghemite nanoparticles (SAMNs) can covalently bind DNA. Plasmid (pDNA) harboring the coding gene for GFP was directly chemisorbed onto SAMNs, leading to a novel DNA nanovector (SAMN@pDNA). The spontaneous internalization of SAMN@pDNA into cells was compared with an extensively studied fluorescent SAMN derivative (SAMN@RITC). Moreover, the transfection efficiency of SAMN@pDNA was evaluated and explained by computational model. SAMN@pDNA was prepared and characterized by spectroscopic and computational methods, and molecular dynamic simulation. The size and hydrodynamic properties of SAMN@pDNA and SAMN@RITC were studied by electron transmission microscopy, light scattering and zeta-potential. The two nanomaterials were tested by confocal scanning microscopy on equine peripheral blood-derived mesenchymal stem cells (ePB-MSCs) and GFP expression by SAMN@pDNA was determined. Nanomaterials characterized by similar hydrodynamic properties were successfully internalized and stored into mesenchymal stem cells. Transfection by SAMN@pDNA occurred and GFP expression was higher than lipofectamine procedure, even in the absence of an external magnetic field. A computational model clarified that transfection efficiency can be ascribed to DNA availability inside cells. Direct covalent binding of DNA on naked magnetic nanoparticles led to an extremely robust gene delivery tool. Hydrodynamic and chemical-physical properties of SAMN@pDNA were responsible of the successful uptake by cells and of the efficiency of GFP gene transfection. SAMNs are characterized by colloidal stability, excellent cell uptake, persistence in the host cells, low toxicity and are proposed as novel intelligent DNA nanovectors for efficient cell transfection. Copyright © 2017 Elsevier B.V. All rights reserved.

A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

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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.

Doxorubicin delivery to 3D multicellular spheroids and tumors based on boronic acid-rich chitosan nanoparticles.

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Wang, Xin; Zhen, Xu; Wang, Jing; Zhang, Jialiang; Wu, Wei; Jiang, Xiqun

2013-06-01

Boronic acid-rich chitosan-poly(N-3-acrylamidophenylboronic acid) nanoparticles (CS-PAPBA NPs) with the tunable size were successfully prepared by polymerizing N-3-acrylamidophenylboronic acid in the presence of chitosan in an aqueous solution. The CS-PAPBA NPs were then functionalized by a tumor-penetrating peptide iRGD and loading doxorubicin (DOX). The interaction between boronic acid groups of hydrophobic PAPBA and the amino groups of hydrophilic chitosan inside the nanoparticles was examined by solid-state NMR measurement. The size and morphology of nanoparticles were characterized by dynamic light scattering and electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using three-dimensional (3-D) multicellular spheroids (MCs) as the in vitro model and H22 tumor-bearing mice as the in vivo model. It was found that the iRGD-conjugated nanoparticles significantly improved the efficiency of DOX penetration in MCs, compared with free DOX and non-conjugated nanoparticles, resulting in the efficient cell killing in the MCs. In vivo antitumor activity examination indicated that iRGD-conjugated CS-PAPBA nanoparticles promoted the accumulation of nanoparticles in tumor tissue and enhanced their penetration in tumor areas, both of which improved the efficiency of DOX-loaded nanoparticles in restraining tumor growth and prolonging the life time of H22 tumor-bearing mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

Science.gov (United States)

Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

2008-07-04

In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, pnanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, pintramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy.

Science.gov (United States)

Xie, Ying; Qiao, Hongzhi; Su, Zhigui; Chen, Minglei; Ping, Qineng; Sun, Minjie

2014-09-01

Lack of safe and effective delivery vehicle is the main obstacle for siRNA mediated cancer therapy. In this study, we synthesized a pH-sensitive polymer of PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery through a single-step self-assembly method in aqueous condition. The formed nanoparticles with charge of around -8.25 mv and average diameter of 102.1 nm exhibited efficient siRNA encapsulation and enhanced colloidal and serum stability. The test in vitro indicated that the nanoparticles entered into HepG2 cells by endocytosis, and achieved endosomal escape of siRNA effectively due to the pH-responsive disassembly of nanoparticles and dissolution of CaP in the endosome. Reporter gene silencing assay showed that luciferase siRNA delivered by the anionic nanoparticles could achieve gene silencing efficacy comparable to that of conventional Lipofectamine 2000. Additionally, dramatic hTERT knockdown mediated by the anionic nanoparticles transfection induced significant apoptosis of HepG2 cells in vitro. After intravenous injection in tumor-bearing BALB/c nude mice, the nanoparticles specifically accumulated into tumor regions by EPR effect, leading to efficient and specific gene silencing sequentially. Most importantly, the nanoparticles carrying hTERT siRNA inhibited tumor growth significantly via silencing hTERT expression and inducing cells apoptosis in HepG2 tumor xenograft. Moreover, comprehensive safety studies of the nanoparticles confirmed their superior safety both in vitro and in vivo. We concluded that the PEG-CMCS/CaP hybrid anionic nanoparticles possessed potential as a safe and effective siRNA delivery system for anticancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative studies of tripolyphosphate and glutaraldehyde cross-linked chitosan-botanical pesticide nanoparticles and their agricultural applications.

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Gabriel Paulraj, Michael; Ignacimuthu, Savarimuthu; Gandhi, Munusamy Rajiv; Shajahan, Azeez; Ganesan, Pathalam; Packiam, Soosaimanickam Maria; Al-Dhabi, Naif Abdhullah

2017-11-01

A nanopesticide formulation was developed using chitosan and a botanical pesticide PONNEEM ® and its antifeedant, larvicidal and growth regulating activities were screened against Helicoverpa armigera, a major lepidopteran pest. Chitosan nanoparticles (CSNs) were prepared by using two different cross-linking agents namely glutaraldehyde (GLA) and tripolyphosphate (TPP). The effects of cross linking agents on CSNs and the biological properties against the insect pest were also studied. Cross linking of chitosan with either TPP or GLA was confirmed through Fourier Transform Infrared (FTIR) spectroscopy. Electron micrograph revealed that the size of CSNs varied from 32 to 90nm. The stability of nanoparticles lasted for 9days in CSNs-TPP-PONNEEM. In CSNs-GLA-PONNEEM, the stability of nanoparticles was higher. CSNs-TPP-PONNEEM treatment recorded 88.5% antifeedant activity and 90.2% larvicidal activity against H. armigera. Weights of H. armigera pupae in CSNs-TPP-PONNEEM treatment were significantly low. Chitosan-based nano-pesticide formulation holds great promise in H. armigera management. Copyright © 2017 Elsevier B.V. All rights reserved.

Particle Size Affects Concentration-Dependent Cytotoxicity of Chitosan Nanoparticles towards Mouse Hematopoietic Stem Cells

International Nuclear Information System (INIS)

Zaki, S. S. O.; Ibrahim, M. N.; Katas, H.

2015-01-01

Chitosan nanoparticles (CSNPs) have been extensively applied in medical and pharmaceutical fields as promising drug delivery systems. Despite that, the safety of CSNPs remains inadequate and needs further investigation, particularly on hematopoietic stem cells (HSCs). CSNPs were prepared by ionic gelation method and later were characterized for their physical characteristics (particle size and zeta potential). Cytotoxicity of CSNPs was assessed by MTT assay. Particle size was highly influenced by chitosan concentration and molecular weight (medium and high molecular weight (MMW and HMW)). Higher chitosan concentration and molecular weight produced larger nanoparticles. Zeta potential of CSNPs was not significantly affected by chitosan concentrations and molecular weights used in the present study. MMW had a better stability than HMW CSNPs as their particle size and zeta potential were not significantly altered after autoclaving. Cytotoxicity of CSNPs was influenced by zeta potential and particle size. On the other hand, chitosan concentration and molecular weight indirectly influenced cytotoxicity by affecting particle size and zeta potential of CSNPs. In conclusion, cytotoxicity of CSNPs was mainly attributed to their physical characteristics and this opens a strategy to ensure the safety of CSNPs applications in stem cell technology.

Amiloride-enhanced gene transfection of octa-arginine functionalized calcium phosphate nanoparticles.

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Juan Ramón Vanegas Sáenz

Full Text Available Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP, the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8, which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems. Here, we present an optimized method for nCaP-mediated gene delivery using an octa-arginine (R8-functionalized nCaP vector containing a marker or functional gene construct. nCaP particle size was between 220-580 nm in diameter and all R8-functionalized nCaPs carried a positive charge. R8 concentration significantly improved nCaP transfection efficiency with high cell compatibility in human mesenchymal stem cells (hMSC and human osteoblasts (hOB in particular, suggesting nCaPs as a good option for non-viral vector gene delivery. Furthermore, pre-treatment with different endocytosis inhibitors identified that the endocytic pathway differed among cell lines and functionalized nanoparticles, with amiloride increasing transfection efficiency of R8-functionalized nCaPs in hMSC and hOB.

Thiolated chitosan nanoparticles as an oral delivery system for Amikacin: in vitro and ex vivo evaluations.

Science.gov (United States)

Atyabi, F; Talaie, F; Dinarvand, R

2009-08-01

The purpose of this study was the synthesis of two thiol conjugated Chitosan polymers, and evaluation of the potential of Thiomer nanoparticle formulation as a carrier for oral delivery system. Mediated by EDAC (Ethylene-3-(3-di-methylaminopropyl)-carbodiimide), either N-acetyl Cysteine (NAC) or N-acetyl D-penicillamine (NAP) were covalently attached to Chitosan. The success of the synthesis was demonstrated by comparing FTIR spectra. Iodometric titration demonstrated that depending on the pH value of the synthesis medium, the Thiomers display 250 +/- 30 microMol and 300 +/- 20 microMol thiol groups per gram of polymer respectively. The interaction between mucin and Thiomers, compared to mucin and Chitosan was studied for assessment of mucoadhesion properties of synthesized polymers. This interaction was determined by the measurement of the amount of mucin adsorbed on Chitosan and the conjugated polymers. Rotating cylinder method demonstrated an average of 20 times improvement in mucoadhesion of Thiomers compared to the unmodified polymer. Chitosan and Thiomer nanoparticles were formulated by two methods; TPP and Sodium Sulfate gelation. SEM micrographs and data achieved by a Malvern nano/zetasizer show nanoparticles formed by TPP gelation have a mean size of 150 +/- 15 nm compared to 300 +/- 25 nm sized nanoparticles obtained by Sodium sulfate gelation. TPP gelation yields smaller, more spherical shaped nanoparticles with a smaller range of size distribution. Amikacin loaded nanoparticles with an average size of 280 nm were prepared by TPP gelation in which disulfide bond formation was achieved by a time dependent oxidation process. In vitro studies were carried out; a recovery rate of 33% and a drug entrapment of 25% were achieved. The amount of release was determined during 18 hr in a carefully prepared media. The permeation time across a biological membrane was observed to be about 150 minutes. Microbiological tests were carried out on two microorganisms

Preparation and functional studies of hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody

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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

Preparation and characterization of oligochitosan-tragacanth nanoparticles as a novel gene carrier.

Science.gov (United States)

Fattahi, Ali; Sadrjavadi, Komail; Golozar, Mohammad Ali; Varshosaz, Jaleh; Fathi, Mohammad-Hossein; Mirmohammad-Sadeghi, Hamid

2013-09-12

The nanoparticles of oligochitosan-water soluble tragacanth (OCH-WST) as novel gene carriers have been prepared and their transfection efficiency has been investigated on Hela and HepG2 cell lines. Different OCH:WST weight ratios were prepared to obtain particles with low size distribution and high surface charge, and also in range of below 200 nm. Nanoparticles with 132.5 ± 6.77 nm size, polydispersity index 1.92 ± 0.061, surface charge 30.45 ± 1.84 and spherical morphology, have been chosen as gene carrier. Nanoparticle-DNA complexes (nanoplexes) showed better transfection efficiency in both Hela and HepG2 cells than chitosan polyplexes, with 1.26 × 10(6) versus 9.05 × 10(5) and 7.76 × 10(5) versus 2.16 × 10(5), respectively. Higher transfection efficiency of nanoplexes could be attributed to their weaker complexation. Decreasing of transfection in presence of galactose in HepG2 cells, indicated receptor mediated endocytosis of nanoplexes. These properties all together, make OCH-WST nanoparticles as potential gene carrier for active gene delivery into cells containing sugar receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chitosan-coated magnetic nanoparticles prepared in one-step by precipitation in a high-aqueous phase content reverse microemulsion.

Science.gov (United States)

Pineda, María Guadalupe; Torres, Silvia; López, Luis Valencia; Enríquez-Medrano, Francisco Javier; de León, Ramón Díaz; Fernández, Salvador; Saade, Hened; López, Raúl Guillermo

2014-07-02

Chitosan-coated magnetic nanoparticles (CMNP) were prepared in one-step by precipitation in a high-aqueous phase content reverse microemulsion in the presence of chitosan. The high-aqueous phase concentration led to productivities close to 0.49 g CMNP/100 g microemulsion; much higher than those characteristic of precipitation in reverse microemulsions for preparing magnetic nanoparticles. The obtained nanoparticles present a narrow particle size distribution with an average diameter of 4.5 nm; appearing to be formed of a single crystallite; furthermore they present superparamagnetism and high magnetization values; close to 49 emu/g. Characterization of CMNP suggests that chitosan is present as a non-homogeneous very thin layer; which explains the slight reduction in the magnetization value of CMNP in comparison with that of uncoated magnetic nanoparticles. The prepared nanoparticles show high heavy ion removal capability; as demonstrated by their use in the treatment of Pb2+ aqueous solutions; from which lead ions were completely removed within 10 min.

Chitosan-Coated Magnetic Nanoparticles Prepared in One-Step by Precipitation in a High-Aqueous Phase Content Reverse Microemulsion

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María Guadalupe Pineda

2014-07-01

Full Text Available Chitosan-coated magnetic nanoparticles (CMNP were prepared in one-step by precipitation in a high-aqueous phase content reverse microemulsion in the presence of chitosan. The high-aqueous phase concentration led to productivities close to 0.49 g CMNP/100 g microemulsion; much higher than those characteristic of precipitation in reverse microemulsions for preparing magnetic nanoparticles. The obtained nanoparticles present a narrow particle size distribution with an average diameter of 4.5 nm; appearing to be formed of a single crystallite; furthermore they present superparamagnetism and high magnetization values; close to 49 emu/g. Characterization of CMNP suggests that chitosan is present as a non-homogeneous very thin layer; which explains the slight reduction in the magnetization value of CMNP in comparison with that of uncoated magnetic nanoparticles. The prepared nanoparticles show high heavy ion removal capability; as demonstrated by their use in the treatment of Pb2+ aqueous solutions; from which lead ions were completely removed within 10 min.

Characterization of Plasmid DNA Location within Chitosan/PLGA/pDNA Nanoparticle Complexes Designed for Gene Delivery

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Hali Bordelon

2011-01-01

Full Text Available Poly(D,L-lactide-co-glycolide- (PLGA-chitosan nanoparticles are becoming an increasingly common choice for the delivery of nucleic acids to cells for various genetic manipulation techniques. These particles are biocompatible, with tunable size and surface properties, possessing an overall positive charge that promotes complex formation with negatively charged nucleic acids. This study examines properties of the PLGA-chitosan nanoparticle/plasmid DNA complex after formation. Specifically, the study aims to determine the optimal ratio of plasmid DNA:nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within these complexes. Such characterization will be necessary for the adoption of these formulations in a clinical setting. The ability of PLGA-chitosan nanoparticles to form complexes with pDNA was evaluated by using the fluorescent intercalating due OliGreen to label free plasmid DNA. By monitoring the fluorescence at different plasmid: nanoparticle ratios, the ideal plasmid:nanoparticle ration for complete complexation of plasmid was determined to be 1:50. Surface-Enhanced Raman Spectroscopy and gel digest studies suggested that even at these optimal complexation ratios, a portion of the plasmid DNA was located on the outer complex surface. This knowledge will facilitate future investigations into the functionality of the system in vitro and in vivo.

Green synthesis of silver and copper nanoparticles using ascorbic acid and chitosan for antimicrobial applications.

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Zain, N Mat; Stapley, A G F; Shama, G

2014-11-04

Silver and copper nanoparticles were produced by chemical reduction of their respective nitrates by ascorbic acid in the presence of chitosan using microwave heating. Particle size was shown to increase by increasing the concentration of nitrate and reducing the chitosan concentration. Surface zeta potentials were positive for all nanoparticles produced and these varied from 27.8 to 33.8 mV. Antibacterial activities of Ag, Cu, mixtures of Ag and Cu, and Ag/Cu bimetallic nanoparticles were tested using Bacillus subtilis and Escherichia coli. Of the two, B. subtilis proved more susceptible under all conditions investigated. Silver nanoparticles displayed higher activity than copper nanoparticles and mixtures of nanoparticles of the same mean particle size. However when compared on an equal concentration basis Cu nanoparticles proved more lethal to the bacteria due to a higher surface area. The highest antibacterial activity was obtained with bimetallic Ag/Cu nanoparticles with minimum inhibitory concentrations (MIC) of 0.054 and 0.076 mg/L against B. subtilis and E. coli, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

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...

Fabrication of β-chitosan nanoparticles and its anticancer potential against human hepatoma cells.

Science.gov (United States)

Subhapradha, Namasivayam; Shanmugam, Annaian

2017-01-01

β-Chitosan from the gladius was enzymatically depolymerized and utilized for the synthesis of β-chitosan nanoparticles using sodium tripolyphosphate by ionotropic gelation. The size and zeta potential of β-Chitosan nanoparticles (β-CNP) were determined. The structural features were evaluated by FT-IR and NMR spectral analysis. The morphological characterization, composition and surface topography of β-CNP were explored by SEM, EDAX and AFM techniques. The thermal and crystallographic nature of β-CNP was also studied. The cell viability of HepG2 cells inhibited by β-CNP was detected in a dose-dependent manner. The inhibitory concentration of β-CNP was 30μg/ml. Various biochemical parameters such as TBARS and lipid hydroperoxides, enzymatic and non-enzymatic antioxidant (SOD, CAT, GPx and GSH) studies proved the anticancer property of β-CNP in HepG2 cells. This study suggests that β-CNP should be a promising drug for treating hepatocellular carcinoma in future. Copyright © 2016. Published by Elsevier B.V.

Release Behavior and Antibacterial Activity of Chitosan/Alginate Blends with Aloe vera and Silver Nanoparticles.

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Gómez Chabala, Luisa Fernanda; Cuartas, Claudia Elena Echeverri; López, Martha Elena Londoño

2017-10-24

Aloe vera is a perennial plant employed for medical, pharmaceutical and cosmetic purposes that is rich in amino acids, enzymes, vitamins and polysaccharides, which are responsible for its therapeutic properties. Incorporating these properties into a biopolymer film obtained from alginate and chitosan allowed the development of a novel wound dressing with antibacterial capacity and healing effects to integrate the antibacterial capacity of silver nanoparticles with the healing and emollient properties of Aloe vera gel. Three alginate-chitosan matrices were obtained through blending methods using different proportions of alginate, chitosan, the Aloe vera (AV) gel and silver nanoparticles (AgNps), which were incorporated into the polymeric system through immersion methods. Physical, chemical and antibacterial characteristics were evaluated in each matrix. Interaction between alginate and chitosan was identified using the Fourier transform infrared spectroscopy technique (FTIR), porosity was studied using scanning electron microscopy (SEM), swelling degree was calculated by difference in weight, Aloe vera gel release capacity was estimated by applying a drug model (Peppas) and finally antibacterial capacity was evaluated against S. Aureus and P. aeruginosa . Results show that alginate-chitosan (A (1:3 Chit 1/Alg 1); B (1:3 Chit 1.5/Alg 1) and C (3:1 Chit 1/Alg 1/B12)) matrices with Aloe vera (AV) gel and silver nanoparticles (AgNps) described here displayed antibacterial properties and absorption and Aloe vera release capacity making it a potential wound dressing for minor injuries.

Gene delivery using calcium phosphate nanoparticles: Optimization of the transfection process and the effects of citrate and poly(l-lysine) as additives.

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Khan, Mohammed A; Wu, Victoria M; Ghosh, Shreya; Uskoković, Vuk

2016-06-01

Despite the long history of nanoparticulate calcium phosphate (CaP) as a non-viral transfection agent, there has been limited success in attempts to optimize its properties for transfection comparable in efficiency to that of viral vectors. Here we focus on the optimization of: (a) CaP nanoparticle precipitation conditions, predominantly supersaturation and Ca/P molar ratios; (b) transfection conditions, mainly the concentrations of the carrier and plasmid DNA; (c) the presence of surface additives, including citrate anion and cationic poly(l-lysine) (PLL). CaP nanoparticles significantly improved transfection with plasmid DNA encoding enhanced green fluorescent protein (eGFP) in pre-osteoblastic MC3T3-E1 cells compared to a commercial non-viral carrier. At the same time they elicited significantly lesser cytotoxicity than the commercial carrier. Plasmid DNA acted as a nucleation promoter, decreasing the nucleation lag time of metastable CaP solutions and leading to a higher rate of nucleation and a lower size of the precipitated particles. The degree of supersaturation (DS) of 15 was found to be more optimal for transfection than that of 12.5 or 17.5 and higher. Because CaP particles precipitated at DS 15 were spherical, while DS 17.5 and 21 yielded acicular particles, it was concluded that spherical particle morphologies were more conducive to transfection than the anisotropic ones. Even though the yield at DS 15 was 10 and 100 times lower than that at DS 17.5 and 21, respectively, transfection rates were higher using CaP nanoparticle colloids prepared at DS 15 than using those made at higher or lower DS, indicating that the right particle morphology can outweigh the difference in the amount of the carrier, even when this difference is close to 100×. In contrast to the commercial carrier, the concentration of CaP-pDNA delivered to the cells was directly proportional to the transfection rate. Osteosarcoma K7M2 cells were four times more easily transfectable with

Red fluorescent chitosan nanoparticles grafted with poly(2-methacryloyloxyethyl phosphorylcholine) for live cell imaging.

Science.gov (United States)

Wang, Ke; Fan, Xingliang; Zhang, Xiaoyong; Zhang, Xiqi; Chen, Yi; Wei, Yen

2016-08-01

Poly(2-methacryloyloxyethyl phosphorylcholine) conjugated red fluorescent chitosan nanoparticles (GCC-pMPC) were facilely fabricated by "grafting from" method via surface initiated atom transfer radical polymerization (ATRP). Firstly, glutaraldehyde crosslinked red fluorescent chitosan nanoparticles (GCC NPs) with many amino groups and hydroxyl groups on their surface were prepared, which were then reacted with 2-bromoisobutyryl bromide to form GCC-Br; subsequently, poly(MPC) (pMPC) brushes were grafted onto GCC NPs surface using GCC-Br as initiator via ATRP. Compared with PEGylated nanoparticles, zwitterionic polymers modified nanoparticles demonstrated better performance in their cellular uptake. Moreover, the obtained GCC-pMPC demonstrated excellent water-dispersibility, biocompatibility, and photostability, which made them highly potential for long-term tracing applications. Importantly, the successful live cell imaging of GCC-pMPC would remarkably advance the research of their further bioapplications. Copyright © 2016 Elsevier B.V. All rights reserved.

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

Directory of Open Access Journals (Sweden)

Teik Hwa Ong

Full Text Available Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles.

Science.gov (United States)

Matos, Breno Noronha; Reis, Thaiene Avila; Gratieri, Taís; Gelfuso, Guilherme Martins

2015-04-01

This work developed minoxidil sulphate-loaded chitosan nanoparticles (MXS-NP) for targeted delivery to hair follicles, which could sustain drug release and improve the topical treatment of alopecia. Chitosan nanoparticles were obtained using low-molecular weight chitosan and tripolyphosphate as crosslink agent. MXS-NP presented a monomodal distribution with hydrodynamic diameter of 235.5 ± 99.9 nm (PDI of 0.31 ± 0.01) and positive zeta potential (+38.6 ± 6.0 mV). SEM analysis confirmed nanoparticles average size and spherical shape. A drug loading efficiency of 73.0 ± 0.3% was obtained with polymer:drug ratio of 1:1 (w/w). Drug release through cellulose acetate membranes from MXS-NP was sustained in about 5 times in comparison to the diffusion rate of MXS from the solution (188.9 ± 6.0 μg/cm(2)/h and 35.4 ± 1.8 μg/cm(2)/h). Drug permeation studies through the skin in vitro, followed by selective recovery of MXS from the hair follicles, showed that MXS-NP application resulted in a two-fold MXS increase into hair follicles after 6h in comparison to the control solution (5.9 ± 0.6 μg/cm(2) and 2.9 ± 0.8 μg/cm(2)). MXS-loading in nanoparticles appears as a promising and easy strategy to target and sustain drug delivery to hair follicles, which may improve the topical treatment of alopecia. Copyright © 2015 Elsevier B.V. All rights reserved.

Incorporation of zinc oxide nanoparticles into chitosan-collagen 3D porous scaffolds: Effect on morphology, mechanical properties and cytocompatibility of 3D porous scaffolds.

Science.gov (United States)

Ullah, Saleem; Zainol, Ismail; Idrus, Ruszymah Hj

2017-11-01

The zinc oxide nanoparticles (particles size chitosan-collagen 3D porous scaffolds and investigated the effect of zinc oxide nanoparticles incorporation on microstructure, mechanical properties, biodegradation and cytocompatibility of 3D porous scaffolds. The 0.5%, 1.0%, 2.0% and 4.0% zinc oxide nanoparticles chitosan-collagen 3D porous scaffolds were fabricated via freeze-drying technique. The zinc oxide nanoparticles incorporation effects consisting in chitosan-collagen 3D porous scaffolds were investigated by mechanical and swelling tests, and effect on the morphology of scaffolds examined microscopically. The biodegradation and cytocompatibility tests were used to investigate the effects of zinc oxide nanoparticles incorporation on the ability of scaffolds to use for tissue engineering application. The mean pore size and swelling ratio of scaffolds were decreased upon incorporation of zinc oxide nanoparticles however, the porosity, tensile modulus and biodegradation rate were increased upon incorporation of zinc oxide nanoparticles. In vitro culture of human fibroblasts and keratinocytes showed that the zinc oxide nanoparticles facilitated cell adhesion, proliferation and infiltration of chitosan-collagen 3D porous scaffolds. It was found that the zinc oxide nanoparticles incorporation enhanced porosity, tensile modulus and cytocompatibility of chitosan-collagen 3D porous scaffolds. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs).

Science.gov (United States)

Shevtsov, Maxim; Nikolaev, Boris; Marchenko, Yaroslav; Yakovleva, Ludmila; Skvortsov, Nikita; Mazur, Anton; Tolstoy, Peter; Ryzhov, Vyacheslav; Multhoff, Gabriele

2018-01-01

Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI). Synthesized hybrid chitosan-dextran superparamagnetic nanoparticles (CS-DX-SPIONs) were characterized using transmission electron microscopy (TEM) and relaxometry studies. Nonlinear magnetic response measurements were employed for confirming the superparamagnetic state of particles. Following in vitro analysis of nanoparticles cellular uptake tumor targeting was assessed in the model of the orthotopic glioma in rodents. CS-DX-SPIONs nanoparticles showed a uniform diameter of 55 nm under TEM and superparamagentic characteristics as determined by T 1 (spin-lattice relaxation time) and T 2 (spin-spin relaxation time) proton relaxation times. Application of the chitosan increased the charge from +8.9 to +19.3 mV of the dextran-based SPIONs. The nonlinear magnetic response at second harmonic of CS-DX-SPIONs following the slow change of stationary magnetic fields with very low hysteresis evidenced superparamagnetic state of particles at ambient temperatures. Confocal microscopy and flow cytometry studies showed an enhanced internalization of the chitosan-based nanoparticles in U87, C6 glioma and HeLa cells as compared to dextran-coated particles. Cytotoxicity assay demonstrated acceptable toxicity profile of the synthesized nanoparticles up to a concentration of 10 μg/ml. Intravenously administered CS-DX-SPIONs in orthotopic C6 gliomas in rats accumulated in the tumor site as shown by high-resolution MRI (11.0 T). Retention of nanoparticles resulted in a significant contrast enhancement of the tumor image that was accompanied with a dramatic drop in T 2 values ( P chitosan-dextran magnetic particles demonstrated high MR contrast enhancing properties for the

Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells.

Science.gov (United States)

Wang, Zhongshan; Wu, Guangsheng; Feng, Zhihong; Bai, Shizhu; Dong, Yan; Wu, Guofeng; Zhao, Yimin

2015-01-01

Dental implants have been widely used for the replacement of missing teeth in the clinic, but further improvements are needed to meet the clinical demands for faster and tighter osseointegration. In this study, we fabricated safe and biocompatible chitosan (CS)/hyaluronic acid (HA) nanoparticles to deliver microRNA-21 (miR-21) and thereby accelerate osteogenesis in human bone marrow mesenchymal stem cells (hBMMSCs). The CS/HA/miR-21 nanoparticles were cross-linked with 0.2% gel solution onto microarc oxidation (MAO)-treated titanium (Ti) surfaces to fabricate the miR-21-functionalized MAO Ti surface, resulting in the development of a novel coating for reverse transfection. To characterize the CS/HA/miR-21 nanoparticles, their particle size, zeta potential, surface morphology, and gel retardation ability were sequentially investigated. Their biological effects, such as cell viability, cytotoxicity, and expression of osteogenic genes by hBMMSCs on the miR-21-functionalized MAO Ti surfaces, were evaluated. Finally, we explored appropriate CS/HA/miR-21 nanoparticles with a CS/HA ratio of 4:1 and N/P ratio 20:1 for transfection, which presented good spherical morphology, an average diameter of 160.4±10.75 nm, and a positive zeta potential. The miR-21-functionalized MAO Ti surfaces demonstrated cell viability, cytotoxicity, and cell spreading comparable to those exhibited by naked MAO Ti surfaces and led to significantly higher expression of osteogenic genes. This novel miR-21-functionalized Ti implant may be used in the clinic to allow more effective and robust osseointegration.

Synergistic antifungal effect of chitosan-stabilized selenium nanoparticles synthesized by pulsed laser ablation in liquids against Candida albicans biofilms.

Science.gov (United States)

Lara, Humberto H; Guisbiers, Gregory; Mendoza, Jonathan; Mimun, Lawrence C; Vincent, Brandy A; Lopez-Ribot, Jose L; Nash, Kelly L

2018-01-01

Candida albicans is a major opportunistic fungal pathogen. One of the most important virulence factors that contribute to the pathogenesis of candidiasis is its ability to form biofilms. A key characteristic of Candida biofilms is their resistance to antifungal agents. Due to significant morbidity and mortality rates related to biofilm-associated drug resistance, there is an urgency to develop novel nanotechnology-based approaches preventing biofilm-related infections. In this study, we report, for the first time, the synthesis of selenium nanoparticles by irradiating selenium pellets by nanosecond pulsed laser ablation in liquid chitosan as a capping agent. Synergy of the fungicidal effect of selenium nanoparticles and chitosan was quantified by the combination index theorem of Chou-Talalay. This drug combination resulted in a potent fungicidal effect against a preformed C. albicans biofilm in a dose-response manner. By advanced electron microscopy techniques, we documented the adhesive and permeabilizing properties of chitosan, therefore allowing selenium nanoparticles to enter as the cell wall of the yeast became disrupted and distorted. Most importantly, we demonstrated a potent quantitative synergistic effect when compounds such as selenium and chitosan are combined. These chitosan-stabilized selenium nanoparticles could be used for ex vivo applications such as sterilizers for surfaces and biomedical devices.

Preparation of mono-dispersed silver nanoparticles assisted by chitosan-g-poly(ε-caprolactone) micelles and their antimicrobial application

Energy Technology Data Exchange (ETDEWEB)

Gu, Chunhua [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhang, Huan [State Key Laboratory of Bioreactor Engineering, New World Biotechnology Institute, East China University of Science and Technology, Shanghai 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

2014-05-01

Graphical abstract: - Highlights: • Chemical modification of chitosan were conducted after phthaloyl protection of amino groups. • Silver nanoparticles were prepared in the presence of chitosan-based copolymer micelles. • The optimal time scale and weight ratios of silver to micelles were monitored by UV–vis spectrometer. - Abstract: Amphiphilic chitosan-graft-poly(ε-caprolactone) (CS-g-PCLs) copolymers were synthesized by a homogeneous coupling method and characterized by {sup 1}H NMR, FTIR and ninhydrin assay. The graft copolymers were subsequently self-assembled into micelles, which were measured by DLS and TEM. The particle size of the micelles decreased as the segment grafting fraction was increased. Thereafter, silver nanoparticles were prepared in the presence of chitosan-based micelles under UV irradiation. The molar ratio and radiation time of silver to micelles were optimized with process monitored via UV–vis spectrophotometer. DLS and TEM were used to illustrate the particle structure and size while XRD patterns were applied to characterize the crystal structures of polymer-assisted silver nanoparticles. Films impregnated with silver nanoparticles were conducted with results of strong antimicrobial activities against Escherichia coli and Staphylococcus aureus as model Gram-negative and positive bacteria.

Preparation of mono-dispersed silver nanoparticles assisted by chitosan-g-poly(ε-caprolactone) micelles and their antimicrobial application

International Nuclear Information System (INIS)

Gu, Chunhua; Zhang, Huan; Lang, Meidong

2014-01-01

Graphical abstract: - Highlights: • Chemical modification of chitosan were conducted after phthaloyl protection of amino groups. • Silver nanoparticles were prepared in the presence of chitosan-based copolymer micelles. • The optimal time scale and weight ratios of silver to micelles were monitored by UV–vis spectrometer. - Abstract: Amphiphilic chitosan-graft-poly(ε-caprolactone) (CS-g-PCLs) copolymers were synthesized by a homogeneous coupling method and characterized by 1 H NMR, FTIR and ninhydrin assay. The graft copolymers were subsequently self-assembled into micelles, which were measured by DLS and TEM. The particle size of the micelles decreased as the segment grafting fraction was increased. Thereafter, silver nanoparticles were prepared in the presence of chitosan-based micelles under UV irradiation. The molar ratio and radiation time of silver to micelles were optimized with process monitored via UV–vis spectrophotometer. DLS and TEM were used to illustrate the particle structure and size while XRD patterns were applied to characterize the crystal structures of polymer-assisted silver nanoparticles. Films impregnated with silver nanoparticles were conducted with results of strong antimicrobial activities against Escherichia coli and Staphylococcus aureus as model Gram-negative and positive bacteria

Synthesis and Characterization of Fe3O4 Magnetic Nanoparticles Coated with Carboxymethyl Chitosan Grafted Sodium Methacrylate

Directory of Open Access Journals (Sweden)

S. Asgari

2014-01-01

Full Text Available N-sodium acrylate-O-carboxymethyl chitosan [CMCH-g-PAA(Na] bound Fe3O4 nanoparticles were developed as a novel magnetic nanoparticles with an ionic structure that can be potentially used in many fields. CMCH-g-PAA (Na was obtained by grafting of sodium polyacrylate on O-carboxymethyl chitosan, which is an amphiphilic polyelectrolyte with the biocompatibility and biodegradability properties. According to the great interest for improving the stability of Fe3O4 nanoparticles, CMCH-g-PAA (Na was used as a stabilizer to prepare a well dispersed suspension of magnetic nanoparticle According to the results,the presence of CMCH-g-PAA(Na could eliminate agglomeration of magnetic nanoparticles without destroying the superparamagnetic  properties

Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin.

Science.gov (United States)

Ridolfi, Daniela M; Marcato, Priscyla D; Justo, Giselle Z; Cordi, Lívia; Machado, Daisy; Durán, Nelson

2012-05-01

Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7±1.4 nm and -31.9±2.0 mV for SLN-TRE, and 284.8±15.0 nm and 55.9±3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne. Copyright © 2011 Elsevier B.V. All rights reserved.

5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol-chitosan copolymer for photodynamic therapy

Directory of Open Access Journals (Sweden)

Chung CW

2013-02-01

Full Text Available Chung-Wook Chung,1,* Kyu-Don Chung,2,* Young-Il Jeong,1 Dae Hwan Kang,1 1National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University, Seoul, Republic of Korea*These authors contributed equally to this workPurpose: The aim of this study was to make 5-aminolevulinic acid (5-ALA-incorporated nanoparticles using methoxy polyethylene glycol/chitosan (PEG-Chito copolymer for application in photodynamic therapy for colon cancer cells.Methods: 5-ALA-incorporated (PEG-Chito-5-ALA nanoparticles were prepared by ion complex formation between 5-ALA and chitosan. Protoporphyrin IX accumulation in the tumor cells and phototoxicity induced by PEG-Chito-5-ALA nanoparticles were assessed using CT26 cells in vitro.Results: PEG-Chito-5-ALA nanoparticles have spherical shapes with sizes diameters 200 nm. More specifically, microscopic observation revealed a core-shell structure of PEG-Chito-5-ALA nanoparticles. 1H NMR spectra showed that 5-ALA was incorporated in the core of the nanoparticles. In the absence of light irradiation, all components such as 5-ALA, empty nanoparticles, and PEG-Chito-5-ALA nanoparticles did not affect the viability of cells. However, 5-ALA or PEG-Chito-5-ALA nanoparticles induced tumor cell death under light irradiation, and the viability of tumor cells was dose-dependently decreased according to the increase in irradiation time. In particular, PEG-Chito-5-ALA nanoparticles induced increased phototoxicity and higher protoporphyrin IX accumulation into the tumor cells than did 5-ALA alone. Furthermore, PEG-Chito-5-ALA nanoparticles accelerated apoptosis/necrosis of tumor cells, compared to 5-ALA alone.Conclusion: PEG-Chito-5-ALA nanoparticles showed superior delivery capacity of 5-ALA and phototoxicity against tumor cells. These results show that PEG-Chito-5-ALA

Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin

International Nuclear Information System (INIS)

Chen, Zhanguang; Wang, Zhen; Chen, Xi; Xu, Haixiong; Liu, Jinbin

2013-01-01

In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2–60 μM (∼6.7 U/mL). The detection limit for heparin is 0.8 μM at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results

Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhanguang, E-mail: kqlu@stu.edu.cn; Wang, Zhen; Chen, Xi [Shantou University, Department of Chemistry (China); Xu, Haixiong [Shantou Central Hospital, Affiliated Shantou Hospital of SUN YAT-SEN University (China); Liu, Jinbin [University of Texasat Dallas, Department of Chemistry (United States)

2013-09-15

In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2-60 {mu}M ({approx}6.7 U/mL). The detection limit for heparin is 0.8 {mu}M at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results.

Protection and systemic translocation of siRNA following oral administration of chitosan/siRNA nanoparticles

DEFF Research Database (Denmark)

Gonzalez, Borja Ballarin; Dagnæs-Hansen, Frederik; Fenton, Robert A.

2013-01-01

, gastrointestinal (GI) deposition, and translocation into peripheral tissue of nonmodified siRNA after oral gavage of chitosan/siRNA nanoparticles in mice. In contrast to naked siRNA, retained structural integrity and deposition in the stomach, proximal and distal small intestine, and colon was observed at 1 and 5...... hours for siRNA within nanoparticles. Furthermore, histological detection of fluorescent siRNA at the apical regions of the intestinal epithelium suggests mucoadhesion provided by chitosan. Detection of intact siRNA in the liver, spleen, and kidney was observed 1 hour after oral gavage, with an organ...

Chitosan-based DNA delivery vector targeted to gonadotropin-releasing hormone (GnRH) receptor.

Science.gov (United States)

Boonthum, Chatwalee; Namdee, Katawut; Boonrungsiman, Suwimon; Chatdarong, Kaywalee; Saengkrit, Nattika; Sajomsang, Warayuth; Ponglowhapan, Suppawiwat; Yata, Teerapong

2017-02-10

The main purpose of this study was to investigate the application of modified chitosan as a potential vector for gene delivery to gonadotropin-releasing hormone receptor (GnRHR)-expressing cells. Such design of gene carrier could be useful in particular for gene therapy for cancers related to the reproductive system, gene disorders of sexual development, and contraception and fertility control. In this study, a decapeptide GnRH was successfully conjugated to chitosan (CS) as confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The synthesized GnRH-conjugated chitosan (GnRH-CS) was able to condense DNA to form positively charged nanoparticles and specifically deliver plasmid DNA to targeted cells in both two-dimensional (2D) and three-dimensional (3D) cell cultures systems. Importantly, GnRH-CS exhibited higher transfection activity compared to unmodified CS. In conclusion, GnRH-conjugated chitosan can be a promising carrier for targeted DNA delivery to GnRHR-expressing cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles.

Science.gov (United States)

Venkatesan, Jayachandran; Lee, Jin-Young; Kang, Dong Seop; Anil, Sukumaran; Kim, Se-Kwon; Shim, Min Suk; Kim, Dong Gyu

2017-05-01

The main aim of this study was to obtain porous antimicrobial composites consisting of chitosan, alginate, and biosynthesized silver nanoparticles (AgNPs). Chitosan and alginate were used owing to their pore-forming capacity, while AgNPs were used for their antimicrobial property. The developed porous composites of chitosan-alginate-AgNPs were characterized using Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy, X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The FT-IR results revealed the presence of a strong chemical interaction between chitosan and alginate due to polyelectrolyte complex; whereas, the XRD results confirmed the presence of AgNPs in the composites. The dispersion of AgNPs in the porous membrane was uniform with a pore size of 50-500μm. Antimicrobial activity of the composites was checked with Escherichia coli and Staphylococcus aureus. The developed composites resulted in the formation of a zone of inhibition of 11±1mm for the Escherichia coli, and 10±1mm for Staphylococcus aureus. The bacterial filtration efficiency of chitosan-alginate-AgNPs was 1.5-times higher than that of the chitosan-alginate composite. The breast cancer cell line MDA-MB-231 was used to test the anticancer activity of the composites. The IC 50 value of chitosan-alginate-AgNPs on MDA-MB-231 was 4.6mg. The developed chitosan-alginate-AgNPs composite showed a huge potential for its applications in antimicrobial filtration and cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

International Nuclear Information System (INIS)

Tao, Y.; Zhang, H.; Gao, B.; Guo, J.; Hu, Y.; Su, Z.

2011-01-01

Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800?nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia

Comparative assessment of poly (D,L-lactide-co-glycolide ...

African Journals Online (AJOL)

... are modified by CTAB and chitosan. Modification with chitosan yields PLGA nanoparticles with higher DNA adsorption and transfection with lower cytotoxicity. Keywords: Chitosan, cetyltrimethyl ammonium bromide (CTAB), Nanoparticle, Poly (D,L-lactide-coglycolide) PLGA, Plasmid DNA adsorption, Gene therapy ...

Comprehensive studies on the interactions between chitosan nanoparticles and some live cells

International Nuclear Information System (INIS)

Zheng Aiping; Liu Huixue; Yuan Lan; Meng Meng; Wang Jiancheng; Zhang Xuan; Zhang Qiang

2011-01-01

As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer and its nanoparticles, especially the effects on the biomembrane. Several techniques, including surface plasmon resonance (SPR), Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, fluorescence polarization spectroscopy (FP), flow cytometry (FCM) with quantitative analysis, and confocal images with antibody staining were employed toward this end. The cytotoxicity in vitro was also evaluated. Chitosan (CS), a polycationic polymer, was used to prepare the nanoparticles. We demonstrate that chitosan nanoparticles (CS-NP) induce strong alterations in the distribution of membrane proteins, fluidity of membrane lipids, and general membrane structure. Furthermore, the uptake of CS-NP into Caco-2 cells was found to have a similar mechanism to that of CS molecules, but the differences in degree were noted. These results indicate that positive charge and nanoscale size were the factors that most significantly affected the interactions between the nanoparticles of polycationic polymers and live cells. However, no difference in cytotoxicity toward the Caco-2 cells was found between CS and CS-NP. This supports the idea that CS-NP is an effective and safe carrier for oral drug delivery.

Fabrication of Well-Aligned ZnO Nanorods Using a Composite Seed Layer of ZnO Nanoparticles and Chitosan Polymer.

Science.gov (United States)

Khun, Kimleang; Ibupoto, Zafar Hussain; AlSalhi, Mohamad S; Atif, Muhammad; Ansari, Anees A; Willander, Magnus

2013-09-30

In this study, by taking the advantage of both inorganic ZnO nanoparticles and the organic material chitosan as a composite seed layer, we have fabricated well-aligned ZnO nanorods on a gold-coated glass substrate using the hydrothermal growth method. The ZnO nanoparticles were characterized by the Raman spectroscopic techniques, which showed the nanocrystalline phase of the ZnO nanoparticles. Different composites of ZnO nanoparticles and chitosan were prepared and used as a seed layer for the fabrication of well-aligned ZnO nanorods. Field emission scanning electron microscopy, energy dispersive X-ray, high-resolution transmission electron microscopy, X-ray diffraction, and infrared reflection absorption spectroscopic techniques were utilized for the structural characterization of the ZnO nanoparticles/chitosan seed layer-coated ZnO nanorods on a gold-coated glass substrate. This study has shown that the ZnO nanorods are well-aligned, uniform, and dense, exhibit the wurtzite hexagonal structure, and are perpendicularly oriented to the substrate. Moreover, the ZnO nanorods are only composed of Zn and O atoms. An optical study was also carried out for the ZnO nanoparticles/chitosan seed layer-coated ZnO nanorods, and the obtained results have shown that the fabricated ZnO nanorods exhibit good crystal quality. This study has provided a cheap fabrication method for the controlled morphology and good alignment of ZnO nanorods, which is of high demand for enhancing the working performance of optoelectronic devices.

Fabrication of Well-Aligned ZnO Nanorods Using a Composite Seed Layer of ZnO Nanoparticles and Chitosan Polymer

Directory of Open Access Journals (Sweden)

Anees A. Ansari

2013-09-01

Full Text Available In this study, by taking the advantage of both inorganic ZnO nanoparticles and the organic material chitosan as a composite seed layer, we have fabricated well-aligned ZnO nanorods on a gold-coated glass substrate using the hydrothermal growth method. The ZnO nanoparticles were characterized by the Raman spectroscopic techniques, which showed the nanocrystalline phase of the ZnO nanoparticles. Different composites of ZnO nanoparticles and chitosan were prepared and used as a seed layer for the fabrication of well-aligned ZnO nanorods. Field emission scanning electron microscopy, energy dispersive X-ray, high-resolution transmission electron microscopy, X-ray diffraction, and infrared reflection absorption spectroscopic techniques were utilized for the structural characterization of the ZnO nanoparticles/chitosan seed layer-coated ZnO nanorods on a gold-coated glass substrate. This study has shown that the ZnO nanorods are well-aligned, uniform, and dense, exhibit the wurtzite hexagonal structure, and are perpendicularly oriented to the substrate. Moreover, the ZnO nanorods are only composed of Zn and O atoms. An optical study was also carried out for the ZnO nanoparticles/chitosan seed layer-coated ZnO nanorods, and the obtained results have shown that the fabricated ZnO nanorods exhibit good crystal quality. This study has provided a cheap fabrication method for the controlled morphology and good alignment of ZnO nanorods, which is of high demand for enhancing the working performance of optoelectronic devices.

Silver deposited carboxymethyl chitosan-grafted magnetic nanoparticles as dual action deliverable antimicrobial materials.

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Vo, Duc-Thang; Sabrina, Sabrina; Lee, Cheng-Kang

2017-04-01

Carboxymethyl chitosan (CMCS) was known to have a much better antimicrobial activity than chitosan due to the increased cationic -NH 3 + groups resulted from the intra- and intermolecular interactions between the carboxyl and amino groups. CMCS was grafted onto the surface of silica coated magnetic nanoparticles (MNPs) to obtain magnetically retrievable and deliverable antimicrobial nanoparticles (MNPs@CMCS). The presence of carboxylate groups in CMCS not only enhanced antimicrobial activity but also enabled Ag ions chelating ability to induce the in situ formation of Ag nanoparticles (AgNPs). The deposition of AgNPs on the surface of MNPs@CMCS could significantly increase its antimicrobial activity against planktonic cells due to the dual action of CMCS and AgNPs. Due to its high magnetism, the as-prepared MNPs@CMCS-Ag could be efficiently delivered into an existing biofilm under the guidance of an applied magnetic field. Without direct contact, the Ag ions and/or radical oxygen species (ROS) released from the deposited Ag nanoparticles could effectively kill the bacteria embedded in the extracellular polymeric substances (EPS) matrix of biofilm. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a Novel Lipophilic, Magnetic Nanoparticle for in Vivo Drug Delivery

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Torben Moos

2013-04-01

Full Text Available The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs (chi-MNPs after encapsulation inside polyethylglycol (PEGylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs, and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4 cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro.

Development of a Novel Lipophilic, Magnetic Nanoparticle for in Vivo Drug Delivery

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Linemann, Thomas; Thomsen, Louiza B.; Du Jardin, Kristian G.; Laursen, Jens C.; Jensen, Jesper B.; Lichota, Jacek; Moos, Torben

2013-01-01

The aim of the present study was to evaluate the transfection potential of chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid-encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these particles would distribute in vivo after systemic injection. The transfection potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain endothelial 4 (RBE4) cells with and without applying a magnetic field. Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro investigations revealed that the application of a magnetic field resulted in an increased cellular uptake of the particles. The lip-MNPs were able to transfect the RBE4 cells with an incidence of approximately 20% of a commercial transfection agent. The in vivo distribution studies revealed that lip-MNPs had superior pharmacokinetic properties due to evasion of the RES, including hepatic Kuppfer cells and macrophages in the spleen. In conclusion, we were able to design a novel lipid-encapsulated MNP with the ability to carry genetic material, with favorable pharmacokinetic properties, and under the influence of a magnetic field with the capability to mediate transfection in vitro. PMID:24300449

Radiation Synthesis of PVA/ Chitosan Membranes Containing Silver Nanoparticles for Biomedical Applications

International Nuclear Information System (INIS)

Elbarbary, A.M.; El-Sawy, N.M.

2015-01-01

Silver Nanoparticles (AgNPs) were synthesized by γ-rays of polyvinyl alcohol/ chitosan (PVA/ CS) membranes containing silver nitrate (AgNO ) with promising antimicrobial and biomedical applications. The synthesized silver nanoparticles characterized by Ultra Violet spectroscopy (UV), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and transmission electron microscopy (TEM). UV studies showed a strong peak around λmax at 420 nm. A uniform distribution of silver nanoparticles inside PVA/ CS membranes was achieved by TEM investigation. The prepared silver nanoparticles showed good antimicrobial activity. The membranes containing AgNPs showed non-thrombogenicity effect and slightly haemolytic potential. The prepared membranes containing AgNPs had promising use in biomedical applications.

Structural and optical properties of Cu-doped ZnS nanoparticles formed in chitosan/sodium alginate multilayer films.

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Wang, Liping; Sun, Yujie; Xie, Xiaodong

2014-05-01

Chitosan/alginate multilayers were fabricated using a spin-coating method, and ZnS:Cu nanoparticles were generated within the network of two natural polysaccharides, chitosan and sodium alginate. The synthesized nanoparticles were characterized using an X-ray diffractometer (XRD), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS) and atomic force microscopy (AFM). The results showed that cubic zinc blende-structured ZnS:Cu nanoparticles with an average crystal size of ~ 3 nm were uniformly distributed. UV-vis spectra indicate a large quantum size effect and the absorption edge for the ZnS:Cu nanoparticles slightly shifted to longer wavelengths with increasing Cu ion concentrations. The photoluminescence of the Cu-doped ZnS nanoparticles reached a maximum at a 1% doping level. The ZnS:Cu nanoparticles form and are distributed uniformly in the composite multilayer films with a surface average height of 25 nm. Copyright © 2013 John Wiley & Sons, Ltd.

Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

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Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

2011-09-01

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

Evaluation of dose dependent antimicrobial activity of self-assembled chitosan, nano silver and chitosan-nano silver composite against several pathogens.

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Tareq, Foysal Kabir; Fayzunnesa, Mst; Kabir, Md Shahariar; Nuzat, Musrat

2018-01-01

The aim of this investigation to preparation of silver nanoparticles organized chitosan nano polymer, which effective against microbial and pathogens, when apply to liquid medium and edible food products surface, will rescue the growth of microbes. Self-assembly approach used to synthesis of silver nanoparticles and silver nanoparticles organized chitosan nano polymer. Silver nanoparticles and silver nanoparticles organized chitosan nano polymer and film characterized using Ultra-violate visible spectrometer (UV-vis), X-ray diffraction (X-ray), and Scanning electronic microscope (SEM). The crystalline structured protein capped nano silver successfully synthesized at range of 12 nm-29 nm and organized into chitosan nano polymer. Antimicrobial ingredient in liquid medium and food product surface provide to rescue oxidative change and growth of microorganism to provide higher safety. The silver nanoparticles organized chitosan nano polymer caused the death of microorganism. The materials in nano scale synthesized successfully using self-assembly method, which showed good antimicrobial properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

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Yi Tao

2011-01-01

Full Text Available Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.

Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

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Islam, Nazrul; Ferro, Vito

2016-07-01

The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

Modified Chitosan Nanoparticle by Radiation Synthesis: An Approach to Drug Delivery and Bio-Based Additive for Biomedical Applications

International Nuclear Information System (INIS)

Pasanphan, W.; Rimdusit, P.; Rattanawongwiboon, T.; Choofong, S.

2010-01-01

Self-assembly chitosan nanoparticle (CsNP) has been synthesized via radiolytic methodology using gamma irradiation. The systematic condition in preparation was studied. Chitosan nanoparticle was modified using hydrophobic core of deoxycholic acid (DC) and stearyl methacrylate (SMA) and the hydrophilic shell of polyethylene glycol monomethacrylate (PEG). The hydrophobic/hydrophilic CsNP was prepared for drug carrier molecule. The SMA-CsNP was also conjugated with pyperidine, hindered amine light stabilizer function, to achieve a bio-based additive for biomedical plastic. (author)

Modified Chitosan Nanoparticle by Radiation Synthesis: An Approach to Drug Delivery and Bio-Based Additive for Biomedical Applications

Energy Technology Data Exchange (ETDEWEB)

Pasanphan, W.; Rimdusit, P.; Rattanawongwiboon, T.; Choofong, S., E-mail: sciwvm@ku.ac.th, E-mail: pwanvimol@yahoo.com [Kasetsart University, Faculty of Science, Department of Applied Radiation and Isotopes, 50 Phahonyothin Road, Chatuchak, Bangkok 1090 (Thailand)

2010-07-01

Self-assembly chitosan nanoparticle (CsNP) has been synthesized via radiolytic methodology using gamma irradiation. The systematic condition in preparation was studied. Chitosan nanoparticle was modified using hydrophobic core of deoxycholic acid (DC) and stearyl methacrylate (SMA) and the hydrophilic shell of polyethylene glycol monomethacrylate (PEG). The hydrophobic/hydrophilic CsNP was prepared for drug carrier molecule. The SMA-CsNP was also conjugated with pyperidine, hindered amine light stabilizer function, to achieve a bio-based additive for biomedical plastic. (author)

Chitosan Capped Silver Nanoparticles as Colorimetric Sensor for the Determination of Iron(III

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Javad Tashkhourian

2017-12-01

Full Text Available A selective, simple and low-cost method for the colorimetric determination of Fe3+ ions based on chitosan capped silver nanoparticles (Chit-AgNPs was presented. Chitosan is a cationic polyelectrolyte and possesses amino and hydroxy groups which make it widely used as a capping agent for Ag NPs. The synthesized chitosan capped silver nanoparticles with excellent colloidal stability were characterized by UV–Visible spectrometry, transmission electron microscopy, Fourier transform infrared, X-ray diffraction. Chit-AgNPs exhibit a strong surface plasmon resonance band which disappears in the presence of increasing concentrations of Fe3+ ions. This system showed a visually detectable color change from brownish-yellow to colorless for the selective determination of Fe3+. The method can be applied for the determination of Fe3+ ions in the concentration range of 1.0×10-6 to 5.0×10-4 M. The detection limit was determined from three times the standard deviation of the blank signal (3σ/slope as 5.3 × 10−7 M. The developed method was successfully applied for the determination of Fe3+in real samples

Cationic Polybutyl Cyanoacrylate Nanoparticles for DNA Delivery

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Jinghua Duan

2009-01-01

Full Text Available To enhance the intracellular delivery potential of plasmid DNA using nonviral vectors, we used polybutyl cyanoacrylate (PBCA and chitosan to prepare PBCA nanoparticles (NPs by emulsion polymerization and prepared NP/DNA complexes through the complex coacervation of nanoparticles with the DNA. The object of our work is to evaluate the characterization and transfection efficiency of PBCA-NPs. The NPs have a zeta potential of 25.53 mV at pH 7.4 and size about 200 nm. Electrophoretic analysis suggested that the NPs with positive charges could protect the DNA from nuclease degradation and cell viability assay showed that the NPs exhibit a low cytotoxicity to human hepatocellular carcinoma (HepG2 cells. Qualitative and quantitative analysis of transfection in HepG2 cells by the nanoparticles carrying plasmid DNA encoding for enhanced green fluorescent protein (EGFP-N1 was done by digital fluorescence imaging microscopy system and fluorescence-activated cell sorting (FACS. Qualitative results showed highly efficient expression of GFP that remained stable for up to 96 hours. Quantitative results from FACS showed that PBCA-NPs were significantly more effective in transfecting HepG2 cells after 72 hours postincubation. The results of this study suggested that PBCA-NPs have favorable properties for nonviral delivery.

Microwave-Assisted Synthesis of Chitosan/Polyvinyl Alcohol Silver Nanoparticles Gel for Wound Dressing Applications

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Nguyen Thi Hiep

2016-01-01

Full Text Available The purpose of this study was to fabricate chitosan/poly(vinyl alcohol/Ag nanoparticles (CPA gels with microwave-assistance for skin applications. Microwave irradiation was employed to reduce silver ions to silver nanoparticles and to crosslink chitosan (CS with polyvinyl alcohol (PVA. The presence of silver nanoparticles in CPA gels matrix was examined using UV-Vis spectroscopy, transmission electron microscopy, and X-ray diffraction. The interaction of CS and PVA was analysed by Fourier transform infrared spectroscopy. The release of silver ions was determined by atomic absorption spectrometry. The antimicrobial properties of CPA gels against P. aeruginosa and S. aureus were investigated using agar diffusion method. Finally, the biocompatibility and wound-healing ability of the gels were studied using fibroblast cells (in vitro and mice models (in vivo. In conclusion, the results showed that CPA gels were successfully fabricated using microwave irradiation method. These gels can be applied to heal an open wound thanks to their antibacterial activity and biocompatibility.

Effects of Aloe Vera and Chitosan Nanoparticle Thin-Film Membranes on Wound Healing in Full Thickness Infected Wounds with Methicillin Resistant Staphylococcus Aureus.

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Ranjbar, Reza; Yousefi, Alireza

2018-01-01

To assess effect of Aleo vera with chitosan nanoparticle biofilm on wound healing in full thickness infected wounds with antibiotic resistant gram positive bacteria. Thirty rats were randomized into five groups of six rats each. Group I: Animals with uninfected wounds treated with 0.9% saline solution. Group II: Animals with infected wounds treated with saline. Group III: Animals with infected wounds were dressed with chitosan nanoparticle thin-film membranes. Group IV: Animals with infected wounds were treated topically with Aloe vera and Group V: Animals with infected wounds were treated topically with Aloe vera and dressed with chitosan nanoparticle thin-film membranes. Wound size was measured on 6, 9, 12, 15, 18 and 21days after surgery. Microbiology, reduction in wound area and hydroxyproline contents indicated that there was significant difference ( p vera with chitosan nanoparticle thin-film membranes had a reproducible wound healing potential and hereby justified its use in practice.

Synthesis and characterization of Chitosan-CuO-MgO polymer nanocomposites

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Praffulla, S. R.; Bubbly, S. G.

2018-05-01

In the present work, we have synthesized Chitosan-CuO-MgO nanocomposites by incorporating CuO and MgO nanoparticles in chitosan matrix. Copper oxide and magnesium oxide nanoparticles synthesized by precipitation method were characterized by X-ray diffraction and the diffraction patterns confirmed the monoclinic and cubic crystalline structures of CuO and MgO nanoparticles respectively. Chitosan-CuO-MgO composite films were prepared using solution- cast method with different concentrations of CuO and MgO nanoparticles (15 - 50 wt % with respect to chitosan) and characterized by XRD, FTIR and UV-Vis spectroscopy. The X-ray diffraction pattern shows that the crystallinity of the chitosan composite increases with increase in nanoparticle concentration. FTIR spectra confirm the chemical interaction between chitosan and metal oxide nanoparticles (CuO and MgO). UV absorbance of chitosan nanocomposites were up to 17% better than pure chitosan, thus confirming its UV shielding properties. The mechanical and electrical properties of the prepared composites are in progress.

Multimodal in vivo MRI and NIRF imaging of bladder tumor using peptide conjugated glycol chitosan nanoparticles

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Key, Jaehong; Dhawan, Deepika; Knapp, Deborah W.; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Leary, James F.

2012-03-01

Exact detection and complete removal of cancer is a key point to minimize cancer recurrence. However, it is currently very difficult to detect small tumors inside human body and continuously monitor tumors using a non-invasive imaging modality. Presently, positron emission tomography (PET) can provide the most sensitive cancer images in the human body. However, PET imaging has very limited imaging time because they typically use isotopes with short halflives. PET imaging cannot also visualize anatomical information. Magnetic resonance imaging (MRI) can provide highresolution images inside the body but it has a low sensitivity, so MRI contrast agents are necessary to enhance the contrast of tumor. Near infrared fluorescent (NIRF) imaging has a good sensitivity to visualize tumor using optical probes, but it has a very limited tissue penetration depth. Therefore, we developed multi-modality nanoparticles for MRI based diagnosis and NIRF imaging based surgery of cancer. We utilized glycol chitosan of 350 nm as a vehicle for MRI contrast agents and NIRF probes. The glycol chitosan nanoparticles were conjugated with NIRF dye, Cy5.5 and bladder cancer targeting peptides to increase the internalization of cancer. For MR contrast effects, iron oxide based 22 nm nanocubes were physically loaded into the glycol chitosan nanoparticles. The nanoparticles were characterized and evaluated in bladder tumor bearing mice. Our study suggests the potential of our nanoparticles by both MRI and NIRF imaging for tumor diagnosis and real-time NIRF image-guided tumor surgery.

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

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Wang, Mengshu; Zhang, Yong; Feng, Jiao; Gu, Tiejun; Dong, Qingguang; Yang, Xu; Sun, Yanan; Wu, Yongge; Chen, Yan; Kong, Wei

2013-01-01

Background Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results Nanoparticles were prepared using a modified water–oil–water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9- and 16.5-fold, respectively

Graphene oxide chemically decorated with hybrid Ag-Ru/chitosan nanoparticles: fabrication and properties

OpenAIRE

Veerapandian, Murugan; Neethirajan, Suresh

2015-01-01

Hybridization of distinct materials into a single nanoplatform is relevant to advance material’s properties for functional application such as biosensor platform. We report the synthesis and characterization of nanosheets of graphene oxide decorated with hybrid nanoparticles of silver-ruthenium bipyridine complex (Ag@[Ru(bpy)3]2+) core and chitosan shell. Hybrid nanoparticles were first obtained through a sequential wet-chemical approach using in situ reduction, electrostatic and coordination...

Copper nanoparticles mediated by chitosan: synthesis and characterization via chemical methods.

Science.gov (United States)

Usman, Muhammad Sani; Ibrahim, Nor Azowa; Shameli, Kamyar; Zainuddin, Norhazlin; Yunus, Wan Md Zin Wan

2012-12-14

Herein we report a synthesis of copper nanoparticles (Cu-NPs) in chitosan (Cts) media via a chemical reaction method. The nanoparticles were synthesized in an aqueous solution in the presence of Cts as stabilizer and CuSO(4)·5H(2)O precursor. The synthesis proceeded with addition of NaOH as pH moderator, ascorbic acid as antioxidant and hydrazine( )as the reducing agent. The characterization of the prepared NPs was done using ultraviolet-visible spectroscopy, which showed a 593 nm copper band. The Field Emission Scanning Electron Microscope (FESEM) images were also observed, and found to be in agreement with the UV-Vis result, confirming the formation of metallic Cu-NPs. The mean size of the Cu-NPs was estimated to be in the range of 35-75 nm using X-ray diffraction. XRD was also used in analysis of the crystal structure of the NPs. The interaction between the chitosan and the synthesized NPs was studied using Fourier transform infrared (FT-IR) spectroscopy, which showed the capping of the NPs by Cts.

Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

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Key J

2016-08-01

, by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging.Keywords: MRI, NIRF, multimodal imaging, chitosan, iron oxide, bladder cancer

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

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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.

Characterization of nanoparticle mediated laser transfection by femtosecond laser pulses for applications in molecular medicine.

Science.gov (United States)

Schomaker, Markus; Heinemann, Dag; Kalies, Stefan; Willenbrock, Saskia; Wagner, Siegfried; Nolte, Ingo; Ripken, Tammo; Murua Escobar, Hugo; Meyer, Heiko; Heisterkamp, Alexander

2015-02-03

In molecular medicine, the manipulation of cells is prerequisite to evaluate genes as therapeutic targets or to transfect cells to develop cell therapeutic strategies. To achieve these purposes it is essential that given transfection techniques are capable of handling high cell numbers in reasonable time spans. To fulfill this demand, an alternative nanoparticle mediated laser transfection method is presented herein. The fs-laser excitation of cell-adhered gold nanoparticles evokes localized membrane permeabilization and enables an inflow of extracellular molecules into cells. The parameters for an efficient and gentle cell manipulation are evaluated in detail. Efficiencies of 90% with a cell viability of 93% were achieved for siRNA transfection. The proof for a molecular medical approach is demonstrated by highly efficient knock down of the oncogene HMGA2 in a rapidly proliferating prostate carcinoma in vitro model using siRNA. Additionally, investigations concerning the initial perforation mechanism are conducted. Next to theoretical simulations, the laser induced effects are experimentally investigated by spectrometric and microscopic analysis. The results indicate that near field effects are the initial mechanism of membrane permeabilization. This methodical approach combined with an automated setup, allows a high throughput targeting of several 100,000 cells within seconds, providing an excellent tool for in vitro applications in molecular medicine. NIR fs lasers are characterized by specific advantages when compared to lasers employing longer (ps/ns) pulses in the visible regime. The NIR fs pulses generate low thermal impact while allowing high penetration depths into tissue. Therefore fs lasers could be used for prospective in vivo applications.

Fabrication and Characterization of Chitosan Nanoparticle-Incorporated Quaternized Poly(Vinyl Alcohol) Composite Membranes as Solid Electrolytes for Direct Methanol Alkaline Fuel Cells

International Nuclear Information System (INIS)

Li, Pin-Chieh; Liao, Guan–Ming; Kumar, S. Rajesh; Shih, Chao-Ming; Yang, Chun-Chen; Wang, Da-Ming; Lue, Shingjiang Jessie

2016-01-01

Highlights: • Preparation of chitosan nanoparticles from bulk to enhance the degree of deacetylation. • The incorporation of chitosan nanoparticles into a QPVA matrix to form a nanocomposite membrane. • The nanocomposite constructed into thin-film membranes using the solution casting method. • To improve permeability, glutaraldehyde was cross-linked with the nanocomposite membranes. • A direct methanol alkaline fuel cell was studied at different temperatures. - Abstract: In this study, we designed a method for the preparation of chitosan nanoparticles incorporated into a quaternized poly(vinyl alcohol) (QPVA) matrix for direct methanol alkaline fuel cells (DMAFCs). The structural and morphological properties of the prepared nanocomposites were studied using X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM) and dynamic laser-light scattering (DLS). The crystallinity of the nanocomposite solid electrolytes containing 0 and 10% chitosan nanoparticles were investigated using differential scanning calorimetry (DSC). The electrochemical measurement of resulting nanocomposite membranes were analyzed according to the following parameters: methanol permeability, liquid uptakes, ionic conductivity and cell performances. The composite membranes with 10% chitosan nanoparticles in a QPVA matrix (CQPVA) show suppressed methanol permeability and higher ionic conductivity than pristine QPVA. In addition, the glutaraldehyde cross-linked nanocomposite film exhibited improvement on the methanol barrier property at 80 °C. The peak power density of the DMAFCs reached 67 mW cm −2 when fed into 1 M of methanol in 6 M of KOH.

pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

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Mukhopadhyay, Piyasi; Chakraborty, Souma; Bhattacharya, Sourav; Mishra, Roshnara; Kundu, P P

2015-01-01

Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Spanish Broom (Spartium junceum L.) fibers impregnated with vancomycin-loaded chitosan nanoparticles as new antibacterial wound dressing: Preparation, characterization and antibacterial activity.

Science.gov (United States)

Cerchiara, Teresa; Abruzzo, Angela; Ñahui Palomino, Rogers Alberto; Vitali, Beatrice; De Rose, Renata; Chidichimo, Giuseppe; Ceseracciu, Luca; Athanassiou, Athanassia; Saladini, Bruno; Dalena, Francesco; Bigucci, Federica; Luppi, Barbara

2017-03-01

In this work, we propose as new wound dressing, the Spanish Broom fibers impregnated with vancomycin (VM) loaded chitosan nanoparticles. Spanish Broom fibers were extracted by patented method DiCoDe and the morphological, physical and mechanical properties were investigated. Chitosan nanoparticles were prepared by ionic gelation using different weight ratios between chitosan (CH) and tripolyphosphate (TPP). Nanoparticles were characterized in terms of size, zeta potential, yield, encapsulation efficiency, stability and drug release. Finally, the antibacterial activity against Staphylococcus aureus as well as in vitro cytotoxicity on HaCaT cells were evaluated. The best formulation CH/TPP 4:1 was selected based on the encapsulation efficiency and yield. Spanish Broom fibers impregnated with loaded nanoparticles showed an increased antibacterial activity against S. aureus compared to the same fibers containing VM without nanoparticles. Moreover, these fibers were not toxic to HaCaT keratinocytes cells. In conclusion, Spanish Broom fibers impregnated with VM loaded CH/TPP nanoparticles would appear to be a promising candidate for wound dressing application. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

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Yan Lu

2014-02-01

Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

Non-viral bone morphogenetic protein 2 transfection of rat dental pulp stem cells using calcium phosphate nanoparticles as carriers.

NARCIS (Netherlands)

Yang, X.; Walboomers, X.F.; Dolder, J. van den; Yang, F.; Bian, Z.; Fan, M.; Jansen, J.A.

2008-01-01

Calcium phosphate nanoparticles have shown potential as non-viral vectors for gene delivery. The aim of this study was to induce bone morphogenetic protein (Bmp)2 transfection in rat dental pulp stem cells using calcium phosphate nanoparticles as a gene vector and then to evaluate the efficiency and

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide nanoparticles for intestinal delivery of exendin-4

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Wang M

2013-03-01

Full Text Available Mengshu Wang,1* Yong Zhang,1* Jiao Feng,1 Tiejun Gu,1 Qingguang Dong,1 Xu Yang,2 Yanan Sun,1 Yongge Wu,1 Yan Chen,1 Wei Kong1 1National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, People’s Republic of China; 2BCHT Biopharm Co, Ltd, Changchun, People’s Republic of China*These authors contributed equally to this workBackground: Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide (CS-PLGA nanoparticles was investigated for intestinal delivery of exendin-4.Methods and results: Nanoparticles were prepared using a modified water–oil–water (w/o/w emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

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Ye, Bai-Liang; Zheng, Ru; Ruan, Xiao-Jiao; Zheng, Zhi-Hai; Cai, Hua-Jie

2018-01-01

Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Chitosan and carboxymethyl-chitosan capping ligands: Effects on the nucleation and growth of hydroxyapatite nanoparticles for producing biocomposite membranes.

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Dumont, Vitor C; Mansur, Alexandra A P; Carvalho, Sandhra M; Medeiros Borsagli, Fernanda G L; Pereira, Marivalda M; Mansur, Herman S

2016-02-01

Synthetic biomaterials based on calcium phosphates (CaP) have been widely studied for bone tissue reconstruction therapies, but no definitive solution that fulfills all of the required properties has been identified. Thus, this study reports the synthesis of composite membranes based on nanohydroxyapatite particles (nHA) embedded in chitosan (CHI) and O-carboxymethyl chitosan (CMC) matrices produced using a one-step co-precipitation method in water media. Biopolymers were used as capping ligands for simultaneously controlling the nucleation and growth of the nHA particles during the precipitation process and also to form the polymeric network of the biocomposites. The bionanocomposites were extensively characterized using light microscopy (LM), scanning and transmission electron microscopy (SEM/TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), atomic force microscopy (AFM), X-ray micro-CT analysis (μCT), andMTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide) cell proliferation assays for cell cytotoxicity. The results demonstrated that the ligands used during the synthesis highly affected the composites produced, primarily due the changes in the mechanisms and kinetics of nucleation and growth of the HA particles at the nanoscale level. The SEMimages revealed that the use of carboxyl-functionalized chitosan (CMC) ligands significantly reduced the average size of theHA nanoparticles and caused the formation of a narrower size distribution (90±20nm) compared to theHAnanoparticles producedwith chitosan ligands (220±50nm). The same trend was verified by the AFM analysis,where the nHA particles were formed evenly dispersed in the polymer matrix. However, the CMC-based composites were more homogeneously distributed, which was endorsed by the images collected via X-ray micro-CT. The FTIR spectra and the XRD analysis indicated that nanosized hydroxyapatite was the predominant calcium

Chitosan Stabilized Gold-Folate-Poly(lactide-co-glycolide) Nanoplexes Facilitate Efficient Gene Delivery in Hepatic and Breast Cancer Cells.

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Akinyelu, Jude; Singh, Moganavelli

2018-07-01

The biodegradable polymer, poly(lactide-co-glycolide) is a popular polymer of choice in many nanotherapeutic studies. Herein, we report on the synthesis and evaluation of four chitosan stabilized poly(lactide-co-glycolide) nanoparticles with and without coating with gold, and the targeting ligand, folic acid, as potential non-viral gene delivery vectors. The poly(lactide-co-glycolide) nanoparticles were synthesized via nanoprecipitation/solvent evaporation method in conjunction with the surface functionalizing folic acid and chitosan. The physiochemical properties (morphology, particle size, zeta potential, folic acid/chitosan presence, DNA binding), and biological properties (nuclease protection, in vitro cytotoxicity and transfection potential in human kidney, hepatocellular carcinoma and breast adenocarcinoma cells), of all four gene bound nanoparticles were evaluated. Gel retardation assays confirmed that all the nanoparticles were able to successfully bind the reporter plasmid, pCMV-luc DNA at varying weight ratios. The gold-folate-poly(lactide-co-glycolide) nanoplexes with the highest binding efficiency (w/w ratio 4:1), best protected the plasmid DNA as evidenced from the nuclease protection assays. Furthermore, these nanoplexes presented as spherical particles with an average particle size of 199.4 nm and zeta potential of 35.7 mV. Folic acid and chitosan functionalization of the nanoparticles was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy. All nanoplexes maintained over 90% cell viability in all cell lines investigated. Interestingly, the gold-folate-poly(lactide-co-glycolide) nanoplexes showed a greater transgene activity in the hepatic and breast cancer cells compared to the other nanocomplexes in the same cell lines. The favorable size, colloidal stability, low cytotoxicity, significant transgene expression, and nuclease protection ability in vitro, all provide support for the use of gold

Preparation of an Environmentally Friendly Formulation of the Insecticide Nicotine Hydrochloride through Encapsulation in Chitosan/Tripolyphosphate Nanoparticles.

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Yang, Ying; Cheng, Jiagao; Garamus, Vasil M; Li, Na; Zou, Aihua

2018-02-07

Insecticide nicotine hydrochloride (NCT) was formulated as nanoparticles composed of chitosan (CS) and sodium tripolyphosphate (TPP) to undermine its adverse impacts on human health and reinforce its physicochemical stability. The study investigated the preparation and characterization of chitosan/tripolyphosphate nanoparticles (CS/TPP NPs) with good encapsulation efficiency (55%), uniform morphology, and physicochemical stability (45 days) through dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS) measurements. A bioassay against Musca domestica NCT CS/TPP NPs exhibited good bioactivity and thermal stability. The effect of the monovalent salt (NaCl) on manipulating the formation and size distribution of ionically cross-linked nanoparticles was demonstrated as well. The formulation of NCT CS/TPP NPs could be a utility candidate in public health and agriculture.

Delivery of chitosan/dsRNA nanoparticles for silencing of wing development vestigial (vg) gene in Aedes aegypti mosquitoes.

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Ramesh Kumar, D; Saravana Kumar, P; Gandhi, M Rajiv; Al-Dhabi, Naif Abdullah; Paulraj, M Gabriel; Ignacimuthu, S

2016-05-01

RNA interference (RNAi) has been used as a gene silencing strategy by the introduction of long double stranded RNA (dsRNA) for the control of pest insects. The aim of the present study was to examine whether the expression of vg gene which is responsible for wing development, can be repressed by chitosan/dsRNA based nanoparticles in Aedes aegypti. The vestigial gene (vg) was amplified from adult mosquito and cloned in pLitmus28i vector. Genetically engineered recombinant plasmid was transformed into RNase III deficient strain for synthesis of bacterially expressed dsRNA. Nanoparticles were prepared via electrostatic interaction between cationic polymer chitosan and anionic nucleic acids (dsRNA). The formation of chitosan/dsRNAnanoparticles and their size were confirmed by Atomic force microscopy (AFM). Chitosan/dsRNA mediated knockdown of Enhanced Green Fluorescence Protein (EGFP) was demonstrated in Sf21 cells. Further, we tested whether such an approach could be used to target vg gene in Ae. aegypti. The results showed that chitosan/dsRNA caused significant mortality, delayed growth development and caused adult wing-malformation. A qRT-PCR analysis confirmed that the chitosan/dsRNA mediated transcriptional level was downregulated. Our findings suggest that vg gene intervention strategies through RNAi can emerge as viable option for pest control. Copyright © 2016 Elsevier B.V. All rights reserved.

Anchoring of ulex europaeus agglutinin to chitosan nanoparticles-in-microparticles and their in vitro binding activity to bovine submaxillary gland mucin.

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Li, Feng-Qian; Fei, Yi-Bo; Chen, Xu; Qin, Xian-Ju; Liu, Ji-Yong; Zhu, Quan-Gang; Hu, Jin-Hong

2009-10-01

Focused on the natural biodegradable material of chitosan (CS), this investigation concerned its spray-dried nanoparticles-in-microparticles (NiMPs) modified with ulex europaeus agglutinin (UEA). Chitosan nanoparticles were obtained by ionotropic gelation process with pentasodium tripolyphosphate as gelatinizer. Then UEA lectin was bound onto the CS nanoparticles activated by glutaraldehyde. The conjugated spherical UEA-CS-NiMPs, prepared by spray drying method, exhibited 12-85% coupling efficiency of UEA depending upon the amount of activator glutaraldehyde. And the UEA-grafted particles showed additional higher binding tendency with bovine submaxillary gland mucin as compared to the plain chitosan microparticles. Furthermore, the activity and intrinsic fucose-specificity of UEA were still maintained after the covalent modification. It is thus evident that the UEA anchored CS-NiMPs might be used as a potential drug delivery system targeted to the specific regions of gastrointestinal tract.

Chitosan nanoparticles-trypsin interactions: Bio-physicochemical and molecular dynamics simulation studies.

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Salar, Safoura; Mehrnejad, Faramarz; Sajedi, Reza H; Arough, Javad Mohammadnejad

2017-10-01

Herein, we investigated the effect of the chitosan nanoparticles (CsNP) on the structure, dynamics, and activity of trypsin. The enzyme activity in complex with the nanoparticles slightly increased, which represents the interactions between the nanoparticles and the enzyme. The kinetic parameters of the enzyme, K m and k cat , increased after adding the nanoparticles, resulting in a slight increase in the catalytic efficiency (k cat /K m ). However, the effect of the nanoparticles on the kinetic stability of trypsin has not exhibited significant variations. Fluorescence spectroscopy did not show remarkable changes in the trypsin conformation in the presence of the nanoparticles. The circular dichroism (CD) spectroscopy results also revealed the secondary structure of trypsin attached to the nanoparticles slightly changed. Furthermore, we used molecular dynamics (MD) simulation to find more information about the interaction mechanisms between the nanoparticles and trypsin. The root mean square deviation (RMSD) of Cα atoms results have shown that in the presence of the nanoparticles, trypsin was stable. The simulation and the calculation of the binding free energy demonstrate that the nonpolar interactions are the most important forces for the formation of stable nanoparticle-trypsin complex. This study has explicitly elucidated that the nanoparticles have not considerable effect on the trypsin. Copyright © 2017. Published by Elsevier B.V.

Effect of chitosan molecular weight on the formation of chitosan-pullulanase soluble complexes and their application in the immobilization of pullulanase onto Fe3O4-κ-carrageenan nanoparticles.

Science.gov (United States)

Long, Jie; Xu, Enbo; Li, Xingfei; Wu, Zhengzong; Wang, Fang; Xu, Xueming; Jin, Zhengyu; Jiao, Aiquan; Zhan, Xiaobei

2016-07-01

The interactions between pullulanase and chitosans of different molecular weights (Mw) were comprehensively studied, and their applications in pullulanase immobilization onto Fe3O4-κ-carrageenan nanoparticles upon chitosan-pullulanase complexation were also evaluated. Chitosan (CS) complexation with pullulanase was found to be dependent on pH and chitosan Mw. The critical pH of structure-forming events during complexation shifted significantly (pproperties of immobilized pullulanase. Pullulanase immobilized upon CS-50 complexation exhibited the most desirable enzymatic properties. These results indicated that the complexation behavior was mainly dependent on chitosan Mw. This study presents a technique for the production of immobilized pullulanase upon complexation that exhibits potential for applications in continuous syrup production. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Chitosan-based nanoparticles for improved anticancer efficacy and bioavailability of mifepristone

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Huijuan Zhang

2016-11-01

Full Text Available In addition to its well-known abortifacient effect, mifepristone (MIF has been used as an anticancer drug for various cancers in many studies with an in-depth understanding of the mechanism of action. However, application of MIF is limited by its poor water solubility and low oral bioavailability. In this work, we developed a drug delivery system based on chitosan nanoparticles (CNs to improve its bioavailability and anticancer activity. The MIF-loaded chitosan nanoparticles (MCNs were prepared by convenient ionic gelation techniques between chitosan (Cs and tripolyphosphate (TPP. The preparation conditions, including Cs concentration, TPP concentration, Cs/MIF mass ratio, and pH value of the TPP solution, were optimized to gain better encapsulation efficiency (EE and drug loading capacity (DL. MCNs prepared with the optimum conditions resulted in spherical particles with an average size of 200 nm. FTIR and XRD spectra verified that MIF was successfully encapsulated in CNs. The EE and DL of MCNs determined by HPLC were 86.6% and 43.3%, respectively. The in vitro release kinetics demonstrated that MIF was released from CNs in a sustained-release manner. Compared with free MIF, MCNs demonstrated increased anticancer activity in several cancer cell lines. Pharmacokinetic studies in male rats that were orally administered MCNs showed a 3.2-fold increase in the area under the curve from 0 to 24 h compared with free MIF. These results demonstrated that MCNs could be developed as a potential delivery system for MIF to improve its anticancer activity and bioavailability.

Intraperitoneal administration of chitosan/DsiRNA nanoparticles targeting TNFα prevents radiation-induced fibrosis

International Nuclear Information System (INIS)

Nawroth, Isabel; Alsner, Jan; Behlke, Mark A.; Besenbacher, Flemming; Overgaard, Jens; Howard, Kenneth A.; Kjems, Jorgen

2010-01-01

Background and purpose: One of the most common and dose-limiting long-term adverse effects of radiation therapy is radiation-induced fibrosis (RIF), which is characterized by restricted tissue flexibility, reduced compliance or strictures, pain and in severe cases, ulceration and necrosis. Several strategies have been proposed to ameliorate RIF but presently no effective one is available. Recent studies have reported that tumor necrosis factor-α (TNFα) plays a role in fibrogenesis. Material and methods: Male CDF1 mice were radiated with a single dose of 45 Gy. Chitosan/DsiRNA nanoparticles targeting TNFα were intraperitoneal injected and late radiation-induced fibrosis (RIF) was assessed using a modification of the leg contracture model. Additionally, the effect of these nanoparticles on tumor growth and tumor control probability in the absence of radiation was examined in a C3H mammary carcinoma model. Results: We show in this work, that targeting TNFα in macrophages by intraperitoneal administration of chitosan/DsiRNA nanoparticles completely prevented radiation-induced fibrosis in CDF1 mice without revealing any cytotoxic side-effects after a long-term administration. Furthermore, such TNFα targeting was selective without any significant influence on tumor growth or irradiation-related tumor control probability. Conclusion: This nanoparticle-based RNAi approach represents a novel approach to prevent RIF with potential application to improve clinical radiation therapeutic strategies.

Chitosan-coated magnetite nanoparticles as adsorbent for the removal of molybdenum ions

International Nuclear Information System (INIS)

Sousa, Jose S.; Egute, Nayara S.; Yamaura, Mitiko; Freitas, Antonio A.; Holland, Helber; Lugao, Ademar B.

2011-01-01

Metal ions in wastewater, even at low concentrations, affect a large number of organisms due to their high degree of toxicity. Research has developed some alternative methods for metal removal from the wastewater, as adsorption using a bio sorbent of combined chitosan with magnetic particles. Chitosan is a natural bio polymer, which has a highly reactive active sites in its structure, composed of amino and hydroxyl groups with affinity to bind to metal ions. In this study, magnetic nanoparticles of coated magnetite with chitosan as an adsorbent of molybdenum(Vi) ions in aqueous medium was investigated. The adsorption experiments were performed varying the time contact from 5 to 150 min, the p H from 0.5 to 11 and the molybdenum concentrations in nitric solutions. All molybdenum analyses were carried out by gamma spectroscopy using a Hp Ge detector and 99 Mo as radioactive tracer. Results showed that the chitosan-coated magnetite particles are good adsorbent for Mo ions from aqueous medium in the range of p H from 0.5 to 9 with a removal higher than 99%. Among the studied isotherm models, the Freundlich model fitted best the equilibrium adsorption isotherm of Mo(VI) ions. (author)

Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery.

Science.gov (United States)

Sajeesh, S; Sharma, Chandra P

2006-02-01

In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery. Copyright 2005 Wiley Periodicals, Inc.

Self-aggregated nanoparticles based on amphiphilic poly(lactic acid-grafted-chitosan copolymer for ocular delivery of amphotericin B

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Zhou WJ

2013-09-01

Full Text Available Wenjun Zhou,1 Yuanyuan Wang,2 Jiuying Jian,2 Shengfang Song1 1Department of Ophthalmology, Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Life Science, Chongqing Medical University, Chongqing, People’s Republic of China Background: The purpose of this study was to develop a self-aggregated nanoparticulate vehicle using an amphiphilic poly(lactic acid-grafted-chitosan (PLA-g-CS copolymer and to evaluate its potential for ocular delivery of amphotericin B. Methods: A PLA-g-CS copolymer was synthesized via a “protection-graft-deprotection” procedure and its structure was confirmed by Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and X-ray diffraction spectra. Amphotericin B-loaded nanoparticles based on PLA-g-CS (AmB/PLA-g-CS were prepared by the dialysis method and characterized for particle size, zeta potential, and encapsulation efficiency. Studies of these AmB/PLA-g-CS nanoparticles, including their mucoadhesive strength, drug release properties, antifungal activity, ocular irritation, ocular pharmacokinetics, and corneal penetration were performed in vitro and in vivo. Results: Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and X-ray diffraction spectra showed that the PLA chains were successfully grafted onto chitosan molecules and that crystallization of chitosan was suppressed. The self-aggregated PLA-g-CS nanoparticles had a core-shell structure with an average particle size of approximately 200 nm and zeta potentials higher than 30 mV. Amphotericin B was incorporated into the hydrophobic core of the nanoparticles with high encapsulation efficiency. Sustained drug release from the nanoparticles was observed in vitro. The ocular irritation study showed no sign of irritation after instillation of the PLA-g-CS nanoparticles into rabbit eyes. The minimal inhibitory concentration of the AmB/PLA-g-CS nanoparticles showed antifungal

Silver Nanoparticles Synthesized Using Mint Extract and their Application in Chitosan/Gelatin Composite Packaging Film

Science.gov (United States)

Bhoir, Shraddha A.; Chawla, S. P.

The present study reports synthesis of silver nanoparticles (AgNPs) using mint extract (ME) in the presence of polyvinyl alcohol (PVA) as capping material. PVA, ME and silver nitrate at concentration of 1%, 0.01% and 0.02%, respectively were found to be optimum for the synthesis of nanoparticles. The formation of AgNPs was confirmed by measuring surface plasmon resonance (SPR) peak. The intensity of SPR peak remained unaltered thus suggesting stability of colloid without aggregation during storage. The nanoparticles inhibited the growth of food borne bacteria namely Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus. The incorporation of these nanoparticles in chitosan and gelatin blend resulted in homogenous films. Mechanical properties and water vapor transmission rate of chitosan-gelatin films improved due to addition of AgNPs, whereas optical (opacity and UV light transmittance) and oxygen permeability properties remained unchanged. These films had the ability to inhibit growth of 5 log CFU of the above test organisms. These findings suggest that the AgNPs obtained by reduction of silver by ME can be effectively utilized to prepare antibacterial eco-friendly food packaging material.

A nonviral DNA delivery system based on surface modified silica-nanoparticles can efficiently transfect cells in vitro.

Science.gov (United States)

Kneuer, C; Sameti, M; Bakowsky, U; Schiestel, T; Schirra, H; Schmidt, H; Lehr, C M

2000-01-01

Diverse polycationic polymers have been used as nonviral transfection agents. Here we report the ability of colloidal silica particles with covalently attached cationic surface modifications to transfect plasmid DNA in vitro and make an attempt to describe the structure of the resulting transfection complexes. In analogy to the terms lipoplex and polyplex, we propose to describe the nanoparticle-DNA complexes by the term "nanoplex". Three batches, Si10E, Si100E, and Si26H, sized between 10 and 100 nm and with zeta potentials ranging from +7 to +31 mV at pH 7.4 were evaluated. The galactosidase expression plasmid DNA pCMVbeta was immobilized on the particle surface and efficiently transfected Cos-1 cells. The transfection activity was accompanied by very low cytotoxicity, with LD(50) values in the milligrams per milliliter range. The most active batch, Si26H, was produced by modification of commercially available silica particles with N-(6-aminohexyl)-3-aminopropyltrimethoxysilane, yielding spherical nanoparticles with a mean diameter of 26 nm and a zeta potential of +31 mV at pH 7.4. Complexes of Si26H and pCMVbeta plasmid DNA formed at w/w ratios of 10 were most effective in promoting transfection of Cos-1 cells in the absence of serum. At this ratio, >90% of the DNA was associated with the particles, yielding nanoplexes with a net negative surface charge. When the transfection medium was supplemented with 10% serum, maximum gene expression was observed at a w/w ratio of 30, at which the resulting particle-DNA complexes possessed a positive surface charge. Transfection was strongly increased in the presence of 100 microM chloroquine in the incubation medium and reached approximately 30% of the efficiency of a 60 kDa polyethylenimine. In contrast to polyethylenimine, no toxicity was observed at the concentrations required. Atomic force microscopy of Si26H-DNA complexes revealed a spaghetti-meatball-like structure. The surface of complexes prepared at a w/w ratio of

Sunlight-assisted synthesis of colloidal silver nanoparticles using chitosan as reducing agent

Science.gov (United States)

Susilowati, E.; Maryani; Ashadi

2018-04-01

The present study we explore an environmentally friendly colloidal silver nanoparticles preparation using chitosan as reducing agent and stabilizer. It develops a new strategy on preparation of silver nanoparticles through the gel phase using sodium hydroxide (NaOH) as accelerator reagent. Sunlight irradiation was employed to assisted reducing process of silver ions to silver nanoparticles. Localized surface plasmon resonance (LSPR) phenomenon of silver nanoparticles was investigated using UV-Vis spectrophotometer. The shape and size of silver particles were analyzed using TEM. The formation of silver nanoparticles was confirmed by the appearance of LSPR absorption peak at 396.0–412.0 nm. The absorption peak of LSPR were affected by NaOH amount, time of sulight irradiation and concentration of AgNO3. The produced silver nanoparticles were spherical with dominant size range of 5 to 8 nm as shown by TEM images. All colloidals were stable without any aggregation for 30 days after preparation.

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations.

Science.gov (United States)

Mahjub, Reza; Radmehr, Moojan; Dorkoosh, Farid Abedin; Ostad, Seyed Naser; Rafiee-Tehrani, Morteza

2014-12-01

The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan. Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined. Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24 h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared

Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.

Science.gov (United States)

Gao, Shan; Hein, San; Dagnæs-Hansen, Frederik; Weyer, Kathrin; Yang, Chuanxu; Nielsen, Rikke; Christensen, Erik I; Fenton, Robert A; Kjems, Jørgen

2014-01-01

RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously. Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan. Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway. Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v. delivery of chitosan/AQP1 siRNA in mice. In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.

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

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

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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.

The novel albumin-chitosan core-shell nanoparticles for gene delivery: preparation, optimization and cell uptake investigation

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Karimi, Mahdi [Tarbiat Modares University, Department of Nanobiotechnology, Faculty of Biological Sciences (Iran, Islamic Republic of); Avci, Pinar [Massachusetts General Hospital, Wellman Center for Photomedicine (United States); Mobasseri, Rezvan [Tarbiat Modares University, Department of Nanobiotechnology, Faculty of Biological Sciences (Iran, Islamic Republic of); Hamblin, Michael R. [Massachusetts General Hospital, Wellman Center for Photomedicine (United States); Naderi-Manesh, Hossein, E-mail: naderman@modares.ac.ir [Tarbiat Modares University, Department of Nanobiotechnology, Faculty of Biological Sciences (Iran, Islamic Republic of)

2013-05-15

Natural polymers and proteins such as chitosan (CS) and albumin (Alb) have recently attracted much attention both in drug delivery and gene delivery. The underlying rationale is their unique properties such as biodegradability, biocompatibility and controlled release. This study aimed to prepare novel albumin-chitosan-DNA (Alb-CS-DNA) core-shell nanoparticles as a plasmid delivery system and find the best conditions for their preparation. Phase separation method and ionic interaction were used for preparation of Alb nanoparticles and Alb-CS-DNA core-shell nanoparticles, respectively. The effects of three important independent variables (1) CS/Alb mass ratio, (2) the ratios of moles of the amine groups of cationic polymers to those of the phosphate groups of DNA (N/P ratio), and (3) Alb concentration, on the nanoparticle size and loading efficiency of the plasmid were investigated and optimized through Box-Behnken design of response surface methodology (RSM). The optimum conditions were found to be CS/Alb mass ratio = 3, N/P ratio = 8.24 and Alb concentration = 0.1 mg/mL. The most critical factors for the size of nanoparticles and loading efficiency were Alb concentration and N/P ratio. The optimized nanoparticles had an average size of 176 {+-} 3.4 nm and loading efficiency of 80 {+-} 3.9 %. Cytotoxicity experiments demonstrated that the prepared nanoparticles were not toxic. The high cellular uptake of nanoparticles ({approx}85 %) was shown by flow cytometry and fluorescent microscopy.

Preparation and Characterization of Chitosan-coated Fe3O4 Nanoparticles using Ex-Situ Co-Precipitation Method and Tripolyphosphate/Sulphate as Dual Crosslinkers

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Wulandari, Ika O.; Mardila, Vita T.; Santjojo, D. J. Djoko H.; Sabarudin, Akhmad

2018-01-01

The unique properties of nanomaterial provide great opportunities to develop in several fields. Several types of nanoparticles have been proven beneficial for biomedical and therapeutic agent development. Particularly for clinical use, nanoparticles must be biocompatible and non-toxic. Iron oxide nanoparticles consist of either magnetite (Fe3O4) or maghemite (γ-Fe2O3) was eligible to use for in vivo application including targeting drug delivery. Due to their distinct properties, these nanoparticles could be directed to the specific target under external magnetic field. However, nanoparticles have a tendency to form agglomeration. Therefore, surface modification was required to reduce the agglomeration. In this study, nanoparticles of Fe3O4 were produced and coated by biomaterial (chitosan) using ex-situ co-precipitation method. Nanoparticles of Fe3O4 were synthesized by adding ammonia water into iron ferric and ferrous solution. Synthesis process of Fe3O4 was conducted prior to adding chitosan. Chitosan was then cross-linked by a combination of tripolyphosphate/sulphate. The different composition ratio and crosslinking time provide the different physical and magnetic characteristics of nanoparticles. Particle and crystallite size was determined by using Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD) respectively, whereas magnetic characteristic was determined by Electron Spin Resonance (ESR). The results showed that the ratio enhancement between chitosan: Fe3O4 increase the particle size, while decreased the crystallite size. Morphology and particle size were influenced by the ratio of crosslinkers. It was found that the higher tripolyphosphate content was contributed to the small size and more spherical morphology. In addition, the influence of crosslinking time toward crystallite size was determined by altering stirring time. The longer duration of crosslinking time, provide the larger crystallite size of chitosan-Fe3O4. There was an interesting

Tuning effect of polysaccharide Chitosan on structural, morphological, optical and photoluminescence properties of ZnO nanoparticles

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Magesh, G.; Bhoopathi, G.; Nithya, N.; Arun, A. P.; Ranjith Kumar, E.

2018-05-01

Chitosan/ZnO nanocomposites was synthesized by in-situ chemical precipitation method. The effect of polysaccharide Chitosan concentration (0.1 g, 0.5 g, 1 g and 3 g) was investigated by X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM) with Energy dispersive spectroscopy (EDX), High Resolution Transmission Electron Microscopy (HRTEM), UV-visible (UV), Fourier Transform Infrared (FTIR) and Photoluminescence Spectroscopy (PL). XRD pattern confirms the hexagonal wurtzite structure of the Chitosan/ZnO nanocomposites. The structural morphology and the elemental composition of the samples were analysed by FESEM and EDX respectively. From TEM analysis, it is observed that the particles in spindle shape morphology with average particle size ranges 10-20 nm. UV-Vis analysis reveals that the Chitosan concentration affect the absorption band edge and shift towards lower wavelength. The oxygen vacancy induced photoluminescence of ZnO nanoparticles was observed and its intensity decreases by tuning the Chitosan concentration.

Amidase encapsulated O-carboxymethyl chitosan nanoparticles for vaccine delivery.

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Smitha, K T; Sreelakshmi, M; Nisha, N; Jayakumar, R; Biswas, Raja

2014-02-01

This work reports the development of amidase encapsulated O-carboxymethyl chitosan nanoparticles (Ami-O-CMC NPs) of 300±50 nm size by ionic cross-linking method. The prepared Ami-O-CMC NPs had an encapsulation efficiency of 55.39%. Haemolysis assay and cytotoxicity studies proved the hemocompatibility and cytocompatibility of the prepared NPs. The sustained release of Ami from the NPs is expected to prolong its immunogenicity and in turn lead to development of better protective immunity against Staphylococcus aureus infections. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation of chitosan/tripolyphosphate nanoparticles with highly tunable size and low polydispersity.

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Sawtarie, Nader; Cai, Yuhang; Lapitsky, Yakov

2017-09-01

Nanoparticles prepared through the ionotropic gelation of chitosan with tripolyphosphate (TPP) have been extensively studied as vehicles for drug and gene delivery. Though a number of these works have focused on preparing particles with narrow size distributions, the monodisperse particles produced by these methods have been limited to narrow size ranges (where the average particle size was not varied by more than twofold). Here we show how, by tuning the NaCl concentration in the parent chitosan and TPP solutions, low-polydispersity particles with z-average diameters ranging between roughly 100 and 900nm can be prepared. Further, we explore how the size of these particles depends on the method by which the TPP is mixed into the chitosan solution, specifically comparing: (1) single-shot mixing; (2) dropwise addition; and (3) a dilution technique, where chitosan and TPP are codissolved at a high (gelation-inhibiting) ionic strength and then diluted to lower ionic strengths to trigger gelation. Though the particle size increases sigmoidally with the NaCl concentration for all three mixing methods, the dilution method delivers the most uniform/gradual size increase - i.e., it provides the most precise control. Also investigated are the effects of mixture composition and mixing procedure on the particle yield. These reveal the particle yield to increase with the chitosan/TPP concentration, decrease with the NaCl concentration, and vary only weakly with the mixing protocol; thus, at elevated NaCl concentrations, it may be beneficial to increase chitosan and TPP concentrations to ensure high particle yields. Finally, possible pitfalls of the salt-assisted size control strategy (and their solutions) are discussed. Taken together, these findings provide a simple and reliable method for extensively tuning chitosan/TPP particle size while maintaining narrow size distributions. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes.

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Gu, Jijin; Al-Bayati, Karam; Ho, Emmanuel A

2017-08-01

RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands. In this study, chitosan nanoparticles (CS-NPs) were prepared by a complex coacervation method in the presence of siRNA, and antibody was chemically conjugated to the nanoparticles. The antibody-modified chitosan nanoparticles (Ab-CS-NPs) were spherical in shape, with an average particle size of 235.7 ± 10.2 nm and a zeta potential of 22.88 ± 1.78 mV. The therapeutic potential of the nanoparticles was evaluated based on their cellular uptake and gene silencing efficiency. Cellular accumulation and gene silencing efficiency of Ab-CS-NPs in astrocytes were significantly improved compared to non-modified CS-NPs and single-antibody-modified CS-NPs. These results suggest that the combination of anti-Tf antibody and anti-B2 antibody significantly increased the knockdown effect of siRNA-loaded nanoparticles. Thus, antibody-mediated dual-targeting nanoparticles are an efficient and promising delivery strategy for inhibiting HIV replication in astrocytes. Graphical abstract Graphic representation of dual-antibody-conjugated chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier (BBB) for inhibiting HIV replication in astrocytes. a Nanoparticle delivery to the BBB and penetration. b Tf

Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

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Yao, Wenjun; Peng, Yixing; Du, Mingzhu; Luo, Juan; Zong, Li

2013-08-05

Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p intramuscular administration of a pGRP solution (p nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

Surface functionalization of chitosan-coated magnetic nanoparticles for covalent immobilization of yeast alcohol dehydrogenase from Saccharomyces cerevisiae

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Li, Gui-yin; Zhou, Zhi-de; Li, Yuan-jian; Huang, Ke-long; Zhong, Ming

2010-12-01

A novel and efficient immobilization of yeast alcohol dehydrogenase (YADH, EC1.1.1.1) from Saccharomyces cerevisiae has been developed by using the surface functionalization of chitosan-coated magnetic nanoparticles (Fe 3O 4/KCTS) as support. The magnetic Fe 3O 4/KCTS nanoparticles were prepared by binding chitosan alpha-ketoglutaric acid (KCTS) onto the surface of magnetic Fe 3O 4 nanoparticles. Later, covalent immobilization of YADH was attempted onto the Fe 3O 4/KCTS nanoparticles. The effect of various preparation conditions on the immobilized YADH process such as immobilization time, enzyme concentration and pH was investigated. The influence of pH and temperature on the activity of the free and immobilized YADH using phenylglyoxylic acid as substrate has also been studied. The optimum reaction temperature and pH value for the enzymatic conversion catalyzed by the immobilized YADH were 30 °C and 7.4, respectively. Compared to the free enzyme, the immobilized YADH retained 65% of its original activity and exhibited significant thermal stability and good durability.

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

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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.

Synthesis and Characterization of Chitosan Coated Manganese Zinc Ferrite Nanoparticles as MRI Contrast Agents

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M. Zahraei

2015-04-01

Full Text Available Manganese zinc ferrite nanoparticles (MZF NPs were synthesized by using a direct, efficient and environmental friendly hydrothermal method. To improve the colloidal stability of MZF NPs for biomedical applications, NPs were coated with chitosan by ionic gelation technique using sodium tripolyphosphate (TPP as crosslinker. The synthesized NPs were characterized by X ray diffraction (XRD analysis, inductively coupled plasma optical emission spectrometry (ICP-OES, fourier transform infrared (FTIR spectroscopy, transmission electron microscopy (TEM, vibrating sample magnetometer (VSM and the dynamic light scattering (DLS methods. The results confirmed the spinel ferrite phase formation without any calcination process after synthesis. Mean particle size of bare NPs was around 14 nm. Moreover, certain molar ratio of chitosan to TPP was required for encapsulation of NPs in chitosan. Coated NPs showed hydrodynamic size of 300 nm and polydispersity index about 0.3.

The impact of vehicles on the mucoadhesive properties of orally administrated nanoparticles: a case study with chitosan-4-thiobutylamidine conjugate.

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Sakloetsakun, Duangkamon; Perera, Glen; Hombach, Juliane; Millotti, Gioconda; Bernkop-Schnürch, Andreas

2010-09-01

The aim of this study was to evaluate the impact of various vehicles on mucoadhesive properties of thiolated chitosan nanoparticles both in vitro and in vivo. Nanoparticles (NPs) were prepared by in situ gelation technique followed by labeling with fluorescein diacetate. Comparative studies on mucoadhesion were done with these thiolated chitosan NPs and unmodified chitosan NPs (control). The obtained nanoparticles displayed a mean diameter of 164.2 ± 6.9 nm and a zeta potential of 21.5 ± 5 mV. In an in vitro adhesion study, unhydrated thiolated NPs adhered strongly to freshly excised porcine small intestine, which was more than threefold increase compared to the control. In contrast, in the presence of various vehicles (PEG 300, miglyol 840, PEG 6000, cremophor EL, and caprylic triglyceride), the mucoadhesive properties of thiolated NPs were comparatively weak. Thiolated NPs suspended in caprylic triglyceride, for example, had a percent mucoadhesion of 22.50 ± 5.35% on the mucosa. Furthermore, results from in vivo mucoadhesion studies revealed that the dry form of nanoparticles exhibits the strongest mucoadhesion, followed by nanoparticles suspended in PEG 300, miglyol, and 100 mM phosphate buffer, in that order. Three hours after administration, the gastrointestinal residence time of the dry form of thiolated NPs was up to 3.6-fold prolonged. These findings should contribute to the design of highly effective oral mucoadhesive nanoparticulate drug delivery systems.

Mean square hydrogen fluctuations in chitosan/lecithin nanoparticles from elastic neutron scattering experiments

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Sonvico, Fabio; Teresa Di Bari, Maria; Bove, Livia; Deriu, Antonio; Cavatorta, Fabrizio; Albanese, Gianfranco

2006-11-01

Recently, we have started a systematic study of the structure and dynamics of nano- and microparticles of interest as highly biocompatible drug carriers. For these particles, that are composed of polymeric and lipid material, a detailed understanding of the particle-solvent interactions is of key importance in order to tailor their characteristics for delivering drugs with specific chemical properties. Here we report results of elastic neutron scattering (ENS) investigations on lecithin/chitosan nanoparticles. They were first prepared by autoassembling the two components in aqueous solution; the samples were then freeze-dried and re-hydrated in a D 2O atmosphere. The experiments were performed in the temperature range of 20-50 K using the backscattering spectrometer IN13 at ILL (Grenoble, France). The comparison of samples in the dry state with similar ones at an hydration level of about 0.3-0.4 (g D 2O/g hydrated sample), indicates that the presence of an outer chitosan ‘‘coating’’ reduces the mean square fluctuations of the hydrogens in the lipid component, leading thus to a stiffer nanoparticle structure.

Chitosan/Carboxymethylcellulose/Ionic Liquid/Ag(0) Nanoparticles Form a Membrane with Antimicrobial Activity

International Nuclear Information System (INIS)

Quadros, C.; Faria, V.W.; Scheeren, C.W.; Klein, M.P.; Hertz, P.F.

2013-01-01

Silver metal nanoparticles were immobilized in chitosan/carboxymethylcellulose/BMI.BF4(1-n-butyl-3-methylimidazolium tetrafluoroborate ionic liquid) (CS/CMC/IL) to form polymeric membrane with 20 μm thickness. The CS/CMC/IL polymeric membrane was prepared using a simple solution blending method. Irregularly shaped Ag(0) nanoparticles with monomodal size distributions of nm Ag(0) were immobilized in the membrane. The presence of small Ag(0) nanoparticles induced an augmentation in the CS/CMC/IL film surface areas. The CS/CMC/IL membrane containing Ag(0) showed increase antimicrobial activity the Ag(0) concentration increased up to saturation at 10 mg. CS/CMC/IL membrane that contains Ag(0) nanoparticles has enhanced durability of the membrane and exhibited stronger antimicrobial activity against Escherichia coli and Staphylococcus aureus.

Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

Science.gov (United States)

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

2012-04-02

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

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Ensminger, Stephan M.; Spriewald, Bernd M.

2012-01-01

Oral tolerance is a promising approach to induce unresponsiveness to various antigens. The development of tolerogenic vaccines could be exploited in modulating the immune response in autoimmune disease and allograft rejection. In this study, we investigated a nonviral gene transfer strategy for inducing oral tolerance via antigen-encoding chitosan-DNA nanoparticles (NP). Oral application of ovalbumin (OVA)-encoding chitosan-DNA NP (OVA-NP) suppressed the OVA-specific delayed-type hypersensitivity (DTH) response and anti-OVA antibody formation, as well as spleen cell proliferation following OVA stimulation. Cytokine expression patterns following OVA stimulation in vitro showed a shift from a Th1 toward a Th2/Th3 response. The OVA-NP-induced tolerance was transferable from donor to naïve recipient mice via adoptive spleen cell transfer and was mediated by CD4+CD25+ T cells. These findings indicate that nonviral oral gene transfer can induce regulatory T cells for antigen-specific immune modulation. PMID:22933401

Chitosan-nanoconjugated hormone nanoparticles for sustained surge of gonadotropins and enhanced reproductive output in female fish.

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Mohd Ashraf Rather

Full Text Available A controlled release delivery system helps to overcome the problem of short life of the leutinizing hormone releasing hormone (LHRH in blood and avoids use of multiple injections to enhance reproductive efficacy. Chitosan- and chitosan-gold nanoconjugates of salmon LHRH of desired size, dispersity and zeta potential were synthesized and evaluated at half the dose rate against full dose of bare LHRH for their reproductive efficacy in the female fish, Cyprinus carpio. Whereas injections of both the nanoconjugates induced controlled and sustained surge of the hormones with peak (P<0.01 at 24 hrs, surge due to bare LHRH reached its peak at 7 hrs and either remained at plateau or sharply declined thereafter. While the percentage of relative total eggs produced by fish were 130 and 67 per cent higher, that of fertilised eggs were 171 and 88 per cent higher on chitosan- and chitosan-gold nanoconjugates than bare LHRH. Chitosan nanoconjugates had a 13 per cent higher and chitosan gold preparation had a 9 per cent higher fertilization rate than bare LHRH. Histology of the ovaries also attested the pronounced effect of nanoparticles on reproductive output. This is the first report on use of chitosan-conjugated nanodelivery of gonadotropic hormone in fish.

Comparative study on antifungal activities of chitosan nanoparticles and chitosan silver nano composites against Fusarium oxysporum species complex.

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Dananjaya, S H S; Erandani, W K C U; Kim, Cheol-Hee; Nikapitiya, Chamilani; Lee, Jehee; De Zoysa, Mahanama

2017-12-01

Though the metal nanoparticles (NPs) have been shown favorable results against fungal diseases, erratic environmental toxicity of NPs have raised serious concerns against their applications. Hence, it is vital to modify antifungal compounds into safe substitutes over synthetic chemicals. In this study, antifungal effects of chitosan nanoparticles (CNPs) and chitosan silver nanocomposites (CAgNCs) were compared against Fusarium oxysporum species complex. CNPs and CAgNCs were synthesized, characterized and compared based on the transmission electron microscope, X-ray diffraction, UV-vis absorbance spectra, particle size distribution, zeta potential and thermal stability analysis. Ultra-structural analysis on mycelium membrane of treated F. oxysporum showed that CNPs and CAgNCs could induce a pronounced membrane damage and disruption of the mycelium surface, increase the membrane permeability, and even cell disintegration. CAgNCs showed a significantly higher radial growth inhibition than CNPs in all the tested concentrations. Both CNPs and CAgNCs were not only effective in reducing the fungal growth, but also caused morphological and ultrastructural changes in the pathogen, thereby suggesting its usage as an antifungal dispersion system to control F. oxysporum. Additionally, CNPs and CAgNCs therapy reduced the F. oxysporum infection in zebrafish. Data demonstrates biologically active CNPs and CAgNCs are promising antifungal agents against F. oxysporum. Copyright © 2017 Elsevier B.V. All rights reserved.

Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model

DEFF Research Database (Denmark)

Nawroth, Isabel; Alsner, Jan; Deleuran, B.W.

2013-01-01

of chitosan/siRNA nanoparticles directed towards silencing TNF alpha in local macrophage populations, but the mechanism for the therapeutic effect at the lesion site remains unclear. Methods. Using the same murine RIF model we utilized an optical imaging technique and fluorescence microscopy to investigate...... the uptake of chitosan/fluorescently labeled siRNA nanoparticles by peritoneal macrophages and their subsequent migration to the inflamed tissue in the RIF model. Results. We observed strong accumulation of the fluorescent signal in the lesion site of the irradiated leg up to 24 hours using the optical...... imaging system. We further confirm by immunohistochemical staining that Cy3 labeled siRNA resides in macrophages of the irradiated leg. Conclusion. We provide a proof-of-concept for host macrophage trafficking towards the inflamed region in a murine RIF model, which thereby suggests that the chitosan...

Adjuvant Activity of Poly-ε-caprolactone/Chitosan Nanoparticles Characterized by Mast Cell Activation and IFN-γ and IL-17 Production.

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Jesus, Sandra; Soares, Edna; Borchard, Gerrit; Borges, Olga

2018-01-02

Polymeric nanoparticles (NPs) are extremely attractive vaccine adjuvants, able to promote antigen delivery and in some instances, exert intrinsic immunostimulatory properties that enhance antigen specific humoral and cellular immune responses. The poly-ε-caprolactone (PCL)/chitosan NPs were designed with the aim of being able to combine the properties of the 2 polymers in the preparation of an adjuvant for the hepatitis B surface antigen (HBsAg). This article reports important results of an in vitro mechanistic study and immunization studies with HBsAg associated with different concentrations of the nanoparticles. The results revealed that PCL/chitosan NPs promoted mast cell (MC) activation (β-hexosaminidase release) and that its adjuvant effect is not mediated by the TNF-α secretion. Moreover, we demonstrated that HBsAg loaded PCL/chitosan NPs, administered through the subcutaneous (SC) route, were able to induce higher specific antibody titers without increasing IgE when compared to a commercial vaccine, and that the IgG titers are nanoparticle-dose dependent. The results also revealed the NPs' capability to promote a cellular immune response against HBsAg, characterized by the production of IFN-γ and IL-17. These results demonstrated that PCL/chitosan NPs are a good hepatitis B antigen adjuvant, with direct influence on the intensity and type of the immune response generated.

Multimodal imaging of lymph nodes and tumors using glycol-chitosan-coated gold nanoparticles (Conference Presentation)

Science.gov (United States)

Sun, In-Cheol; Dumani, Diego S.; Emelianov, Stanislav Y.

2017-03-01

A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages. The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

Study on fluorouracil–chitosan nanoparticle preparation and its antitumor effect

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Gaimin Chen

2016-05-01

Full Text Available To successfully prepare fluorouracil–chitosan nanoparticles, and further analyze its anti-tumor activity mechanism, this paper makes a comprehensive study of existing preparation prescription and makes a detailed analysis of fluorouracil–chitosan in vitro release and pharmacodynamic behavior of animals. Two-step synthesis method is adopted to prepare 5-FU–CS–mPEG prodrugs, and infrared, 1H NMR and differential thermal analysis are adopted to analyze characterization synthetic products of prepared drugs. To ensure clinical efficacy of prepared drugs, UV spectrophotometry is adopted for determination of drug loading capacity of prepared drugs, transmission electron microscopy is adopted to observe the appearance, dynamic dialysis method is used to observe in vitro drug release of prepared drugs and fitting of various release models is done. Anti-tumor effect is studied via level of animal pharmacodynamics. After the end of the experiment, tumor inhibition rate, spleen index and thymus index of drugs are calculated. Experimental results show that the prepared drugs are qualified in terms of regular shape, dispersion, drug content, etc. Animal pharmacodynamics experiments have shown that concentration level of drug loading capacity of prepared drugs has a direct impact on anti-tumor rate. The higher the concentration, the higher the anti-tumor rate. Results of pathological tissue sections of mice show that the prepared drugs cause varying degrees of damage to receptor cells, resulting in cell necrosis or apoptosis problem. It can thus be concluded that ion gel method is an effective method to prepare drug-loading nanoparticles, with prepared nanoparticles evenly distributed in regular shape which demonstrate good slow-release characteristics in receptor vitro and vivo. At the same time, after completion of drug preparation, relatively strong anti-tumor activity can be generated for the receptor, so this mode of preparation enjoys broad

Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

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Cai, Limei; Yu, Rufen; Hao, Xi; Ding, Xiangcui

2017-08-01

In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

Chitosan-based nanoparticles of avermectin to control pine wood nematodes.

Science.gov (United States)

Liang, Wenlong; Yu, Aixin; Wang, Guodong; Zheng, Feng; Jia, Jinliang; Xu, Hanhong

2018-06-01

Pine wood nematode disease is a most devastating disease of pine trees. Avermectin (AVM) is a widely used bio-nematocide which can effectively to kill the pine wood nematode (PWN). However, its poor solubility in water and rapid photolysis are responsible for its poor bioavailability, which causes environmental pollution because of excessive applied rates. Here, a simple electrostatic interaction method was used to encapsulate AVM within nanoparticles composed of poly-γ-glutamic acid (γ-PGA) and chitosan (CS). The loading capacity of the resulting AVM-CS/γ-PGA nanoparticles was as much as 30.5%. The encapsulation of AVM within these nanoparticles reduced its losses by more than 20.0% through photolysis. An in vitro test showed that the rate of release of AVM from the nanoparticles was dependent on the ambient pH, with rapid release occurring in an alkaline environment. The mortality rate of nematodes which were treated with 1ppm of AVM content of AVM-CS/γ-PGA was 98.6% after 24h, while one of free AVM was only 69.9%. In addition, FITC-labeled CS/γ-PGA nanoparticles (FITC-CS/γ-PGA) showed that the nanoparticles could enrich in intestines and head of nematodes. All of these results showed that those nanoparticles of AVM are a potential multifunctional formulation to control the pest and reduce environment pollution. Copyright © 2018 Elsevier B.V. All rights reserved.

Determination of diffusion coefficient for released nanoparticles from developed gelatin/chitosan bilayered buccal films.

Science.gov (United States)

Mahdizadeh Barzoki, Zahra; Emam-Djomeh, Zahra; Mortazavian, Elaheh; Rafiee-Tehrani, Niyousha; Behmadi, Homa; Rafiee-Tehrani, Morteza; Moosavi-Movahedi, Ali Akbar

2018-06-01

This study aims at the mathematical optimization by Box-Behnken statistical design, fabrication by ionic gelation technique and in vitro characterization of insulin nanoparticles containing thiolated N- dimethyl ethyl chitosan (DMEC-Cys) conjugate. Then Optimized insulin nanoparticles were loaded into the buccal film, and in-vitro drug release from films was investigated, and diffusion coefficient was predicted. The optimized nanoparticles were shown to have mean particle size diameter of 148nm, zeta potential of 15.5mV, PdI of 0.26 and AE of 97.56%. Cell viability after incubation with optimized nanoparticles and films were assessed using an MTT biochemical assay. In vitro release study, FTIR and cytotoxicity also indicated that nanoparticles made of this thiolated polymer are suitable candidates for oral insulin delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

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) ...

Development and Characterization of VEGF165-Chitosan Nanoparticles for the Treatment of Radiation-Induced Skin Injury in Rats

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Daojiang Yu

2016-10-01

Full Text Available Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth factors on skin healing by observing the changes of microcirculation and cell apoptosis. Vascular endothelial growth factor (VEGF was more effective at inhibiting apoptosis and preventing injury progression than other factors. A new strategy for improving the bioavailability of vascular growth factors was developed by loading VEGF with chitosan nanoparticles. The VEGF-chitosan nanoparticles showed a protective effect on vascular endothelial cells, improved the local microcirculation, and delayed the development of radioactive skin damage.

In vitro cytotoxicity of iron oxide nanoparticles: effects of chitosan and polyvinyl alcohol as stabilizing agents

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Tran, Phong A.; Nguyen, Hiep T.; Fox, Kate; Tran, Nhiem

2018-03-01

Iron oxide magnetic nanoparticles have significant potential in biomedical applications such as in diagnosis, imaging and therapeutic agent delivery. The choice of stabilizers and surface functionalization is important as it is known to strongly influence the cytotoxicity of the nanoparticles. The present study aimed at investigating the effects of surface charges on the cytotoxicity of iron oxide nanoparticles. We used a co-precipitation method to synthesize iron oxide nanoparticles which were then stabilized with either chitosan (CS) or polyvinyl alcohol (PVA) which have net positive charge and zero charge at physiological pH, respectively. The nanoparticles were characterized in terms of size, charges and chemical oxidation state. Cytotoxicity of the nanoparticles was assessed using mouse fibroblast cells and was correlated with surface charges of the nanoparticles and their aggregation.

Poloxamer surface modified trimethyl chitosan nanoparticles for the effective delivery of methotrexate in osteosarcoma.

Science.gov (United States)

Li, Shenglong; Xiong, Yuyuan; Zhang, Xiaojing

2017-06-01

The present work is an effort to explore the poloxamer-modified trimethyl chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve the therapeutic efficacy and minimize severe toxicity associated with the clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles (MTCN) was nanosized and exhibited a controlled release of drug from the carrier system. The MTCN showed higher accumulation in cell cytoplasm region evident by the high red fluorescence indicating its uptake through energy-dependent endocytosis process. MTCN exhibited the increased cytotoxicity in MG63 cells compared free MTX due to its enhanced cellular uptake. Especially, MTCN exhibited a superior apoptosis effect with bright chromatin condensation and nuclear fragmentation was observed and showed remarkably higher apoptosis (∼48%) compared to that of free drug. The results of this investigation clearly demonstrate that the poloxamer-modified trimethyl chitosan (TMC) seems to have a great potential as a drug carrier in cancer chemotherapy. The present research work offers immense scope for further exploitation of poloxamer-modified trimethyl chitosan (TMC) in future for the development of nanoparticulate drug delivery system for cancer chemotherapy. Copyright © 2017. Published by Elsevier Masson SAS.

Microarc-oxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells

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Wang Z

2015-10-01

Full Text Available Zhongshan Wang,1,* Guangsheng Wu,2,3,* Zhihong Feng,1 Shizhu Bai,1 Yan Dong,1 Guofeng Wu,1 Yimin Zhao1 1State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, 2State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi’an, People’s Republic of China; 3Qingdao First Sanatorium, Jinan Military Region, Qingdao, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Dental implants have been widely used for the replacement of missing teeth in the clinic, but further improvements are needed to meet the clinical demands for faster and tighter osseointegration. In this study, we fabricated safe and biocompatible chitosan (CS/hyaluronic acid (HA nanoparticles to deliver microRNA-21 (miR-21 and thereby accelerate osteogenesis in human bone marrow mesenchymal stem cells (hBMMSCs. The CS/HA/miR-21 nanoparticles were cross-linked with 0.2% gel solution onto microarc oxidation (MAO-treated titanium (Ti surfaces to fabricate the miR-21-functionalized MAO Ti surface, resulting in the development of a novel coating for reverse transfection. To characterize the CS/HA/miR-21 nanoparticles, their particle size, zeta potential, surface morphology, and gel retardation ability were sequentially investigated. Their biological effects, such as cell viability, cytotoxicity, and expression of osteogenic genes by hBMMSCs on the miR-21-functionalized MAO Ti surfaces, were evaluated. Finally, we explored appropriate CS/HA/miR-21 nanoparticles with a CS/HA ratio of 4:1 and N/P ratio 20:1 for transfection, which presented good spherical morphology, an average diameter of 160.4±10.75 nm, and a positive zeta potential. The miR-21-functionalized MAO Ti surfaces demonstrated cell viability, cytotoxicity, and cell spreading comparable to those exhibited by naked MAO Ti surfaces and led to significantly higher

Chitosan-based nanoparticles for improving immunization against hepatitis B infection.

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Prego, Cecilia; Paolicelli, Patrizia; Díaz, Belen; Vicente, Sara; Sánchez, Alejandro; González-Fernández, Africa; Alonso, María José

2010-03-19

The design of effective vaccine delivery vehicles is opening up new possibilities for making immunization more equitable, safe and efficient. In this work, we purpose polysaccharidic-based nanoparticles as delivery structures for virus-like particle antigens, using recombinant hepatitis B surface antigen (rHBsAg) as a model. Polysaccharidic-based nanoparticles were prepared using a very mild ionic gelation technique, by cross-linking the polysaccharide chitosan (CS) with a counter ion. The resulting nanoparticles could be easily isolated with a size in the nanometric range (160-200 nm) and positive surface charge (+6 to +10 mV). More importantly, CS-based nanoparticles allowed the efficient association of the antigen (>60%) while maintaining the antigenic epitope intact, as determined by ELISA and Western blot. The entrapped antigen was further released in vitro from the nanoparticles in a sustained manner without compromising its antigenicity. In addition, loaded CS-based nanoparticles were stable, and protected the associated antigen during storage, either as an aqueous suspension under different temperature conditions (+4 degrees C and -20 degrees C), or as a dried form after freeze-drying the nanoparticles. Finally, immunization studies showed the induction of important seroprotection rates after intramuscular administration of the nanoparticles, indicating their adjuvant capacity. In fact, CS-based nanoparticles were able to induce anti-HBsAg IgG levels up to 5500 mIU/ml, values 9-fold the conventional alum-adsorbed vaccine. In conclusion, we report here a polysaccharidic nanocarrier which exhibits a number of in vitro and in vivo features that make it a promising adjuvant for vaccine delivery of subunit antigens. Copyright 2010 Elsevier Ltd. All rights reserved.

Preparation of gold/carboxymethyl chitosan nanoparticles by radiation technique for application as an antioxidant

International Nuclear Information System (INIS)

Le Quang Luan; Nguyen Thanh Long; Nguyen Hai Nam; Do Thi Phuong Linh

2015-01-01

Gold nanoparticles (AuNPs) with the sizes of 5.2, 6.7 and 7.3 nm have been synthesised by γ-irradiation of Au 3+ solutions with the corresponding concentrations of 0.25, 0.5 and 1.0 mM using carboxylmethyl chitosan as stabiliser. The optical characteristics and particle sizes of AuNPs have been determined by UV-Vis spectra and TEM images respectively. The antioxidant activity of AuNPs has been investigated at the concentrations of 0.025 mM and 0.5 mM using ABTS scavenging activity. The results have shown that the higher concentration of AuNPs displays the stronger antioxidant activity and the faster reaction time. The highest antioxidant activity has been found at the concentration of 0.375 mM within 2-3 minutes. The antioxidant activity of AuNPs increases by the increase of reaction time and is higher than that of ascorbic acid. Thus, gold/carboxymethyl chitosan nanoparticles prepared by γ-irradiation method can be potentially utilised for the production of antioxidant products in pharmaceutics, functional foods and cosmetics. (author)

Structure and properties of solid polymer electrolyte based on chitosan and ZrO{sub 2} nanoparticle for lithium ion battery

Energy Technology Data Exchange (ETDEWEB)

Sudaryanto,, E-mail: dryanto@batan.go.id; Yulianti, Evi, E-mail: yulianti@batan.go.id [Center for Sains and Technology Advanced Materials – BATAN Kawasan Puspiptek Serpong, Tangerang Selatan, BantenV 15314 (Indonesia); Patimatuzzohrah, E-mail: pzohrah@yahoo.com [Department Of Physics, Mataram University, Jl. Majapahit 62, Mataram, NTB 83125 (Indonesia)

2016-02-08

In order to develop all solid lithium ion battery, study on the structure and properties of solid polymer electrolytes (SPE) based on chitosan has been done. The SPE were prepared by adding Zirconia (ZrO{sub 2}) nanoparticle and LiClO{sub 4} as lithium salt into the chitosan solution followed by casting method. Effect of the ZrO{sub 2} and salt concentration to the structure and properties of SPE were elaborated using several methods. The structure of the SPE cast film, were characterized mainly by using X-ray diffractometer (XRD). While the electrical properties of SPE were studied by electrochemical impedance spectrometer (EIS) and ion transference number measurement. XRD profiles show that the addition of ZrO{sub 2} and LiClO{sub 4} disrupts the crystality of chitosan. The decrease in sample crytalinity with the nanoparticle and salt addition may increase the molecular mobility result in the increasing sample conductivity and cathionic transference number as determined by EIS and ion transference number measurement, respectively. The highest ionic conductivity (3.58×10{sup −4} S cm{sup −1}) was obtained when 4 wt% of ZrO{sub 2} nanoparticle and 40 wt% of LiClO{sub 4} salt were added to the chitosan. The ion transference number with that composition was 0.55. It is high enough to be used as SPE for lithium ion battery.

Fabrication, nanomechanical characterization, and cytocompatibility of gold-reinforced chitosan bio-nanocomposites

International Nuclear Information System (INIS)

Patel, Nimitt G.; Kumar, Ajeet; Jayawardana, Veroni N.; Woodworth, Craig D.; Yuya, Philip A.

2014-01-01

Chitosan, a naturally derived polymer represents one of the most technologically important classes of active materials with applications in a variety of industrial and biomedical fields. Gold nanoparticles (∼ 32 nm) were synthesized via a citrate reduction method from chloroauric acid and incorporated in Chitosan matrix. Bio-nanocomposite films with varying concentrations of gold nanoparticles were prepared through solution casting process. Uniform distribution of gold nanoparticles was achieved throughout the chitosan matrix and was confirmed with SEM. Synthesis outcomes and prepared nanocomposites were characterized using SEM, TEM, EDX, SAED, UV–vis, XRD, DLS, and Zeta potential for their physical, morphological and structural properties. Nanoscale properties of materials under the influence of temperature were characterized through nanoindentation techniques. From quasi-static nanoindentation, it was observed that hardness and reduced modulus of the nanocomposites were increased significantly in direct proportion to the gold nanoparticle concentration. Gold nanoparticle concentration also showed positive impact on storage modulus and thermal stability of the material. The obtained films were confirmed to be biocompatible by their ability to support growth of human cells in vitro. In summary, the results show enhanced mechanical properties with increasing gold nanoparticle concentration, and provide better understanding of the structure–property relationships of such biocompatible materials for potential biomedical applications. - Highlights: • We fabricated gold reinforced chitosan nanocomposite for biomedical applications. • Gold nanoparticles significantly enhanced nanomechanical properties of chitosan. • Nanocomposite films supported growth of human cells in vitro. • Gold nanoparticles significantly improved cell proliferation on chitosan films

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.

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)

Application of Ferriferous Oxide Modified by Chitosan in Gene Delivery

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Yu Kuang

2012-01-01

Full Text Available New approaches to improve the traditional gene carriers are still required. Here we explore Fe3O4 modified with degradable polymers that enhances gene delivery and target delivery using permanent magnetic field. Two magnetic Fe3O4 nanoparticles coated with chitosan (CTS and polyethylene glycol (PEG were synthesized by means of controlled chemical coprecipitation. Plasmid pEGFP was encapsulated as a reported gene. The ferriferous oxide complexes were approximately spherical; surface charge of CTS-Fe3O4 and PEG-Fe3O4 was about 20 mv and 0 mv, respectively. The controlled release of DNA from the CTS-Fe3O4 nanoparticles was observed. Concurrently, a desired Fe3O4 concentration of less than 2 mM was verified as safe by means of a cytotoxicity test in vitro. Presence of the permanent magnetic field significantly increased the transfection efficiency. Furthermore, the passive target property and safety of magnetic nanoparticles were also demonstrated in an in vivo test. The novel gene delivery system was proved to be an effective tool required for future target expression and gene therapy in vivo.

Structural mediation on polycation nanoparticles by sulfadiazine to enhance DNA transfection efficiency and reduce toxicity.

Science.gov (United States)

Long, Xingwen; Zhang, Zhihui; Han, Shangcong; Tang, Minjie; Zhou, Junhui; Zhang, Jianhua; Xue, Zhenyi; Li, Yan; Zhang, Rongxin; Deng, Liandong; Dong, Anjie

2015-04-15

Reducing the toxicity while maintaining high transfection efficiency is an important issue for cationic polymers as gene carriers in clinical application. In this paper, a new zwitterionic copolymer, polycaprolactone-g-poly(dimethylaminoethyl methyacrylate-co-sulfadiazine methacrylate) (PC-SDZ) with unique pH-sensitivity, was designed and prepared. The incorporation of sulfadiazine into poly(dimethylaminoethyl methacrylate) (PDMAEMA) chains successfully mediates the surface properties including compacter shell structure, lower density of positive charges, stronger proton buffer capability, and enhanced hydrophobicity, which lead to reduction in toxicity and enhancements in stability, cellular uptake, endosome escape, and transfection efficiency for the PC-SDZ2 nanoparticles (NPs)/DNA complexes. Excellent transfection efficiency at the optimal N/P ratio of 10 was observed for PC-SDZ2 NPs/DNA complexes, which was higher than that of the commercial reagent-branched polyethylenimine (PEI). The cytotoxicity was evaluated by CCK8 measurement, and the results showed significant reduction in cytotoxicity even at high concentration of complexes after sulfadiazine modification. Therefore, this work may demonstrate a new way of structural mediation of cationic polymer carriers for gene delivery with high efficiency and low toxicity.

pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight heparin delivery: in vitro and in vivo evaluation.

Science.gov (United States)

Fan, Bo; Xing, Yang; Zheng, Ying; Sun, Chuan; Liang, Guixian

2016-01-01

The aim of present study was to investigate a pH-responsive and mucoadhesive nanoparticle system for oral bioavailability enhancement of low-molecular weight heparin (LMWH). The thioglycolic acid (TGA) was first covalently attached to chitosan (CS) with 396.97 ± 54.54 μmol thiol groups per gram of polymer and then the nanoparticles were prepared with thiolated chitosan (TCS) and pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) by ionic cross-linking method. The obtained nanoparticles were characterized for the shape, particle size, zeta potential, drug entrapment efficiency and loading capacity. In vitro results revealed the acid stability of pH-responsive nanoparticles, which had a significant control over LMWH release and could effectively protect entrapped drugs in simulated gastric conditions. By the attachment of the thiol ligand, an improvement of permeation-enhancing effect on freshly excised carp intestine (1.86-fold improvement) could be found. The mucoadhesive properties were evaluated using fluorescently labeled TCS or CS nanoparticles. As compared with the controls, a significant improvement of mucoadhesion on rat intestinal mucosa was observed in TCS/HPMCP nanoparticles via confocal laser scanning microscopy. The activated partial thromboplastin time (APTT) was significantly prolonged and an increase in the oral bioavailability of LMWH was turned out to be pronounced after oral delivered LMWH-loaded TCS/HPMCP nanoparticles in rats, which suggested enhanced anticoagulant effects and improved absorption of LMWH. In conclusion, pH-responsive TCS/HPMCP nanoparticles hold promise for oral delivery of LMWH.

Synthesis and characterisation of cross-linked chitosan composites functionalised with silver and gold nanoparticles for antimicrobial applications

Science.gov (United States)

Ryan, Catherine; Alcock, Emma; Buttimer, Finbarr; Schmidt, Michael; Clarke, David; Pemble, Martyn; Bardosova, Maria

2017-12-01

We present a study of a range of cross-linked chitosan composites with potential antimicrobial applications. They were formed by cross-linking chitosan and siloxane networks and by introducing silver and gold nanoparticles (NPs). The aim was to investigate whether adding the metal NPs to the chitosan-siloxane composite would lead to a material with enhanced antimicrobial ability as compared to chitosan itself. The composites were synthesised in hydrogel form with the metal NPs embedded in the cross-linked chitosan network. Spectroscopic and microscopic techniques were employed to investigate the structural properties of the composite and the tensile strength of the structures was measured. It was found that the addition of metal NPs did not influence the mechanical strength of the composite. A crystal violet attachment assay results displayed a significant reduction in the attachment of E. coli to the cross-linked chitosan surfaces. Release profile tests suggest that the metal NPs do not contribute to the overall antimicrobial activity under neutral conditions. The contribution to the mechanical and antimicrobial properties from cross-linking with siloxane is significant, giving rise to a versatile, durable, antimicrobial material suitable for thin film formation, wound dressings or the coating of various surfaces where robustness and antimicrobial control are required.

A facile method for electrospinning of Ag nanoparticles/poly (vinyl alcohol)/carboxymethyl-chitosan nanofibers

International Nuclear Information System (INIS)

Zhao, Yinghui; Zhou, Ying; Wu, Xiaomian; Wang, Lu; Xu, Ling; Wei, Shicheng

2012-01-01

Highlights: ► AgNPs/PVA/CM-chitosan nanofibers were prepared via electrospinning method. ► AgNPs were in situ synthesized in electrospinning solution via a facile method. ► AgNPs distributed homogeneously on the surface of nanofibers. ► The prepared nanofibers possessed certain antibacterial ability against Escherichia coli. ► The AgNPs containing nanofibers had potential as antibacterial biomaterial. - Abstract: A facile method to prepare silver nanoparticles (AgNPs) containing nanofibers via electrospinning has been demonstrated. AgNPs were in situ synthesized in poly (vinyl alcohol) (PVA)/carboxymethyl-chitosan (CM-chitosan) blend aqueous solution before electrospinning. UV–vis spectra, viscosity and conductivity of the electrospinning solution were measured to investigate their effects on the electrospinning procedure. The morphology of AgNPs/PVA/CM-chitosan nanofibers was observed by Field Emission Scanning Electron Microscopy. The formation and morphology of AgNPs were investigated by Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy. The resulted nanofibers have smooth surface and uniform diameters ranging from 295 to 343 nm. The diameters of AgNPs mainly distributed in the range of 4–14 nm, and the electrostatic interaction between AgNPs and fibers was observed. Finally, in vitro Ag release from the nanofibers was measured and the antibacterial behavior of the nanofibers against Escherichia coli was studied by bacterial growth inhibition halos and bactericidal kinetic testing. The AgNPs/PVA/CM-chitosan nanofibers possessed certain antibacterial ability, which makes them capable for antibacterial biomaterials.

Development, optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box-Behnken experimental design.

Science.gov (United States)

Adena, Sandeep Kumar Reddy; Upadhyay, Mansi; Vardhan, Harsh; Mishra, Brahmeshwar

2018-03-01

The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs). Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP. The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39 ± 1.82 nm, apparent drug content (ADC) of 72.06 ± 0.86%, and zeta potential (ZP) of -13.91 ± 1.21 mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48 h and followed Korsmeyer-Peppas release kinetic model. A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.

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

Mucoadhesive properties of low molecular weight chitosan- or glycol chitosan- and corresponding thiomer-coated poly(isobutylcyanoacrylate) core-shell nanoparticles.

Science.gov (United States)

Palazzo, Claudio; Trapani, Giuseppe; Ponchel, Gilles; Trapani, Adriana; Vauthier, Christine

2017-08-01

The aim of the present work was to evaluate the mucoadhesive properties of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles (NPs) coated with Low Molecular Weight (LMW) chitosan (CS)- and glycol chitosan (GCS)-based thiomers as well as with the corresponding LMW unmodified polysaccharides. For this purpose, all the CS- and GCS-based thiomers were prepared under simple and mild conditions starting from the LMW unmodified polymers CS and GCS. The resulting NPs were of spherical shape with diameters ranging from 400 to 600nm and 187 to 309nm, for CS- and GCS-based NPs, respectively. The mucoadhesive characteristics of these core shell NPs were studied in Ussing chambers measuring the percentage of NPs stuck on the mucosal of fresh intestinal tissue after 2h of incubation. Moreover, incubation of nanoparticle formulations with the intestinal tissue induced changes in transmucosal electrical resistance which were measured to gain information into the opening of tight junctions and to control the integrity of the mucosa. Thus, it was found that PIBCA NPs coated with the GCS-Glutathione conjugate (GCGPIBCA NPs) possessed the most favorable mucoadhesive performances. Moreover, both GCGPIBCA- and GCS-N-acetyl-cysteine (GCNPIBCA)-core-shell NPs might induced an enlargement of the epithelial cell tight junctions. In conclusion, coating of PIBCA NPs with GCS-based thiomers may be useful for improving the mucoadhesive and permeation properties of these nanocarriers. Copyright © 2017 Elsevier B.V. All rights reserved.

Two-step preparation of nano-scaled magnetic chitosan particles using Triton X-100 reversed-phase water-in-oil microemulsion system

International Nuclear Information System (INIS)

Zhou, Zhengkun; Jiang, Feihong; Lee, Tung-Ching; Yue, Tianli

2013-01-01

Highlights: •A new two-step route for nano-scaled magnetic chitosan particles preparation. •Triton X-100 reversed-phase microemulsion system was used for chitosan coating. •Narrow size distribution of magnetic chitosan nanoparticles was achieved. •Quantitative evaluation of recoverability for the magnetic chitosan nanoparticles. -- Abstract: A new two-step route for the preparation of nano-scaled magnetic chitosan particles has been developed, different from reported one-step in situ preparation and two-step preparation method of reversed-phase suspension, Triton X-100 reversed-phase water-in-oil microemulsion encapsulation method was employed in coating the pre-prepared Fe 3 O 4 nanoparticles with chitosan. The resultant magnetic chitosan particles owned a narrow size distribution ranging from 50 to 92 nm. X-ray diffraction patterns (XRD) indicated that the chitosan coating procedure did not change the spinal structure of Fe 3 O 4 magnetic nanoparticles. The results of Fourier transform infrared (FTIR) analysis and thermogravimetric analysis (TGA) demonstrated that the chitosan was coated on Fe 3 O 4 nanoparticles and its average mass content was ∼50%. The saturated magnetization of the magnetic Fe 3 O 4 /chitosan nanoparticles reached 18.62 emu/g, meanwhile, the nanoparticles showed the characteristics of superparamagnetism. The magnetic chitosan nanoparticles showed a high recoverability of 99.99% in 10 min when pH exceeded 4. The results suggested that the as-prepared magnetic chitosan particles were nano-scaled with a narrow size distribution and a high recoverability

Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Choi, Seon Young; Jang, Soo Hwa [Seoul National University, Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Institute for Veterinary Science (Korea, Republic of); Park, Jin; Jeong, Saeromi; Park, Jin Ho; Ock, Kwang Su [Soongsil University, Department of Chemistry (Korea, Republic of); Lee, Kangtaek [Yonsei University, Department of Chemical and Biomolecular Engineering (Korea, Republic of); Yang, Sung Ik [Kyung Hee University, College of Environment and Applied Chemistry (Korea, Republic of); Joo, Sang-Woo, E-mail: sjoo@ssu.ac.kr [Soongsil University, Department of Chemistry (Korea, Republic of); Ryu, Pan Dong; Lee, So Yeong, E-mail: leeso@snu.ac.kr [Seoul National University, Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Institute for Veterinary Science (Korea, Republic of)

2012-12-15

Cellular uptake, cytotoxicity, and mechanisms of cytotoxicity of the positively charged Au nanoparticles (NPs) were examined in A549 cells, which are one of the most characterized pulmonary cellular systems. Positively charged Au NPs were prepared by chemical reduction using chitosan. The dimension and surface charge of Au NPs were examined by transmission electron microscopy (TEM), dynamic light scattering, and zeta potential measurements. The uptake of Au NPs into A549 cells was also monitored using TEM and dark-field microscopy (DFM) and z-stack confocal microRaman spectroscopy. DFM live cell imaging was also performed to monitor the entry of chitosan Au NPs in real time. The cytotoxic assay, using both methylthiazol tetrazolium and lactate dehydrogenase assays revealed that positively charged Au NPs decreased cell viability. Flow cytometry, DNA fragmentation, real-time PCR, and western blot analysis suggest that positively charged chitosan Au NPs provoke cell damage through both apoptotic and necrotic pathways.

Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells

International Nuclear Information System (INIS)

Choi, Seon Young; Jang, Soo Hwa; Park, Jin; Jeong, Saeromi; Park, Jin Ho; Ock, Kwang Su; Lee, Kangtaek; Yang, Sung Ik; Joo, Sang-Woo; Ryu, Pan Dong; Lee, So Yeong

2012-01-01

Cellular uptake, cytotoxicity, and mechanisms of cytotoxicity of the positively charged Au nanoparticles (NPs) were examined in A549 cells, which are one of the most characterized pulmonary cellular systems. Positively charged Au NPs were prepared by chemical reduction using chitosan. The dimension and surface charge of Au NPs were examined by transmission electron microscopy (TEM), dynamic light scattering, and zeta potential measurements. The uptake of Au NPs into A549 cells was also monitored using TEM and dark-field microscopy (DFM) and z-stack confocal microRaman spectroscopy. DFM live cell imaging was also performed to monitor the entry of chitosan Au NPs in real time. The cytotoxic assay, using both methylthiazol tetrazolium and lactate dehydrogenase assays revealed that positively charged Au NPs decreased cell viability. Flow cytometry, DNA fragmentation, real-time PCR, and western blot analysis suggest that positively charged chitosan Au NPs provoke cell damage through both apoptotic and necrotic pathways.

Chitosan/bioactive glass nanoparticles scaffolds with shape memory properties.

Science.gov (United States)

Correia, Cristina O; Leite, Álvaro J; Mano, João F

2015-06-05

We propose a combination of chitosan (CHT) with bioactive glass nanoparticles (BG-NPs) in order to produce CHT/BG-NPs scaffolds that combine the shape memory properties of chitosan and the biomineralization ability of BG-NPs for applications in bone regeneration. The addition of BG-NPs prepared by a sol-gel route to the CHT polymeric matrix improved the bioactivity of the nanocomposite scaffold, as seen by the precipitation of bone-like apatite layer upon immersion in simulated body fluid (SBF). Shape memory tests were carried out while the samples were immersed in varying compositions of water/ethanol mixtures. Dehydration with ethanol enables to fix a temporary shape of a deformed scaffold that recovers the initial geometry upon water uptake. The scaffolds present good shape memory properties characterized by a recovery ratio of 87.5% for CHT and 89.9% for CHT/BG-NPs and a fixity ratio of 97.2% for CHT and 98.2% for CHT/BG-NPs (for 30% compressive deformation). The applicability of such structures was demonstrated by a good geometrical accommodation of a previously compressed scaffold in a bone defect. The results indicate that the developed CHT/BG-NPs nanocomposite scaffolds have potential for being applied in bone tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multifunctional glucose biosensors from Fe3O4 nanoparticles modified chitosan/graphene nanocomposites

Science.gov (United States)

Zhang, Wenjing; Li, Xiaojian; Zou, Ruitao; Wu, Huizi; Shi, Haiyan; Yu, Shanshan; Liu, Yong

2015-01-01

Novel water-dispersible and biocompatible chitosan-functionalized graphene (CG) has been prepared by a one-step ball milling of carboxylic chitosan and graphite. Presence of nitrogen (from chitosan) at the surface of graphene enables the CG to be an outstanding catalyst for the electrochemical biosensors. The resulting CG shows lower ID/IG ratio in the Raman spectrum than other nitrogen-containing graphene prepared using different techniques. Magnetic Fe3O4 nanoparticles (MNP) are further introduced into the as-synthesized CG for multifunctional applications beyond biosensors such as magnetic resonance imaging (MRI). Carboxyl groups from CG is used to directly immobilize glucose oxidase (GOx) via covalent linkage while incorporation of MNP further facilitated enzyme loading and other unique properties. The resulting biosensor exhibits a good glucose detection response with a detection limit of 16 μM, a sensitivity of 5.658 mA/cm2/M, and a linear detection range up to 26 mM glucose. Formation of the multifunctional MNP/CG nanocomposites provides additional advantages for applications in more clinical areas such as in vivo biosensors and MRI agents. PMID:26052919

Electrophoretic deposition of composite hydroxyapatite-chitosan coatings

International Nuclear Information System (INIS)

Pang Xin; Zhitomirsky, Igor

2007-01-01

Cathodic electrophoretic deposition has been utilized for the fabrication of composite hydroxyapatite-chitosan coatings on 316L stainless steel substrates. The addition of chitosan to the hydroxyapatite suspensions promoted the electrophoretic deposition of the hydroxyapatite nanoparticles and resulted in the formation of composite coatings. The obtained coatings were investigated by X-ray diffraction, thermogravimetric and differential thermal analysis, scanning and transmission electron microscopy, potentiodynamic polarization measurements, and electrochemical impedance spectroscopy. It was shown that the deposit composition can be changed by a variation of the chitosan or hydroxyapatite concentration in the solutions. Experimental conditions were developed for the fabrication of hydroxyapatite-chitosan nanocomposites containing 40.9-89.8 wt.% hydroxyapatite. The method enabled the formation of adherent and uniform coatings of thicknesses up to 60 μm. X-ray studies revealed that the preferred orientation of the hydroxyapatite nanoparticles in the chitosan matrix increases with decreasing hydroxyapatite content in the composite coatings. The obtained coatings provided the corrosion protection for the 316L stainless steel substrates

Effect of chitosan nanoparticles and pectin content on mechanical properties and water vapor permeability of banana puree films.

Science.gov (United States)

Martelli, Milena R; Barros, Taís T; de Moura, Márcia R; Mattoso, Luiz H C; Assis, Odilio B G

2013-01-01

Puree prepared from over-ripe peeled bananas was used as raw material for films processing in a laboratory padder. Pectin and glycerol as plasticizer were added in small concentrations and chitosan nanoparticles (88.79 ± 0.42 nm medium size) incorporated at 0.2% (dry weight basis) as reinforcement material. The mechanical properties, water vapor transmission, thermal stability, and scanning electron microscopy of fractured film surfaces were characterized. Both pectin and glycerol demonstrated an important role in promoting elongation and film handability as was expected. The incorporation of nanoparticles promoted noticeable improvement of the mechanical properties and acted in reducing the water vapor permeation rate, by 21% for films processed with pectin and up to 38% for films processed without pectin, when compared to the control (puree films with no pectin and nanoparticles additions). Microscopic observation revealed a denser matrix when nanoparticles are incorporated into the films. The development of films from fruit purees head to a new strategy for plastic processing from natural resources. The over-ripe or even waste banana can be adequately prepared for batch films processed with reasonable mechanical and barrier properties, suitable for applications in the food segment. The addition of small fractions of chitosan nanoparticles, form nanocomposites enhancing mechanical and thermal stability broadening potential film applications. © 2012 Institute of Food Technologists®

Photoenhanced gene transfection by a curcumin loaded CS-g-PZLL micelle.

Science.gov (United States)

Lin, Jian-Tao; Pan, Wen-Jia; Zhang, Jun-Ai; Wang, Wei; Zhong, Jia; Su, Jia-Min; Li, Tong; Zou, Ying; Wang, Guan-Hai

2017-09-01

The codelivery of drug and gene is a promising method for cancer treatment. In our previous works, we prepared a cationic micelles based on chitosan and poly-(N-3-carbobenzyloxylysine) (CS-g-PZLL), but transfection ratio of CS-g-PZLL to Hela cell was low. Herein, to improve the transfection efficiency of CS-g-PZLL, curcumin was loaded in the CS-g-PZLL micelle. After irradiation, the obtained curcumin loaded micelle showed a better transfection, and the p53 protein expression in Hela cells was higher. The apoptosis assay showed that the complex could induce a more significant apoptosis to Hela cells than that of curcumin or p53 used alone, and the curcumin loaded micelle inducing apoptosis was best after irradiation. Therefore, CS-g-PZLL is a safe and effective carrier for the codelivery of drug/gene, and curcumin could be used as a photosensitizer to induce a photoenhanced gene transfection, which should be encouraged in improving transfection and tumor therapy. Copyright © 2017. Published by Elsevier B.V.

Two-step preparation of nano-scaled magnetic chitosan particles using Triton X-100 reversed-phase water-in-oil microemulsion system

Energy Technology Data Exchange (ETDEWEB)

Zhou, Zhengkun; Jiang, Feihong [College of Food Science and Engineering, Northwest A and F University, Yangling, Shaanxi 712100 (China); Lee, Tung-Ching, E-mail: lee@aesop.rutgers.edu [Department of Food Science, Rutgers, the State University of New Jersey, 65 Dudley Road, New Brunswick, NJ 08901 (United States); Yue, Tianli, E-mail: yuetl305@nwsuaf.edu.cn [College of Food Science and Engineering, Northwest A and F University, Yangling, Shaanxi 712100 (China)

2013-12-25

Highlights: •A new two-step route for nano-scaled magnetic chitosan particles preparation. •Triton X-100 reversed-phase microemulsion system was used for chitosan coating. •Narrow size distribution of magnetic chitosan nanoparticles was achieved. •Quantitative evaluation of recoverability for the magnetic chitosan nanoparticles. -- Abstract: A new two-step route for the preparation of nano-scaled magnetic chitosan particles has been developed, different from reported one-step in situ preparation and two-step preparation method of reversed-phase suspension, Triton X-100 reversed-phase water-in-oil microemulsion encapsulation method was employed in coating the pre-prepared Fe{sub 3}O{sub 4} nanoparticles with chitosan. The resultant magnetic chitosan particles owned a narrow size distribution ranging from 50 to 92 nm. X-ray diffraction patterns (XRD) indicated that the chitosan coating procedure did not change the spinal structure of Fe{sub 3}O{sub 4} magnetic nanoparticles. The results of Fourier transform infrared (FTIR) analysis and thermogravimetric analysis (TGA) demonstrated that the chitosan was coated on Fe{sub 3}O{sub 4} nanoparticles and its average mass content was ∼50%. The saturated magnetization of the magnetic Fe{sub 3}O{sub 4}/chitosan nanoparticles reached 18.62 emu/g, meanwhile, the nanoparticles showed the characteristics of superparamagnetism. The magnetic chitosan nanoparticles showed a high recoverability of 99.99% in 10 min when pH exceeded 4. The results suggested that the as-prepared magnetic chitosan particles were nano-scaled with a narrow size distribution and a high recoverability.

Multifunctional nanocomposites of chitosan, silver nanoparticles, copper nanoparticles and carbon nanotubes for water treatment: Antimicrobial characteristics.

Science.gov (United States)

Morsi, Rania E; Alsabagh, Ahmed M; Nasr, Shimaa A; Zaki, Manal M

2017-04-01

Multifunctional nanocomposites of chitosan with silver nanoparticles, copper nanoparticles and carbon nanotubes either as bi- or multifunctional nanocomposites were prepared. Change in the overall morphology of the prepared nanocomposites was observed; carbon nanotubes, Ag NPs and Cu NPs are distributed homogeneously inside the polymer matrix individually in the case of the bi-nanocomposites while a combination of different dimensional shapes; spherical NPs and nanotubes was observed in the multifunctional nanocomposite. Multifunctional nanocomposites has a higher antimicrobial activity, in relative short contact times, against both Gram negative and Gram positive bacteria; E. coli, Staphylococcus aureus; respectively in addition to the fungal strain; Aspergillus flavus isolated from local wastewater sample. The nanocomposites are highly differentiable at the low contact time and low concentration; 1% concentration of the multifunctional nanocomposite is very effective against the tested microbes at contact time of only 10min. Copyright © 2017 Elsevier B.V. All rights reserved.

A facile method for electrospinning of Ag nanoparticles/poly (vinyl alcohol)/carboxymethyl-chitosan nanofibers

Energy Technology Data Exchange (ETDEWEB)

Zhao, Yinghui; Zhou, Ying [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Wu, Xiaomian [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Orthodontics College of Stomatology, Chongqing Medical University, Chongqing 401147 (China); Wang, Lu [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Xu, Ling, E-mail: lingxu@pku.edu.cn [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); PKU-HKUST ShenZhen-HongKong Institution, Shenzhen 518057 (China); Wei, Shicheng, E-mail: sc-wei@pku.edu.cn [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University, Beijing 100081 (China)

2012-09-01

Highlights: Black-Right-Pointing-Pointer AgNPs/PVA/CM-chitosan nanofibers were prepared via electrospinning method. Black-Right-Pointing-Pointer AgNPs were in situ synthesized in electrospinning solution via a facile method. Black-Right-Pointing-Pointer AgNPs distributed homogeneously on the surface of nanofibers. Black-Right-Pointing-Pointer The prepared nanofibers possessed certain antibacterial ability against Escherichia coli. Black-Right-Pointing-Pointer The AgNPs containing nanofibers had potential as antibacterial biomaterial. - Abstract: A facile method to prepare silver nanoparticles (AgNPs) containing nanofibers via electrospinning has been demonstrated. AgNPs were in situ synthesized in poly (vinyl alcohol) (PVA)/carboxymethyl-chitosan (CM-chitosan) blend aqueous solution before electrospinning. UV-vis spectra, viscosity and conductivity of the electrospinning solution were measured to investigate their effects on the electrospinning procedure. The morphology of AgNPs/PVA/CM-chitosan nanofibers was observed by Field Emission Scanning Electron Microscopy. The formation and morphology of AgNPs were investigated by Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy. The resulted nanofibers have smooth surface and uniform diameters ranging from 295 to 343 nm. The diameters of AgNPs mainly distributed in the range of 4-14 nm, and the electrostatic interaction between AgNPs and fibers was observed. Finally, in vitro Ag release from the nanofibers was measured and the antibacterial behavior of the nanofibers against Escherichia coli was studied by bacterial growth inhibition halos and bactericidal kinetic testing. The AgNPs/PVA/CM-chitosan nanofibers possessed certain antibacterial ability, which makes them capable for antibacterial biomaterials.

Nano-biolistics: a method of biolistic transfection of cells and tissues using a gene gun with novel nanometer-sized projectiles

Directory of Open Access Journals (Sweden)

Lummis Sarah CR

2011-06-01

Full Text Available Abstract Background Biolistic transfection is proving an increasingly popular method of incorporating DNA or RNA into cells that are difficult to transfect using traditional methods. The technique routinely uses 'microparticles', which are ~1 μm diameter projectiles, fired into tissues using pressurised gas. These microparticles are efficient at delivering DNA into cells, but cannot efficiently transfect small cells and may cause significant tissue damage, thus limiting their potential usefulness. Here we describe the use of 40 nm diameter projectiles - nanoparticles - in biolistic transfections to determine if they are a suitable alternative to microparticles. Results Examination of transfection efficiencies in HEK293 cells, using a range of conditions including different DNA concentrations and different preparation procedures, reveals similar behaviour of microparticles and nanoparticles. The use of nanoparticles, however, resulted in ~30% fewer damaged HEK293 cells following transfection. Biolistic transfection of mouse ear tissue revealed similar depth penetration for the two types of particles, and also showed that 20% in microparticle-transfected samples. Visualising details of small cellular structures was also considerably enhanced when using nanoparticles. Conclusions We conclude that nanoparticles are as efficient for biolistic transfection as microparticles, and are more appropriate for use in small cells, when examining cellular structures and/or where tissue damage is a problem.

Tailorable thiolated trimethyl chitosans for covalently stabilized nanoparticles.

Science.gov (United States)

Verheul, Rolf J; van der Wal, Steffen; Hennink, Wim E

2010-08-09

A novel four-step method is presented to synthesize partially thiolated trimethylated chitosan (TMC) with a tailorable degree of quaternization and thiolation. First, chitosan was partially N-carboxylated with glyoxylic acid and sodium borohydride. Next, the remaining amines were quantitatively dimethylated with formaldehyde and sodium borohydride and then quaternized with iodomethane in NMP. Subsequently, these partially carboxylated TMCs dissolved in water were reacted with cystamine at pH 5.5 using EDC as coupling agent. After addition of DTT and dialysis, thiolated TMCs were obtained, varying in degree of quaternization (25-54%) and degree of thiolation (5-7%), as determined with (1)H NMR and Ellman's assay. Gel permeation chromatography with light scattering detection indicated limited intermolecular cross-linking. All thiolated TMCs showed rapid oxidation to yield disulfide cross-linked TMC at pH 7.4, while the thiolated polymers were rather stable at pH 4.0. When Calu-3 cells were used, XTT and LDH cell viability tests showed a slight reduction in cytotoxicity for thiolated TMCs as compared to the nonthiolated polymers with similar DQs. Positively charged nanoparticles loaded with fluorescently labeled ovalbumin were made from thiolated TMCs and thiolated hyaluronic acid. The stability of these particles was confirmed in 0.8 M NaCl, in contrast to particles made from nonthiolated polymers that dissociated under these conditions, demonstrating that the particles were held together by intermolecular disulfide bonds.

Chitosan-silica complex membranes from sulfonic acid functionalized silica nanoparticles for pervaporation dehydration of ethanol-water solutions.

Science.gov (United States)

Liu, Ying-Ling; Hsu, Chih-Yuan; Su, Yu-Huei; Lai, Juin-Yih

2005-01-01

Nanosized silica particles with sulfonic acid groups (ST-GPE-S) were utilized as a cross-linker for chitosan to form a chitosan-silica complex membranes, which were applied to pervaporation dehydration of ethanol-water solutions. ST-GPE-S was obtained from reacting nanoscale silica particles with glycidyl phenyl ether, and subsequent sulfonation onto the attached phenyl groups. The chemical structure of the functionalized silica was characterized with FTIR, (1)H NMR, and energy-dispersive X-ray. Homogeneous dispersion of the silica particles in chitosan was observed with electronic microscopies, and the membranes obtained were considered as nanocomposites. The silica nanoparticles in the membranes served as spacers for polymer chains to provide extra space for water permeation, so as to bring high permeation rates to the complex membranes. With addition of 5 parts per hundred of functionalized silica into chitosan, the resulting membrane exhibited a separation factor of 919 and permeation flux of 410 g/(m(2) h) in pervaporation dehydration of 90 wt % ethanol aqueous solution at 70 degrees C.

Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin.

Science.gov (United States)

He, Zhiyu; Santos, Jose Luis; Tian, Houkuan; Huang, Huahua; Hu, Yizong; Liu, Lixin; Leong, Kam W; Chen, Yongming; Mao, Hai-Quan

2017-06-01

Controlled delivery of protein would find diverse therapeutic applications. Formulation of protein nanoparticles by polyelectrolyte complexation between the protein and a natural polymer such as chitosan (CS) is a popular approach. However, the current method of batch-mode mixing faces significant challenges in scaling up while maintaining size control, high uniformity, and high encapsulation efficiency. Here we report a new method, termed flash nanocomplexation (FNC), to fabricate insulin nanoparticles by infusing aqueous solutions of CS, tripolyphosphate (TPP), and insulin under rapid mixing condition (Re > 1600) in a multi-inlet vortex mixer. In comparison with the bulk-mixing method, the optimized FNC process produces CS/TPP/insulin nanoparticles with a smaller size (down to 45 nm) and narrower size distribution, higher encapsulation efficiency (up to 90%), and pH-dependent nanoparticle dissolution and insulin release. The CS/TPP/insulin nanoparticles can be lyophilized and reconstituted without loss of activity, and produced at a throughput of 5.1 g h -1 when a flow rate of 50 mL min -1 is used. Evaluated in a Type I diabetes rat model, the smaller nanoparticles (45 nm and 115 nm) control the blood glucose level through oral administration more effectively than the larger particles (240 nm). This efficient, reproducible and continuous FNC technique is amenable to scale-up in order to address the critical barrier of manufacturing for the translation of protein nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chitosan magnetic microspheres for technological applications: Preparation and characterization

International Nuclear Information System (INIS)

Podzus, P.E.; Daraio, M.E.; Jacobo, S.E.

2009-01-01

One of the major applications of chitosan and its many derivatives are based on its ability to bind strongly heavy and toxic metal ions. In this study chitosan magnetic microspheres have been synthesized. Acetic acid (1%w/v) solution was used as solvent for the chitosan polymer solution (2%w/v) where magnetite nanoparticles were suspended in order to obtain a stable ferrofluid. Glutaraldehyde was used as cross-linker. The magnetic characteristic of these materials allows an easy removal after use if is necessary. The morphological characterization of the microspheres shows that they can be produced in the size range 800-1100 μm. The adsorption of Cu(II) onto chitosan-magnetite nanoparticles was studied in batch system. A second-order kinetic model was used to fit the kinetic data, leading to an equilibrium adsorption capacity of 19 mg Cu/g chitosan.

Positively charged gold nanoparticles capped with folate quaternary chitosan: Synthesis, cytotoxicity, and uptake by cancer cells.

Science.gov (United States)

Yen, Hui-Ju; Young, Yen-An; Tsai, Tsung-Neng; Cheng, Kuang-Ming; Chen, Xin-An; Chen, Ying-Chuan; Chen, Cheng-Cheung; Young, Jenn-Jong; Hong, Po-da

2018-03-01

In this study, we synthesized various quaternary chitosan derivatives and used them to stabilize gold nanoparticles (AuNPs). These chitosan derivatives comprised N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC), folate-HTCC, galactosyl-HTCC, and their fluorescein isothiocyanate-conjugated derivatives. Various positively surface-charged AuNPs were prepared under alkaline conditions using glucose as a reducing agent in the presence of the HTCC derivatives (HTCCs). The effects of the concentration of NaOH, glucose, and HTCCs on the particles size, zeta potential, and stability were studied in detail. Cell cycle assays verify that none of the HTCCs or HTCCs-AuNPs was cytotoxic to human umbilical vein endothelial cells. Flow cytometry analysis showed that the folate HTCC-AuNPs were internalized in Caco-2, HepG2, and HeLa cancer cells to a significantly greater extent than AuNPs without folate. But, galactosyl HTCC-AuNPs only showed high cell uptake by HepG2 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo

OpenAIRE

Cheng, Mingrong; Gao, Xiaoyan; Wang, Yong; Chen, Houxiang; He, Bing; Xu, Hongzhi; Li, Yingchun; Han, Jiang; Zhang, Zhiping

2013-01-01

Nanoparticle drug delivery (NDDS) is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA), to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by Fourier transformed inf...

OPTIMIZATION OF STIRRING SPEED AND STIRRING TIME TOWARD NANOPARTICLE SIZE OF CHITOSAN-SIAM CITRUS PEEL (Citrus nobilis L.var Microcarpa 70% ETHANOL EXTRACT

Directory of Open Access Journals (Sweden)

Wintari Taurina

2017-04-01

Full Text Available Siam citrus peel (Citrus nobilis L. var. Microcarpa is a plant derived from Sambas Regency, West Kalimantan Province. Bioavailability of herbal active compounds can be enhanced by formulating extract into nanoparticle. The polymer used was chitosan with crosslinker Na-TPP. Stirring speed and stirring time play an important role to produce small particle size in forming nanoparticle using ionic gelation method. Enhancement of stirring speed and stirring time could reduce particle size. Nanoparticles were prepared using ionic gelation method by mixing Na-TPP, extract and chitosan (1:1:6 with varying the stirring speed 500 rpm, 1000 rpm, 1500 rpm and stirring time 1 hrs, 2 hrs, 3 hrs. The particle size of nanoparticle was found to be 85.3 nm at 1000 rpm of stirring speed and 3 hrs of stirring times, with polidispersity index 0.287, zeta potential +32.37 mV and entrapment efficiency 87.12 %.

A strong adjuvant based on glycol-chitosan-coated lipid-polymer hybrid nanoparticles potentiates mucosal immune responses against the recombinant Chlamydia trachomatis fusion antigen CTH522

DEFF Research Database (Denmark)

Rose, Fabrice; Erbo Wern, Jeanette; Gavins, Francesca

2018-01-01

with the cationic surfactant dimethyldioctadecylammonium bromide and the immunopotentiator trehalose-6,6'-dibehenate. Here we show that immunization with these lipid-polymer hybrid nanoparticles (LPNs) coated with the mucoadhesive polymer chitosan enhances mucosal immune responses. Glycol chitosan (GC......-specific IgG/IgA antibodies, together with CTH522-specific interferon γ-producing Th1 cells. This study demonstrates that mucosal administration of chitosan-coated LPNs represents a promising strategy to modulate the magnitude of mucosal vaccine responses....

Silencage du gene MDR1 et resensibilisation des cellules MCF-7 MDR a la doxorubicine en utilisant les nanoparticules chitosane/MDR1-siARN

Science.gov (United States)

El-Ariss, Mohamad

ARN_2M are complementary to a sequence shifted slightly downstream in the same gene (583-607 nucleic acids). RNA duplexes siRNA_1 and siARN_2 consist exclusively of DNA while "modifed" siRNA_1M and si RNA_2M consist of RNA overhangs. siRNA duplexes (siRNA_1 and siRNA_2) were chosen from the work published by Hao Wu et al. (2003), Stege et al. (2004) and Miletti-Gonzalez et al. (2005) which showed that these siRNA sequences are effective to silence MDR1 gene in cancer cells (breast cancer cells MCF-7 / AdrR and MCF-7 / BC-19 and stomach cancer cells: EPG85-257RDB).[3-5] Moreover, Strapps et al. (2010) showed that the use of siRNA having overhangs formed of ribonucleotides leads to a similar silencing but lasting longer in vivo and in vitro compared to the use of siRNA containing deoxyribonucleotides overhangs.[6] Thus siARN_1M and siARN_2M sequences correspond to siARN_1 and siARN_2 sequences but whose overhangs are formed of ribonucleotides. These siRNA specific to the MDR1 gene (MDR1-siRNA) were combined to chitosan to form nanoparticles capable of protecting these MDR1-siRNA and delivering it into the MCF-7 MDR cells. Chitosan used here as a delivery system, is a natural and biodegradable polysaccharide whose biological properties are defined by its average molecular weight (MW) and by its degree of deacetylation (DD). When the positively charged chitosan is added with the negatively charged siRNA, there is formation of nanoparticles by electrostatic attraction. In this project, chitosan 92-10 (DDA- MW) was used as a delivery system with a N:P (ratio chitosan amino groups: RNA phosphate) of 5. Analysis by dynamic light scattering (DLS) demonstrated that the nanoparticles have a diameter between 62.56 and 82.72 nm and a zeta potential ranging from 17.4 to 23.5 mV. Analysis by confocal microscopy showed that chitosan (92-10-5)/labeled siRNA are internalized in MCF-7 MDR cells and that siRNAs are released in the cytoplasm. MCF-7 cells resistant MDR were transfected in

Cationic nanoparticles with quaternary ammonium-functionalized PLGA–PEG-based copolymers for potent gene transfection

Energy Technology Data Exchange (ETDEWEB)

Wang, Yan-Hsung [Kaohsiung Medical University, School of Dentistry, College of Dental Medicine (China); Fu, Yin-Chih [Kaohsiung Medical University, Graduate Institute of Medicine, College of Medicine (China); Chiu, Hui-Chi [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry, College of Life Science (China); Wang, Chau-Zen [Kaohsiung Medical University, Department of Physiology, College of Medicine (China); Lo, Shao-Ping [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry, College of Life Science (China); Ho, Mei-Ling [Kaohsiung Medical University, Department of Physiology, College of Medicine (China); Liu, Po-Len [Kaohsiung Medical University, Department of Respiratory Therapy, College of Medicine (China); Wang, Chih-Kuang, E-mail: ckwang@kmu.edu.tw [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry, College of Life Science (China)

2013-11-15

The objective of the present work was to develop new cationic nanoparticles (cNPs) with amphiphilic cationic copolymers for the delivery of plasmid DNA (pDNA). Cationic copolymers were built on the synthesis of quaternary ammonium salt compounds from diethylenetriamine (DETA) to include the positively charged head group and amphiphilic multi-grafts. PLGA-phe-PEG-qDETA (PPD), phe-PEG-qDETA-PLGA (PDP), and PLGA-phe-PEG-qDETA-PLGA (PPDP) cationic copolymers were created by this moiety of DETA quaternary ammonium, heterobifunctional polyethylene glycol (COOH-PEG-NH{sub 2}), phenylalanine (phe), and poly(lactic-co-glycolic acid) (PLGA). These new cNPs were prepared by the water miscible solvent displacement method. They exhibit good pDNA binding ability, as shown in a retardation assay that occurred at a particle size of ∼217 nm. The zeta potential was approximately +21 mV when the cNP concentration was 25 mg/ml. The new cNPs also have a better buffering capacity than PLGA NPs. However, the pDNA binding ability was demonstrated starting at a weight ratio of approximately 6.25 cNPs/pDNA. Gene transfection results showed that these cNPs had transfection effects similar to those of Lipofectamine 2000 in 293T cells. Furthermore, cNPs can also transfect human adipose-derived stem cells. The results indicate that the newly developed cNP is a promising candidate for a novel gene delivery vehicle.

Radiation induced synthesis of colloidal silver nanoparticles stabilized by PVP/chitosan

International Nuclear Information System (INIS)

Dang Van Phu; Nguyen Trieu; Vo Thi Kim Lang; Nguyen Quoc Hien; Bui Duy Du

2008-01-01

Colloidal silver nanoparticle solution (10 mmol) was prepared by gamma 60 Co irradiation using polyvinyl pyrrolidone (PVP), water soluble chitosan (WSC) and mixture of PVP/WSC as stabilizers. Saturated conversion doses (Ag + → Ag 0 ) and maximum absorption wavelengths (λ max ) were determined by UV-vis spectra to be of 28 kGy (405.5 nm), 20 kGy (418.5 nm), 24 kGy (415.0 nm) and 24 kGy (407.0 nm) for PVP 1% (C1), WSC 0.5% (C2), PVP 1%/WSC 0.5% (C3) and PVP 1%/ethanol 1 M (C4), respectively. Results of the conversion doses indicated that WSC and ethanol plays a role in scavenging the OH* and H* arising from radiolysis of water, which reduced the conversion dose from 28 kGy (C1) to 20 kGy (C2). The average size of silver nanoparticles was characterized by Transmission Electron Microscopy (TEM) as 15.96 ± 0.51, 5.55 ± 0.25, 2.92 ± 0.05, and 11.44 ±2.07 nm for C1, C2, C3 and C4, respectively. The obtained result of silver nanoparticle sizes showed that WSC exhibited the effect of reducing silver nanoparticle size in colloids, especially the mixture of PVP/WSC that reduced the size of silver nanoparticle from ∼16 nm (C1) to about 3 nm (C3). The effect of NaNO 3 on stability of colloidal silver nanoparticles has been also investigated. (author)

Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells.

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Baumgart, Judith; Humbert, Laure; Boulais, Étienne; Lachaine, Rémi; Lebrun, Jean-Jaques; Meunier, Michel

2012-03-01

A femtosecond laser based transfection method using off-resonance plasmonic gold nanoparticles is described. For human cancer melanoma cells, the treatment leads to a very high perforation rate of 70%, transfection efficiency three times higher than for conventional lipofection, and very low toxicity (transfection for skin cancer treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of the genotoxicity of chitosan nanoparticles for use in food packaging films.

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De Lima, Renata; Feitosa, Leandro; do Espírito Santo Pereira, Anderson; de Moura, Márcia Regina; Ahmad Aouada, Fauze; Henrique Capparelli Mattoso, Luiz; Fernandes Fraceto, Leonardo

2010-08-01

The use of nanoparticles in food packaging has been proposed on the basis that it could improve protection of foods by, for example, reducing permeation of gases, minimizing odor loss, and increasing mechanical strength and thermal stability. Consequently, the impacts of such nanoparticles on organisms and on the environment need to be investigated to ensure their safe use. In an earlier study, Moura and others (2008a) described the effect of addition of chitosan (CS) and poly(methacrylic acid) (PMAA) nanoparticles on the mechanical properties, water vapor, and oxygen permeability of hydroxypropyl methylcellulose films used in food packaging. Here, the genotoxicity of different polymeric CS/PMAA nanoparticles (size 60, 82, and 111 nm) was evaluated at different concentration levels, using the Allium cepa chromosome damage test as well as cytogenetic tests employing human lymphocyte cultures. Test substrates were exposed to solutions containing nanoparticles at polymer mass concentrations of 1.8, 18, and 180 mg/L. Results showed no evidence of DNA damage caused by the nanoparticles (no significant numerical or structural changes were observed), however the 82 and 111 nm nanoparticles reduced mitotic index values at the highest concentration tested (180 mg/L), indicating that the nanoparticles were toxic to the cells used at this concentration. In the case of the 60 nm CS/PMAA nanoparticles, no significant changes in the mitotic index were observed at the concentration levels tested, indicating that these particles were not toxic. The techniques used show promising potential for application in tests of nanoparticle safety envisaging the future use of these materials in food packaging.

Chitosan-functionalized gold nanoparticles for colorimetric detection of mercury ions based on chelation-induced aggregation

International Nuclear Information System (INIS)

Chen, Zhengbo; Zhang, Chenmeng; Tan, Yuan; Zhou, Tianhui; Ma, He; Wan, Chongqing; Lin, Yuqing; Li, Kai

2015-01-01

We are presenting a colorimetric assay for mercury (II) ions. It is based on citosan-functionalized gold nanoparticles (AuNPs) that act as a signaling probe. Hg (II) induces the aggregation of the chitosan-AuNPs through a chelation reaction that occurs between chitosan and Hg (II). This results in a strong decrease of the absorbance of the modified AuNPs and a color change from red to blue. This sensing system displays excellent selectivity over other metal ions and a detection limit as low as 1.35 μM which is lower than the allowed level of Hg (II) in drinking water (30 μM) as defined by World Health Organization. The method is inexpensive, facile, sensitive, and does not require the addition of other reagents in order to improving sensitivity. (author)

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

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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.

Preparation and characterization of chitosan-silver nanocomposite films and their antibacterial activity against Staphylococcus aureus

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Regiel, Anna; Irusta, Silvia; Kyzioł, Agnieszka; Arruebo, Manuel; Santamaria, Jesus

2013-01-01

In this work different variables have been analyzed in order to optimize the bactericidal properties of chitosan films loaded with silver nanoparticles. The goal was to achieve complete elimination of antibiotic resistant and biofilm forming strains of Staphylococcus aureus after short contact times. The films were produced by solution casting using chitosan as both a stabilizing and reducing agent for the in situ synthesis of embedded silver nanoparticles. We have applied an innovative approach: the influence of the chitosan molecular weight and its deacetylation degree (DD) were analyzed together with the influence of the bacterial concentration and contact time. The best results were obtained with high DD chitosan where a fast reduction was favored; leading to smaller nanoparticles (nucleation is promoted), and a sufficiently high polymer viscosity prevented the resulting nanoparticles from undesired agglomeration. In addition, for the first time, potential detachment of the silver nanoparticles from the films was evaluated and neglected, demonstrating that uncontrolled release of silver nanoparticles from the chitosan films is prevented. The influence of the ionic silver released from the films, silver loading, nanoparticle sizes, contact, and initial number of bacteria was also analyzed to elucidate the mechanism responsible for the strong bactericidal action observed.

In vitro studies of magnetically enhanced transfection in COS-7 cells

International Nuclear Information System (INIS)

Ang, D.; Tay, C.Y.; Tan, L.P.; Preiser, P.R.; Ramanujan, R.V.

2011-01-01

In the magnetically enhanced gene delivery technique, DNA complexed with polymer coated aggregated magnetic nanoparticles (AMNPs) is used for effecting transfection. The aim of this study is to examine the relationship between transfection efficiency and the physical characteristics of the polymer coated AMNPs. In vitro studies of transfection efficiency in COS-7 cells were carried out using pEGFP-N1 and pMIR-REPORT complexed polyethylenimine (PEI) coated iron oxide magnetic nanoparticles. PEI coated AMNPs (PEI-AMNPs) with average individual particle diameters in the range of 8 nm to 30 nm were studied and characterized by transmission electron microscopy, vibrating sample magnetometry, X-ray diffractometry, thermal gravimetric analysis and photon correlation spectroscopy methods. PEI-A8MNP and PEI-A30MNP yielded higher transfection efficiency compared to commercial polyMAG particles as well as PEI of equivalent molar ratio of nitrogen/phosphorous (N/P ratio). The transfection efficiency was related to the physical characteristics of the PEI-AMNPs and its complexes: transfection efficiency was strongly positively correlated with saturation magnetization (Ms) and susceptibility (χ), strongly negatively correlated with N/P ratio, moderately positively correlated to zeta potential and moderately negatively correlated to hydrodynamic diameter of the complex. PEI-A8MNP and PEI-A30MNP possessing higher Ms, χ, lower N/P ratio and smaller complex size exhibited higher transfection efficiency compared to PEI-A16MNP which have weaker magnetic properties, higher N/P ratio and larger complex size. We have demonstrated that optimization of the physical properties of PEI-AMNPs is needed to maximize transfection efficiency. - Research highlights: →The transfection efficiency in magnetically enhanced gene delivery was studied. →Transfection efficiency was strongly positively correlated to magnetic properties. →Transfection efficiency was strongly negatively correlated with

Chitosan/o-carboxymethyl chitosan nanoparticles for efficient and safe oral anticancer drug delivery: in vitro and in vivo evaluation.

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Feng, Chao; Wang, Zhiguo; Jiang, Changqing; Kong, Ming; Zhou, Xuan; Li, Yang; Cheng, Xiaojie; Chen, Xiguang

2013-11-30

The present study investigated the ability of a polyelectrolyte complex (CS/CMCS-NPs), composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) as a pH responsive carrier for oral delivery of doxorubicin hydrochloride (DOX). The obtained CS/CMCS-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency and stability under the simulated GI tract conditions. The pH responsive stability of the DOX-loaded CS/CMCS nanoparticles (DOX:CS/CMCS-NPs) determined the drug release rate, which was lower in acidic pH than the neutral. Ex vivo intestinal adhesion and permeation indicated DOX:CS/CMCS-NGs were able to enhance absorption of DOX throughout the entire small intestine, especially in jejunum and ileum. Oral administration of DOX:CS/CMCS-NPs was effective to deliver DOX into blood, giving an absolute bioavailability of 42%. The tissue distribution and toxicity of DOX:CS/CMCS-NPs in rats showed low level of DOX in heart and kidney, and obviously decreased cardiac and renal toxicities. These results indicated CS/CMCS-NPs were highly efficient and safe as an oral delivery system for DOX. Copyright © 2013 Elsevier B.V. All rights reserved.

Multilayer sodium alginate beads with porous core containing chitosan based nanoparticles for oral delivery of anticancer drug.

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Li, Jing; Jiang, Changqing; Lang, Xuqian; Kong, Ming; Cheng, Xiaojie; Liu, Ya; Feng, Chao; Chen, Xiguang

2016-04-01

To develop efficient and safe anticancer drug doxorubicin hydrochloride (DOX) delivery system for oral chemotherapy, chitosan based nanoparticles (CS/CMCS-NPs) composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) were immobilized in multilayer sodium alginate beads (NPs-M-Beads). Two kinds of NPs-M-Beads, with or without porous core, were respectively prepared by internal or external ionic gelation method. In the small intestine, the intact CS/CMCS-NPs were able to escape from porous-beads and sustained release the loading DOX. In vivo results showed that the DOX could be efficiently absorbed by small intestine of SD rat and the higher concentration of the DOX in major organs of rats were found after oral administration of Porous-Beads, which were about 2-4 folds higher than that of non-porous-beads. These results suggested that the NPs-M-Beads with porous core to be exciting and promising for oral delivery of DOX. Copyright © 2015 Elsevier B.V. All rights reserved.

Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid-chitosan nanoparticles enhances periodontal regeneration in dogs

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Lee BS

2016-01-01

Full Text Available Bor-Shiunn Lee,1 Chien-Chen Lee,2 Yi-Ping Wang,2 Hsiao-Jan Chen,3 Chern-Hsiung Lai,4 Wan-Ling Hsieh,1 Yi-Wen Chen2 1Graduate Institute of Oral Biology, 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University and National Taiwan University Hospital, 3Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 4College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid (PLGA nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in

Structure determination of chitosan-stabilized Pt and Pd based bimetallic nanoparticles by X-ray photoelectron spectroscopy and transmission electron microscopy

International Nuclear Information System (INIS)

Wu, Lihua; Shafii, Salimah; Nordin, Mohd Ridzuan; Liew, Kong Yong; Li, Jinlin

2012-01-01

Chitosan (CTS)-stabilized bimetallic nanoparticles were prepared at room temperature (rt.) in aqueous solution. Palladium (Pd) and platinum (Pt) were selected as the first metals while iron (Fe) and nickel (Ni) functioned as the second metals. In order to obtain the noble metal core-transition metal shell structures, bimetallic nanoparticles were prepared in a two-step process: the preparation of mono noble metallic (Pd or Pt) nanoparticles and the deposition of transition metals (Fe or Ni) on the surface of the monometallic nanoparticles. The structures of the nanoparticles were studied using X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The XPS results show that Pd and Pt exist mainly in zero valences. The presence of Fe and Ni in the bimetallic nanoparticles affects the binding energy of Pd and Pt. Moreover, the studies of O 1s spectra indicate the presence of Fe or Ni shells. The analyses of TEM micrographs give the particle size and size distributions while the high-resolution TEM (HRTEM) micrographs show the existence of noble metal core lattices. The results confirm the formation of noble metal core-transition metal shell structures. -- Highlights: ► Chitosan-stabilized bimetallic nanoparticles were prepared at room temperature in aqueous solution. ► The presence of Fe or Ni shells was proven by XPS study. ► The existence of noble metal cores covered by amorphous shells was indicated by TEM study. ► The formation of noble metal core-transition metal shell structures was confirmed.

Topographic characterization of the self-assembled nanostructures of chitosan on mica surface by atomic force microscopy

International Nuclear Information System (INIS)

Wang, Li; Wu, Jiafeng; Guo, Yan; Gong, Coucong; Song, Yonghai

2015-01-01

Graphical abstract: - Highlights: • Nanocomposites of chitosan film were prepared by simple self-assembly from solvent media. • Chitosan molecules assembled on mica surface of nanoparticles, fibril and membrane with varied chitosan concentration. • Chitosan molecules assembled with different nanostructure under varied pH. • The optimum drying temperature for forming chitosan membrane is about 65 °C. - Abstract: In this work, the self-assembled nanostructures of chitosan on mica surface formed from various solvents were investigated by using atomic force microscopy. The effects of various factors on the self-assembled nanostructures of chitosan on mica surface, including solvents, the concentration of chitosan, the pH of solution and the drying temperature, were explored in detail. Our experimental data resulted in the conclusion that chitosan molecules could self-assemble on mica surface to form various nanostructures such as nanoparticles, fibril and film. Nanoparticles were always formed on mica surface from CCl_4, C_6H_6, CH_2Cl_2 solution, fibril preferred to form on mica surface from CH_3CH_2OH and CH_3OH solution and the optimal solvent to form film was found to be CH_3CN. Low concentration, pH and temperature were helpful for the formation of nanoparticles, medium concentration, pH and temperature resulted in fibril and high concentration, pH and temperature were often beneficial to forming chitosan films. The study of self-assembled nanostructures of chitosan on mica surface would provide new insight into the development of chitosan-based load-bearing materials.

Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study

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Alam S

2012-11-01

Full Text Available Sanjar Alam,1 Zeenat I Khan,1 Gulam Mustafa,1 Manish Kumar,2 Fakhrul Islam,3 Aseem Bhatnagar,4 Farhan J Ahmad11Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India; 2Advanced Instrumentation Research Facility, Jawaharlal Nehru University, New Delhi, India; 3Department of Medical Elementology and Toxicology, Neurotoxicology Laboratory, Jamia Hamdard, Hamdard Nagar, New Delhi, India; 4Government of India, Ministry of Defence, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Marg, Delhi, IndiaAbstract: Chitosan (CS nanoparticles of thymoquinone (TQ were prepared by the ionic gelation method and are characterized on the basis of surface morphology, in vitro or ex vivo release, dynamic light scattering, and X-ray diffractometry (XRD studies. Dynamic laser light scattering and transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. The results showed that the particle size of the formulation was significantly affected by the drug:CS ratio, whereas it was least significantly affected by the tripolyphosphate:CS ratio. The entrapment efficiency and loading capacity of TQ was found to be 63.3% ± 3.5% and 31.23% ± 3.14%, respectively. The drug-entrapment efficiency and drug-loading capacity of the nanoparticles appears to be inversely proportional to the drug:CS ratio. An XRD study proves that TQ dispersed in the nanoparticles changes its form from crystalline to amorphous. This was further confirmed by differential scanning calorimetry thermography. The flat thermogram of the nanoparticle data indicated that TQ formed a molecular dispersion within the nanoparticles. Optimized nanoparticles were evaluated further with the help of scintigraphy imaging, which ascertains the uptake of drug into the brain. Based on maximum concentration, time-to-maximum concentration, area-under-curve over 24 hours, and elimination rate constant, intranasal TQ

Gene expression profiles in primary duodenal chick cells following transfection with avian influenza virus H5 DNA plasmid encapsulated in silver nanoparticles

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Jazayeri SD

2013-02-01

Full Text Available Seyed Davoud Jazayeri,1 Aini Ideris,1,2 Kamyar Shameli,3 Hassan Moeini,1 Abdul Rahman Omar1,21Institute of Bioscience, 2Faculty of Veterinary Medicine, 3Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaAbstract: In order to develop a systemically administered safe and effective nonviral gene delivery system against avian influenza virus (AIV that induced cytokine expression, the hemagglutinin (H5 gene of AIV, A/Ck/Malaysia/5858/04 (H5N1 and green fluorescent protein were cloned into a coexpression vector pIRES (pIREGFP-H5 and formulated using green synthesis of silver nanoparticles (AgNPs with poly(ethylene glycol and transfected into primary duodenal cells taken from 18-day-old specific-pathogen-free chick embryos. The AgNPs were prepared using moderated temperature and characterized for particle size, surface charge, ultraviolet-visible spectra, DNA loading, and stability. AgNPs and AgNP-pIREGFP-H5 were prepared in the size range of 13.9 nm and 25 nm with a positive charge of +78 ± 0.6 mV and +40 ± 6.2 mV, respectively. AgNPs with a positive surface charge could encapsulate pIREGFP-H5 efficiently. The ultraviolet-visible spectra for AgNP-pIREGFP-H5 treated with DNase I showed that the AgNPs were able to encapsulate pIREGFP-H5 efficiently. Polymerase chain reaction showed that AgNP-pIREGFP-H5 entered into primary duodenal cells rapidly, as early as one hour after transfection. Green fluorescent protein expression was observed after 36 hours, peaked at 48 hours, and remained stable for up to 60 hours. In addition, green fluorescent protein expression generally increased with increasing DNA concentration and time. Cells were transfected using Lipocurax in vitro transfection reagent as a positive control. A multiplex quantitative mRNA gene expression assay in the transfected primary duodenal cells via the transfection reagent and AgNPs with pIREGFP-H5 revealed expression of interleukin (IL-18, IL-15, and IL-12�

The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure.

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Jesus, Sandra; Fragal, Elizangela H; Rubira, Adley F; Muniz, Edvani C; Valente, Artur J M; Borges, Olga

2018-01-01

This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system. A quantitative 6-month stability study showed that the inclusion of chitosan in PCL NPs did not induce a change in adsorbed ovalbumin (OVA) secondary structure characterized by the increase in the unordered conformation (random coil), as it was observed for OVA adsorbed to chitosan NPs. Additionally, the slight conformational changes occurred, are not expected to compromise ovalbumin secondary structure and activity, during a 6-month storage even at high temperatures (45°C). In simulated biological fluids, PCL/chitosan NPs showed an advantageous release profile for oral delivery. Overall, the combination of PCL and chitosan characteristics provide PCL/chitosan NPs valuable features particularly important to the development of vaccines for developing countries, where it is difficult to ensure cold chain transportation and non-parenteral formulations would be preferred.

Drying of a plasmid containing formulation: chitosan as a protecting agent

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Mohajel Nasir

2012-09-01

Full Text Available Abstract Background The purpose of the study. Along with research on development of more efficient gene delivery systems, it is necessary to search on stabilization processes to extend their active life span. Chitosan is a nontoxic, biocompatible and available gene delivery carrier. The aim of this study was to assess the ability of this polymer to preserve transfection efficiency during spray-drying and a modified freeze-drying process in the presence of commonly used excipients. Method Molecular weight of chitosan was reduced by a chemical reaction and achieved low molecular weight chitosan (LMWC was complexed with pDNA. Obtained nanocomplex suspensions were diluted by solutions of lactose and leucine, and these formulations were spray dried or freeze dried using a modified technique. Size, polydispersity index, zeta potential, intensity of supercoiled DNA band on gel electrophoresis, and transfection efficiency of reconstituted nanocomplexes were compared with freshly prepared ones. Results and major conclusion Size distribution profiles of both freeze dried, and 13 out of 16 spray-dried nanocomplexes remained identical to freshly prepared ones. LMWC protected up to 100% of supercoiled structure of pDNA in both processes, although DNA degradation was higher in spray-drying of the nanocomplexes prepared with low N/P ratios. Both techniques preserved transfection efficiency similarly even in lower N/P ratios, where supercoiled DNA content of spray dried formulations was lower than freeze-dried ones. Leucine did not show a significant effect on properties of the processed nanocomplexes. It can be concluded that LMWC can protect DNA structure and transfection efficiency in both processes even in the presence of leucine.

Influence of charge on FITC-BSA-loaded chondroitin sulfate-chitosan nanoparticles upon cell uptake in human Caco-2 cell monolayers

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Hu CS

2012-09-01

Full Text Available Chieh-shen Hu,1 Chiao-hsi Chiang,2 Po-da Hong,1,4,* Ming-kung Yeh1–3,*1Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology; 2School of Pharmacy, National Defence Medical Center; 3Bureau of Pharmaceutical Affairs, Ministry of National Defence Medical Affairs Bureau; 4Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taiwan, Republic of China*These authors contributed equally to this workBackground and methods: Chondroitin sulfate-chitosan (ChS-CS nanoparticles and positively and negatively charged fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA-loaded ChS-CS nanoparticles were prepared and characterized. The properties of ChS-CS nanoparticles, including cellular uptake, cytotoxicity, and transepithelial transport, as well as findings on field emission-scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy were evaluated in human epithelial colorectal adenocarcinoma (Caco-2 fibroblasts. ChS-CS nanoparticles with a mean particle size of 250 nm and zeta potentials ranging from –30 to +18 mV were prepared using an ionic gelation method.Results: Standard cell viability assays demonstrated that cells incubated with ChS-CS and FITC-BSA-loaded ChS-CS nanoparticles remained more than 95% viable at particle concentrations up to 0.1 mg/mL. Endocytosis of nanoparticles was confirmed by confocal laser scanning microscopy and measured by flow cytometry. Ex vivo transepithelial transport studies using Caco-2 cells indicated that the nanoparticles were effectively transported into Caco-2 cells via endocytosis. The uptake of positively charged FITC-BSA-loaded ChS-CS nanoparticles across the epithelial membrane was more efficient than that of the negatively charged nanoparticles.Conclusion: The ChS-CS nanoparticles fabricated in this study were

Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation.

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Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani R; Vyas, S P

2010-05-01

In clinical practices, solution of dorzolamide hydrochloride (DH) and timolol maléate (TM) is recommended for the treatment of glaucoma. However, low drug-contact time and poor ocular bioavailability of drugs due to drainage of solution, tear turnover and its dilution or lacrimation limits its uses. In addition, systemic absorption of TM may induce undesirable cardiovascular side effects. Chitosan (CS) is a polycationic biodegradable polymer which provides sustained and local delivery of drugs to the ocular sites. Hyaluronic acid (HA) also provides synergistic effect for mucoadhesion in association with chitosan. In the present study, hyaluronic acid modified chitosan nanoparticles (CS-HA-NPs) loaded with TM and DH were developed and characterized. The CS-HA-NPs were evaluated for size, shape, zeta potential, entrapment efficiency, and mucoadhesive strength. The in vitro release study was also performed in PBS pH 7.4. The ocular irritation potential of CS-HA-NPs was estimated using draize test on albino rabbits. A significant reduction in IOP level was obtained using CS-HA-NPs as compared to plain solution of drug and a comparable higher reduction in IOP level was observed as to CS-NPs. These results suggest that HA potentialy enhance the mucoadhesiveness and efficiency of CS-NPs and may be promising carrier for ocular drug delivery.

Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent.

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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.

3D-macroporous chitosan-based scaffolds with in situ formed Pd and Pt nanoparticles for nitrophenol reduction.

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Berillo, Dmitriy; Cundy, Andrew

2018-07-15

3D-macroporous chitosan-based scaffolds (cryogels) were produced via growth of metal-polymer coordinated complexes and electrostatic interactions between oppositely charged groups of chitosan and metal ions under subzero temperatures. A mechanism of reduction of noble metal complexes inside the cryogel walls by glutaraldehyde is proposed, which produces discrete and dispersed noble metal nanoparticles. 3D-macroporous scaffolds prepared under different conditions were characterised using TGA, FTIR, nitrogen adsorption, SEM, EDX and TEM, and the distribution of platinum nanoparticles (PtNPs) and palladium nanoparticles (PdNPs) in the material assessed. The catalytic activity of the in situ synthesised PdNPs, at 2.6, 12.5 and 21.0 μg total mass, respectively, was studied utilising a model system of 4-nitrophenol reduction. The kinetics of the reaction under different conditions (temperature, concentration of catalyst) were examined, and a decrease of catalytic activity was not observed over 17 treatment cycles. Increasing the temperature of the catalytic reaction from 10 to 22 and 35 °C by PdNPs supported within the cryogel increased the kinetic rate by 44 and 126%, respectively. Turnover number and turnover frequency of the PdNPs catalysts at room temperature were in the range 0.20-0.53 h -1 . The conversion degree of 4-nitrophenol at room temperature reached 98.9% (21.0 μg PdNPs). Significantly less mass of palladium nanoparticles (by 30-40 times) was needed compared to published data to obtain comparable rates of reduction of 4-nitrophenol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid Protein

OpenAIRE

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R.

2012-01-01

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for non-invasive receptor mediated gene delivery to na...

Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB.

Science.gov (United States)

Parajó, Yolanda; D'Angelo, Ivana; Welle, Alexander; Garcia-Fuentes, Marcos; Alonso, María José

2010-11-01

The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.

Quaternized Chitosan-Capped Mesoporous Silica Nanoparticles as Nanocarriers for Controlled Pesticide Release.

Science.gov (United States)

Cao, Lidong; Zhang, Huirong; Cao, Chong; Zhang, Jiakun; Li, Fengmin; Huang, Qiliang

2016-06-28

Nanotechnology-based pesticide formulations would ensure effective utilization of agricultural inputs. In the present work, mesoporous silica nanoparticles (MSNs) with particle diameters of ~110 nm and pore sizes of ~3.7 nm were synthesized via a liquid crystal templating mechanism. A water-soluble chitosan (CS) derivative ( N -(2-hydroxyl)propyl-3-trimethyl ammonium CS chloride, HTCC) was successfully capped on the surface of pyraclostrobin-loaded MSNs. The physicochemical and structural analyses showed that the electrostatic interactions and hydrogen bonding were the major forces responsible for the formation of HTCC-capped MSNs. HTCC coating greatly improved the loading efficiency (LC) (to 40.3%) compared to using bare MSNs as a single encapsulant (26.7%). The microstructure of the nanoparticles was revealed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The pyraclostrobin-loaded nanoparticles showed an initial burst and subsequent sustained release behavior. HTCC-capped MSNs released faster than bare MSNs in the initial stage. Pyraclostrobin-loaded HTCC-capped MSNs with half doses of pyraclostrobin technical demonstrated almost the same fungicidal activity against Phomopsis asparagi (Sacc.), which obviously reduced the applied pesticide and enhanced the utilization efficiency. Therefore, HTCC-decorated MSNs demonstrated great potential as nanocarriers in agrochemical applications.

Folate-decorated chitosan/doxorubicin poly(butyl)cyanoacrylate nanoparticles for tumor-targeted drug delivery

Energy Technology Data Exchange (ETDEWEB)

Duan Jinghua [Xiangya Hospital, Central South University, Hepatobiliary and Enteric Surgery Research Center (China); Liu Mujun [Central South University, School of Biological Science and Technology (China); Zhang Yangde; Zhao Jinfeng; Pan Yifeng [Xiangya Hospital, Central South University, Hepatobiliary and Enteric Surgery Research Center (China); Yang Xiyun, E-mail: bax_2007@126.com [Central South University, School of Metallurgical Science and Engineering (China)

2012-03-15

A novel chitosan coated poly(butyl cyanoacrylate) (PBCA) nanoparticles loaded doxorubicin (DOX) were synthesized and then conjugated with folic acid to produce a folate-targeted drug carrier for tumor-specific drug delivery. Prepared nanoparticles were surface modified by folate for targeting cancer cells, which is confirmed by FTIR spectroscopy and characterized for shape, size, and zeta potential measurements. The size and zeta potential of prepared DOX-PBCA nanoparticles (DOX-PBCA NPs) were almost 174 {+-} 8.23 nm and +23.14 {+-} 4.25 mV, respectively with 46.8 {+-} 3.32% encapsulation capacity. The transmission electron microscopy study revealed that preparation allowed the formation of spherical nanometric and homogeneous. Fluorescent microscopy imaging and flow cytometry analysis revealed that DOX-PBCA NPs were endocytosed into MCF-7 cells through the interaction with overexpressed folate receptors on the surface of the cancer cells. The results demonstrate that folate-conjugated DOX-PBCA NPs drug delivery system could provide increased therapeutic benefit by delivering the encapsulated drug to the folate receptor positive cancer cells.

Biofunctionalized nanoparticles with pH-responsive and cell penetrating blocks for gene delivery

International Nuclear Information System (INIS)

Gaspar, V M; Marques, J G; Sousa, F; Queiroz, J A; Correia, I J; Louro, R O

2013-01-01

Bridging the gap between nanoparticulate delivery systems and translational gene therapy is a long sought after requirement in nanomedicine-based applications. However, recent developments regarding nanoparticle functionalization have brought forward the ability to synthesize materials with biofunctional moieties that mimic the evolved features of viral particles. Herein we report the versatile conjugation of both cell penetrating arginine and pH-responsive histidine moieties into the chitosan polymeric backbone, to improve the physicochemical characteristics of the native material. Amino acid coupling was confirmed by 2D TOCSY NMR and Fourier transform infrared spectroscopy. The synthesized chitosan–histidine–arginine (CH–H–R) polymer complexed plasmid DNA biopharmaceuticals, and spontaneously assembled into stable 105 nm nanoparticles with spherical morphology and positive surface charge. The functionalized delivery systems were efficiently internalized into the intracellular compartment, and exhibited remarkably higher transfection efficiency than unmodified chitosan without causing any cytotoxic effect. Additional findings regarding intracellular trafficking events reveal their preferential escape from degradative lysosomal pathways and nuclear localization. Overall, this assembly of nanocarriers with bioinspired moieties provides the foundations for the design of efficient and customizable materials for cancer gene therapy. (paper)

Carboxymethyl chitosan based nanocomposites containing chemically bonded quantum dots and magnetic nanoparticles

Science.gov (United States)

Ding, Yongling; Yin, Hong; Chen, Rui; Bai, Ru; Chen, Chunying; Hao, Xiaojuan; Shen, Shirley; Sun, Kangning; Liu, Futian

2018-03-01

A biocompatible nanocomposite consisting of fluorescent quantum dots (QDs) and magnetic nanoparticles (MNPs) has been constructed via carboxymethyl chitosan (CMCS), resulting in magnetic-fluorescent nanoparticles (MFNPs). In these MFNPs, QDs and MNPs are successfully conjugated via covalent bonds onto the surface of CMCS. The composite retains favorable magnetic and fluorescent properties and shows a good colloidal stability in physiological environments. Folate (FA) as a specific targeting ligand was further incorporated into the nanocomposites to form a delivery vehicle with a targeting function. The therapeutic activity was achieved by loading chemotherapeutic drug doxorubicin (DOX) through electrostatic and hydrophobic interactions. The cumulative DOX release profile shows pH-sensitive. Both flow cytometry analysis and confocal laser scanning microscopic observation suggested that these nanocomposites were uptaken by cancer cells via FA receptor-mediated endocytosis pathway. In summary, the CMCS based nanocomposites developed in this work have a great potential for effective cancer-targeting and drug delivery, as well as in situ cellular imaging.

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.

An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles.

Science.gov (United States)

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2013-12-01

Peptide (insulin) loaded nanoparticles (NPs) have been embedded into buccal chitosan films (Ch-films-NPs). These films were produced by solvent casting and involved incorporating in chitosan gel (1.25% w/v), NPs-Insulin suspensions at three different concentrations (1, 3, and 5mg of NPs per film) using glycerol as plasticiser. Film swelling and mucoadhesion were investigated using 0.01M PBS at 37°C and texture analyzer, respectively. Formulations containing 3mg of NPs per film produced optimised films with excellent mucoadhesion and swelling properties. Dynamic laser scattering measurements showed that the erosion of the chitosan backbone controlled the release of NPs from the films, preceding in vitro drug (insulin) release from Ch-films-NPs after 6h. Modulated release was observed with 70% of encapsulated insulin released after 360h. The use of chitosan films yielded a 1.8-fold enhancement of ex vivo insulin permeation via EpiOral™ buccal tissue construct relative to the pure drug. Flux and apparent permeation coefficient of 0.1μg/cm(2)/h and 4×10(-2)cm(2)/h were respectively obtained for insulin released from Ch-films-NPs-3. Circular dichroism and FTIR spectroscopy demonstrated that the conformational structure of the model peptide drug (insulin) released from Ch-films-NPs was preserved during the formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.