Enzyme decorated drug carriers: Targeted swords to cleave and overcome the mucus barrier.

Science.gov (United States)

Menzel, Claudia; Bernkop-Schnürch, Andreas

2018-01-15

The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Cyclodextrins in drug carrier systems.

Science.gov (United States)

Uekama, K; Otagiri, M

1987-01-01

One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.

Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation.

Science.gov (United States)

Đorđević, Sanela M; Cekić, Nebojša D; Savić, Miroslav M; Isailović, Tanja M; Ranđelović, Danijela V; Marković, Bojan D; Savić, Saša R; Timić Stamenić, Tamara; Daniels, Rolf; Savić, Snežana D

2015-09-30

This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters--co-emulsifier type, aqueous phase type, homogenization temperature--on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution Solutol(®) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

International Nuclear Information System (INIS)

Li Yanan; An Feifei; Zhang Xiaohong; Yang Yinlong; Liu Zhuang; Zhang Xiujuan

2013-01-01

A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines. (paper)

Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

Science.gov (United States)

Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

2015-12-30

Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Subia, B; Kundu, S C

2013-01-01

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

Improvement of dissolution behavior of poorly water soluble drugs by biodegradable polymeric submicron carriers containing sparingly methylated β-cyclodextrin.

Science.gov (United States)

Singhavi, Dilesh J; Khan, Shagufta; Yeole, Pramod G

2013-04-01

The objective of this study was to develop submicron carriers of two drugs that are practically insoluble in water, i.e. meloxicam and aceclofenac, to improve their dissolution behavior. The phase solubility of the drugs was studied using different concentrations of sparingly methylated β-cyclodextrin, Kleptose(®) Crysmeβ (Crysmeb), in the presence and absence of 0.2 % w/v water-soluble chitosan. Drug-loaded submicron particles (SMPs) were prepared using chitosan chlorhydrate and Crysmeb by the ionotropic gelation method. The SMPs were characterized in terms of powder X-ray diffraction, Fourier transforms infrared spectroscopy, size determination, process yield, drug loading, encapsulation efficiency, surface morphology and in vitro release. The drug loading in the SMPs was enhanced in the presence of Crysmeb. The in vitro drug release was found to be enhanced with SMPs prepared using higher concentrations of Crysmeb. These results indicate that SMPs formed from chitosan chlorhydrate and Crysmeb are promising submicron carriers for enhancing the dissolution of meloxicam and aceclofenac.

Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite.

Science.gov (United States)

Hao, Xiaohong; Hu, Xixue; Zhang, Cuimiao; Chen, Shizhu; Li, Zhenhua; Yang, Xinjian; Liu, Huifang; Jia, Guang; Liu, Dandan; Ge, Kun; Liang, Xing-Jie; Zhang, Jinchao

2015-10-27

Potential bioaccumulation is one of the biggest limitations for silica nanodrug delivery systems in cancer therapy. In this study, a mesoporous silica nanoparticles/hydroxyapatite (MSNs/HAP) hybrid drug carrier, which enhanced the biodegradability of silica, was developed by a one-step method. The morphology and structure of the nanoparticles were characterized by TEM, DLS, FT-IR, XRD, N2 adsorption-desorption isotherms, and XPS, and the drug loading and release behaviors were tested. TEM and ICP-OES results indicate that the degradability of the nanoparticles has been significantly improved by Ca(2+) escape from the skeleton in an acid environment. The MSNs/HAP sample exhibits a higher drug loading content of about 5 times that of MSNs. The biological experiment results show that the MSNs/HAP not only exhibits good biocompatibility and antitumor effect but also greatly reduces the side effects of free DOX. The as-synthesized hybrid nanoparticles may act as a promising drug delivery system due to their good biocompatibility, high drug loading efficiency, pH sensitivity, and excellent biodegradability.

Versatile Chemical Derivatizations to Design Glycol Chitosan-Based Drug Carriers

Directory of Open Access Journals (Sweden)

Sung Eun Kim

2017-10-01

Full Text Available Glycol chitosan (GC and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules, and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy.

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)

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

Science.gov (United States)

Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

2013-04-01

We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

International Nuclear Information System (INIS)

Stoika, R; Boiko, N; Panchuk, R; Filyak, Y; Senkiv, Y; Finiuk, N; Shlyakhtina, Y; Bilyy, R; Kit, Y; Skorohyd, N; Klyuchivska, O; Zaichenko, A; Mitina, N; Ryabceva, A

2013-01-01

We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

Science.gov (United States)

Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

2017-12-01

Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

Drug targeting and the carriers. Application to chemoembolization and medical imaging

International Nuclear Information System (INIS)

Puisieux, F.; Benoit, J.P.; Roblot-Treupel, L.

1987-01-01

The last fifteen years have seen an increased interest in drug targeting which can be considered as a new way to control the body distribution of drugs when associated with an appropriate carrier. The systems currently studied possess different structures (macromolecular, vesicular and particular) and can be classified into carriers of first, second and third generation. After a brief review of the three types of carriers, this paper focuses on their respective interest in the different fields of radiology: carriers of first generation (microcapsules, microspheres) in chemoembolization, carriers of second generation (liposomes, nanocapsules, nanospheres) in conventional radiology, in computerized tomography, in scintigraphy, in RMN; carriers of third generation (monoclonal antibodies...) in immunoscintigraphy of tumors [fr

Design of colon targeting drug delivery systems using natural polymeric carriers and their evaluation by gamma scintigraphy technique

International Nuclear Information System (INIS)

Soni, P.S.; Sawarkar, S.P.; Deshpande, S.G.; Bajaj, A.N.

2004-01-01

Of late, there has been a great awareness in the concept of drug targeting and delivery to a specific site (organ, tissue or cell) in the body to maximize therapeutic effect and reduce toxicity. The various approaches of site-specific drug delivery are implantable pumps, adhesive patches impregnated with drugs, vesicle enclosed drugs and drug carriers. Colonic drug delivery is intended for local and systemic treatment in the diseases of colon like inflammatory bowel conditions. Several approaches using viz. pro-drugs, biodegradable polymers and pH sensitive polymer coatings have been used to achieve colonic delivery. Natural polysaccarides like guar gum and pectin are promising candidates because they are susceptible to degradation by colonic bacteria and thus can release the entrapped drug in the colonic region. These indigenous natural polymers are cheaply and readily available. They comprise of polygalactouronic acid and refractory to host enzymes present in the upper gastrointestinal tract and are degraded by the enzymes produced by the colonic microflora. They were evaluated as a colonic carrier using 5-amino salicylic acid (5-ASA) as a model drug. After successful in vitro testing, gamma scintigraphy technique was used to assess in-vivo behavior of the colon specific drug delivery after a coat of Guar gum and Pectin

From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers.

Science.gov (United States)

MacEwan, Sarah R; Chilkoti, Ashutosh

2017-06-06

The molecular complexity and heterogeneity of cancer has led to a persistent, and as yet unsolved, challenge to develop cures for this disease. The pharmaceutical industry focuses the bulk of its efforts on the development of new drugs, but an alternative approach is to improve the delivery of existing drugs with drug carriers that can manipulate when, where, and how a drug exerts its therapeutic effect. For the treatment of solid tumors, systemically delivered drug carriers face significant challenges that are imposed by the pathophysiological barriers that lie between their site of administration and their site of therapeutic action in the tumor. Furthermore, drug carriers face additional challenges in their translation from preclinical validation to clinical approval and adoption. Addressing this diverse network of challenges requires a systems engineering approach for the rational design of optimized carriers that have a realistic prospect for translation from the laboratory to the patient. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

Energy Technology Data Exchange (ETDEWEB)

Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: huabing.yin@glasgow.ac.uk [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: lijuan17@hotmail.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

2012-12-01

Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

Science.gov (United States)

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protein encapsulated magnetic carriers for micro/nanoscale drug delivery systems.

Energy Technology Data Exchange (ETDEWEB)

Xie, Y.; Kaminski, M. D.; Mertz, C. J.; Finck, M. R.; Guy, S. G.; Chen, H.; Rosengart, A. J.; Chemical Engineering; Univ. of Chicago, Pritzker School of Medicine

2005-01-01

Novel methods for drug delivery may be based on nanotechnology using non-invasive magnetic guidance of drug loaded magnetic carriers to the targeted site and thereafter released by external ultrasound energy. The key building block of this system is to successfully synthesize biodegradable, magnetic drug carriers. Magnetic carriers using poly(D,L-lactide-co-glycolide) (PLGA) or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) as matrix materials were loaded with bovine serum albumin (BSA) by a double-emulsion technique. BSA-loaded magnetic microspheres were characterized for size, morphology, surface charge, and magnetization. The BSA encapsulation efficiency was determined by recovering albumin from the microspheres using dimethyl sulfoxide and 0.05N NaOH/0.5% SDS then quantifying with the Micro-BCA protein assay. BSA release profiles were also determined by the Micro-BCA protein assay. The microspheres had drug encapsulation efficiencies up to 90% depending on synthesis parameters. Particles were spherical with a smooth or porous surface having a size range less than 5 {mu}m. The surface charge (expressed as zeta potential) was near neutral, optimal for prolonged intravascular survival. The magnetization of these BSA loaded magnetic carriers was 2 to 6 emu/g, depending on the specific magnetic materials used during synthesis.

Synthesis, characterization, and property of biodegradable PEG-PCL-PLA terpolymers with miktoarm star and triblock architectures as drug carriers.

Science.gov (United States)

Zhang, Yixin; Luo, Song; Liang, Yan; Zhang, Hai; Peng, Xinyu; He, Bin; Li, Sai

2018-03-01

A series of amphiphilic terpolymers with miktoarm star and triblock architectures of poly(ethylene glycol) (PEG), poly(ε-caprolactone) (PCL) and poly(l-lactide acid) (PLLA) or poly(DL-lactide acid) (PDLLA) terpolymers were synthesized as carriers for drug delivery. The architecture, molecular weight and crystallization behavior of the terpolymers were characterized. Anticancer drug doxorubicin was encapsulated in the micelles to investigate their drug loading properties. The miktoarm star terpolymers exhibited stronger crystallization capability, smaller size and better stability than that of triblock polymeric micelle, owing to the lower CMC values of miktoarm star polymeric micelle. Furthermore, the drug-loaded miktoarm star polymeric micelles showed the cumulative DOX release account of the micelles with PDLLA blocks was 65.3% while the release account of the corresponding micelles containing PLLA blocks was 45.2%. The IC 50 values of drug-loaded miktoarm star polymeric micelle were lower than triblock polymeric micelle. Meanwhile, Confocal laser scanning microscopy (CLSM) and Flow Cytometry results demonstrated that the miktoarm star micelles were more favorable for cellular internalization. The miktoarm star micelles with PDLLA blocks were promising carriers for anticancer drug delivery.

Biomacromolecules as carriers in drug delivery and tissue engineering.

Science.gov (United States)

Zhang, Yujie; Sun, Tao; Jiang, Chen

2018-01-01

Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

Directory of Open Access Journals (Sweden)

Ana Grenha

2012-09-01

Full Text Available Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.

Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific.

Science.gov (United States)

Gikanga, Benson; Adeniji, Nia S; Patapoff, Thomas W; Chih, Hung-Wei; Yi, Li

2016-04-20

Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the V(H), V(L), or C(H)2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in K(M) or k(cat) values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different

Solid lipid nanoparticles: A drug carrier system

Directory of Open Access Journals (Sweden)

Rashmi R Kokardekar

2011-01-01

Full Text Available Solid lipid nanoparticles (SLN are a type of nanoparticles. They are submicron colloidal carriers which are composed of physiological lipids, dispersed in water or in aqueous surfactant solutions. SLN have wide range of advantages over other types of nanoparticles. These include availability of large-scale production methods and no signs of cytotoxicity, which are main hindrances in the application of other types of nanoparticles. Hot and cold homogenization techniques are mainly employed for its production. They are mainly evaluated on the basis of their drug release profile and particle internal structure. The products based on SLN are under development. They have a very wide range of applications in cosmetics and pharmaceuticals. They can be applied for any purpose, for which nanoparticles have a distinct advantage. Thus, SLN can be used extensively as an alternative to the existing drug carrier systems, providing more flexibility with respect to the area of applications and also aspects for commercialization.

Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

Science.gov (United States)

Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

2014-01-01

During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

NARCIS (Netherlands)

Srinarong, Parinda; Kouwen, Sander; Visser, Marinella R; Hinrichs, Wouter L J; Frijlink, Henderik W

2010-01-01

The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides

[In vitro drug release behavior of carrier made of porous glass ceramics].

Science.gov (United States)

Wang, De-ping; Huang, Wen-hai; Zhou, Nai

2002-09-01

To conduct the in vitro test on drug release of rifampin encapsulated in a carrier made of porous phosphate glass ceramics and to analyze main factors which affect the drug release rate. A certain quantitative of rifampin was sealed in a hollow cylindrical capsule which consisted of chopped calcium phosphate crystal fiber obtained from glass crystallization. The rifampin concentration was measured in the simulated physiological solution in which the capsule soaked. Rifampin could be released in a constant rate from the porous glass ceramic carrier in a long time. The release rate was dependent on the size of crystal fiber and the wall thickness of the capsule. This kind of calcium phosphate glass ceramics can be a candidate of the carrier materials used as long term drug therapy after osteotomy surgery.

Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size.

Science.gov (United States)

Azad, Mohammad; Moreno, Jacqueline; Bilgili, Ecevit; Davé, Rajesh

2016-11-20

Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub-50μm lactose (GranuLac ® 200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50μm lactose (GranuLac ® 200) carrier particles or larger carrier particles of median size >300μm (PrismaLac ® 40). The resulting finer composite powders (sub-100μm) based on GranuLac ® 200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

Directory of Open Access Journals (Sweden)

Like Zeng

2011-01-01

Full Text Available Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.

NEOGLYCOPROTEINS AS CARRIERS FOR ANTIVIRAL DRUGS - SYNTHESIS AND ANALYSIS OF PROTEIN DRUG CONJUGATES

NARCIS (Netherlands)

Molema, Grietje; Jansen, Robert W.; Visser, Jan; Herdewijn, Piet; Moolenaar, Frits; Meijer, Dirk K.F.

In order to investigate whether neoglycoproteins can potentially act as carriers for targeting of antiviral drugs to certain cell types in the body, various neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl sugar derivatives. These neoglycoproteins were conjugated with the

Mucoadhesive microspheres: a promising tool in drug delivery.

Science.gov (United States)

Patil, Sanjay B; Sawant, Krutika K

2008-10-01

Mucoadhesive polymers have recently gained interest among pharmaceutical scientists as a means of improving drug delivery by promoting the residence time and contact time of the dosage form with the mucous membranes. Mucoadhesion is the process whereby synthetic and natural polymers adhere to mucosal surfaces in the body. If these materials are then incorporated into pharmaceutical formulations, drug absorption by mucosal cells may be enhanced or the drug will be released at the site for an extended period of time. Microspheres, in general, have the potential to be used for targeted and controlled release drug delivery; however, coupling of mucoadhesive properties to microspheres has additional advantages like, a much more intimate contact with the mucus layer, efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio. The present review describes the potential applications of mucoadhesive microspheres as a novel carrier system to improve drug delivery by various routes of administration like buccal, oral, nasal, ocular, vaginal and rectal, either for systemic or for local effects. The mucoadhesive polymers, methods of preparation of microspheres and their in vitro and in vivo evaluation are also described.

Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast.

Science.gov (United States)

Lanthaler, Karin; Bilsland, Elizabeth; Dobson, Paul D; Moss, Harry J; Pir, Pınar; Kell, Douglas B; Oliver, Stephen G

2011-10-24

The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.

Nanoparticle-based drug delivery systems: promising approaches against infections

International Nuclear Information System (INIS)

Ranghar, Shweta; Sirohi, Parul; Verma, Pritam; Agarwal, Vishnu

2014-01-01

Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

Nanoparticle-based drug delivery systems: promising approaches against infections

Energy Technology Data Exchange (ETDEWEB)

Ranghar, Shweta; Sirohi, Parul [Department of Applied Mechanics, Motilal Nehru National Institute of Technology, Allahabad (India); Verma, Pritam; Agarwal, Vishnu [Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad (India)

2014-03-15

Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

Antimicrobial drug susceptibility of Neisseria meningitidis strains isolated from carriers

Directory of Open Access Journals (Sweden)

Dayamí García

2000-06-01

Full Text Available When it is necessary to determine the susceptibility of Neisseria meningitidis (Nm strains to antimicrobial drugs, it is important to consider that it should be analyzed in a double context. One of them related to the use of drugs in a specific medical treatment; and the other; to chemoprophylatic drugs, both with the same purpose: the accurate selection of the “in vivo” antimicrobial agent. This requires the study of the sensitivity and resistance of strains isolated in both carriers and patients. With the aim of further studying the behavior of the strains that currently circulate in Cuba, an antimicrobial drug susceptibility study was conducted in 90 strains isolated from carriers during the first half of 1998. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs to: penicillin, ampicillin, rifampin, sulfadiazine, chloramphenicol, ciprofloxacin, ceftriaxone, cefotaxime. The study of the three latter drugs was done for the first time in our country. The search for β- lactamase-producer strains was also performed. There was a predominance of penicillin sensitive strains (82,2% with an intermediate sensitivity to ampicillin (57,8%, while 70% of the strains were sensitive to sulfadiazine. Regarding the rest of the antimicrobial drugs, 100% of the strains were sensitive. The paper shows the MICs for each drug as well as the phenotypic characteristics of the strains with the penicillin and sulfadiazine sensitivity and resistance patterns. No β-lactamase-producer strains were found.

An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

Directory of Open Access Journals (Sweden)

Juan P de Macêdo

2015-05-01

Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin.

Science.gov (United States)

Liu, Ying; Wang, Lan; Zhao, Yiqing; He, Man; Zhang, Xin; Niu, Mengmeng; Feng, Nianping

2014-12-10

Nanostructured lipid carriers and microemulsions effectively deliver poorly water-soluble drugs. However, few studies have investigated their ability and difference in improving drug bioavailability, especially the factors contributed to the difference. Thus, this study was aimed at investigating their efficiency in bioavailability enhancement based on studying two key processes that occur in NLC and ME during traverse along the intestinal tract: the solubilization process and the intestinal permeability process. The nanostructured lipid carriers and microemulsions had the same composition except that the former were prepared with solid lipids and the latter with liquid lipids; both were evaluated for particle size and zeta potential. Transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction were performed to characterize their properties. Furthermore, in vitro drug release, in situ intestinal absorption, and in vitro lipolysis were studied. The bioavailability of luteolin delivered using nanostructured lipid carriers in rats was compared with that delivered using microemulsions and suspensions. The in vitro analysis revealed different release mechanisms for luteolin in nanostructured lipid carriers and microemulsions, although the in situ intestinal absorption was similar. The in vitro lipolysis data indicated that digestion speed and extent were higher for microemulsions than for nanostructured lipid carriers, and that more of the former partitioned to the aqueous phase. The in vivo bioavailability analysis in rats indicated that the oral absorption and bioavailability of luteolin delivered using nanostructured lipid carriers and microemulsions were higher than those of luteolin suspensions. Nanostructured lipid carriers and microemulsions improved luteolin's oral bioavailability in rats. The rapid lipid digestion and much more drug solubilized available for absorption in microemulsions may contribute to better absorption and

Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery.

Science.gov (United States)

Patil, Sharvil; Mahadik, Abhijeet; Nalawade, Pradeep; More, Priyesh

2017-12-01

Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr's index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose ® (SV003, Goch, Germany)] used in DPI formulations. EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose ® (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose ® (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.

P-glycoprotein targeted nanoscale drug carriers

KAUST Repository

Li, Wengang

2013-02-01

Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug carrying processes that shuttle the drugs out of tumor cells. Thus, P -gp inhibitors have attracted a lot of attention as they can stop cancer drugs from being pumped out of target cells with the consumption of ATP. Using quantitive structure activity relationship (QSAR), we have successfully synthesized a series of novel P -gp inhibitors. The obtained dihydropyrroloquinoxalines series were fully characterized and then tested against bacterial and tumor assays with over-expressed P -gps. All compounds were bioactive especially compound 1c that had enhanced antibacterial activity. Furthermore, these compounds were utilized as targeting vectors to direct drug delivery vehicles such as silica nanoparticles (SNPs) to cancerous Hela cells with over expressed P -gps. Cell uptake studies showed a successful accumulation of these decorated SNPs in tumor cells compared to undecorated SNPs. The results obtained show that dihydropyrroloquinoxalines constitute a promising drug candidate for targeting cancers with MDR. Copyright © 2013 American Scientific Publishers All rights reserved.

Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

Science.gov (United States)

Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

2017-05-01

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay

DEFF Research Database (Denmark)

Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith

2016-01-01

Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit...... in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated...... the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, boththe kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl...

Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

Directory of Open Access Journals (Sweden)

Wei Xu

2013-01-01

Full Text Available Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1 protection of the loaded drug from the harsh environment of the GI tract, (2 release of the drug in a controlled manner at target sites, (3 prolongation of the residence time in the gut by mucoadhesion, and (4 inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

A review on proniosomal drug delivery system for targeted drug action.

Science.gov (United States)

Radha, G V; Rani, T Sudha; Sarvani, B

2013-03-01

Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of proniosomes in targeted drug action.

Synthesis and characterization of Zinc (II)-loaded Zeolite/Graphene oxide nanocomposite as a new drug carrier

Energy Technology Data Exchange (ETDEWEB)

Khatamian, M. [Inorganic Chemistry Department, Faculty of Chemistry, University of Tabriz, C.P. 51664 Tabriz (Iran, Islamic Republic of); Divband, B., E-mail: baharakdivband@yahoo.com [Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); Inorganic Chemistry Department, Faculty of Chemistry, University of Tabriz, C.P. 51664 Tabriz (Iran, Islamic Republic of); Farahmand-zahed, F. [Inorganic Chemistry Department, Faculty of Chemistry, University of Tabriz, C.P. 51664 Tabriz (Iran, Islamic Republic of)

2016-09-01

Current research has focused on the preparation of Zinc-clinoptilolite/Graphene Oxide (Zn-Clin/GO) hybrid nanostructure and investigating its biocompatibility for the first time. As prepared samples were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Thermo gravimetric analysis (TGA) and Fourier transform infrared (FT-IR). In order to use it as a drug carrier two important factors were investigated: cytocompatibility of nanocomposites and their drug loading capacity. The results showed that the prepared nanocomposite is cytocompatible and its high loading capacity and slow release performance for Doxorubicin (DOX), as a cancer drug, proved that it can be used as a drug carrier. At last in-vitro toxicity of DOX loaded nanocomposite was compared with pure DOX. - Graphical abstract: Biocompatible Zn-clinoptilolite/Graphene oxide hybrid nanostructure as in vitro drug delivery systems (DDS) was able to store and release substantial amounts of doxorubicin to the lung cancer cell lines. Display Omitted - Highlights: • Zn-Clin/GO nanocomposite as a new in vitro drug carrier with high loading capacity is synthesized. • Two synthesis methods (Microwave assisted hydrothermal method and Reflux method) are used. • All of the carriers (Zn-Clin, Zn-Clin/GO, GO) showed high biocompatibility.

Synthesis and characterization of Zinc (II)-loaded Zeolite/Graphene oxide nanocomposite as a new drug carrier

International Nuclear Information System (INIS)

Khatamian, M.; Divband, B.; Farahmand-zahed, F.

2016-01-01

Current research has focused on the preparation of Zinc-clinoptilolite/Graphene Oxide (Zn-Clin/GO) hybrid nanostructure and investigating its biocompatibility for the first time. As prepared samples were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Thermo gravimetric analysis (TGA) and Fourier transform infrared (FT-IR). In order to use it as a drug carrier two important factors were investigated: cytocompatibility of nanocomposites and their drug loading capacity. The results showed that the prepared nanocomposite is cytocompatible and its high loading capacity and slow release performance for Doxorubicin (DOX), as a cancer drug, proved that it can be used as a drug carrier. At last in-vitro toxicity of DOX loaded nanocomposite was compared with pure DOX. - Graphical abstract: Biocompatible Zn-clinoptilolite/Graphene oxide hybrid nanostructure as in vitro drug delivery systems (DDS) was able to store and release substantial amounts of doxorubicin to the lung cancer cell lines. Display Omitted - Highlights: • Zn-Clin/GO nanocomposite as a new in vitro drug carrier with high loading capacity is synthesized. • Two synthesis methods (Microwave assisted hydrothermal method and Reflux method) are used. • All of the carriers (Zn-Clin, Zn-Clin/GO, GO) showed high biocompatibility.

CHARACTERIZATION OF TERNARY SYSTEM OF POORLY SOLUBLE DRUG IN VARIOUS HYDROPHILIC CARRIERS

OpenAIRE

Vijay Kumar; Shankaraiah MM; Venkatesh JS; Rangaraju D; C.Nagesh

2011-01-01

The present study aims to experiment the solid dispersion of poorly water soluble drug fenbendazole as model drug. Fenbendazole is an Antihelmintic drug (BCS class 2).The purpose of this study was to enhance the dissolution of Fenbendazole by solid dispersions consisting of the drug, a polymeric carrier, Binary and ternary system were prepared by kneading method using hydrophilic polymers like polyvinylpyrrolidone K-25 (PVP K25), beta-cyclodextrin (BCD),mannitol and urea. The prepared form...

Elastic liposomes as novel carriers: recent advances in drug delivery

Science.gov (United States)

Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

2017-01-01

Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

(Glyco)-protein drug carriers with an intrinsic therapeutic activity : The concept of dual targeting

NARCIS (Netherlands)

Meijer, D.K F; Molema, Ingrid; Moolenaar, Frits; de Zeeuw, D; Swart, P.J

Dual targeting can in principle be achieved by using intrinsically active carriers that not only deliver the conjugated drug but also otherwise influence the pathological process. Potential carriers of this kind are monoclonal antibodies, certain interferons and interleukins, as well as certain

Microencapsulation: A promising technique for controlled drug delivery.

Science.gov (United States)

Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

2010-07-01

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

Structural and chemical aspects of HPMA copolymers as drug carriers.

Science.gov (United States)

Ulbrich, Karel; Subr, Vladimír

2010-02-17

Synthetic strategies and chemical and structural aspects of the synthesis of HPMA copolymer conjugates with various drugs and other biologically active molecules are described and discussed in this chapter. The discussion is held from the viewpoint of design and structure of the polymer backbone and biodegradable spacer between a polymer and drug, structure and methods of attachment of the employed drugs to the carrier and structure and methods of conjugation with targeting moieties. Physicochemical properties of the water-soluble polymer-drug conjugates and polymer micelles including mechanisms of drug release are also discussed. Detailed description of biological behavior of the polymer-drug conjugates as well as application of the copolymers for surface modification and targeting of gene delivery vectors are not included, they are presented and discussed in separate chapters of this issue. Copyright 2009 Elsevier B.V. All rights reserved.

Carrier-inside-carrier: polyelectrolyte microcapsules as reservoir for drug-loaded liposomes.

Science.gov (United States)

Maniti, Ofelia; Rebaud, Samuel; Sarkis, Joe; Jia, Yi; Zhao, Jie; Marcillat, Olivier; Granjon, Thierry; Blum, Loïc; Li, Junbai; Girard-Egrot, Agnès

2015-01-01

Conventional liposomes have a short life-time in blood, unless they are protected by a polymer envelope, most often polyethylene glycol. However, these stabilizing polymers frequently interfere with cellular uptake, impede liposome-membrane fusion and inhibit escape of liposome content from endosomes. To overcome such drawbacks, polymer-based systems as carriers for liposomes are currently developed. Conforming to this approach, we propose a new and convenient method for embedding small size liposomes, 30-100 nm, inside porous calcium carbonate microparticles. These microparticles served as templates for deposition of various polyelectrolytes to form a protective shell. The carbonate particles were then dissolved to yield hollow polyelectrolyte microcapsules. The main advantage of using this method for liposome encapsulation is that carbonate particles can serve as a sacrificial template for deposition of virtually any polyelectrolyte. By carefully choosing the shell composition, bioavailability of the liposomes and of the encapsulated drug can be modulated to respond to biological requirements and to improve drug delivery to the cytoplasm and avoid endosomal escape.

Polymeric Micelles as Novel Carriers for Poorly Soluble Drugs--A Review.

Science.gov (United States)

Reddy, B Pavan Kumar; Yadav, Hemant K S; Nagesha, Dattatri K; Raizaday, Abhay; Karim, Abdul

2015-06-01

Polymeric micelles are used as 'smart drug carriers' for targeting certain areas of the body by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. The main aim of using polymeric micelles is to deliver the poorly water soluble drugs. Now-a-days they are used especially in the areas of cancer therapy also. In this article we have reviewed several aspects of polymeric micelles concerning their mechanism of formation, chemical nature, preparation and characterization techniques, and their applications in the areas of drug delivery.

Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

Science.gov (United States)

Vadlamudi, Harini Chowdary; Raju, Y Prasanna; Asuntha, G; Nair, Rahul; Murthy, K V Ramana; Vulava, Jayasri

2014-01-01

There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs

Directory of Open Access Journals (Sweden)

Kyeong-Ok Choi

2016-05-01

Full Text Available The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

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Choi, Kyeong-Ok; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

2016-05-20

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Promising Practices in Drug Treatment: Findings from Southeast Asia

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Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda

2005-01-01

In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…

Walnut kernel-like mesoporous silica nanoparticles as effective drug carrier for cancer therapy in vitro

Energy Technology Data Exchange (ETDEWEB)

Ge, Kun; Ren, Huihui; Sun, Wentong [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China); Zhao, Qi [Hebei University, College of Clinical Science (China); Jia, Guang [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China); Zang, Aimin [Affiliated Hospital of Hebei University (China); Zhang, Cuimiao, E-mail: cmzhanghbu@163.com; Zhang, Jinchao, E-mail: jczhang6970@163.com [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China)

2016-03-15

In drug delivery systems, nanocarriers could reduce the degradation and renal clearance of drugs, increase the half-life in the bloodstream and payload of drugs, control the release patterns, and improve the solubility of some insoluble drugs. In particular, mesoporous silica nanoparticles (MSNs) are considered to be attractive nanocarriers for application of delivery systems because of their large surface areas, large pore volume, tunable pore sizes, good biocompatibility, and the ease of surface functionalization. However, the large-scale synthesis of monodisperse MSNs that are smaller than 200 nm remains a challenge. In this study, monodisperse walnut kernel-like MSNs with diameters of approximately 100 nm were synthesized by a sol–gel route on a large scale. The morphology and structure of MSNs were characterized by scanning electron microscope, and transmission electron microscopy, N{sub 2} adsorption–desorption isotherms, Zeta potentials, and dynamic light scattering. Drug loading and release profile, cellular uptake, subcellular localization, and anticancer effect in vitro were further investigated. The results indicated that the loading efficiency of doxorubicinhydrochloride (DOX) into the MSNs was 57 %. The MSNs–DOX delivery system exhibited a drug-pronounced initial burst release within 12 h, followed by the slow sustained release of DOX molecules; moreover, MSNs could improve DOX release efficiency in acidic medium. Most free DOX was localized in the cytoplasm, whereas the MSNs–DOX was primarily distributed in lysosome. MSNs–DOX exhibited a potential anticancer effect against MCF-7, HeLa, and A549 cells in dose- and time-dependent manners. In summary, the as-synthesized MSNs may have well function as a promising drug carrier in drug delivery fields.Graphical Abstract.

An overview on the delivery of antitumor drug doxorubicin by carrier proteins.

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Agudelo, D; Bérubé, G; Tajmir-Riahi, H A

2016-07-01

Serum proteins play an increasing role as drug carriers in the clinical settings. In this review, we have compared the binding modalities of anticancer drug doxorubicin (DOX) to three model carrier proteins, human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (β-LG) in order to determine the potential application of these model proteins in DOX delivery. Molecular modeling studies showed stronger binding of DOX with HSA than BSA and β-LG with the free binding energies of -10.75 (DOX-HSA), -9.31 (DOX-BSA) and -8.12kcal/mol (DOX-β-LG). Extensive H-boding network stabilizes DOX-protein conjugation and played a major role in drug-protein complex formation. DOX complexation induced major alterations of HSA and BSA conformations, while did not alter β-LG secondary structure. The literature review shows that these proteins can potentially be used for delivery of DOX in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

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Wang, Xue-Qing; Zhang, Qiang

2012-10-01

pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

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Lu, Wei; Zhang, Yan; Tan, Yu-Zhen; Hu, Kai-Li; Jiang, Xin-Guo; Fu, Shou-Kuan

2005-10-20

a promising brain drug delivery carrier with low toxicity.

Characterization of gelation process and drug release profile of thermosensitive liquid lecithin/poloxamer 407 based gels as carriers for percutaneous delivery of ibuprofen.

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Djekic, Ljiljana; Krajisnik, Danina; Martinovic, Martina; Djordjevic, Dragana; Primorac, Marija

2015-07-25

Suitability of liquid lecithin (i.e., solution of lecithin in soy bean oil with ∼ 60% w/w of phospholipids) for formation of gels, upon addition of water solution of poloxamer 407, was investigated, and formulated systems were evaluated as carriers for percutaneous delivery of ibuprofen. Formulation study of pseudo-ternary system liquid lecithin/poloxamer 407/water at constant liquid lecithin/poloxamer 407 mass ratio (2.0) revealed that minimum concentrations of liquid lecithin and poloxamer 407 required for formation of gel like systems were 15.75% w/w and 13.13% w/w, respectively, while the maximum content of water was 60.62% w/w. The systems comprising water concentrations in a range from 55 to 60.62% w/w were soft semisolids suitable for topical application, and they were selected for physicochemical and biopharmaceutical evaluation. Analysis of conductivity results and light microscopy examination revealed that investigated systems were water dilutable dispersions of spherical oligolamellar associates of phospholipids and triglyceride molecules in the copolymer water solution. Rheological behavior evaluation results indicated that the investigated gels were thermosensitive shear thinning systems. Ibuprofen (5% w/w) was incorporated by dispersing into the previously prepared carriers. Drug-loaded systems were physically stable at storage temperature from 5 ± 3°C to 40 ± 2°C, for 30 days. In vitro ibuprofen release was in accordance with the Higuchi model (rH>0.95) and sustained for 12h. The obtained results implicated that formulated LLPBGs, optimized regarding drug release and organoleptic properties, represent promising carriers for sustained percutaneous drug delivery of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Cyclodextrins as drug carriers in Pharmaceutical Technology: The state of the art.

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Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, Jose Manuel Sousa

2017-12-18

Cyclodextrins (CDs) are versatile excipients with an essential role in drug delivery, as they can form non-covalently bonded inclusion complexes (host-guest complexes) with several drugs either in solution or in the solid state. The main purpose of this publication was to carry out a state of the art of CDs as complexing agents in drug carrier systems. In this way, the history, properties and pharmaceutical applications of the CDs were highlighted with typical examples. The methods to enhance the complexation efficiency (CE) and the CDs applications in solid dosage forms were emphasized in more detail. The main advantages of using these cyclic oligosaccharides are as follows: (1) to enhance solubility/dissolution/ bioavailability of poorly soluble drugs; (2) to enhance drug stability; (3) to modify the drug release site and/or time profile; and (4) to reduce drug side effects (for example, gastric or ocular irritation). These compounds present favorable toxicological profile for human use and therefore there are various medicines containing CDs approved by regulatory authorities worldwide. On the other hand, the major drawback of CDs is the increase in formulation bulk, once the CE is, in general, very low. This aspect is particularly relevant in solid dosage forms and limits the use of CDs to potent drugs. CDs have great potential as drug carriers in Pharmaceutical Technology and can be used by the formulator in order to improve the drug properties such as solubility, bioavailability and stability. Additionally, recent studies have shown that these compounds can be applied as active pharmaceutical ingredients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Red blood cells and polyelectrolyte multilayer capsules: natural carriers versus polymer-based drug delivery vehicles.

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Kolesnikova, Tatiana A; Skirtach, Andre G; Möhwald, Helmuth

2013-01-01

Red blood cells (RBCs) and lipid-based carriers on the one hand and polymeric capsules on the other hand represent two of the most widely used carriers in drug delivery. Each class of these carriers has its own set of properties, specificity and advantages. Thorough comparative studies of such systems are reported here for the first time. In this review, RBCs are described in comparison with synthetic polymeric drug delivery vehicles using polyelectrolyte multilayer capsules as an example. Lipid-based composition of the shell in the former case is particularly attractive due to their inherent biocompatibility and flexibility of the carriers. On the other hand, synthetic approaches to fabrication of polyelectrolyte multilayer capsules permit manipulation of the permeability of their shell as well as tuning their composition, mechanical properties, release methods and targeting. In conclusion, properties of RBCs and polyelectrolyte multilayer capsules are reported here highlighting similarities and differences in their preparation and applications. In addition, their advantages and disadvantages are discussed.

INTERPOLYELECTROLYTE COMPLEXES AS PROSPECTIVE CARRIERS FOR CONTROLLED DRUG DELIVERY

OpenAIRE

Kaur Jasmeet; Harikumar S.L.; Kaur Amanpreet

2012-01-01

In the current scenario, polymers as carriers have revolutionized the drug delivery system. A more successful approach, to exploit the different properties of polymers in a solitary system is the complexation of polymers to form polyelectrolyte complexes. These complexes circumvent the use of chemical crosslinking agents, thereby reducing the risk of toxicity. The complex formed is generally applied in different dosage forms for the formulation of stable aggregated macromolecules. There are t...

Well-Defined Poly(Ortho Ester Amides) for Potential Drug Carriers: Probing the Effect of Extra- and Intracellular Drug Release on Chemotherapeutic Efficacy.

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Yan, Guoqing; Wang, Jun; Qin, Jiejie; Hu, Liefeng; Zhang, Panpan; Wang, Xin; Tang, Rupei

2017-07-01

To compare the chemotherapeutic efficacy determined by extra- and intracellular drug release strategies, poly(ortho ester amide)-based drug carriers (POEAd-C) with well-defined main-chain lengths, are successfully constructed by a facile method. POEAd-C3-doxorubicin (DOX) can be rapidly dissolved to release drug at tumoral extracellular pH (6.5-7.2), while POEAd-C6-DOX can rapidly release drug following gradual swelling at intracellular pH (5.0-6.0). In vitro cytotoxicity shows that POEAd-C3-DOX exhibits more toxic effect on tumor cells than POEAd-C6-DOX at extracellular pH, but POEAd-C6-DOX has stronger tumor penetration and inhibition in vitro and in vivo tumor models. So, POEAd-C6-DOX with the intracellular drug release strategy has stronger overall chemotherapeutic efficacy than POEAd-C3-DOX with extracellular drug release strategy. It is envisioned that these poly(ortho ester amides) can have great potential as drug carriers for efficient chemotherapy with further optimization. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

Science.gov (United States)

Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

2018-04-01

The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

Simulations of magnetic capturing of drug carriers in the brain vascular system

Energy Technology Data Exchange (ETDEWEB)

Kenjeres, S., E-mail: S.Kenjeres@tudelft.nl [Department of Multi-Scale Physics, Faculty of Applied Sciences, J.M. Burgerscentre for Fluid Dynamics, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft (Netherlands); Righolt, B.W. [Department of Multi-Scale Physics, Faculty of Applied Sciences, J.M. Burgerscentre for Fluid Dynamics, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft (Netherlands)

2012-06-15

Highlights: Black-Right-Pointing-Pointer Blood flow and magnetic particles distributions in the brain vascular system simulated. Black-Right-Pointing-Pointer Numerical mesh generated from raw MRI images. Black-Right-Pointing-Pointer Significant increase in local capturing of magnetic particles obtained. Black-Right-Pointing-Pointer Promising technique for localised non-invasive treatment of brain tumours. - Abstract: The present paper reports on numerical simulations of blood flow and magnetic drug carrier distributions in a complex brain vascular system. The blood is represented as a non-Newtonian fluid by the generalised power law. The Lagrangian tracking of the double-layer spherical particles is performed to estimate particle deposition under influence of imposed magnetic field gradients across arterial walls. Two situations are considered: neutral (magnetic field off) and active control (magnetic field on) case. The double-layer spherical particles that mimic a real medical drug are characterised by two characteristic diameters - the outer one and the inner one of the magnetic core. A numerical mesh of the brain vascular system consisting of multi-branching arteries is generated from raw MRI scan images of a patient. The blood is supplied through four main inlet arteries and the entire vascular system includes more than 30 outlets, which are modelled by Murray's law. The no-slip boundary condition is applied for velocity components along the smooth and rigid arterial walls. Numerical simulations revealed detailed insights into blood flow patterns, wall-shear-stress and local particle deposition efficiency along arterial walls. It is demonstrated that magnetically targeted drug delivery significantly increased the particle capturing efficiency in the pre-defined regions. This feature can be potentially useful for localised, non-invasive treatment of brain tumours.

Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO2, and their nanocomposites as appropriate drug carriers.

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Papadimitriou, Sofia; Bikiaris, Dimitrios

2009-09-01

Creation of immediate release formulations for the poorly water-soluble drug Tibolone through the use of solid dispersions (SDs). SD systems of Tibolone (Tibo) with poly(vinylpyrrolidone) (PVP), fumed SiO(2) nanoparticles, and their corresponding ternary systems (PVP/SiO(2)/Tibo) were prepared and studied in order to produce formulations with enhanced drug dissolution rates. The prepared SDs were characterized by the use of differential scanning calorimetry and wide-angle X-ray diffractometry techniques. Also dissolution experiments were performed. From the results it was concluded that PVP as well as SiO(2) can be used as appropriate carriers for the amorphization of Tibo, even when the drug is used at high concentrations (20-30%, w/w). This is due to the evolved interactions taking place between the drug and the used carriers, as was verified by Fourier transform infrared spectroscopy. At higher concentrations the drug was recrystallized. Similar are the observations on the ternary PVP/SiO(2)/Tibo SDs. The dissolution profiles of the drug in PVP/Tibo and SiO(2)/Tibo SDs are directly dependent on the physical state of the drug. Immediately release rates are observed in SD with low drug concentrations, in which Tibo was in amorphous state. However, these release profiles are drastically changed in the ternary PVP/SiO(2)/Tibo SDs. An immediate release profile is observed for low drug concentrations and an almost sustained release as the concentration of Tibo increases. This is due to the weak interactions that take place between PVP and SiO(2), which result in alterations of the characteristics of the carrier (PVP/SiO(2) nanocomposites). Immediate release formulation was created for Tibolone as well as new nanocomposite matrices of PVP/SiO((2)), which drastically change the release profile of the drug to a sustained delivery.

POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

Directory of Open Access Journals (Sweden)

M. V. Grigoreva

2013-10-01

Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

AlPcS4-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic® F127 nanomicellar drug carriers.

Science.gov (United States)

Xin, Jing; Wang, Sijia; Wang, Bing; Wang, Jiazhuang; Wang, Jing; Zhang, Luwei; Xin, Bo; Shen, Lijian; Zhang, Zhenxi; Yao, Cuiping

2018-01-01

As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS 4 ) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS 4 /PDT effect, the AlPcS 4 delivery sys tems with different drug carriers were synthesized and investigated. Gold nanorods, cationic liposomes, and Pluronic ® F127 nanomicellars were used to formulate the AlPcS 4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS 4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca 2+ ] i ) concentration were further measured to evaluate the mechanism of cell death. The series of synthesized AlPcS 4 delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS 4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS 4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS 4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS 4 delivery efficiency and ability to block serum albumin. In addition, AlPcS 4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127-AlPcS 4 is used for prolonged gastric cancer therapy. The described AlPcS 4 drug delivery systems provide promising agents for gastric cancer therapy.

Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

Directory of Open Access Journals (Sweden)

Qing-Xi Wu

2014-12-01

Full Text Available Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail.

Design of chitosan and its water soluble derivatives-based drug carriers with polyelectrolyte complexes.

Science.gov (United States)

Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

2014-12-19

Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail.

Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

Science.gov (United States)

Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

2014-01-01

Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

Directory of Open Access Journals (Sweden)

Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

2016-12-01

Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

Science.gov (United States)

Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

2013-01-01

Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

Science.gov (United States)

Sun, Dajun D; Lee, Ping I

2015-08-10

The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the

Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems.

Science.gov (United States)

Malekzad, Hedieh; Mirshekari, Hamed; Sahandi Zangabad, Parham; Moosavi Basri, S M; Baniasadi, Fazel; Sharifi Aghdam, Maryam; Karimi, Mahdi; Hamblin, Michael R

2018-02-01

For thousands of years, plants and their products have been used as the mainstay of medicinal therapy. In recent years, besides attempts to isolate the active ingredients of medicinal plants, other new applications of plant products, such as their use to prepare drug delivery vehicles, have been discovered. Nanobiotechnology is a branch of pharmacology that can provide new approaches for drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In this article, we review recent studies with four important plant proteins that have been used as carriers for targeted delivery of drugs and genes. Zein is a water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble protein from wheat and corn; legumin is a casein-like protein from leguminous seeds such as peas; lectins are glycoproteins naturally occurring in many plants that recognize specific carbohydrate residues. NPs formed from these proteins show good biocompatibility, possess the ability to enhance solubility, and provide sustained release of drugs and reduce their toxicity and side effects. The effects of preparation methods on the size and loading capacity of these NPs are also described in this review.

Recent advances in liposomal nanohybrid cerasomes as promising drug nanocarriers.

Science.gov (United States)

Yue, Xiuli; Dai, Zhifei

2014-05-01

Liposomes have been extensively investigated as possible carriers for diagnostic or therapeutic agents due to their unique properties. However, liposomes still have not attained their full potential as drug and gene delivery vehicles because of their insufficient morphological stability. Recently, a super-stable and freestanding hybrid liposomal cerasome (partially ceramic- or silica-coated liposome) has drawn much attention as a novel drug delivery system because its atomic layer of polyorganosiloxane surface imparts higher morphological stability than conventional liposomes and its liposomal bilayer structure reduces the overall rigidity and density greatly compared to silica nanoparticles. Cerasomes are more biocompatible than silica nanoparticles due to the incorporation of the liposomal architecture into cerasomes. Cerasomes combine the advantages of both liposomes and silica nanoparticles but overcome their disadvantages so cerasomes are ideal drug delivery systems. The present review will first highlights some of the key advances of the past decade in the technology of cerasome production and then review current biomedical applications of cerasomes, with a view to stimulating further research in this area of study. Copyright © 2013 Elsevier B.V. All rights reserved.

Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

Science.gov (United States)

Labib, Gihan

2018-01-01

Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

Science.gov (United States)

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

IMPROVEMENT OF SOLUBILITY OF BADLY WATER SOLUBLE DRUG (IBUPROFEN) BY USING SURFACTANTS AND CARRIERS

OpenAIRE

Md. Zakaria Faruki*, Rishikesh, Elizabeth Razzaque, Mohiuddin Ahmed Bhuiyan

2013-01-01

ABSTRACT: Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of badly water-soluble drugs, their profitable use has been very limited, primarily because of manufacturing difficulties and stability problems. In this study solid solutions of drugs were generally produced by fusion method. The drug along with the excipients (surfactants and carriers) was heated first and then hardened by cooling to room te...

Comparison of different zeolite framework types as carriers for the oral delivery of the poorly soluble drug indomethacin.

Science.gov (United States)

Karavasili, Christina; Amanatiadou, Elsa P; Kontogiannidou, Eleni; Eleftheriadis, Georgios K; Bouropoulos, Nikolaos; Pavlidou, Eleni; Kontopoulou, Ioanna; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

2017-08-07

Microporous zeolites of distinct framework types, textural properties and crystal morphologies namely BEA, ZSM and NaX, have been employed as carriers to assess their effect on modulating the dissolution behavior of a BCS II model drug (indomethacin). Preparation of the loaded carriers via the incipient wetness method induced significant drug amorphization for the BEA and NaX samples, as well as high drug payloads. The stability of the amorphous drug content was retained after stressing test evaluation of the porous carriers. The dissolution profile of loaded indomethacin was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluids FaSSIF (fasted) and FeSSIF (fed state) conditions and was found to be dependent on the aluminosilicate ratio of the zeolites and the degree of crystalline drug content. The feasibility of the zeolitic particles as oral drug delivery systems was appraised with cytocompatibility and cellular toxicity studies in Caco-2 cultures in a time- and dose-dependent manner by means of the MTT assay and flow cytometry analysis, respectively. Intracellular accumulation of the zeolite particles was observed with no apparent cytotoxic effects at the lower concentrations tested, rendering such microporous zeolites pertinent candidates in oral drug delivery applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Advertising and drugs: a world of images and promises

Directory of Open Access Journals (Sweden)

Jurema Barros Dantas

2010-11-01

Full Text Available The aim of this article is to discuss the relation between the contemporary use and advertising of pharmaceutical drugs based on the so-called culture of consumption. We discuss advertising as a means of strengthening the belief in the power of these drugs, presenting them as a synthesis of science and technology to promote health and well being and, particularly, as a quick solution for typical problems of the contemporary world. The obligation to buy the latest medicines is becoming a symbol of social affirmation as well as the only way to weaken our daily problems. Using a logic of consumption as ownership, we create, with the help of advertising, a world of promises concerning immediate solutions, easily sold through on line shopping, supermarkets, department stores and shopping centers. We discuss this set of contemporary practices and values which are turning our way of life into a disposable product.   Keywords: advertising; consumption; pharmaceutical drugs.

Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

Directory of Open Access Journals (Sweden)

Murilo L Bello

Full Text Available Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation. We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.

Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

OpenAIRE

Maree, M. David; Neuse, Eberhard W.; Erasmus, Elizabeth; Swarts, Jannie C.

2007-01-01

The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymer...

[Pharmaceutical application of cyclodextrins as multi-functional drug carriers].

Science.gov (United States)

Uekama, Kaneto

2004-12-01

Owing to the increasingly globalized nature of the cyclodextrin (CyD)-related science and technology, development of the CyD-based pharmaceutical formulation is rapidly progressing. The pharmaceutically useful CyDs are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in drug delivery and pharmaceutical formulation, focusing on the following evidences. 1) The hydrophilic CyDs enhance the rate and extent of bioavailability of poorly water-soluble drugs. 2) The amorphous CyDs such as 2-hydroxypropyl-beta-CyD are useful for inhibition of polymorphic transition and crystallization rates of drugs during storage. 3) The delayed release formulation can be obtained by the use of enteric type CyDs such as O-carboxymethyl-O-ethyl-beta-CyD. 4) The hydrophobic CyDs are useful for modification of the release site and/or time profile of water-soluble drugs with prolonged therapeutic effects. 5) The branched CyDs are particularly effective in inhibiting the adsorption to hydrophobic surface of containers and aggregation of polypeptide and protein drugs. 6) The combined use of different CyDs and/or pharmaceutical additives can serve as more functional drug carriers, improving efficacy and reducing side effects. 7) The CyD/drug conjugates may provide a versatile means for the constructions of not only colonic delivery system but also site-specific drug release system, including gene delivery. On the basis of the above-mentioned knowledge, the advantages and limitations of CyDs in the design of advanced dosage forms will be discussed.

Elastic liposomes as novel carriers: recent advances in drug delivery

Directory of Open Access Journals (Sweden)

Hussain A

2017-07-01

Full Text Available Afzal Hussain,1,2 Sima Singh,1 Dinesh Sharma,3 Thomas J Webster,4 Kausar Shafaat,2 Abdul Faruk5 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 2Faculty of Pharmacy, Sachchidananda Sinha College, Aurangabad, Bihar, India; 3Zifam Pyrex Myanmar Co. Ltd., Yangon, Myanmar; 4Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 5Department of Pharmaceutical Sciences, Hemwati Nandan Bahuguna Garhwal University, Srinagar, Uttarakhand, India Abstract: Elastic liposomes (EL are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. Keywords: elastic liposomes, drug delivery, topical, transdermal, enhanced delivery 

Scintigraphic evaluation of the pharmacokinetics of a soluble polymeric drug carrier

International Nuclear Information System (INIS)

Pimm, M.V.; Perkins, A.C.; Hudecz, F.

1992-01-01

There is a growing interest in the use of macromolecular carriers for therapeutic agents. If these carriers can be labelled with an appropriate gamma-emitter, their biodistribution could be followed by scintigraphy. We have imaged the biodistribution of a synthetic branched polypeptide, based on a poly-L-lysine backbone (average molecular mass 45 kDa). The polymer was conjugated to diethylene triamine penta-acetic acid and labelled by chelation with indium-111. Mice were injected i.v. with labelled material and imaged with a gamma-camera with a pin-hole collimator. Images showed the majority of tracer remaining in the blood pool, but about 35% appeared in the urinary bladder within 1.5 h. When the 111 In-polymer was fractionated by gel filtration chromatography on S-300, the imaging showed that the early eluting material was retained, the intermediate showed some renal clearance, and the late was rapidly excreted. These findings show the value of gamma-scintigraphy for biodistribution studies with such polymeric drug carriers and its potential for clinical pharmacokinetic studies. (orig.)

Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay.

Science.gov (United States)

Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Bauer-Brandl, Annette; Brandl, Martin

2016-06-28

Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated with liposome bilayers even upon extensive dilution. Upon i.v. injection, in contrast, rapid drug loss often occurs due to drug transfer from the liposomal carriers to endogenous lipophilic sinks such as lipoproteins, plasma proteins or membranes of red blood cells and endothelial cells. Here we report on the application of a recently introduced in vitro predictive drug transfer assay based on incubation of the liposomal drug carrier with large multilamellar liposomes, the latter serving as a biomimetic model sink, using flow field-flow fractionation as a tool to separate the two types of liposomes. By quantifying the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, both the kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one liposome to another was found rate determining as compared to redistribution from the outermost to the inner concentric bilayers, such that the overall

In vivo imaging of passively tumor targeted polymer carrier and the enzymatically cleavable drug model

Czech Academy of Sciences Publication Activity Database

Pola, Robert; Heinrich, A. K.; Mueller, T.; Kostka, Libor; Mäder, K.; Pechar, Michal; Etrych, Tomáš

2017-01-01

Roč. 6, 4 (Suppl) (2017), s. 90 ISSN 2325-9604. [International Conference and Exhibition on Nanomedicine and Drug Delivery. 29.05.2017-31.05.2017, Osaka] R&D Projects: GA MZd(CZ) NV16-28594A Institutional support: RVO:61389013 Keywords : polymer drug carrier * tumor targeting * enzymatic release Subject RIV: FD - Oncology ; Hematology

Applications of nanodiamonds in drug delivery and catalysis

KAUST Repository

Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khachatur; Ezzeddine, Alaa; Khashab, Niveen M.

2014-01-01

The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles

Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions.

Science.gov (United States)

Swain, Suryakanta; Beg, Sarwar; Babu, Sitty M

2016-01-01

Researchers are facing challenges to develop robust formulation and to enhance the bioavailability of poorly water-soluble drugs towards clinical applications. The development of new drug molecule alone is not adequate to assure ample pharmacotherapy of various diseases. Considerable results obtained from in vitro studies are not supported by in vivo data due to inadequate plasma drug concentrations. This may occur due to limited drug solubility and absorption. To resolve these problems, development of new drug delivery systems will be a promising approach. One of the promising pharmaceutical strategies is the use of lipospheres drug delivery system to deliver the poorly water-soluble drugs. Therefore, the present review described the methodology for manufacturing of lipospheres and factors influencing the formulation to deliver the drugs to the targeted site. Apart from that, this review also enlisted briefly the various applications of liposphers in medical and biomedical fields and critically discussed the recent patent system.

Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Huang, Ya-Shu [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Lu, Yu-Jen [Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Graduate Institute of Health Industry and Technology, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan, ROC (China)

2017-04-01

A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of

Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

International Nuclear Information System (INIS)

Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

2017-01-01

A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe 3 O 4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe 3 O 4 MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of m

Progress and promise for the MDMA drug development program.

Science.gov (United States)

Feduccia, Allison A; Holland, Julie; Mithoefer, Michael C

2018-02-01

Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug "Ecstasy." MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.

A targeted drug delivery system based on dopamine functionalized nano graphene oxide

Science.gov (United States)

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

2017-01-01

The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

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.

Polymeric micelles as a drug carrier for tumor targeting

Directory of Open Access Journals (Sweden)

Neha M Dand

2013-01-01

Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

Directory of Open Access Journals (Sweden)

Junmin Lai

2017-02-01

Full Text Available The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU was used as a model drug, and two non-ordered mesoporous materials of commercial silica Syloid® 244FP (S244FP and Neusilin® US2 (NS2 were selected in the study. The IBU-loaded mesoporous samples were prepared by a solvent immersion method with a rotary evaporation drying technique and characterized by polarized light microscopy (PLM, Fourier transform infrared (FTIR spectroscopy, X-ray powder diffraction (XRPD and differential scanning calorimetry (DSC. Dissolution experiments were performed in simulated gastric media at 37 °C under non-sink conditions. The concentration of IBU in solution was determined by HPLC. The study showed that the dissolution rate of IBU can be improved significantly using the mesoporous S224FP carriers due to the conversion of crystalline IBU into the amorphous form. Both of the loading factors affected the IBU dissolution kinetics. Due to the molecular interaction between the IBU and NS2 carriers, the loading factors had little effects on the drug release kinetics with incomplete drug desorption recovery and insignificant dissolution enhancement. Care and extensive evaluation must therefore be taken when mesoporous materials are chosen as carrier delivery systems.

Interaction of tricyclic drugs with copper phthalocyanine dye immobilized on magnetic carriers

Czech Academy of Sciences Publication Activity Database

Šafaříková, Miroslava; Šafařík, Ivo

3(Suppl.2), - (2002), s. 188-191 ISSN 1473-2262. [International Conference on the Scientific and Clinical Applications of Magnetic Carriers /4./. Tallahassee, 09.05.2002-11.05.2002] R&D Projects: GA MŠk OC 523.80; GA AV ČR IBS6087204 Institutional research plan: CEZ:AV0Z6087904 Keywords : magnetic * tricyclic drugs * phthalocyanine Subject RIV: CE - Biochemistry

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

Science.gov (United States)

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-06-01

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

Science.gov (United States)

Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

2016-05-01

The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

Cyclodextrin-based nanosponges as drug carriers

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Francesco Trotta

2012-11-01

Full Text Available Cyclodextrin-based nanosponges, which are proposed as a new nanosized delivery system, are innovative cross-linked cyclodextrin polymers nanostructured within a three-dimensional network. This type of cyclodextrin polymer can form porous insoluble nanoparticles with a crystalline or amorphous structure and spherical shape or swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and biodegradable material with negligible toxicity on cell cultures and are well-tolerated after injection in mice. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The release of the entrapped molecules can be varied by modifying the structure to achieve prolonged release kinetics or a faster release. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances, obtain sustained delivery systems or design innovative drug carriers for nanomedicine.

Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane.

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Yu, Zhan; Yu, Min; Zhou, Zhimin; Zhang, Zhibao; Du, Bo; Xiong, Qingqing

2014-01-01

Controlled-release carriers for local drug delivery have attracted increasing attention for inner-ear treatment recently. In this paper, flower-shaped bovine serum albumin (FBSA) particles were prepared by a modified desolvation method followed by glutaraldehyde or heat denaturation. The size of the FBSA particles varied from 10 μm to 100 μm, and most were 50-80 μm. Heat-denatured FBSA particles have good cytocompatibility with a prolonged survival time for L929 cells. The FBSA particles were utilized as carriers to investigate the release behaviors of the model drug - rhodamine B. Rhodamine B showed a sustained-release effect and penetrated the round-window membrane of guinea pigs. We also confirmed the attachment of FBSA particles onto the round-window membrane by microscopy. The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive capability, and biodegradability, may have potential applications in the field of local drug delivery for inner-ear disease treatment.

A close collaboration of chitosan with lipid colloidal carriers for drug delivery applications.

Science.gov (United States)

Bugnicourt, Loïc; Ladavière, Catherine

2017-06-28

Chitosan and lipid colloids have separately shown a growing interest in the field of drug delivery applications. Their success is mainly due to their interesting physicochemical behaviors, as well as their biological properties such as bioactivity and biocompatibility. While chitosan is a well-known cationic polysaccharide with the ability to strongly interact with drugs and biological matrices through mainly electrostatic interactions, lipid colloids are carriers particularly recognized for the drug vectorization. In recent years, the combination of both entities has been considered because it offers new systems which gather the advantages of each of them to efficiently deliver various types of bioactive species. The purpose of this review is to describe these associations between chemically-unmodified chitosan chains (solubilized or dispersed) and lipid colloids (as nanoparticles or organized in lipid layers), as well as their potential in the drug delivery area so far. Three assemblies have mainly been reported in the literature: i) lipid nanoparticles (solid lipid nanoparticles or nanostructured lipid carriers) coated with chitosan chains, ii) lipid vesicles covered with chitosan chains, and iii) chitosan chains structured in nanoparticles with a lipid coating. Their elaboration processes, their physicochemical characterization, and their biological studies are detailed and discussed herein. The different bioactive species (drugs and bio(macro)molecules) incorporated in these assemblies, their maximal incorporation efficiency, and their loading capacity are also presented. This review reveals the versatility of these assemblies. Depending on the organization of lipids (i.e., nanoparticles or vesicles) and the state of polymer chains (i.e., solubilized or dispersed under the form of nanoparticles), a large variety of drugs can be successfully incorporated, and various routes of administration can be considered. Copyright © 2017 Elsevier B.V. All rights reserved.

Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

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Praveen Kumar Gaur

2013-01-01

Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

Promising applications in drug delivery systems of a novel β-cyclodextrin derivative obtained by green synthesis.

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García, Agustina; Leonardi, Darío; Lamas, María C

2016-01-15

An efficient and green method has been developed for the synthesis of succinyl-β-cyclodextrin in aqueous media obtaining very good yield. Acidic groups have been introduced in the synthesized carrier molecule to improve the guest-host affinity. To evaluate the suitability of the novel excipient focused to develop oral dosage forms, albendazole, a BSC class II compound, was chosen as a model drug. The β-cyclodextrin derivative and the inclusion complex were thoroughly characterized in solution and solid state by phase solubility studies, FT-IR spectroscopy, SEM, XRD, ESI-MS, DSC, 1D (1)H NMR, 1D (13)C NMR, selective 1D TOCSY, 2D COSY, 2D HSQC, 2D HMBC and ROESY NMR spectroscopy. Phase solubility studies indicated that both of them β-cyclodextrin and succinyl-β-cyclodextrin formed 1:1 inclusion complexes with albendazole, and the stability constants were 68M(-1) (β-cyclodextrin), 437M(-1) (succinyl-β-cyclodextrin), respectively. Water solubility and dissolution rate of albendazole were significantly improved in complex forms. Thus, the succinyl-β-cyclodextrin derivative could be a promising excipient to design oral dosage forms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

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Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Budko, Andrei P. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kovarskii, Alexander L. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Zontov, Sergei V. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kogan, Boris Ya. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)], E-mail: kuznetsov_oa@yahoo.com

2009-05-15

Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

International Nuclear Information System (INIS)

Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A.; Budko, Andrei P.; Kovarskii, Alexander L.; Zontov, Sergei V.; Kogan, Boris Ya.; Kuznetsov, Oleg A.

2009-01-01

Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

Science.gov (United States)

Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

2006-08-10

Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to

Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

Energy Technology Data Exchange (ETDEWEB)

Hsu, Shu-Hui [Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China); Wen, Chih-Jen; Yen, Tzu-Chen [Animal Molecular Imaging Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan (China); Al-Suwayeh, S A; Fang, Jia-You [Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Chang, Hui-Wen, E-mail: fajy@mail.cgu.edu.tw [Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

2010-10-08

Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

International Nuclear Information System (INIS)

Hsu, Shu-Hui; Wen, Chih-Jen; Yen, Tzu-Chen; Al-Suwayeh, S A; Fang, Jia-You; Chang, Hui-Wen

2010-01-01

Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

Carrier-Based Drug Delivery System for Treatment of Acne

Science.gov (United States)

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

Thiomers and thiomer-based nanoparticles in protein and DNA drug delivery.

Science.gov (United States)

Hauptstein, Sabine; Bernkop-Schnürch, Andreas

2012-09-01

Thanks to advances in biotechnology, more and more highly efficient protein- and DNA-based drugs have been developed. Unfortunately, these kinds of drugs underlie poor non-parental bioavailability. To overcome hindrances like low mucosal permeability and enzymatic degradation polymeric excipients are utilized as drug carrier whereat thiolated excipients showed several promising qualities in comparison to the analogical unmodified polymer. The article deals with the comparatively easy modification of well-established polymers like chitosan or poly(acrylates) to synthesize thiomers. Further, the recently developed "next generation" thiomers e.g. preactivated or S-protected thiomers are introduced. Designative properties like mucoadhesion, uptake and permeation enhancement, efflux pump inhibition and protection against enzymatic degradation will be discussed and differences between first and next generation thiomers will be pointed out. Additionally, nanoparticles prepared with thiomers will be dealt with regarding to protein and DNA drug delivery as thiomers seem to be a promising approach to avoid parenteral application. Properties of thiomers per se and results of in vivo studies carried out so far for peptide and DNA drugs demonstrate their potential as multifunctional excipients. However, further investigations and optimizations have to be done before establishing a carrier system ready for clinical approval.

Hydroxyapatite nanorod-assembled porous hollow polyhedra as drug/protein carriers.

Science.gov (United States)

Yu, Ya-Dong; Zhu, Ying-Jie; Qi, Chao; Jiang, Ying-Ying; Li, Heng; Wu, Jin

2017-06-15

Hydroxyapatite (HAP) with a porous hollow structure is an ideal biomaterial owing to its excellent biocompatibility and unique architecture. In this study, HAP nanorod-assembled porous hollow polyhedra, consisting of nanorod building blocks, have been successfully prepared at room temperature or under hydrothermal circumstances using a self-sacrificing Ca(OH) 2 template strategy. The hydrothermal treatment (at 180°C for 1h) can promote the HAP nanorods to be arranged with their axial direction normal to the polyhedron surface. The HAP nanorod-assembled porous hollow polyhedra have been explored for the potential application in drug/protein delivery, using ibuprofen (IBU) as a model drug and hemoglobin (Hb) as a model protein. The experimental results indicate that the HAP nanorod-assembled porous hollow polyhedra have a relatively high drug loading capacity and protein adsorption ability, and sustained drug and protein release. The HAP nanorod-assembled porous hollow polyhedra have promising applications in various biomedical fields such as the drug and protein delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

Science.gov (United States)

Deshmane, Subhash; Deshmane, Snehal; Shelke, Santosh; Biyani, Kailash

2018-06-01

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD 50 ). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery

International Nuclear Information System (INIS)

Kayal, S.; Ramanujan, R.V.

2010-01-01

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

Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications

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Miguel Gama

2010-02-01

Full Text Available Hydrogel nanoparticles—also referred to as polymeric nanogels or macromolecular micelles—are emerging as promising drug carriers for therapeutic applications. These nanostructures hold versatility and properties suitable for the delivery of bioactive molecules, namely of biopharmaceuticals. This article reviews the latest developments in the use of self-assembled polymeric nanogels for drug delivery applications, including small molecular weight drugs, proteins, peptides, oligosaccharides, vaccines and nucleic acids. The materials and techniques used in the development of self-assembling nanogels are also described.

Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

Science.gov (United States)

Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

2014-09-01

Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Bioactive albumin-based carriers for tumour chemotherapy.

Science.gov (United States)

Shahzad, Yasser; Khan, Ikram Ullah; Hussain, Talib; Alamgeer; Serra, Christophe A; Rizvi, Syed A A; Gerber, Minja; du Plessis, Jeanetta

2014-01-01

Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.

The promises and pitfalls of retrieval-extinction procedures in preventing relapse to drug seeking

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Gavan P McNally

2013-03-01

Full Text Available Relapse to drug seeking after treatment or a period of abstinence remains a fundamental challenge for drug users. The retrieval – extinction procedure offers promise in augmenting the efficacy of exposure based treatment for drug use and for protecting against relapse to drug seeking. Preceding extinction training with a brief retrieval or reminder trial, retrieval – extinction training, has been shown to reduce reinstatement of extinguished drug seeking in animal models and also to produce profound and long lasting decrements in cue-induced craving in human heroin users. However, the mechanisms that mediate these effects of retrieval - extinction training are unclear. Moreover, under some circumstances, the retrieval – extinction procedure can significantly increase vulnerability to reinstatement in animal models.

A water-soluble pillar[5]arene as a new carrier for an old drug.

Science.gov (United States)

Barbera, Lucia; Franco, Domenico; De Plano, Laura M; Gattuso, Giuseppe; Guglielmino, Salvatore P P; Lentini, Germana; Manganaro, Nadia; Marino, Nino; Pappalardo, Sebastiano; Parisi, Melchiorre F; Puntoriero, Fausto; Pisagatti, Ilenia; Notti, Anna

2017-04-11

The remarkable affinity of deca-carboxylatopillar[5]arene WP5 towards the aminoglycoside antibiotic, amikacin, in aqueous media is reported; in vitro studies on Gram-positive bacteria (Staphylococcus aureus) show that drug entrapment inside WP5 also takes place in the presence of the microrganisms, thus pointing to WP5 as an appealing carrier for amikacin targeted delivery.

Preparation and Drug-Release Kinetics of Porous Poly(L-lactic acid)/Rifampicin Blend Particles

OpenAIRE

Takashi Sasaki; Hiroaki Matsuura; Kazuki Tanaka

2014-01-01

Porous polymer spheres are promising materials as carriers for controlled drug release. As a new drug-carrier material, blend particles composed of poly(L-lactic acid) (PLLA) and rifampicin were developed using the freeze-drying technique. The blend particles exhibit high porosity with a specific surface area of 10–40 m2 g−1. Both the size and porosity of the particles depend on the concentration of the original solution and on the method of freezing. With respect to the latter, we used the d...

Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

Directory of Open Access Journals (Sweden)

Zhiyue Zhang

2012-01-01

Full Text Available The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis.

Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

International Nuclear Information System (INIS)

Zhang, Z.; Huang, G.

2012-01-01

The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis

Preparation and characterization of celecoxib solid dispersions; comparison of poloxamer-188 and PVP-K30 as carriers

Directory of Open Access Journals (Sweden)

Alireza Homayouni

2014-05-01

Full Text Available Objective(s:Solid dispersion formulation is the most promising strategy to improve oral bioavailability of poorly water soluble drugs. The aim of this study was to compare the effect of polyvinylpyrrolidone K30 (PVP and poloxamer-188 (PLX as carrier in solid dispersion formulations of celecoxib (CLX. Materials and Methods: Solid dispersions of CLX:PVP or CLX:PLX were prepared at different ratios (2:1, 1:1, 1:2, 1:4, 1:6 by solvent evaporation and melting methods, respectively. The characterization of samples was performed using differential scanning calorimetery (DSC, X-Ray powder diffraction (XRPD and Fourier transform infrared spectroscopy (FT-IR. The Gordon-Taylor equation was used to estimate the Tg of solid dispersion systems and the possibility of the interaction between CLX and PVP. Also, the dissolution rate of all samples was determined. Results: DSC and XRPD analyses confirmed the presence of amorphous state of drug in solid dispersion systems. FT-IR studies showed CLX could participate in hydrogen bonding with PVP whilst no specific interaction between CLX and PLX was observed. Both PVP and PLX enhanced the dissolution rate of drug in solid dispersion samples. The dissolution rate was dependent on the ratio of drug: carrier. Interestingly, the solid dispersion samples of PLX at 2:1 and 1:1 drug: carrier showed slower dissolution rate than pure CLX, whilst these results were not observed for PVP. Conclusion: The effect of PVP on dissolution rate enhancement was more pronounced compared to the other carrier. Having a higher Tg and more effect on dissolution rate, PVP could be considered as a more suitable carrier compared to PLX in solid dispersion formulation of CLX.

{beta}-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

Energy Technology Data Exchange (ETDEWEB)

Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylene, E-mail: hiva.baradari@etu.unilim.fr [SPCTS-Centre Europeen de la Ceramique, 12 Rue Atlantis, 87068 Limoges CEDEX (France)

2011-10-15

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous {beta}-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous {beta}-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and {beta}-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on {beta}-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

International Nuclear Information System (INIS)

Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylene

2011-01-01

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

Preparation of Polysaccharide-Based Microspheres by a Water-in-Oil Emulsion Solvent Diffusion Method for Drug Carriers

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Yodthong Baimark

2013-01-01

Full Text Available Polysaccharide-based microspheres of chitosan, starch, and alginate were prepared by the water-in-oil emulsion solvent diffusion method for use as drug carriers. Blue dextran was used as a water-soluble biomacromolecular drug model. Scanning electron microscopy showed sizes of the resultant microspheres that were approximately 100 μm or less. They were spherical in shape with a rough surface and good dispersibility. Microsphere matrices were shown as a sponge. Drug loading efficiencies of all the microspheres were higher than 80%, which suggested that this method has potential to prepare polysaccharide-based microspheres containing a biomacromolecular drug model for drug delivery applications.

Archaeosomes: an excellent carrier for drug and cell delivery.

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Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-09-01

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis

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Pinheiro M

2016-08-01

Full Text Available Marina Pinheiro,1,* Ricardo Ribeiro,1,* Alexandre Vieira,1,* Fernanda Andrade,2 Salette Reis1 1IUCIBIO, REQUIMTE, Chemistry Department, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal *These authors contributed equally to this work Abstract: This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC, were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles’ diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide (MTT assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175–213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of

Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

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Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

2016-01-01

Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

Square Wave Voltammetry: An Alternative Technique to Determinate Piroxicam Release Profiles from Nanostructured Lipid Carriers.

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Otarola, Jessica; Garrido, Mariano; Correa, N Mariano; Molina, Patricia G

2016-08-04

A new, simple, and fast electrochemical (EC) method has been developed to determine the release profile of piroxicam, a nonsteroidal anti-inflammatory drug, loaded in a drug delivery system based on nanostructured lipid carriers (NLCs). For the first time, the samples were analyzed by using square wave voltammetry, a sensitive EC technique. The piroxicam EC responses allow us to propose a model that explains the experimental results and to subsequently determine the amount of drug loaded into the NLCs formulation as a function of time. In vitro drug release studies showed prolonged drug release (up to 5 days), releasing 60 % of the incorporated drug. The proposed method is a promising and stable alternative for the study of different drug delivery systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual-controlled release system of drugs for bone regeneration.

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Kim, Yang-Hee; Tabata, Yasuhiko

2015-11-01

Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

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Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

2017-11-01

Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

Activated Charge-Reversal Polymeric Nano-System: The Promising Strategy in Drug Delivery for Cancer Therapy

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Yichen Hu

2016-04-01

Full Text Available Various polymeric nanoparticles (NPs with optimal size, tumor-targeting functionalization, or microenvironment sensitive characteristics have been designed to solve several limitations of conventional chemotherapy. Nano-sized polymeric drug carrier systems have remarkably great advantages in drug delivery and cancer therapy, which are still plagued with severe deficiencies, especially insufficient cellular uptake. Recently, surface charge of medical NPs has been demonstrated to play an important role in cellular uptake. NPs with positive charge show higher affinity to anionic cell membranes such that with more efficient cellular internalization, but otherwise cause severe aggregation and fast clearance in circulation. Thus, surface charge-reversal NPs, specifically activated at the tumor site, have shown to elegantly resolve the enhanced cellular uptake in cancer cells vs. non-specific protein adsorption dilemma. Herein, this review mainly focuses on the effect of tumor-site activated surface charge reversal NPs on tumor treatment, including the activated mechanisms and various applications in suppressing cancer cells, killing cancer stem cell and overcoming multidrug resistance, with the emphasis on recent research in these fields. With the comprehensive and in-depth understanding of the activated surface charge reversal NPs, this approach might arouse great interest of scientific research on enhanced efficient polymeric nano-carriers in cancer therapy.

Crucial factors and emerging concepts in ultrasound-triggered drug delivery.

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Geers, Bart; Dewitte, Heleen; De Smedt, Stefaan C; Lentacker, Ine

2012-12-28

Time and space controlled drug delivery still remains a huge challenge in medicine. A novel approach that could offer a solution is ultrasound guided drug delivery. “Ultrasonic drug delivery” is often based on the use of small gas bubbles (so-called microbubbles) that oscillate and cavitate upon exposure to ultrasound waves. Some microbubbles are FDA approved contrast agents for ultrasound imaging and are nowadays widely investigated as promising drug carriers. Indeed, it has been observed that upon exposure to ultrasound waves, microbubbles may (a) release the encapsulated drugs and (b) simultaneously change the structure of the cell membranes in contact with the microbubbles which may facilitate drug entrance into cells. This review aims to highlight (a) major factors known so far which affect ultrasonic drug delivery (like the structure of the microbubbles, acoustic settings, etc.) and (b) summarizes the recent preclinical progress in this field together with a number of promising new concepts and applications.

Bacterial Carriers for Glioblastoma Therapy

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Nalini Mehta

2017-03-01

Full Text Available Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

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Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Majidi, Jafar

2018-09-01

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR). © 2018 Wiley Periodicals, Inc.

Delivery of peptide and protein drugs over the blood-brain barrier.

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Brasnjevic, Ivona; Steinbusch, Harry W M; Schmitz, Christoph; Martinez-Martinez, Pilar

2009-04-01

Peptide and protein (P/P) drugs have been identified as showing great promises for the treatment of various neurodegenerative diseases. A major challenge in this regard, however, is the delivery of P/P drugs over the blood-brain barrier (BBB). Intense research over the last 25 years has enabled a better understanding of the cellular and molecular transport mechanisms at the BBB, and several strategies for enhanced P/P drug delivery over the BBB have been developed and tested in preclinical and clinical-experimental research. Among them, technology-based approaches (comprising functionalized nanocarriers and liposomes) and pharmacological strategies (such as the use of carrier systems and chimeric peptide technology) appear to be the most promising ones. This review combines a comprehensive overview on the current understanding of the transport mechanisms at the BBB with promising selected strategies published so far that can be applied to facilitate enhanced P/P drug delivery over the BBB.

Anti-chemokine small molecule drugs: a promising future?

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Proudfoot, Amanda E I; Power, Christine A; Schwarz, Matthias K

2010-03-01

Chemokines have principally been associated with inflammation due to their role in the control of leukocyte migration, but just over a decade ago chemokine receptors were also identified as playing a pivotal role in the entry of the HIV virus into cells. Chemokines activate seven transmembrane G protein-coupled receptors, making them extremely attractive therapeutic targets for the pharmaceutical industry. Although there are now a large number of molecules targeting chemokines and chemokine receptors including neutralizing antibodies in clinical trials for inflammatory diseases, the results to date have not always been positive, which has been disappointing for the field. These failures have often been attributed to redundancy in the chemokine system. However, other difficulties have been encountered in drug discovery processes targeting the chemokine system, and these will be addressed in this review. In this review, the reader will get an insight into the hurdles that have to be overcome, learn about some of the pitfalls that may explain the lack of success, and get a glimpse of the outlook for the future. In 2007, the FDA approved maraviroc, an inhibitor of CCR5 for the prevention of HIV infection, the first triumph for a small-molecule drug acting on the chemokine system. The time to market, 11 years from discovery of CCR5, was fast by industry standards. A second small-molecule drug, a CXCR4 antagonist for hematopoietic stem cell mobilization, was approved by the FDA at the end of 2008. The results of a Phase III trial with a CCR9 inhibitor for Crohn's disease are also promising. This could herald the first success for a chemokine receptor antagonist as an anti-inflammatory therapeutic and confirms the importance of chemokine receptors as a target class for anti-inflammatory and autoimmune diseases.

[Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].

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Kubo, Yoshiyuki

2015-01-01

Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopathy and macular degeneration can cause neurological dysfunction that dramatically affects patients' QOL. The BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs was investigated at the inner BRB, which is known to nourish two thirds of the retina. Blood-to-retinal transport of verapamil suggested that the barrier function of the BRB differs from that of the BBB. Moreover, carrier-mediated transport of verapamil and pyrilamine revealed the involvement of novel organic cation transporters at the inner BRB. The identified transport systems for cationic drugs are sensitive to several cationic neuroprotective and anti-angiogenic agents such as clonidine and propranolol, and the involvement of novel transporters was also suggested in their blood-to-retina transport across the inner BRB.

Impulsion of nanoparticles as a drug carrier for the theoretical investigation of stenosed arteries with induced magnetic effects

Energy Technology Data Exchange (ETDEWEB)

Nadeem, S.; Ijaz, S., E-mail: shagufta.me2011@yahoo.com

2016-07-15

In this paper hemodynamics of stenosis are discussed to predict effect of atherosclerosis by means of mathematical models in the presence of uniform transverse magnetic field. The analysis is carried out using silver and copper nanoparticles as a drug carrier. Exact solution for the fluid temperature, velocity, axial induced magnetic field and current density distribution are obtained under mild stenosis approximation. The results indicate that with an increase in the concentration of nanoparticle hemodynamics effects of stenosis reduces throughout the inclined composite stenosed arteries. The considered analysis also summarizes that the drug silver nanoparticles is more efficient to reduce hemodynamics of stenosis when compare to the drug copper nanoparticle. In future this model could be helpful to predict important properties in some biomedical applications. - Highlights: • The contribution of copper and silver nanoparticles as drug carrier reveals that they are important to reduce hemodynamic of stenosis. • The heat is dissipated throughout the considered inclined artery with an increase in the nanoparticle volume fraction. • The stress on the wall of inclined arteries decreases with an increase in the magnetic Reynolds number and Strommers number.

Impact of carriers in oral absorption

DEFF Research Database (Denmark)

Gram, Luise Kvisgaard; Rist, Gerda Marie; Lennernäs, Hans

2009-01-01

Carriers may mediate the permeation across enterocytes for drug substances being organic anions. Carrier mediated permeation for the organic anions estrone-3-sulfate (ES) and glipizide across Caco-2 cells were investigated kinetically, and interactions on involved carriers evaluated. Initial...

In Vivo Biological Evaluation of High Molecular Weight Multifunctional Acid-Degradable Polymeric Drug Carriers with Structurally Different Ketals.

Science.gov (United States)

Shenoi, Rajesh A; Abbina, Srinivas; Kizhakkedathu, Jayachandran N

2016-11-14

Understanding the influence of degradable chemical moieties on in vivo degradation, tissue distribution, and excretion is critical for the design of novel biodegradable drug carriers. Polyketals have recently emerged as a promising therapeutic delivery platform due to their ability to degrade under mild acidic intracellular compartments and generation of nontoxic degradation products. However, the effect of chemical structure of the ketal groups on the in vivo degradation, biodistribution, and pharmacokinetics of water-soluble ketal-containing polymers has not been explored. In the present work, we synthesized high molecular weight, water-soluble biodegradable hyperbranched polyglycerols (BHPGs) through the incorporation of structurally different ketal groups into the main chain of highly biocompatible polyglycerols. BHPGs showed pH and ketal group structure dependent degradation in buffer solutions. When the polymers were intravenously administered in mice, a strong dependence of in vivo degradation, biodistribution, and clearance on the ketal group structure was observed. All the BHPGs demonstrated degradation and clearance in vivo, with minimal tissue accumulation. Interestingly, an unanticipated degradation behavior of BHPGs with structurally different ketal groups was observed in vivo in comparison to their degradation in buffer solutions. BHPGs with cyclohexyl ketal (CHK) and cyclopentyl ketal (CPK) groups degraded much faster and were cleared from circulation much rapidly, while BHPG with glycerol hydroxy butanone ketal (GHBK) group degraded at a much slower rate and exhibited similar plasma half-life as that of nondegradable HPG. BHPG-GHBK also showed significantly lower tissue accumulation than nondegradable HPG after 30 days of administration. The difference in in vivo degradation may be attributed to the difference in hydrophobic characteristics of different ketal containing polymers, which may change their interaction with proteins and cells in vivo

β-secretase inhibitor; a promising novel therapeutic drug in AD

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Kelly Willemijn Menting

2014-07-01

Full Text Available Alzheimer’s disease (AD and vascular dementia are responsible for up to 90% of dementia cases. According to the World Health Organization (WHO, a staggering number of 35.6 million people are currently diagnosed with dementia. Blocking disease progression or preventing AD altogether is desirable for both social and economic reasons and recently focus has shifted to a new and promising drug: the β-secretase inhibitor. Much of AD research has investigated the amyloid cascade hypothesis, which postulates that AD is caused by changes in amyloid beta (Aβ stability and aggregation. Blocking Aβ production by inhibiting the first protease required for its generation, β-secretase/BACE1, may be the next step in blocking AD progression. In April 2012, promising phase I data on inhibitor MK-8931 was presented. This drug reduced Aβ CSF levels up to 92% and was well tolerated by patients. In March 2013 data was added from a one week trial in 32 mild to moderate AD patients, showing CSF Aβ levels decreased up to 84%. However, BACE1 inhibitors require further research. First, greatly reducing Aβ levels through BACE1 inhibition may have harmful side effects. Second, BACE1 inhibitors have yet to pass clinical trial phase II/III and no data on possible side effects on AD patients are available. And third, there remains doubt about the clinical efficacy of BACE1 inhibitors. In moderate AD patients, Aβ plaques have already been formed. BACE1 inhibitors prevent production of new Aβ plaques, but hypothetically do not influence already existing Aβ peptides. Therefore, BACE1 inhibitors are potentially better at preventing AD instead of having therapeutic use.

Effect of PEGylation on ligand-based targeting of drug carriers to the vascular wall in blood flow.

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Onyskiw, Peter J; Eniola-Adefeso, Omolola

2013-09-03

The blood vessel wall plays a prominent role in the development of many life-threatening diseases and as such is an attractive target for treatment. To target diseased tissue, particulate drug carriers often have their surfaces modified with antibodies or epitopes specific to vascular wall-expressed molecules, along with poly(ethylene glycol) (PEG) to improve carrier blood circulation time. However, little is known about the effect of poly(ethylene glycol) on carrier adhesion dynamics-specifically in blood flow. Here we examine the influence of different molecular weight PEG spacers on particle adhesion in blood flow. Anti-ICAM-1 or Sialyl Lewis(a) were grafted onto polystyrene 2 μm and 500 nm spheres via PEG spacers and perfused in blood over activated endothelial cells at physiological shear conditions. PEG spacers were shown to improve, reduce, or have no effect on the binding density of targeted-carriers depending on the PEG surface conformation, shear rate, and targeting moiety.

Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

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Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

2018-05-30

Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cell membrane-inspired polymeric micelles as carriers for drug delivery.

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Liu, Gongyan; Luo, Quanqing; Gao, Haiqi; Chen, Yuan; Wei, Xing; Dai, Hong; Zhang, Zongcai; Ji, Jian

2015-03-01

In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.

The application of carbon nanotubes in target drug delivery systems for cancer therapies

Science.gov (United States)

Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

2011-10-01

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

Plant lectins as carriers for oral drugs: Is wheat germ agglutinin a suitable candidate?

International Nuclear Information System (INIS)

Dalla Pellegrina, Chiara; Rizzi, Corrado; Mosconi, Silvia; Zoccatelli, Gianni; Peruffo, Angelo; Chignola, Roberto

2005-01-01

Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. 3 H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 μM, ∼0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and time-dependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis

Biomimetic synthesized chiral mesoporous silica: Structures and controlled release functions as drug carrier

Energy Technology Data Exchange (ETDEWEB)

Li, Jing; Xu, Lu, E-mail: xl2013109@163.com; Yang, Baixue; Bao, Zhihong; Pan, Weisan; Li, Sanming, E-mail: li_sanming2013@163.com

2015-10-01

This work initially illustrated the formation mechanism of chiral mesoporous silica (CMS) in a brand new insight named biomimetic synthesis. Three kinds of biomimetic synthesized CMS (B-CMS, including B-CMS1, B-CMS2 and B-CMS3) were prepared using different pH or stirring rate condition, and their characteristics were tested with transmission electron microscope and small angle X-ray diffraction. The model drug indomethacin was loaded into B-CMS and drug loading content was measured using ultraviolet spectroscopy. The result suggested that pH condition influenced energetics of self-assembly process, mainly packing energetics of the surfactant, while stirring rate was the more dominant factor to determine particle length. In application, indomethacin loading content was measured to be 35.3%, 34.8% and 35.1% for indomethacin loaded B-CMS1, indomethacin loaded B-CMS2 and indomethacin loaded B-CMS3. After loading indomethacin into B-CMS carriers, surface area, pore volume and pore diameter of B-CMS carriers were reduced. B-CMS converted crystalline state of indomethacin to amorphous state, leading to the improved indomethacin dissolution. B-CMS1 controlled drug release without burst-release, while B-CMS2 and B-CMS3 released indomethacin faster than B-CMS1, demonstrating that the particle length, the ordered lever of multiple helixes, the curvature degree of helical channels and pore diameter greatly contributed to the release behavior of indomethacin loaded B-CMS. - Highlights: • Chiral mesoporous silica was synthesized using biomimetic method. • pH influenced energetics of self-assembly process of chiral mesoporous silica. • Stirring rate determined the particle length of chiral mesoporous silica. • Controlled release behaviors of chiral mesoporous silica varied based on structures.

Biomimetic synthesized chiral mesoporous silica: Structures and controlled release functions as drug carrier

International Nuclear Information System (INIS)

Li, Jing; Xu, Lu; Yang, Baixue; Bao, Zhihong; Pan, Weisan; Li, Sanming

2015-01-01

This work initially illustrated the formation mechanism of chiral mesoporous silica (CMS) in a brand new insight named biomimetic synthesis. Three kinds of biomimetic synthesized CMS (B-CMS, including B-CMS1, B-CMS2 and B-CMS3) were prepared using different pH or stirring rate condition, and their characteristics were tested with transmission electron microscope and small angle X-ray diffraction. The model drug indomethacin was loaded into B-CMS and drug loading content was measured using ultraviolet spectroscopy. The result suggested that pH condition influenced energetics of self-assembly process, mainly packing energetics of the surfactant, while stirring rate was the more dominant factor to determine particle length. In application, indomethacin loading content was measured to be 35.3%, 34.8% and 35.1% for indomethacin loaded B-CMS1, indomethacin loaded B-CMS2 and indomethacin loaded B-CMS3. After loading indomethacin into B-CMS carriers, surface area, pore volume and pore diameter of B-CMS carriers were reduced. B-CMS converted crystalline state of indomethacin to amorphous state, leading to the improved indomethacin dissolution. B-CMS1 controlled drug release without burst-release, while B-CMS2 and B-CMS3 released indomethacin faster than B-CMS1, demonstrating that the particle length, the ordered lever of multiple helixes, the curvature degree of helical channels and pore diameter greatly contributed to the release behavior of indomethacin loaded B-CMS. - Highlights: • Chiral mesoporous silica was synthesized using biomimetic method. • pH influenced energetics of self-assembly process of chiral mesoporous silica. • Stirring rate determined the particle length of chiral mesoporous silica. • Controlled release behaviors of chiral mesoporous silica varied based on structures

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

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Xian-bin Kong

2017-01-01

Full Text Available Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels: (1 polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury. (2 Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers. (3 Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

Institute of Scientific and Technical Information of China (English)

Xian-bin Kong; Qiu-yan Tang; Xu-yi Chen; Yue Tu; Shi-zhong Sun; Zhong-lei Sun

2017-01-01

Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compellingfindings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels: (1) polyethylene glycol as an adjustable bio-molecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury. (2) Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers. (3) Polyethylene glycol hydrogels have been used as supporting sub-strates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.

p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

Energy Technology Data Exchange (ETDEWEB)

Swami, Rajan; Singh, Indu [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India); Kulhari, Hitesh [CSIR-Indian Institute of Chemical Technology, Medicinal Chemistry & Pharmacology Division (India); Jeengar, Manish Kumar [National Institute of Pharmaceutical Education & Research (NIPER), Departmentof Pharmacology (India); Khan, Wahid, E-mail: wahid@niperhyd.ac.in; Sistla, Ramakrishna, E-mail: sistla@iict.res.in, E-mail: rksistla@yahoo.com [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India)

2015-06-15

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by {sup 1}HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere{sup ®}). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

International Nuclear Information System (INIS)

Swami, Rajan; Singh, Indu; Kulhari, Hitesh; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

2015-01-01

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1 HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere ® ). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors

p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

Science.gov (United States)

Swami, Rajan; Singh, Indu; Kulhari, Hitesh; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

2015-06-01

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

Promising psyllium-based composite containing TiO2 nanoparticles as aspirin-carrier matrix

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Marcela-Corina Rosu

2014-06-01

Full Text Available Composite nanomaterials represent a new trend in the biomedical field. Coupling inorganic/organic constituents with non-toxicity/biocompatibility properties leads to develop the new systems having special characteristics that can be used in various bio-applications. This paper describes the preparation and characterization of psyllium-based composites containing TiO2 nanoparticles in order to develop new therapeutic strategies for aspirin drug delivery. The structural characteristics of obtained materials were investigated by FTIR spectroscopy. The UV–vis spectrophotometric analysis was performed to evaluate the aspirin release behavior under different pH conditions at 37 °C. Combining psyllium (as an excellent source of fiber with TiO2 inorganic unit (as vehicle of aspirin it was found that polymeric-TiO2 networks have promising potential for controlled aspirin release as therapeutic agent.

N-succinyl-chitosan as a drug carrier: water-insoluble and water-soluble conjugates.

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Kato, Yoshinori; Onishi, Hiraku; Machida, Yoshiharu

2004-02-01

N-succinyl-chitosan (Suc-Chi) has favourable properties as a drug carrier such as biocompatibility, low toxicity and long-term retention in the body. It was long retained in the systemic circulation after intravenous administration, and the plasma half-lives of Suc-Chi (MW: 3.4 x 10(5); succinylation degree: 0.81 mol/sugar unit; deacetylation degree: 1.0 mol/sugar unit) were ca. 100.3h in normal mice and 43 h in Sarcoma 180-bearing mice. The biodistribution of Suc-Chi into other tissues was trace apart from the prostate and lymph nodes. The maximum tolerable dose for the intraperitoneal injection of Suc-Chi to mice was greater than 2 g/kg. The water-insoluble and water-soluble conjugates could be prepared using a water-soluble carbodiimide and mitomycin C (MMC) or using an activated ester of glutaric MMC. In vitro release characteristics of these conjugates showed similar patterns, i.e. a pH-dependent manner, except that water-insoluble conjugates showed a slightly slower release of MMC than water-soluble ones. The conjugates of MMC with Suc-Chi showed good antitumour activities against various tumours such as murine leukaemias (L1210 and P388), B16 melanoma, Sarcoma 180 solid tumour, a murine liver metastatic tumour (M5076) and a murine hepatic cell carcinoma (MH134). This review summarizes the utilization of Suc-Chi as a drug carrier for macromolecular conjugates of MMC and the therapeutic efficacy of the conjugates against various tumours.

Investigation of interaction of vanillin with Alpha, Beta and Gamma-cyclodextrin as drug delivery carriers: brief report

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Batoolalsadat Mousavi Fard

2015-05-01

Methods: All theoretical calculations were performed on a Intel® Core™ i5 Processors computer at Kerman University using Gaussian 09 program package (Gaussian, Inc., Wallingford, USA in a three month period (February 2014 to May 2014. Starting geometries were generated employing GaussView software, version 5 (Gaussian, Inc., Wallingford, USA and then the resulting coordinates were optimized using density functional theory (DFT calculations. The natural bond orbital method (NBO program, under Gaussian 09 program package was carried out to study charge transfer energy associated with the intermolecular interactions. The quantum theory of atoms in molecules was applied for DFT results to get insight in the nature of interaction existing in the investigated systems. The calculations were carried out with AIM2000 program and AIMAll 14.10.27 package (Todd A. Keith, TK Gristmill software, Overland Park KS, USA to find and characterize bond critical points. Results: The vanillin molecule is adsorbed on the surface of carriers by hydrogen bonding between its oxygen atom and hydrogen atoms of cyclodextrin. The hydrogen of -OH group on the cyclodextrin can form hydrogen bond to the oxygen atom of carbonyl group of vanillin molecule. This study indicates a decrease of total energy with increasing surface of cyclodextrin. So gamma-cyclodextrin and its complex with the maximum surface in between carriers have the highest stabilities. The gamma-cyclodextrin shows the strongest interaction with vanillin. In all complexes of vanillin-cyclodextrin, the direction of charge transfer is from drug to carrier. Conclusion: Due to the high solubility of gamma-cyclodxtrin and its stronger interaction with the molecule vanillin, it can be the best option as drug carrier.

Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

Science.gov (United States)

Ozeki, Tetsuya; Tagami, Tatsuaki

2013-01-01

The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

Drug loading to lipid-based cationic nanoparticles

International Nuclear Information System (INIS)

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

2005-01-01

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

Radiation preparation of drug carriers based on poly(N-isopropylacrylamide) hydrogels, their loading capacities and controlled release rates for dexamethasone and tegafur

International Nuclear Information System (INIS)

Hoang Dang Sang; Nguyen Van Binh; Tran Bang Diep; Nguyen Thi Thom; Hoang Phuong Thao; Pham Duy Duong; Tran Minh Quynh

2015-01-01

Thermo-sensitive hydrogels have great potential in some applications. In order to use as the drug delivery systems, the hydrogels should be biocompatibility. New polymers with more biocompatibility and better biodegradability, and environmental friendly crosslinking agents would be necessary for the successful drug carriers. Poly (N-isopropylacrylamide-co-dimethylacrylamide) based hydrogels have been prepared from the admixture solutions of N-isopropylacrylamide (NIPA) and N,N’-dimethyl acrylamide (DMA) by radiation copolymerization and crosslinking at radiation dose of 20 kGy as reported in our previous study. Water swelling behaviour of the resulting hydrogels were much depended on their nature such as initial ratio of NIPA and DMA. The drug-loaded hydrogels were prepared by merging hydrogel in the solutions containing corresponding drugs. Loading capacity of the hydrogels were about 48.6 and 95.7 mg per g dried hydrogel for dexamethasone and tegafur. The release studies showed that the presence of ions in simulated body fluid and temperature of the solution much affecting to in vitro release behaviors of hydrogels for dexamethasone and tegafur. The release rates were fast for both drug models. The result also revealed that these drug carriers were biocompatibility without skin irritation, suggested the drug-loaded hydrogels may be used as controlled release drug delivery systems. (author)

Optimization and design of ibuprofen-loaded nanostructured lipid carriers using a hybrid-design approach for ocular drug delivery

Science.gov (United States)

Rathod, Vishal

The objective of the present project was to develop the Ibuprofen-loaded Nanostructured Lipid Carrier (IBU-NLCs) for topical ocular delivery based on substantial pre-formulation screening of the components and understanding the interplay between the formulation and process variables. The BCS Class II drug: Ibuprofen was selected as the model drug for the current study. IBU-NLCs were prepared by melt emulsification and ultrasonication technique. Extensive pre-formulation studies were performed to screen the lipid components (solid and liquid) based on drug's solubility and affinity as well as components compatibility. The results from DSC & XRD assisted in selecting the most suitable ratio to be utilized for future studies. DynasanRTM 114 was selected as the solid lipid & MiglyolRTM 840 was selected as the liquid lipid based on preliminary lipid screening. The ratio of 6:4 was predicted to be the best based on its crystallinity index and the thermal events. As there are many variables involved for further optimization of the formulation, a single design approach is not always adequate. A hybrid-design approach was applied by employing the Plackett Burman design (PBD) for preliminary screening of 7 critical variables, followed by Box-Behnken design (BBD), a sub-type of response surface methodology (RSM) design using 2 relatively significant variables from the former design and incorporating Surfactant/Co-surfactant ratio as the third variable. Comparatively, KolliphorRTM HS15 demonstrated lower Mean Particle Size (PS) & Polydispersity Index (PDI) and KolliphorRTM P188 resulted in Zeta Potential (ZP) ibuprofen thereafter over several hours. These values also confirm that the production method, and all other selected variables, effectively promoted the incorporation of ibuprofen in NLC. Quality by Design (QbD) approach was successfully implemented in developing a robust ophthalmic formulation with superior physicochemical and morphometric properties. NLCs as the

Promise and deceit: pharmakos, drug replacement therapy, and the perils of experience.

Science.gov (United States)

Meyers, Todd

2014-06-01

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

Cell-Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals

DEFF Research Database (Denmark)

Kristensen, Mie; Nielsen, Hanne Mørck

2016-01-01

Oral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor permeation across the intestinal mucosa, to a large extent limiting the mode of administration to injections, which is not favouring...... patient compliance. Nevertheless, cell-penetrating peptides (CPPs) have shown promising potential as carriers to overcome the epithelium, and this minireview highlights recent knowledge gained within the field of CPP-mediated transepithelial delivery of therapeutic peptides and proteins from the intestine...... is to be preferred depends on the physicochemical properties of both the specific CPP and the specific cargo. In addition to the physical epithelial barrier, a metabolic barrier must be overcome in order to obtain CPP-mediated delivery of a cargo drug from the intestine, and a number of strategies have been employed...

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

Science.gov (United States)

Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

2013-01-01

This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

Polymeric micelles for drug targeting.

Science.gov (United States)

Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

2007-11-01

Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

Nanovesicles released by Dictyostelium cells: a potential carrier for drug delivery.

Science.gov (United States)

Lavialle, Françoise; Deshayes, Sophie; Gonnet, Florence; Larquet, Eric; Kruglik, Sergei G; Boisset, Nicolas; Daniel, Régis; Alfsen, Annette; Tatischeff, Irène

2009-10-01

Nanovesicles released by Dictyostelium discoideum cells grown in the presence of the DNA-specific dye Hoechst 33342 have been previously shown to mediate the transfer of the dye into the nuclei of Hoechst-resistant cells. The present investigation extends this work by conducting experiments in the presence of hypericin, a fluorescent therapeutic photosensitizer assayed for antitumoral photodynamic therapy. Nanovesicles released by Dictyostelium cells exhibit an averaged diameter between 50 and 150 nm, as measured by transmission cryoelectron microscopy. A proteomic analysis reveals a predominance of actin and actin-related proteins. The detection of a lysosomal membrane protein (LIMP II) indicates that these vesicles are likely generated in the late endosomal compartment. The use of the hypericin-containing nanovesicles as nanodevices for in vitro drug delivery was investigated by fluorescence microscopy. The observed signal was almost exclusively located in the perinuclear area of two human cell lines, skin fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by confocal microscopy with specific markers of cell organelles, provided evidence that hypericin was accumulated in the Golgi apparatus. All these data shed a new light on in vitro drug delivery by using cell-released vesicles as carriers.

Carrier-Mediated Prodrug Uptake to Improve the Oral Bioavailability of Polar Drugs: An Application to an Oseltamivir Analogue.

Science.gov (United States)

Incecayir, Tuba; Sun, Jing; Tsume, Yasuhiro; Xu, Hao; Gose, Tomoka; Nakanishi, Takeo; Tamai, Ikumi; Hilfinger, John; Lipka, Elke; Amidon, Gordon L

2016-02-01

The goal of this study was to improve the intestinal mucosal cell membrane permeability of the poorly absorbed guanidino analogue of a neuraminidase inhibitor, oseltamivir carboxylate (GOC) using a carrier-mediated strategy. Valyl amino acid prodrug of GOC with isopropyl-methylene-dioxy linker (GOC-ISP-Val) was evaluated as the potential substrate for intestinal oligopeptide transporter, hPEPT1 in Xenopus laevis oocytes heterologously expressing hPEPT1, and an intestinal mouse perfusion system. The diastereomers of GOC-ISP-Val were assessed for chemical and metabolic stability. Permeability of GOC-ISP-Val was determined in Caco-2 cells and mice. Diastereomer 2 was about 2 times more stable than diastereomer 1 in simulated intestinal fluid and rapidly hydrolyzed to the parent drug in cell homogenates. The prodrug had a 9 times-enhanced apparent permeability (P(app)) in Caco-2 cells compared with the parent drug. Both diastereomer exhibited high effective permeability (P(eff)) in mice, 6.32 ± 3.12 and 5.20 ± 2.81 × 10(-5) cm/s for diastereomer 1 and 2, respectively. GOC-ISP-Val was found to be a substrate of hPEPT1. Overall, this study indicates that the prodrug, GOC-ISP-Val, seems to be a promising oral anti-influenza agent that has sufficient stability at physiologically relevant pHs before absorption, significantly improved permeability via hPEPT1 and potentially rapid activation in the intestinal cells. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Novel catalytic micromotor of porous zeolitic imidazolate framework-67 for precise drug delivery.

Science.gov (United States)

Wang, Linlin; Zhu, Hongli; Shi, Ying; Ge, You; Feng, Xiaomiao; Liu, Ruiqing; Li, Yi; Ma, Yanwen; Wang, Lianhui

2018-06-07

Micromotors hold promise as drug carriers for targeted drug delivery owing to the characteristics of self-propulsion and directional navigation. However, several defects still exist, including high cost, short movement life, low drug loading and slow release rate. Herein, a novel catalytic micromotor based on porous zeolitic imidazolate framework-67 (ZIF-67) synthesized by a greatly simplified wet chemical method assisted with ultrasonication is described as an efficient anticancer drug carrier. These porous micromotors display effective autonomous motion in hydrogen peroxide and long durable movement life of up to 90 min. Moreover, the multifunctional micromotor ZIF-67/Fe3O4/DOX exhibits excellent performance in precise drug delivery under external magnetic field with high drug loading capacity of fluorescent anticancer drug DOX up to 682 μg mg-1 owing to its porous nature, high surface area and rapid drug release based on dual stimulus of catalytic reaction and solvent effects. Therefore, these porous ZIF-67-based catalytic micromotors combine the domains of metal-organic frameworks (MOFs) and micomotors, thus developing potential resources for micromotors and holding great potential as label-free and precisely controlled high-quality candidates of drug delivery systems for biomedical applications.

Halloysite nanotubes-polymeric nanocomposites: characteristics, modifications and controlled drug delivery approaches

Directory of Open Access Journals (Sweden)

P. C. Ferrari

Full Text Available Abstract Halloysite nanotubes (HNTs are aluminosilicate nanoclay mineral which have a hollow tubular structure and occurs naturally. They are biocompatible and viable carrier for inclusion of biologically active molecules due to the empty space inside the tubular structure. In this article, the HNTs main characteristics, and the HNTs-polymeric nanocomposite formation and their potential application as improvement of the mechanical performance of polymers and entrapment of hydrophilic and lipophilic substances are summarized. Recent works covering the increment of HNTs-polymeric nanocomposites and presenting promising employment of these systems as nanosized carrier, being suitable for pharmaceutical and biomedical applications, based on earlier evidence in literature of its nature to sustain the release of loaded drugs, presenting low cytotoxicity, and providing evidence for controlled drug delivery are reviewed.

Organic solute carrier 22 (SLC22 family: Potential for interactions with food, herbal/dietary supplements, endogenous compounds, and drugs

Directory of Open Access Journals (Sweden)

Raymond E. Lai

2018-04-01

Full Text Available Many drugs, hormones, components of herbal medicines, environmental pesticides and toxins are Solute Carrier family 22 (SLC22 substrates. The last twenty years has seen great progress in determining SLC22 tissue expression profiles, membrane localization, energetics, substrate profiles and biopharmaceutical significance. However, much still remains to be answered in terms of SLC22 family member's roles in ‘normal’ physiology as compared to pathophysiological states, as well as in drug interactions that impact pharmacokinetics, efficacy and toxicity. This review begins with a brief synopsis of SLC22 family discovery, function and tissue expression. Subsequent sections provide examples establishing a role for SLC22 transporters in food-drug, herbal supplement-drug, endogenous substrate-drug and drug–drug interactions. Keywords: Hepatic transport, Nephrotoxicity, Organic anion transporter, Organic cation transporter, Renal transport

Erythrocytes as Carriers for Drugs and Contrast Agents

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Mauro Magnani

2014-01-01

Full Text Available Erythrocytes, also known as Red Blood Cells (RBC, are typically used in transfusion medicine to replace lost blood in patients who underwent different kinds of medical treatments as well as those involved in accidents resulting in blood loss. In addition to these common uses, RBC are being used for a variety of new applications either as therapeutics or as diagnostics. Most of these novel approaches are made possible due to the peculiar properties of these cells. We have invented a technology that allows cells to be opened and resealed without affecting their main physiological characteristics with a minimal amount of patient blood.  Uses of processed RBCs in biomedical engineering include work with drugs, biomedical compounds and/or nanomaterials. These constructs are a new armamentarium available to the physicians for the release of drugs in circulation, for targeting drugs to selected sites in the body, or for in vivo diagnostic procedures based on magnetic and/or optical methods. Autologous human RBC loaded with dexamethasone (EryDex, a common corticosteroid,  have been used in the treatment of Cystic Fibrosis, Crohn’s Disease, and other severe inflammatory conditions. Benefits and safety of this technology have been documented in over 2,500 treatments. EryDel SpA is a company focused on developing and commercializing innovative therapies and diagnostics based on the use of autologous RBCs as agent carriers. More recently, EryDel SpA completed a Phase II Proof of Concept study in patients with Ataxia Telangiectasia (AT, a rare progressive neurological autosomal recessive disorder that leads to mortality in most patients at an early age, with significant benefit seen on primary and secondary end-points. EryDex treatment has received Orphan Drug Designation by EMA for the treatment of Cystic Fibrosis and both by EMA and FDA for the treatment of AT. The encapsulation of superparamagnetic nanoparticles within RBC has lead to the generation

Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane

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Yu Z

2014-07-01

Full Text Available Zhan Yu,1,* Min Yu,2,* Zhimin Zhou,3 Zhibao Zhang,3 Bo Du,3 Qingqing Xiong3 1Second Artillery General Hospital, Beijing, 2Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, College of Basic Medicine, China Medical University, Shenyang, 3Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, Key Laboratory of Biomedical Material of Tianjin, Tianjin, People’s Republic of China *These authors contributed equallyto this work Abstract: Controlled-release carriers for local drug delivery have attracted increasing attention for inner-ear treatment recently. In this paper, flower-shaped bovine serum albumin (FBSA particles were prepared by a modified desolvation method followed by glutaraldehyde or heat denaturation. The size of the FBSA particles varied from 10 µm to 100 µm, and most were 50–80 µm. Heat-denatured FBSA particles have good cytocompatibility with a prolonged survival time for L929 cells. The FBSA particles were utilized as carriers to investigate the release behaviors of the model drug – rhodamine B. Rhodamine B showed a sustained-release effect and penetrated the round-window membrane of guinea pigs. We also confirmed the attachment of FBSA particles onto the round-window membrane by microscopy. The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive capability, and biodegradability, may have potential applications in the field of local drug delivery for inner-ear disease treatment. Keywords: bovine serum albumin (BSA, controlled release, local delivery, round-window membrane

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

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Ban, Junfeng; Zhang, Yan; Huang, Xin; Deng, Guanghan; Hou, Dongzhi; Chen, Yanzhong; Lu, Zhufen

2017-01-01

Drug delivery carriers can maintain effective therapeutic concentrations in the eye. To this end, we developed lipid nanoparticles (L/NPs) in which the surface was modified with positively charged chitosan, which engaged in hydrogen bonding with the phospholipid membrane. We evaluated in vitro corneal permeability and release characteristics, ocular irritation, and drug dynamics of modified and unmodified L/NPs in aqueous humor. The size of L/NPs was uniform and showed a narrow distribution. Corneal permeation was altered by the presence of chitosan and was dependent on particle size; the apparent permeability coefficient of dexamethasone increased by 2.7 and 1.8 times for chitosan-modified and unmodified L/NPs, respectively. In conclusion, a chitosan-modified system could be a promising method for increasing the ocular bioavailability of unmodified L/NPs by enhancing their retention time and permeation into the cornea. These findings provide a theoretical basis for the development of effective drug delivery systems in the treatment of ocular disease. PMID:28243093

Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design.

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Kraisit, Pakorn; Sarisuta, Narong

2018-04-23

The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X₁), soybean oil (X₂), and Tween 80 (X₃) were used as solid lipid, liquid lipid, and stabilizer, respectively. The particle size of TA-loaded NLCs was lower than 200 nm and the zeta potential displayed the negative charge in all formulations. The percentage encapsulation efficiency (%EE) of the TA-loaded NLCs showed that it was higher than 80% for all formulations. Field emission scanning electron microscope (FESEM) confirmed that the size of TA-loaded NLCs was approximately 100 nm and energy-dispersive X-ray spectroscopy (EDS) confirmed that the TA could be incorporated in the NLC system. The Higuchi model gave the highest value of the R², indicating that this model was a fit for the TA release profiles of TA-loaded NLCs. Confocal laser scanning microscopy (CLSM) was used to observe the drug penetration within the porcine buccal mucosa and Nile red-loaded NLCs showed significantly higher penetration depth at 8 h than at 2 h. Therefore, TA-loaded NLCs could be an efficient carrier for drug delivery through the buccal mucosa.

Mechanism of erosion of nanostructured porous silicon drug carriers in neoplastic tissues

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Tzur-Balter, Adi; Shatsberg, Zohar; Beckerman, Margarita; Segal, Ester; Artzi, Natalie

2015-01-01

Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance. PMID:25670235

Chitosan microspheres in novel drug delivery systems.

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Mitra, Analava; Dey, Baishakhi

2011-07-01

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.

Functionalized silica nanoparticles as a carrier for Betamethasone Sodium Phosphate: Drug release study and statistical optimization of drug loading by response surface method.

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Ghasemnejad, M; Ahmadi, E; Mohamadnia, Z; Doustgani, A; Hashemikia, S

2015-11-01

Mesoporous silica nanoparticles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane (APTES), and their performance as a carrier for drug delivery system was studied. Chemical structure and morphology of the synthesized and modified SBA-15 were characterized by SEM, BET, TEM, FT-IR and CHN technique. Betamethasone Sodium Phosphate (BSP) as a water soluble drug was loaded on the mesoporous silica particle for the first time. The response surface method was employed to obtain the optimum conditions for the drug/silica nanoparticle preparation, by using Design-Expert software. The effect of time, pH of preparative media, and drug/silica ratio on the drug loading efficiency was investigated by the software. The maximum loading (33.69%) was achieved under optimized condition (pH: 1.8, time: 3.54 (h) and drug/silica ratio: 1.7). The in vitro release behavior of drug loaded particles under various pH values was evaluated. Finally, the release kinetic of the drug was investigated using the Higuchi and Korsmeyer-Peppas models. Cell culture and cytotoxicity assays revealed the synthesized product doesn't have any cytotoxicity against human bladder cell line 5637. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as implantation and topical or oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.

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Marwan Moussa

Full Text Available To determine the effect of different drug-loaded nanocarriers (micelles and liposomes on delivery and treatment efficacy for radiofrequency ablation (RFA combined with nanodrugs.Fischer 344 rats were used (n = 196. First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm, with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm or liposomal (100 nm preparations of doxorubicin (Dox; targeting HIF-1α or quercetin (Qu; targeting HSP70. Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA, and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.. Tumor coagulation and HIF-1α or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr.Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm and liver (100 nm (p<0.05. Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05. RFA/Mic-Dox had greater early (4 hr intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post-RFA (p<0.04. No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03.With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly

New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.

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Lienhardt, Christian; Raviglione, Mario; Spigelman, Mel; Hafner, Richard; Jaramillo, Ernesto; Hoelscher, Michael; Zumla, Alimuddin; Gheuens, Jan

2012-05-15

For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.

Theoretical study on the cage-like nanostructures formed by amino acids and their potential applications as drug carriers

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Weng, Pei Pei; Fan, Jian Fen; Lin, Hui Fang; Zhao, Xin; Si, Xia Lan

2017-12-01

The cage-like octamer, decamer and dodecamer constructed from aspartic acid monomers have been studied to explore their potential applications as drug carriers using the density functional theory. The calculation results indicate that these stable cage-like oligomers are mainly connected by the -C=O…HOOC- and -HN…HOOC- H-bonds and still keep stability and good drum-shaped topologies after the incorporation of 5-fluorouracil, paraldehyde and C24, respectively. The self-assembled cage-like oligomers may be applied to the preparation of new biological materials and the design of drug delivery systems.

Renal targeting potential of a polymeric drug carrier, poly-L-glutamic acid, in normal and diabetic rats

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Chai HJ

2017-01-01

Full Text Available Hann-Juang Chai,1 Lik-Voon Kiew,1 Yunni Chin,1 Anwar Norazit,2 Suzita Mohd Noor,2 Yoke-Lin Lo,3,4 Chung-Yeng Looi,1 Yeh-Siang Lau,1 Tuck-Meng Lim,5 Won-Fen Wong,6 Nor Azizan Abdullah,1 Munavvar Zubaid Abdul Sattar,7 Edward J Johns,8 Zamri Chik,1 Lip-Yong Chung3 1Department of Pharmacology, 2Department of Biomedical Science, 3Department of Pharmacy, Faculty of Medicine, University of Malaya, 4School of Pharmacy, International Medical University, Kuala Lumpur, 5Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 6Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 7School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Malaysia; 8Department of Physiology, University College Cork, Cork, Republic of Ireland Background and purpose: Poly-L-glutamic acid (PG has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier.Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido fluorescein (fluoresceinyl glycine amide-labeled PG (PG-AF. To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethylbenzenesulfonyl fluoride hydrochloride (AEBSF was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF.Results: In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular �

Nanomedicine formulations for the delivery of antiviral drugs: a promising solution for the treatment of viral infections.

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Lembo, David; Donalisio, Manuela; Civra, Andrea; Argenziano, Monica; Cavalli, Roberta

2018-01-01

Viral infections represent a public health problem and one of the leading causes of global mortality. Nanomedicine strategies can be considered a powerful tool to enhance the effectiveness of antiviral drugs, often associated with solubility and bioavailability issues. Consequently, high doses and frequent administrations are required, resulting in adverse side effects. To overcome these limitations, various nanomedicine platforms have been designed. Areas covered: This review focuses on the state of the art of organic-based nanoparticles for the delivery of approved antivirals. A brief description of the main characteristics of nanocarriers is followed by an overview of the most promising research addressing the treatment of most important viral infections. Expert opinion: The activity of antiviral drugs could be improved with nanomedicine formulations. Indeed, nanoparticles can affect the fate of the encapsulated drugs, allowing controlled release kinetics, enhanced bioavailability, modified pharmacokinetics, and reduced side effects. In addition, the physicochemical properties of nanocarriers can enable their capability to target specific sites and to interact with virus structures. In this regard, nanomedicines can be considered an opportunity to enhance the therapeutic index of antivirals. Efficacy, safety, and manufacturing issues need to be carefully assessed to bring this promising approach to the clinic.

Genetically engineered nanocarriers for drug delivery

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Shi P

2014-03-01

Full Text Available Pu Shi, Joshua A Gustafson, J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USAAbstract: Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.Keywords: polymeric drug carrier, non-polymeric drug carrier, gene delivery, GE drug carriers

Fabrication and characterization of size-controlled starch-based nanoparticles as hydrophobic drug carriers.

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Han, Fei; Gao, Chunmei; Liu, Mingzhu

2013-10-01

Acetylated corn starch was successfully synthesized and optimized by the reaction of native corn starch with acetic anhydride and acetic acid in the presence of sulfuric acid as a catalyst. The optimal degree of substitution of 2.85 was obtained. Starch-based nanoparticles were fabricated by a simple and novel nanoprecipitation procedure, by the dropwise addition of water to acetone solution of acetylated starch under stirring. Fourier transform infrared spectrometry showed that acetylated starch had some new bands at 1750, 1375 and 1240 cm(-1) while acetylated starch nanoparticles presented the identical peaks as the drug-loaded acetylated starch nanoparticles and the acetylated starch. Wide angle X-ray diffraction indicated that A-type pattern of native starch was completely transformed into the V-type pattern of Acetylated starch and starch-based nanoparticles show the similar type pattern with the acetylated starch. The scanning electron microscopy showed that the different sizes of pores formed on the acetylated starch granules were utterly converted into the uniform-sized spherical nanoparticles after the nanoprecipitation. The encapsulation efficiency and diameter of nanoparticle can be adjusted by the degree of substitution, the volume ratio of nonsolvent to solvent and the weight ratio of acetylated starch to drug. It was also depicted that the release behaviors of drug-loaded nanoparticles depend on the size of nanoparticles and the degree of substitution of the acetylated starch. Release studies prove that the starch-based nanoparticles with uniform size can be used for the encapsulation of hydrophobic drug and attained the sustained and controllable drug release carriers.

Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

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María Martínez-Hoyos

2016-06-01

Full Text Available Despite being one of the first antitubercular agents identified, isoniazid (INH is still the most prescribed drug for prophylaxis and tuberculosis (TB treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI of the enoyl-ACP reductase (InhA has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb, but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR and extensively (XDR drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment.

REVIEW: CHITOSAN BASED HYDROGEL POLYMERIC BEADS – AS DRUG DELIVERY SYSTEM

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Manjusha Rani

2010-11-01

Full Text Available Chitosan obtained by alkaline deacetylation of chitin is a non-toxic, biocompatible, and biodegradable natural polymer. Chitosan-based hydrogel polymeric beads have been extensively studied as micro- or nano-particulate carriers in the pharmaceutical and medical fields, where they have shown promise for drug delivery as a result of their controlled and sustained release properties, as well as biocompatibility with tissue and cells. To introduce desired properties and enlarge the scope of the potential applications of chitosan, graft copolymerization with natural or synthetic polymers on it has been carried out, and also, various chitosan derivatives have been utilized to form beads. The desired kinetics, duration, and rate of drug release up to therapeutical level from polymeric beads are limited by specific conditions such as beads material and their composition, bead preparation method, amount of drug loading, drug solubility, and drug polymer interaction. The present review summarizes most of the available reports about compositional and structural effects of chitosan-based hydrogel polymeric beads on swelling, drug loading, and releasing properties. From the studies reviewed it is concluded that chitosan-based hydrogel polymeric beads are promising drug delivery systems.

The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers as drug carriers

International Nuclear Information System (INIS)

Ajun Wan; Yuxia, Kou

2008-01-01

The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers (HP-g-PEO) as drug carriers were investigated. The HP-g-PEO consisting of hydrophobic HP-g-PEO core and hydrophilic poly(ethylene glycol) arms was prepared by the cation ring-opening polymerization. A series of HP-g-PEO samples with different degree of branching (DB) were synthesized under various reaction temperatures. Nanoparticles (NP) were obtained by self-assembly of HP-g-PEO in aqueous media. The structure of resulting HP-g-PEO was characterized by IR, 13 CNMR and GPC. Dynamic light scattering and transmission electron microscopy were applied to characterize the sizes and size distributions of NP. The results demonstrated that the mean diameters of NP were less than 100 nm, which exhibited uniform spherical formations and narrow size distributions. Using hydrophobic drug Probucol (PRO) as model drug, the particle sizes of drug loaded NP were larger than relative blank NP. The drug loading efficiency (LE) and incorporation efficiency (IE) of these NP were achieved to 35 and 89%, respectively. The in vitro release of PRO from the NP exhibited a sustained release and the cumulative drugs released for more than 600 h. The most important factor to affect drug release was the value of DB of HP-g-PEO. With the DB of HP-g-PEO increasing, the size and size distribution of NP decreased as well as the release rate. However, the small DB was beneficial to the LE of NP. Nanoparticle size and size distribution, LE, IE, and drug release rate were slightly affected by the initial solution concentration of polyethers. The co-incorporated hydrophilic drug had influence slightly on the release of drug from drug loaded NP. The results of in vitro drug release suggested that the core/shell NP performed good controlled release behaviors with potential practice as novelty drug delivery vehicles

Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation.

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Abdulbaqi, Ibrahim M; Darwis, Yusrida; Assi, Reem Abou; Khan, Nurzalina Abdul Karim

2018-01-01

Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers. Colchicine-loaded transethosomes (TEs) were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940 ® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats' back skin. The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel. These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration.

Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

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Kanika Madaan

2014-01-01

Full Text Available Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.

Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

Science.gov (United States)

Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

2014-01-01

Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

Dissolution enhancement of a model poorly water-soluble drug, atorvastatin, with ordered mesoporous silica: comparison of MSF with SBA-15 as drug carriers.

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Maleki, Aziz; Hamidi, Mehrdad

2016-01-01

The purpose of this study was to develop mesoporous silica materials incorporated with poorly water-soluble drug atorvastatin calcium (AC) in order to improve drug dissolution, and intended to be orally administrated. A comparison between 2D-hexagonal silica nanostructured SBA-15 and mesocellular siliceous foam (MSF) with continuous 3D pore system on drug release rate was investigated. AC-loaded mesoporous silicas were characterized thorough N2 adsorption-desorption analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dynamic light scattering (DLS). Results demonstrated a successful incorporation of AC into the silica-based hosts. The results taken from the drug release tests were also analyzed using different parameters, namely similarity factor (f2), difference factor (f1), dissolution efficiency (DE%), mean dissolution rate (MDR) and dissolution time (tm%). It confirmed a significant enhancement in the release profile of atorvastatin calcium with SBA-15, and MSF as drug carrier. Moreover, in comparison with SBA-15, MSF showed faster release rate of AC in enzyme-free simulated gastric fluid (pH 1.2). We believed that our findings can help the use of mesoporous silica materials in improving bioavailability of poorly water-soluble drugs.

Benzothiophen-pyrazine scaffold as a potential membrane targeting drug carrier

International Nuclear Information System (INIS)

Mazuryk, Olga; Niemiec, Elżbieta; Stochel, Grażyna; Gillaizeau, Isabelle; Brindell, Małgorzata

2013-01-01

The fluorescent properties of 2,5-di(benzo[b]thiophen-2-yl)pyrazine as a potential membrane targeting drug carrier were characterized and it was shown that its fluorescence intensity was much higher in organic solvent than in water. The embedding of studied compound by liposomes leads to ca. 2 orders of magnitude increase in its fluorescence intensity, suggesting its preferential accumulation in membranes. Preliminary biological studies showed its ability to accumulate in cells, and the concentration of 10 μM was sufficient for homogeneous staining of cells. The treatment of mouse carcinoma CT26 cells with studied compound up to 200 μM resulted in decreasing of viable cells by ca. 30%. Its reactivity towards albumin was found to be moderate with an association constant of 6×10 4 M −1 , while no interaction with DNA was observed. Our findings encourage for further studies on functionalization of this molecule to obtain a new class of anticancer drugs targeting membrane. Highlights: ► The fluorescence of 2,5-di(benzo[b]thiophen-2-yl)pyrazine is solvent dependent. ► Weak fluorescence is found in water while high in organic solvents (DMSO, chloroform). ► Embedding of compound in liposomes remarkably increased its fluorescence. ► No interaction with DNA is observed but moderate reactivity towards albumin is found. ► Homogeneous staining of cells is feasible using nontoxic dose of compound

Biomimetics in drug delivery systems: A critical review.

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Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Graft Polymerization of Acryloyloxystarch with Poly(D,L-lactide) Macromonomer--A Potential Drug Delivery Carrier for Oral Administration

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

@@ Starch is the second largest natural biopolymer. Its unique biodegradable and biocompatible properties make it be increasingly applied to the field of biomedicine[1～4]. As one kind of polysaccharide, starch is easily degraded into small organic molecules by amylase in the alimentary canal. The fact that the activity of amylase is restrained in the high acid environment in stomach provides an opportunity to prepare an intestinal-specific delivery carrier with starch. In order to protect the drugs that are sensitive to the enzyms in alimentary canal, a hydrophobic layer should be constructed between the outer bioadhensive shell and the drug.

Carbon Nanotropes: A Contemporary Paradigm in Drug Delivery

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Avinash C. Tripathi

2015-05-01

Full Text Available Discovery of fullerenes and other nanosized carbon allotropes has opened a vast new field of possibilities in nanotechnology and has become one of the most promising research areas. Carbon nanomaterials have drawn interest as carriers of biologically pertinent molecules due to their distinctive physical, chemical and physiological properties. We have assigned the nomenclature “Carbon Nanotropes” to the nanosized carbon allotropes. Carbon nanotropes such as fullerenes, carbon nanotubes (CNTs and graphenes, have exhibited wide applicability in drug delivery, owing to their small size and biological activity. The nanotherapeutics/diagnostics will allow a deeper understanding of human ills including cancer, neurodegenerative diseases, genetic disorders and various other complications. Recently, nanomaterials with multiple functions, such as drug carrier, MRI, optical imaging, photothermal therapy, etc., have become more and more popular in the domain of cancer and other areas of research. This review is an endeavor to bring together the usefulness of the carbon nanomaterials in the field of drug delivery. The last section of the review encompasses the recent patents granted on carbon nanotropes at United State Patent Trademark Office (USPTO in the related field.

Co-delivery of antigen and a lipophilic anti-inflammatory drug to cells via a tailorable nanocarrier emulsion.

Science.gov (United States)

Chuan, Yap Pang; Zeng, Bi Yun; O'Sullivan, Brendan; Thomas, Ranjeny; Middelberg, Anton P J

2012-02-15

Nanotechnology promises new drug carriers that can be tailored to specific applications. Here we report a new approach to drug delivery based on tailorable nanocarrier emulsions (TNEs), motivated by a need to co-deliver a protein antigen and a lipophilic drug for specific inhibition of nuclear factor kappa B (NF-κB) in antigen presenting cells (APCs). Co-delivery for NF-κB inhibition holds promise as a strategy for the treatment of rheumatoid arthritis. We used a highly surface-active peptide (SAP) to prepare a nanosized emulsion having defined surface properties predictable from the SAP sequence. Incorporating the lipophilic drug into the oil phase at the time of emulsion formation enabled its facile packaging. The SAP is depleted from bulk during emulsification, allowing simple subsequent addition of the drug-loaded oil-in-water emulsion to a solution of protein antigen. Decoration of emulsion surface with antigen was achieved via electrostatic deposition. In vitro data showed that the TNE prepared this way was internalized and well-tolerated by model APCs, and that good suppression of NF-κB expression was achieved. This work reports a new type of nanotechnology-based carrier, a TNE, which can potentially be tailored for co-delivery of multiple therapeutic components, and can be made using simple methods using only biocompatible materials. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model.

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Jämbeck, Joakim P M; Eriksson, Emma S E; Laaksonen, Aatto; Lyubartsev, Alexander P; Eriksson, Leif A

2014-01-14

Liposomes are proposed as drug delivery systems and can in principle be designed so as to cohere with specific tissue types or local environments. However, little detail is known about the exact mechanisms for drug delivery and the distributions of drug molecules inside the lipid carrier. In the current work, a coarse-grained (CG) liposome model is developed, consisting of over 2500 lipids, with varying degrees of drug loading. For the drug molecule, we chose hypericin, a natural compound proposed for use in photodynamic therapy, for which a CG model was derived and benchmarked against corresponding atomistic membrane bilayer model simulations. Liposomes with 21-84 hypericin molecules were generated and subjected to 10 microsecond simulations. Distribution of the hypericins, their orientations within the lipid bilayer, and the potential of mean force for transferring a hypericin molecule from the interior aqueous "droplet" through the liposome bilayer are reported herein.

Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective β₁-adrenoreceptor blocker Talinolol.

Science.gov (United States)

Ghai, Damanjeet; Sinha, Vivek Ranjan

2012-07-01

To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Spray-Drying and Choice of Solid Carriers on Concentrations of Labrasol® and Transcutol® in Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS

Directory of Open Access Journals (Sweden)

Christopher Wai-Kei Lam

2013-01-01

Full Text Available Solid self-microemulsifying drug delivery systems (SMEDDS have been used increasingly for improving the bioavailability of hydrophobic drugs. Labrasol® and Transcutol® are used widely as surfactant and solubilizer in the formulation of solid SMEDDS. We investigated the effects of spray-drying and the use of different solid carriers on concentrations of Labrasol® and Transcutol® in solid SMEDDS with scutellarin as the formulated drug. Liquid and gas chromatography tandem mass spectrometry (LC-MS and GC-MS methods were developed for measuring low concentrations of Labrasol® and Transcutol®. In the preparation of solid SMEDDS, lactose, hydroxypropylmethyl cellulose (HPMC and microcrystalline cellulose (MCC were used as solid carriers. Judging from the retention ratios of Labrasol® and Transcutol®, the droplet size of solid SMEDDS increased after spray-drying of liquid SMEDDS, and concentrations of these excipients decreased after the solidifying procedure. In such reduction, Lactose and HPMC were found to preserve Labrasol® and Transcutol® better than MCC during spray-drying, and the resultant droplet sizes were smaller than that of MCC. Labrasol® and Transcutol® showed good thermal stability at 60 °C degree for 10 days. It can be concluded that spray-drying could increase the droplet size of solid SMEDDS and decreased the concentration of Labrasol® and Transcutol® therein, while water-soluble solid carriers could preserve Labrasol® and Transcutol® better than insoluble carriers in the solid SMEDDS.

Radiation preparation of drug carriers based polyacrylic acid (PAAc) using poly(vinyl pyrrolidone) (PVP) as a template polymer

Science.gov (United States)

Abd El-Rehim, H. A.; Hegazy, E. A.; Khalil, F. H.; Hamed, N. A.

2007-01-01

The present study deals with the radiation synthesis of stimuli response hydrophilic polymers from polyacrylic acid (PAAc). To maintain the property of PAAc and control the water swellibility for its application as a drug delivery system, radiation polymerization of AAc in the presence of poly(vinyl pyrrolidone) (PVP) as a template polymer was carried out. Characterization of the prepared PAA/PVP inter-polymer complex was investigated by determining gel content, swelling property, hydrogel microstructure and the release rate of caffeine as a model drug. The release rate of caffeine from the PAA/PVP inter-polymer complexes showed pH-dependency, and seemed to be mainly controlled by the dissolution rate of the complex above a p Ka of PAAc. The prepared inter-polymer complex could be used for application as drug carriers.

Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.

Science.gov (United States)

Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra

2016-09-01

Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

Multifunctional Amine Mesoporous Silica Spheres Modified with Multiple Amine as Carriers for Drug Release

Directory of Open Access Journals (Sweden)

Yan Li

2018-01-01

Full Text Available Mesoporous silica spheres were synthesized by using Stöber theory (MSN-40. Calcination of the mesostructured phase resulted in the starting solid. Organic modification with aminopropyl groups resulted in two MSN-40 materials: named MSN-NH2 and MSN-DQ-40, respectively. These two kinds of samples with different pore sizes (obtained from 3-[2-(2-aminoethylaminoethylamino]propyl-trimethox-ysilane (NQ-62 and modified NQ-62 showed control of the delivery rate of ibuprofen (IBU from the siliceous matrix. The obtained sample from modified NQ-62 has an increased loading rate and shows better control of the delivery rate of IBU than the obtained sample from NQ-62. These three solids were characterized using standard solid state procedures. During tests of in vitro drug release, an interesting phenomenon was observed: at high pH (pH 7.45, IBU in all carriers was released slowly; at low pH (pH 4.5, only a part of the IBU was slowly released from this carrier within 25 hours; most IBU was effectively confined in mesoporous material, but the remaining IBU was released rapidly and completely after 25 hours.

Physical stability, biocompatibility and potential use of hybrid iron oxide-gold nanoparticles as drug carriers

Energy Technology Data Exchange (ETDEWEB)

Barnett, Christopher M. [School of Pharmacy, Keele University (United Kingdom); Gueorguieva, Mariana [Institute of Medical Science and Technology, University of Dundee (United Kingdom); Lees, Martin R. [University of Warwick, Physics Department (United Kingdom); McGarvey, David J. [School of Physical and Geographical Sciences, Keele University, Lennard-Jones Laboratories (United Kingdom); Hoskins, Clare, E-mail: c.hoskins@keele.ac.uk [Institute for Science and Technology in Medicine, Keele University (United Kingdom)

2013-06-15

Hybrid nanoparticles (HNPs) such as iron oxide-gold nanoparticles are currently being exploited for their potential application in image-guided therapies. However, little investigation has been carried out into their physical or chemical stability and potential cytotoxicity in biological systems. Here, we determine the HNPs physical stability over 6 months and chemical stability in physiological conditions, and estimate the biological activity of uncoated and poly(ethylene glycol) coated nanoparticles on human pancreatic adenocarcinoma (BxPC-3) and differentiated human monocyte cells (U937). The potential of these HNPs to act as drug carrier vehicles was determined using the model drug 6-Thioguanine (6-TG). The data showed that the HNPs maintained their structural integrity both physically and chemically throughout the duration of the studies. In addition, negligible cytotoxicity or free radical production was observed in the cell lines tested. The 6-TG was successfully conjugated; with a ratio of 3:1:10 Fe:Au:6-TG (wt:wt:wt). After incubation with BxPC-3 cells, enhanced cellular uptake was reported with the 6-TG-conjugated HNPs compared with free drug along with a 10-fold decrease in IC{sub 50}. This exciting data highlights the potential of HNPs for use in image-guided drug delivery.

Applications of polymeric nanocapsules in field of drug delivery systems.

Science.gov (United States)

Rong, Xinyu; Xie, Yinghua; Hao, Xiaomei; Chen, Tao; Wang, Yingming; Liu, Yuanyuan

2011-09-01

Drug-loaded polymeric nanocapsules have exhibited potential applications in the field of drug delivery systems in recent years. This article entails the biodegradable polymers generally used for preparing nanocapsules, which include both natural polymers and synthetic polymers. Furthermore, the article presents a general review of the different preparation methods: nanoprecipitation method, emulsion-diffusion method, double emulsification method, emulsion-coacervation method, layer-by-layer assembly method. In addition, the analysis methods of nanocapsule characteristics, such as mean size, morphology, surface characteristics, shell thickness, encapsulation efficiency, active substance release, dispersion stability, are mentioned. Also, the applications of nanocapsules as carriers for use in drug delivery systems are reviewed, which primarily involve targeting drug delivery, controlled/sustained release drug delivery systems, transdermal drug delivery systems and improving stability and bioavailability of drugs. Nanocapsules, prepared with different biodegradable polymers, have received more and more attention and have been regarded as one of the most promising drug delivery systems.

Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

Science.gov (United States)

Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

2012-07-01

This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Carrier dynamics in graphene. Ultrafast many-particle phenomena

Energy Technology Data Exchange (ETDEWEB)

Malic, E.; Brem, S.; Jago, R. [Department of Physics, Chalmers University of Technology, Goeteborg (Sweden); Winzer, T.; Wendler, F.; Knorr, A. [Institut fuer Theoretische Physik, Technische Universitaet Berlin (Germany); Mittendorff, M.; Koenig-Otto, J.C.; Schneider, H.; Helm, M.; Winnerl, S. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Ploetzing, T.; Neumaier, D. [Advanced Microelectronic Center Aachen, AMO GmbH, Aachen (Germany)

2017-11-15

Graphene is an ideal material to study fundamental Coulomb- and phonon-induced carrier scattering processes. Its remarkable gapless and linear band structure opens up new carrier relaxation channels. In particular, Auger scattering bridging the valence and the conduction band changes the number of charge carriers and gives rise to a significant carrier multiplication - an ultrafast many-particle phenomenon that is promising for the design of highly efficient photodetectors. Furthermore, the vanishing density of states at the Dirac point combined with ultrafast phonon-induced intraband scattering results in an accumulation of carriers and a population inversion suggesting the design of graphene-based terahertz lasers. Here, we review our work on the ultrafast carrier dynamics in graphene and Landau-quantized graphene is presented providing a microscopic view on the appearance of carrier multiplication and population inversion. (copyright 2017 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Mesoporous Silica Molecular Sieve based Nanocarriers: Transpiring Drug Dissolution Research.

Science.gov (United States)

Pattnaik, Satyanarayan; Pathak, Kamla

2017-01-01

Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs. Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture. This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

International Nuclear Information System (INIS)

Pentak, Danuta

2016-01-01

Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

Energy Technology Data Exchange (ETDEWEB)

Pentak, Danuta, E-mail: danuta.pentak@us.edu.pl [University of Silesia, Department of Materials Chemistry and Chemical Technology, Institute of Chemistry (Poland)

2016-05-15

Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

Nanoparticle carriers based on copolymers of poly(l-aspartic acid co-l-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine for drug delivery

Energy Technology Data Exchange (ETDEWEB)

Han Siyuan; Wang Huan; Liang Xingjie [National Center for Nanoscience and Technology, Laboratory of Nanobiomedicine and Nanosafety, Division of Nanomedicine and Nanobiology (China); Hu Liming, E-mail: huliming@bjut.edu.cn [Beijing University of Technology, College of Life Science and Bioengineering (China); Li Min; Wu Yan, E-mail: wuy@nanoctr.cn [National Center for Nanoscience and Technology, Laboratory of Nanobiomedicine and Nanosafety, Division of Nanomedicine and Nanobiology (China)

2011-09-15

A novel poly(l-aspartic) derivative (PAL-DPPE) containing polylactide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments has been successfully synthesized. The chemical structures of the copolymers were confirmed by Fourier-transform infrared spectroscopy (FTIR), NMR ({sup 1}H NMR, {sup 13}C NMR, {sup 31}P NMR), and thermogravimetric analysis (TGA). Fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) confirmed the formation of micelles of the PAL-DPPE copolymers. In order to estimate the feasibility as novel drug carriers, an anti-tumor model drug doxorubicin (DOX) was incorporated into polymeric micelles by double emulsion and nanoprecipitation method. The DOX-loaded micelle size, size distribution, and encapsulation efficiency (EE) were influenced by the feed weight ratio of the copolymer to DOX. In addition, in vitro release experiments of the DOX-loaded PAL-DPPE micelles exhibited that faster release in pH 5.0 than their release in pH 7.4 buffer. The poly(l-aspartic) derivative copolymer was proved to be an available carrier for the preparation of micelles for anti-tumor drug delivery.

Nanoparticle carriers based on copolymers of poly(l-aspartic acid co-l-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine for drug delivery

International Nuclear Information System (INIS)

Han Siyuan; Wang Huan; Liang Xingjie; Hu Liming; Li Min; Wu Yan

2011-01-01

A novel poly(l-aspartic) derivative (PAL-DPPE) containing polylactide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments has been successfully synthesized. The chemical structures of the copolymers were confirmed by Fourier-transform infrared spectroscopy (FTIR), NMR ( 1 H NMR, 13 C NMR, 31 P NMR), and thermogravimetric analysis (TGA). Fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) confirmed the formation of micelles of the PAL-DPPE copolymers. In order to estimate the feasibility as novel drug carriers, an anti-tumor model drug doxorubicin (DOX) was incorporated into polymeric micelles by double emulsion and nanoprecipitation method. The DOX-loaded micelle size, size distribution, and encapsulation efficiency (EE) were influenced by the feed weight ratio of the copolymer to DOX. In addition, in vitro release experiments of the DOX-loaded PAL-DPPE micelles exhibited that faster release in pH 5.0 than their release in pH 7.4 buffer. The poly(l-aspartic) derivative copolymer was proved to be an available carrier for the preparation of micelles for anti-tumor drug delivery.

Herbal carrier-based floating microparticles of diltiazem ...

African Journals Online (AJOL)

Purpose: To formulate and characterize a gastroretentive floating drug delivery system for diltiazem hydrochloride using psyllium husk and sodium alginate as natural herbal carriers to improve the therapeutic effect of the drug in cardiac patients. Methods: Floating microparticles containing diltiazem hydrochloride were ...

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

Science.gov (United States)

Tan, Angel; Rao, Shasha; Prestidge, Clive A

2013-12-01

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

Energy Technology Data Exchange (ETDEWEB)

Mai, Binh Khanh [Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City (Viet Nam); Li, Mai Suan, E-mail: masli@ifpan.edu.pl [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland)

2011-07-08

Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

International Nuclear Information System (INIS)

Mai, Binh Khanh; Li, Mai Suan

2011-01-01

Highlights: → We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. → It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. → We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. → The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

Thiomers for oral delivery of hydrophilic macromolecular drugs.

Science.gov (United States)

Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

2004-11-01

In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs.

Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy.

Science.gov (United States)

Yuan, Youyong; Liu, Bin

2014-09-10

A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 μg mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 μg mL(-1)) or chemotherapy (132.8 μg mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin αvβ3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment.

Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

Science.gov (United States)

Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

2017-05-01

In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

Passive tumor targeting of polymer therapeutics: in vivo imaging of both the polymer carrier and the enzymatically cleavable drug model

Czech Academy of Sciences Publication Activity Database

Pola, Robert; Heinrich, A. K.; Mueller, T.; Kostka, Libor; Mäder, K.; Pechar, Michal; Etrych, Tomáš

2016-01-01

Roč. 16, č. 11 (2016), s. 1577-1582 ISSN 1616-5187 R&D Projects: GA ČR(CZ) GA15-02986S; GA ČR(CZ) GA16-17207S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : polymer drug carriers * tumor targeting * enzymatic release Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.238, year: 2016

Pharmacogenetics in drug regulation: promise, potential and pitfalls

Science.gov (United States)

Shah, Rashmi R

2005-01-01

Pharmacogenetic factors operate at pharmacokinetic as well as pharmacodynamic levels—the two components of the dose–response curve of a drug. Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose–response relationship between individuals. For some drugs, although retrospective data from case studies suggests that these polymorphisms are frequently associated with adverse drug reactions or failure of efficacy, the clinical utility of such data remains unproven. There is, therefore, an urgent need for prospective data to determine whether pre-treatment genotyping can improve therapy. Various regulatory guidelines already recommend exploration of the role of genetic factors when investigating a drug for its pharmacokinetics, pharmacodynamics, dose–response relationship and drug interaction potential. Arising from the global heterogeneity in the frequency of variant alleles, regulatory guidelines also require the sponsors to provide additional information, usually pharmacogenetic bridging data, to determine whether data from one ethnic population can be extrapolated to another. At present, sponsors explore pharmacogenetic influences in early clinical pharmacokinetic studies but rarely do they carry the findings forward when designing dose–response studies or pivotal studies. When appropriate, regulatory authorities include genotype-specific recommendations in the prescribing information. Sometimes, this may include the need to adjust a dose in some genotypes under specific circumstances. Detailed references to pharmacogenetics in prescribing information and pharmacogenetically based prescribing in routine therapeutics will require robust prospective data from well-designed studies. With greater integration of pharmacogenetics in drug development, regulatory authorities expect to receive more detailed genetic data. This is likely to complicate the drug evaluation process as well as

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

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Romero EL

2013-08-01

Full Text Available Eder Lilia Romero, Maria Jose Morilla Nanomedicine Research Program, Department of Science and Technology, National University of Quilmes, Bernal, Buenos Aires, Argentina Abstract: Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes® (IDEA AG, Munich, Germany, ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route. Keywords: Transfersomes, ethosomes, antitumoral, anti-inflammatory, topical delivery

A high-density lipoprotein-mediated drug delivery system.

Science.gov (United States)

Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

2016-11-15

High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation into Alternative Sugars as Potential Carriers for Dry Powder Formulation of Budesonide

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Ali Nokhodchi

2011-08-01

Full Text Available Introduction: Dry powder inhaler (DPI formulations are so far being used for pulmonary drug delivery, mainly for the treatment of asthma and chronic obstructive pulmonary disease (COPD. Currently most of DPI formulations rely on lactose as a carrier in the drug powder blend. However, due to reducing sugar function of lactose which makes it incompatible with some drugs such as budesonide, it is realistic to investigate for alternative sugars that would overcome the concerned drawback but still have the positive aspects of lactose. Methods: The study was conducted by characterizing carriers for their physico-chemical properties and preparing drug/carrier blends with concentration of 5% and 10% drug with the carrier. The mixing uniformity (homogeneity of Budesonide in the blends was analyzed using spectrophotometer. The blend was then filled into NB7/2 Airmax inhaler device and the deposition profiles of the drug were determined using multi stage liquid impinger (MSLI after aerosolization at 4 kPa via the inhaler. The morphology of the carriers conducted using the scanning electron microscope. Results: The results determined that the mean fine particle fraction (FPF of 5% and 10% blends of mannitol was 61%, possibly due to fine elongated particles. Dextrose exhibited excellent flowability. Scanning electron microscope illustrated mannitol with fine elongated particles and dextrose presenting larger and coarse particles. It was found out that type of carriers, particle size distribution, and morphology would influence the FPF of budesonide. Conclusion: It may be concluded that mannitol could be suitable as a carrier on the basis of its pharmaceutical performance and successful achievement of FPF whereas the more hygroscopic sugars such as sorbitol or xylitol showed poor dispersibility leading to lower FPF.

Perfluorocarbon (PFC) emulsions as potential drug carriers

International Nuclear Information System (INIS)

Yuhas, J.M.; Goodman, R.L.; Moore, R.E.

1984-01-01

PFC emulsions have excellent oxygen transporting properties and have been reported to enhance the response of murine tumors to both radiation and BCNU. While the presently available emulsions are far too toxic to the immune system to be used in cancer therapy, they can be used to investigate the overall potential of this approach. As an example, the authors have found that these emulsions can alter drug availability. The lipophilicity of both the PFC and the drug in question determine the partitioning of the drug between the organic and aqueous phases of an emulsion. In vitro, this can reduce drug effectiveness by reducing the amount of drug available to the cells. In vivo, however, this partitioning may produce sustained drug exposure, which could be of benefit in cancer therapy and other applications. In brief, as the drug is absorbed from the circulating aqueous phase, additional drug would leach from the PFC, thereby providing a sustained drug exposure similar to that obtained with liposomes. While a great deal more work will be required to evaluate the practicality of this approach, the existence of this phenomenon must be taken into account in both the design and interpretation of efficacy studies in which anesthetics, chemotherapeutics, etc are employed

P-glycoprotein targeted nanoscale drug carriers

KAUST Repository

Li, Wengang; Abu Samra, Dina Bashir Kamil; Merzaban, Jasmeen; Khashab, Niveen M.

2013-01-01

Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug

A multifunctional β-CD-modified Fe3O4@ZnO:Er3+,Yb3+ nanocarrier for antitumor drug delivery and microwave-triggered drug release

International Nuclear Information System (INIS)

Peng, Hongxia; Cui, Bin; Li, Guangming; Wang, Yingsai; Li, Nini; Chang, Zhuguo; Wang, Yaoyu

2015-01-01

We constructed a novel core–shell structured Fe 3 O 4 @ZnO:Er 3+ ,Yb 3+ @(β-CD) nanoparticles used as drug carrier to investigate the loading and controllable release properties of the chemotherapeutic drug etoposide (VP-16). The cavity of β-cyclodextrin is chemically inert, it can store etoposide molecules by means of hydrophobic interactions. The Fe 3 O 4 core and ZnO:Er 3+ ,Yb 3+ shell functioned successfully for magnetic targeting and up-conversion fluorescence imaging, respectively. In addition, the ZnO:Er 3+ ,Yb 3+ shell acts as a good microwave absorber with excellent microwave thermal response property for microwave triggered drug release (the VP-16 release of 18% under microwave irradiation for 15 min outclass the 2% within 6 h without microwave irradiation release). The release profile could be controlled by the duration and number of cycles of microwave application. This material therefore promises to be a useful noninvasive, externally controlled drug-delivery system in cancer therapy. - Graphical abstract: We functionalized a multifunctional core–shell Fe 3 O 4 @ZnO:Er 3+ ,Yb 3+ nanocarriers by adding β-cyclodextrin, which is capable of carrying drug molecules and triggered release of the drug by microwave treatment. - Highlights: • We constructed Fe 3 O 4 @ZnO:Er 3+ ,Yb 3+ @(β-CD) nanoparticles used as a drug carrier. • The nanoparticles have magnetic and up-conversion fluorescence properties. • The nanoparticles have excellent microwave thermal response property. • The nanocomposite could be a controllable drug release triggered by microwave

Improving Dry Powder Inhaler Performance by Surface Roughening of Lactose Carrier Particles.

Science.gov (United States)

Tan, Bernice Mei Jin; Chan, Lai Wah; Heng, Paul Wan Sia

2016-08-01

This study investigated the impact of macro-scale carrier surface roughness on the performance of dry powder inhaler (DPI) formulations. Fluid-bed processing and roller compaction were explored as processing methods to increase the surface roughness (Ra) of lactose carrier particles. DPI formulations containing either (a) different concentrations of fine lactose at a fixed concentration of micronized drug (isoniazid) or (b) various concentrations of drug in the absence of fine lactose were prepared. The fine particle fraction (FPF) and aerodynamic particle size of micronized drug of all formulations were determined using the Next Generation Impactor. Fluid-bed processing resulted in a modest increase in the Ra from 562 to 907 nm while roller compaction led to significant increases in Ra > 1300 nm. The roller compacted carriers exhibited FPF > 35%, which were twice that of the smoothest carriers. The addition of up to 5%, w/w of fine lactose improved the FPF of smoother carriers by 60-200% whereas only lactose carrier particles by roller compaction was immensely beneficial to improving DPI performance, primarily due to increased surface roughness at the macro-scale.

Novel cryomilled physically cross-linked biodegradable hydrogel microparticles as carriers for inhalation therapy.

Science.gov (United States)

El-Sherbiny, I M; Smyth, H D C

2010-01-01

In this study, novel biodegradable physically cross-linked hydrogel microparticles were developed and evaluated in-vitro as potential carriers for inhalation therapy. These hydrogel microparticles were prepared to be respirable (desired aerodynamic size) when dry and also designed to avoid the macrophage uptake (attain large swollen size once deposited in lung). The swellable microparticles, prepared using cryomilling, were based on Pluronic® F-108 in combination with PEG grafted onto both chitosan (Cs) and its N-phthaloyl derivative (NPHCs). Polymers synthesized in the study were characterized using EA, FTIR, 2D-XRD and DSC. Morphology, particle size, density, biodegradation and moisture content of the microparticles were quantified. Swelling characteristics for both drug-free and drug-loaded microparticles showed excellent size increases (between 700-1300%) and the release profiles indicated sustained release could be achieved for up to 20 days. The respirable microparticles showed drug loading efficiency up to 92%. The enzymatic degradation of developed microparticles started within the first hour and only ∼10% weights were remaining after 10 days. In conclusion, these respirable microparticles demonstrated promising in-vitro performance for potential sustained release vectors in pulmonary drug delivery.

Drug-loaded erythrocytes: on the road toward marketing approval

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Bourgeaux V

2016-02-01

Full Text Available Vanessa Bourgeaux,1 José M Lanao,2 Bridget E Bax,3 Yann Godfrin11ERYTECH Pharma, Lyon, France; 2Department of Pharmacy and Pharmaceutical Technology, University of Salamanca, Salamanca, Spain; 3Cardiovascular and Cell Sciences Research Institute, St George’s University of London, London, UKAbstract: Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor, slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding. The manufacture of this type of product can be either centralized or bedside based, and different procedures are employed for the encapsulation of therapeutic agents. The major challenges for successful industrialization include production scalability, process validation, and quality control of the released therapeutic agents. Advantages and drawbacks of the different manufacturing processes as well as success key points of clinical development are discussed. Several entrapment technologies based on osmotic methods have been industrialized. Companies have already achieved many of the critical clinical stages, thus providing the opportunity in the future to cover a wide range of diseases for which effective therapies are not currently available.Keywords: red blood cell, encapsulation method, drug carrier, industrial development, clinical use

In vitro characterization and in vivo evaluation of nanostructured lipid curcumin carriers for intragastric administration

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Fang M

2012-10-01

Full Text Available Min Fang, Yilin Jin, Wei Bao, Hui Gao, Mengjin Xu, Di Wang, Xia Wang, Ping Yao, Liegang LiuDepartment of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, and Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, People’s Republic of ChinaBackground: Curcumin has a variety of pharmacological effects. However, poor water solubility and low oral bioavailability limit its clinical utility. A delivery system for nanostructured lipid carriers has been reported to be a promising approach to enhancing the oral absorption of curcumin. The aim of the present study was to investigate the pharmacokinetics, tissue distribution, and relative bioavailability of curcumin in rats after a single intragastric dose of a nanostructured lipid curcumin carrier formulation.Methods: Nanostructured lipid curcumin carriers were prepared using the ethanol dripping method and characterized in terms of the particle size, polydispersity index, zeta potential, differential scanning calorimetry, drug-loading capacity, encapsulation efficiency, and in vitro release. The pharmacokinetics and tissue distribution of nanostructured lipid curcumin carriers and curcumin suspension were compared after intragastric administration.Results: Nanostructured lipid curcumin carriers showed a significantly higher peak plasma concentration (564.94 ± 14.98 ng/mL versus 279.43 ± 7.21 ng/mL, P < 0.01, a shorter time taken to reach peak plasma concentration (0.5 ± 0.01 hour versus 1.0 ± 0.12 hour, P < 0.01, and a greater AUC0–∞ (820.36 ± 25.11 mg × hour/L versus 344.11 ± 10.01 mg × hour/L, P < 0.05 compared with curcumin suspension. In the tissue distribution studies, curcumin could be detected in the spleen, heart, liver, kidneys, lungs, and brain. Following intragastric administration of the nanostructured lipid curcumin

Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study.

Science.gov (United States)

Mohamed, Heba A; Radwan, Rasha R; Raafat, Amany I; Ali, Amr El-Hag

2018-02-01

In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior). In vitro release studies of the antifungal (AmB) were performed to evaluate the hydrogel potential as a drug carrier. The antifungal activity of the prepared oral formulation was investigated in a mouse model of systemic candidiasis. Data revealed that (Trag/AAc)-AmB has a potent antifungal efficacy as demonstrated by prolonging the survival time and reducing the tissue fungal burden, serum antibody titers, as well as inflammatory cytokines in kidney and liver tissues. Furthermore, in vivo toxicity of (Trag/AAc)-AmB was assessed via measuring kidney and liver functions, and results displayed the safety of this novel AmB formulation which was confirmed by histopathological examination. Overall, results indicated that the prepared (Trag/AAc)-AmB is an effective oral delivery system for AmB with better bioavailability and minimal toxicity and could represent a promising approach for improving the therapeutic index of the drug.

Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation

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Abdulbaqi IM

2018-04-01

Full Text Available Ibrahim M Abdulbaqi, Yusrida Darwis, Reem Abou Assi, Nurzalina Abdul Karim Khan School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia Introduction: Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers.Methods: Colchicine-loaded transethosomes (TEs were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats’ back skin.Results: The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel.Conclusion: These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration. Keywords: transethosomes, ethosomal nanocarriers, colchicine, factorial design, skin permeation, rheology

Solute carrier transporters: Pharmacogenomics research ...

African Journals Online (AJOL)

Aghogho

2010-12-27

Dec 27, 2010 ... This paper reviews the solute carrier transporters and highlights the fact that there is much to be learnt from .... transporters, drug targets, effect or proteins and meta- ... basolateral or apical plasma membrane of polarized cells,.

Controllable fabrication and characterization of biocompatible core-shell particles and hollow capsules as drug carrier

Science.gov (United States)

Hao, Lingyun; Gong, Xinglong; Xuan, Shouhu; Zhang, Hong; Gong, Xiuqing; Jiang, Wanquan; Chen, Zuyao

2006-10-01

SiO 2@CdSe core-shell particles were fabricated by controllable deposition CdSe nanoparticles on silica colloidal spheres. Step-wise coating process was tracked by the TEM and XRD measurements. In addition, SiO 2@CdSe/polypyrrole(PPy) multi-composite particles were synthesized based on the as-prepared SiO 2@CdSe particles by cationic polymerization. The direct electrochemistry of myoglobin (Mb) could be performed by immobilizing Mb on the surface of SiO 2@CdSe particles. Immobilized with Mb, SiO 2@CdSe/PPy-Mb also displayed good bioelectrochemical activity. It confirmed the good biocompatible property of the materials with protein. CdSe hollow capsules were further obtained as the removal of the cores of SiO 2@CdSe spheres. Hollow and porous character of CdSe sub-meter size capsules made them becoming hopeful candidates as drug carriers. Doxorubicin, a typical an antineoplastic drug, was introduced into the capsules. A good sustained drug release behavior of the loading capsules was discovered via performing a release test in the PBS buffer (pH 7.4) solution at 310 k. Furthermore, SiO 2@CdSe/PPy could be converted to various smart hollow capsules via selectively removal of their relevant components.

Copper-gold nanoparticles: Fabrication, characteristic and application as drug carriers

Energy Technology Data Exchange (ETDEWEB)

Woźniak-Budych, Marta J., E-mail: marta.budych@amu.edu.pl; Langer, Krzysztof; Peplińska, Barbara; Przysiecka, Łucja; Jarek, Marcin; Jarzębski, Maciej; Jurga, Stefan

2016-08-15

In this investigation, the fabrication of porous core/shell nanostructures consisting of copper (core) and copper-gold nanoalloy (shell) for medical applications is presented. As a core triangular-shaped copper nanoparticles were used. The porous bimetallic nanoshell was prepared via galvanic reaction in the presence of oil-in water emulsion. It was proved that porous nanoalloy layer can be prepared at pH 7 and in the presence 0.1% and 0.5% oil-in water emulsion. The porous structure fabrication was mainly determined by volume fraction of hexadecane to acetone in the oil-in water emulsion and Zeta-potential of emulsion droplets (pH of emulsion). The influence of emulsion droplets size before galvanic reaction on porous structure preparation was negligible. It was found that doxorubicin could be easily introduced and released from porous core/shell nanostructures, due to spontaneous adsorption on the copper-gold nanoporous surface. The in vitro test showed that cytotoxic effect was more prominent once the doxorubicin was adsorbed on the porous copper-gold nanocarriers. It was demonstrated, that doxorubicin-loaded copper-gold nanostructures caused inhibition cell proliferation and viability of cancer cells, in a concentration-dependent manner. The results indicates that presented coper-gold nanocarrier have potential to be used in targeted cancer therapy, due to its porous structure and cytotoxic effect in cancer cells. - Highlights: • Porous copper-gold nanostructure as a cytostatic drug carrier was prepared. • Kinetics and thermodynamics of drug adsorption were studied. • DOX-loaded copper-gold nanoparticles showed a pH-controlled release rate. • DOX-loaded copper-gold NPs caused inhibition cell proliferation of cancer cells. • The Cu-Au NPs could serve as a theranostic platform for biomedical applications.

In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

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Bronckers Antonius LJJ

2006-02-01

Full Text Available Abstract Background Polymethyl-methacrylate (PMMA beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days, the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days. The relative release of all cements (36–85% and granules (30–62% was higher than previously reported for injectable PMMA-cements (up to 17% and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained may be achieved.

Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy

Energy Technology Data Exchange (ETDEWEB)

Wang, Meili; Zhao, Tingting; Liu, Yanping; Wang, Qianqian; Xing, Shanshan; Li, Lei; Wang, Longgang [Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004 (China); Liu, Lanxiang [The First Hospital of Qinhuangdao, No. 258 Cultural Road, Qinhuangdao 066000 (China); Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004 (China)

2017-02-01

There are tremendous challenges on antitumor and its therapeutic drugs, and preparation of highly efficient nano-vehicles represents one of the novel topics in antitumor pharmaceutical field. Herein, the novel chitosan-coated ursolic acid (UA) liposome (CS-UA-L) was efficiently prepared with highly tumor targeting, drug controlled release and low side-effect. The CS-UA-L was uniformly spherical particles with diameter of ~ 130 nm, and the size was more easily trapped into the tumor tissues. Chitosan modification can make liposomes carrying positive charges, which were inclined to combine with the negative charges on the surface of tumor cells, and then the CS-UA-L could release UA rapidly at pH 5.0 comparing with pH 7.4. Meanwhile, the CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells and significantly antitumor activity (61.26%) in mice bearing U14 cervical cancer. The tumor tissues of CS-UA-L treated mice had enhanced cell apoptosis, extensive necrosis and low cell proliferation activity. These results demonstrated that the multifunctional CS-UA-L allowed a precision treatment for localized tumor, and reducing the total drug dose and side-effect, which hold a great promise in new safe and effective tumor therapy. - Graphical abstract: Schematic diagram representing the principle of synthesis of CS-UA-L and pH-triggered sequential UA release after treatment on tumor bearing mouse. - Highlights: • The novel chitosan-coated ursolic acid liposomes (CS-UA-L) were successfully prepared. • CS-UA-L possessed sensitive pH-response, which could release UA rapidly at pH 5.0 comparing with pH 7.4. • CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells than UA and UA-L. • CS-UA-L suppressed tumor growth more efficiently than those with UA and UA-L in mice bearing U14 cervical cancer. • The CS-UA-L allow for precision treatment of the tumor and potential to reduce the total drug dose and side-effect.

Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

Science.gov (United States)

Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre

2013-10-01

Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Polyphenols as Promising Drugs against Main Breast Cancer Signatures

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María Losada-Echeberría

2017-11-01

Full Text Available Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs and epidermal growth factor receptor 2 (HER2. Tumors with none of these receptors are classified as triple negative breast cancer (TNBC and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation.

Polyphenols as Promising Drugs against Main Breast Cancer Signatures

Science.gov (United States)

Herranz-López, María; Micol, Vicente

2017-01-01

Breast cancer is one of the most common neoplasms worldwide, and in spite of clinical and pharmacological advances, it is still a clinical problem, causing morbidity and mortality. On the one hand, breast cancer shares with other neoplasms some molecular signatures such as an imbalanced redox state, cell cycle alterations, increased proliferation and an inflammatory status. On the other hand, breast cancer shows differential molecular subtypes that determine its prognosis and treatment. These are characterized mainly by hormone receptors especially estrogen receptors (ERs) and epidermal growth factor receptor 2 (HER2). Tumors with none of these receptors are classified as triple negative breast cancer (TNBC) and are associated with a worse prognosis. The success of treatments partially depends on their specificity and the adequate molecular classification of tumors. New advances in anticancer drug discovery using natural compounds have been made in the last few decades, and polyphenols have emerged as promising molecules. They may act on various molecular targets because of their promiscuous behavior, presenting several physiological effects, some of which confer antitumor activity. This review analyzes the accumulated evidence of the antitumor effects of plant polyphenols on breast cancer, with special attention to their activity on ERs and HER2 targets and also covering different aspects such as redox balance, uncontrolled proliferation and chronic inflammation. PMID:29112149

Applications of nanodiamonds in drug delivery and catalysis.

Science.gov (United States)

Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khatchatur; Ezzeddine, Alaa; Khashab, Niveen M

2014-01-01

The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial.

Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

Directory of Open Access Journals (Sweden)

Julia M. Tan

2014-01-01

Full Text Available Carbon nanotubes (CNTs have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate via π-π stacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminary in vitro cytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

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Liang Y

2017-03-01

Full Text Available Yan Liang,1 Baocheng Tian,1 Jing Zhang,1 Keke Li,1 Lele Wang,1 Jingtian Han,1,* Zimei Wu2,* 1School of Pharmacy, Binzhou Medical University, 2School of Pharmacy, Yantai University, Yantai, China *These authors contributed equally to this work Abstract: Gemcitabine (GEM and paclitaxel (PTX are effective combination anticancer agents against non-small-cell lung cancer (NSCLC. At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic and PTX (hydrophobic into simplex tumor-targeted nanostructured lipid carriers (NLCs for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N-acetyl-D-glucosamine (NAG is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6-O-methacryloyl-d-galactopyranose–GEM/PTX (PMAGP-GEM/PTX conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1 exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor

Basic evaluation of typical nanoporous silica nanoparticles in being drug carrier: Structure, wettability and hemolysis.

Science.gov (United States)

Li, Jing; Guo, Yingyu

2017-04-01

Herein, the present work devoted to study the basic capacity of nanoporous silica nanoparticles in being drug carrier that covered structure, wettability and hemolysis so as to provide crucial evaluation. Typical nanoporous silica nanoparticles that consist of nanoporous silica nanoparticles (NSN), amino modified nanoporous silica nanoparticles (amino-NSN), carboxyl modified nanoporous silica nanoparticles (carboxyl-NSN) and hierachical nanoporous silica nanoparticles (hierachical-NSN) were studied. The results showed that their wettability and hemolysis were closely related to structure and surface modification. Basically, wettability became stronger as the amount of OH on the surface of NSN was higher. Both large nanopores and surface modification can reduce the wettability of NSN. Furthermore, NSN series were safe to be used when they circulated into the blood in low concentration, while if high concentration can not be avoided during administration, high porosity or amino modification of NSN were safer to be considered. It is believed that the basic evaluation of NSN can make contribution in providing scientific instruction for designing drug loaded NSN systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

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Bhaskar Daravath

2018-05-01

Full Text Available ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05 in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%. The mean dissolution time (MDT was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min. indicating faster drug release. The DE (% dissolution efficiency was increased by 2.5 folds (61.63% compared to conventional tablets (23.71%. From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Zeolites: promising candidates for drug delivery systems (DDSs)

OpenAIRE

Vilaça, Natália; Amorim, Ricardo; Baltazar, Fátima; Fonseca, António Manuel; Neves, Isabel C.

2012-01-01

[Excerpt] The aim of controlled drug delivery systems (DDSs) is to administer the necessary amount of drug safely and effectively to specific sites in the human body and to regulate the temporal drug profile for maximum therapeutic benefits.[1] Zeolites are crystalline aluminosilicates solids with very regular microporous structures and they have been recently considered for medical use due to their biological properties and stability in biological environments.[1,2] The large variety in ...

Polyelectrolyte Multilayer Film Coated Silver Nanorods: An Effective Carrier System for Externally Activated Drug Delivery

Science.gov (United States)

Paramasivam, Gokul; Sharma, Varsha; Sundaramurthy, Anandhakumar

2017-08-01

Nanoparticle anisotropy offers unique functions and features in comparison with spherical nanoparticles (NPs) and makes anisotropic nanoparticles (ANPs) promising candidates in applications like drug delivery, imaging, biosensing and theranostics. Presence of surface active groups (e.g. amine, and carboxylate groups) on their surface provides binding sites for ligands or other biomolecules, and hence, this could be targeted for specific part or cells in our body. In the quest of such surface modification, functionalization of ANPs along Layer-by-Layer (LbL) coating of oppositely charged polyelectrolytes (PE) reduces cellular toxicity and promotes easy encapsulation of drugs. In this work, we report the silver nanorods (AgNRs) synthesis by adsorbate directed synthetic approach using cetyltrimethyl ammonium bromide (CTAB). The formed ANPs is investigated by scanning electron microscopy (SEM) and UV-Visible (UV-Vis) spectroscopy revealing the shaping of AgNRs of 3-16 nm aspect ratio with some presence of triangles. These NRs were further coated with bio polymers of chitosan (CH) and dextran sulphate (DS) through LbL approach and used for encapsulation of water soluble anti-bacterial drugs like ciprofloxacin hydrochloride (CFH). The encapsulation of drugs and profiles of drug release were investigated and compared to that of spherical silver nanoparticles (AgNPs). The added advantages of the proposed drug delivery system (DDS) can be externally activated to release the loaded drug and used as contrast agents for biological imaging under exposure to NIR light. Such system shows unique and attractive characteristics required for drug delivery and bioimaging thus offering the scope for further development as theranostic material.

Development, optimization and evaluation of surfactant-based pulmonary nanolipid carrier system of paclitaxel for the management of drug resistance lung cancer using Box-Behnken design.

Science.gov (United States)

Kaur, Prabhjot; Garg, Tarun; Rath, Goutam; Murthy, R S Rayasa; Goyal, Amit K

2016-07-01

In the present study, nanostructured lipid carriers (NLCs) along with various surfactants loaded with paclitaxel (PTX) were prepared by an emulsification technique using a Box-Behnken design. The Box-Behnken design indicated that the most effective factors on the size and PDI were at high surfactant concentration (1.5%), low lipids ratio (6:4) and medium homogenization speed (6000 rpm). Among all the formulations, Tween 20-loaded NLCs show least particle size compared to Tween 80 and Tween 60. Entrapment efficiency of Tween 20, Tween 80 and Tween 60-loaded formulations were 82.40, 85.60 and 79.78%, respectively. Drug release of Tween 80, Tween 20 and Tween 60-loaded NLCs is 64.9, 62.3 and 59.7%, respectively (within 72 h). Maximum cellular uptake was observed with Tween 20 formulation on Caco-2 cell lines. Furthermore, spray drying of resultant NLCs was showed good flow properties and was selected for drug delivery to deeper airways. In-vivo studies demonstrated the better localization of drug within the lungs using different surfactant-based pulmonary delivery systems. From this study, we have concluded that delivering drugs through pulmonary route is advantageous for local action in lungs as maximum amount of drug concentration was observed in lungs. The surfactants could prove to be beneficial in treating drug resistance lung cancer by inhibiting P-gp efflux in the form of nano lipidic carriers.

Preparation and characterization of PEGylated chitosan nanocapsules as a carrier for pharmaceutical application

Science.gov (United States)

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

2014-03-01

A new method to conjugate methoxy polyethylene glycol (mPEG) to C6 position of chitosan under the mild condition is introduced that improves the biocompatibility and water solubility of chitosan. Harsh deprotecting step and several purification cycles are two major disadvantages of the current methods for preparing PEGylated chitosan. In this study, the amine groups at C2 position of chitosan are protected using SDS followed by grafting the PEG. The protecting group of chitosan is simply removed by dialyzing against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and 1H NMR spectroscopy. Fourier transformed-infrared (FT-IR) and 1H NMR spectra confirmed that the mPEG is successfully grafted to C6 position of chitosan. Prepared methoxy polyethylene glycol (mPEG) is then employed to prepare the nanocapsules for the encapsulation of poor water-soluble drug, propofol. The TEM, AFM, and DLS techniques are used to characterize the prepared nanocapsules size and morphology. The results show a size of about 80 nm with spherical shape for nanocapsules. In vitro drug release is carried out to evaluate the potential of nanocarriers for the intravenous delivery of drugs. The profile of release from formulated nanocapsules is similar to those of commercial lipid emulsion (CLE). In vivo animal sleep-recovery test on rats shows a close similarity between the time of unconsciousness and recovery of righting reflex between nanoparticles and CLE. This study provides an efficient, novel, and easy method for preparing a carrier system that requires less intensive reaction conditions, fewer reaction steps, and less purification steps. In addition, the nanocapsules introduced here could be a promising nano carrier for the delivery of poor water-soluble drugs.

A novel oral delivery system consisting in "drug-in cyclodextrin-in nanostructured lipid carriers" for poorly water-soluble drug: vinpocetine.

Science.gov (United States)

Lin, Congcong; Chen, Fen; Ye, Tiantian; Zhang, Lina; Zhang, Wenji; Liu, Dandan; Xiong, Wei; Yang, Xinggang; Pan, Weisan

2014-04-25

The purpose of this study was to develop a new delivery system based on drug cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC) to improve the oral bioavailability of vinpocetine (VP). Three different CDs and three different methods to obtain solid vinpocetine-cyclodextrin-tartaric acid complexes (VP-CD-TA) were contrasted. The co-evaporation vinpocetine-β-cyclodextrin-tartaric acid loaded NLC (VP-β-CD-TA COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. VP-β-CD-TA COE-loaded NLC was suitably characterized for particle size, polydispersity index, zeta potential, entrapment efficiency and the morphology. The crystallization of drug in VP-CD-TA and NLC was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out at pH 1.2, pH 6.8 and pH 7.4 medium. New Zealand rabbits were applied to investigate the pharmacokinetic behavior in vivo. The VP-β-CD-TA COE-loaded NLC presented a superior physicochemical property and selected to further study. In the in vitro release study, VP-β-CD-TA COE-loaded NLC exhibited a higher dissolution rate in the pH 6.8 and pH 7.4 medium than VP suspension and VP-NLC. The relative bioavailability of VP-β-CD-TA COE-loaded NLC was 592% compared with VP suspension and 92% higher than VP-NLC. In conclusion, the new formulation significantly improved bioavailability of VP for oral delivery, demonstrated a perspective way for oral delivery of poorly water-soluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Advances in the synthesis and application of nanoparticles for drug delivery.

Science.gov (United States)

Park, Wooram; Na, Kun

2015-01-01

The continuous development of drug delivery systems (DDSs) has been extensively researched by the need to maximize therapeutic efficacy while minimizing undesirable side effects. Nanoparticle technology was recently shown to hold great promise for drug delivery applications in nanomedicine due to its beneficial properties, such as better encapsulation, bioavailability, control release, and lower toxic effect. Despite the great progress in nanomedicine, there remain many limitations for clinical application. To overcome these limitations, advanced nanoparticles for drug delivery have been developed to enable the spatially and temporally controlled release of drugs in response to specific stimuli at disease sites. Furthermore, the controlled self-assembly of organic and inorganic materials may enable their use in theranostic applications. This review presents an overview of a recent advanced nanoparticulate system that can be used as a potential drug delivery carrier and focuses on the potential applications of nanoparticles in various biomedical fields for human health care. © 2015 Wiley Periodicals, Inc.

Soluble polymer conjugates for drug delivery.

Science.gov (United States)

Minko, Tamara

2005-01-01

The use of water-soluble polymeric conjugates as drug carriers offers several possible advantages. These advantages include: (1) improved drug pharmacokinetics; (2) decreased toxicity to healthy organs; (3) possible facilitation of accumulation and preferential uptake by targeted cells; (4) programmed profile of drug release. In this review, we will consider the main types of useful polymeric conjugates and their role and effectiveness as carriers in drug delivery systems.: © 2005 Elsevier Ltd . All rights reserved.

Applications of nanodiamonds in drug delivery and catalysis

KAUST Repository

Moosa, Basem

2014-01-01

The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial. Copyright © 2014 American Scientific Publishers All rights reserved.

Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects.

Science.gov (United States)

Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

2016-01-01

Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of -31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. B-NLCs described in this study are well-suited for the delivery of baicalin. Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ

Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms.

Science.gov (United States)

Taranejoo, Shahrouz; Janmaleki, Mohsen; Pachenari, Mohammad; Seyedpour, Seyed Morteza; Chandrasekaran, Ramya; Cheng, Wenlong; Hourigan, Kerry

2016-11-20

A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K 1 and K 2 ) and the coefficient of viscosity (μ). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach. Copyright �

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

Science.gov (United States)

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

2018-05-01

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

Drug delivery interfaces in the 21st century: from science fiction ideas to viable technologies.

Science.gov (United States)

Chertok, Beata; Webber, Matthew J; Succi, Marc D; Langer, Robert

2013-10-07

Early science fiction envisioned the future of drug delivery as targeted micrometer-scale submarines and "cyborg" body parts. Here we describe the progression of the field toward technologies that are now beginning to capture aspects of this early vision. Specifically, we focus on the two most prominent types of systems in drug delivery: the intravascular micro/nano drug carriers for delivery to the site of pathology and drug-loaded implantable devices that facilitate release with the predefined kinetics or in response to a specific cue. We discuss the unmet clinical needs that inspire these designs, the physiological factors that pose difficult challenges for their realization, and viable technologies that promise robust solutions. We also offer a perspective on where drug delivery may be in the next 50 years based on expected advances in material engineering and in the context of future diagnostics.

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

Directory of Open Access Journals (Sweden)

Panoraia I. Siafaka

2016-08-01

Full Text Available Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting

OpenAIRE

?urga, Simon; Nanut, Milica Peri?i?; Kos, Janko; Saboti?, Jerica

2017-01-01

Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin ?3?1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initia...

Synthesis and characterization of chitosan quaternary ammonium salt and its application as drug carrier for ribavirin.

Science.gov (United States)

Li, Si-Dong; Li, Pu-Wang; Yang, Zi-Ming; Peng, Zheng; Quan, Wei-Yan; Yang, Xi-Hong; Yang, Lei; Dong, Jing-Jing

2014-11-01

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is hydro-soluble chitosan (CS) derivative, which can be obtained by the reaction between epoxypropyl trimethyl ammonium chloride (ETA) and CS. The preparation parameters for the synthesis of HTCC were optimized by orthogonal experimental design. ETA was successfully grafted into the free amino group of CS. Grafting of ETA with CS had great effect on the crystal structure of HTCC, which was confirmed by the XRD results. HTCC displayed higher capability to form nanoparticles by crosslinking with negatively charged sodium tripolyphosphate (TPP). Ribavrin- (RIV-) loaded HTCC nanoparticles were positively charged and were spherical in shape with average particle size of 200 nm. More efficient drug encapsulation efficiency and loading capacity were obtained for HTCC in comparison with CS, however, HTCC nanoparticles displayed faster release rate due to its hydro-soluble properties. The results suggest that HTCC is a promising CS derivative for the encapsulation of hydrophilic drugs in obtaining sustained release of drugs.

Conditions for a carrier multiplication in amorphous-selenium based photodetector

Energy Technology Data Exchange (ETDEWEB)

Masuzawa, Tomoaki; Kuniyoshi, Shingo; Onishi, Masanori; Kato, Richika; Saito, Ichitaro; Okano, Ken [Department of Material Science, International Christian University, S102 Science Hall, ICU, 3-10-2 Osawa, Mitaka, Tokyo 181-8585 (Japan); Yamada, Takatoshi [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, Tsukuba, Ibaraki 305-8568 (Japan); Koh, Angel T. T.; Chua, Daniel H. C. [Department of Materials Science and Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574 (Singapore); Shimosawa, Tatsuo [Department of Clinical Laboratory, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-8655 (Japan)

2013-02-18

Amorphous selenium is a promising candidate for high sensitivity photodetector due to its unique carrier multiplication phenomenon. More than 10 carriers can be generated per incident photon, which leads to high photo-conversion efficiency of 1000% that allows real-time imaging in dark ambient. However, application of this effect has been limited to specific devices due to the lack in material characterization. In this article, mechanism of carrier multiplication has been clarified using time-of-flight secondary ion mass spectroscopy and Raman spectroscopy. A prototype photodetector achieved photo conversion efficiency of 4000%, which explains the signal enhancement mechanism in a-Se based photodetector.

Conditions for a carrier multiplication in amorphous-selenium based photodetector

International Nuclear Information System (INIS)

Masuzawa, Tomoaki; Kuniyoshi, Shingo; Onishi, Masanori; Kato, Richika; Saito, Ichitaro; Okano, Ken; Yamada, Takatoshi; Koh, Angel T. T.; Chua, Daniel H. C.; Shimosawa, Tatsuo

2013-01-01

Amorphous selenium is a promising candidate for high sensitivity photodetector due to its unique carrier multiplication phenomenon. More than 10 carriers can be generated per incident photon, which leads to high photo-conversion efficiency of 1000% that allows real-time imaging in dark ambient. However, application of this effect has been limited to specific devices due to the lack in material characterization. In this article, mechanism of carrier multiplication has been clarified using time-of-flight secondary ion mass spectroscopy and Raman spectroscopy. A prototype photodetector achieved photo conversion efficiency of 4000%, which explains the signal enhancement mechanism in a-Se based photodetector.

Supersaturating drug delivery systems

DEFF Research Database (Denmark)

Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

2017-01-01

of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

pH responsive controlled release of anti-cancer hydrophobic drugs from sodium alginate and hydroxyapatite bi-coated iron oxide nanoparticles.

Science.gov (United States)

Manatunga, Danushika C; de Silva, Rohini M; de Silva, K M Nalin; de Silva, Nuwan; Bhandari, Shiva; Yap, Yoke Khin; Costha, N Pabakara

2017-08-01

Developing a drug carrier system which could perform targeted and controlled release over a period of time is utmost concern in the pharmaceutical industry. This is more relevant when designing drug carriers for poorly water soluble drug molecules such as curcumin and 6-gingerol. Development of a drug carrier system which could overcome these limitations and perform controlled and targeted drug delivery is beneficial. This study describes a promising approach for the design of novel pH sensitive sodium alginate, hydroxyapatite bilayer coated iron oxide nanoparticle composite (IONP/HAp-NaAlg) via the co-precipitation approach. This system consists of a magnetic core for targeting and a NaAlg/HAp coating on the surface to accommodate the drug molecules. The nanocomposite was characterized using FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. The loading efficiency and loading capacity of curcumin and 6-gingerol were examined. In vitro drug releasing behavior of curcumin and 6-gingerol was studied at pH 7.4 and pH 5.3 over a period of seven days at 37°C. The mechanism of drug release from the nanocomposite of each situation was studied using kinetic models and the results implied that, the release is typically via diffusion and a higher release was observed at pH 5.3. This bilayer coated system can be recognized as a potential drug delivery system for the purpose of curcumin and 6-gingerol release in targeted and controlled manner to treat diseases such as cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Study of the Dynamic Uptake of Free Drug and Nanostructures for Drug Delivery Based on Bioluminescence Measurements

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Zhongjian Fang

2017-01-01

Full Text Available The past two decades have witnessed the great growth of the development of novel drug carriers. However, the releasing dynamics of drug from drug carriers in vivo and the interactions between cells and drug carriers remain unclear. In this paper, liposomes were prepared to encapsulate D-luciferin, which was the substrate of luciferase and served as a model drug. Based on the theoretical calculation of active loading, methods of preparation for liposomes were optimized. Only when D-luciferin was released from liposomes or taken in by the cells could bioluminescence be produced under the catalysis of luciferase. Models of multicellular tumor spheroid (MCTS were built with 4T1-luc cells that expressed luciferase stably. The kinetic processes of uptake and distribution of free drugs and liposomal drugs were determined with models of cell suspension, monolayer cells, MCTS, and tumor-bearing nude mice. The technology platform has been demonstrated to be effective for the study of the distribution and kinetic profiles of various liposomes as drug delivery systems.

Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites.

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Kevin Ii, Dion A; Meujo, Damaris Af; Hamann, Mark T

2009-02-01

As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics.

Dendrimer-conjugated iron oxide nanoparticles as stimuli-responsive drug carriers for thermally-activated chemotherapy of cancer.

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Nigam, Saumya; Bahadur, Dhirendra

2017-07-01

In recent years, functional nanomaterials have found an appreciable place in the understanding and treatment of cancer. This work demonstrates the fabrication and characterization of a new class of cationic, biocompatible, peptide dendrimers, which were then used for stabilizing and functionalizing magnetite nanoparticles for combinatorial therapy of cancer. The synthesized peptide dendrimers have an edge over the widely used PAMAM dendrimers due to better biocompatibility and negligible cytotoxicity of their degradation products. The surface engineering efficacy of the peptide dendrimers and their potential use as drug carriers were compared with their PAMAM counterparts. The peptide dendrimer was found to be as efficient as PAMAM dendrimers in its drug-carrying capacity, while its drug release profiles substantially exceeded those of PAMAM's. A dose-dependent study was carried out to assess their half maximal inhibitory concentration (IC 50 ) in vitro with various cancer cell lines. A cervical cancer cell line that was incubated with these dendritic nanoparticles was exposed to alternating current magnetic field (ACMF) to investigate the effect of elevated temperatures on the live cell population. The DOX-loaded formulations, in combination with the ACMF, were also assessed for their synergistic effects on the cancer cells for combinatorial therapy. The results established the peptide dendrimer as an efficient alternative to PAMAM, which can be used successfully in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding interparticle interactions in dry powder inhalation : glass beads as an innovative model carrier system

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Renner, Niklas Ludwig

2017-01-01

Delivery of drugs via the pulmonary route is the most common approach to treat diseases of the respiratory system, e.g. asthma bronchiale. Here, the active pharmaceutical ingredient is generally formulated in a so-called interactive mixture with a coarse and inert carrier. This enhances flowability and therefore dose metering and dispersibility. Interparticle interactions between carrier and drug govern aerosolisation behaviour of the blend and consequently the efficacy of the drug deposition...

Preparation and Characterization of Minoxidil Loaded Nanostructured Lipid Carriers.

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Wang, Wenxi; Chen, Lina; Huang, Xinyan; Shao, Anna

2017-02-01

Nanostructured lipid carriers (NLCs) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. The present paper described the development of a novel NLCs for minoxidil (MXD) topical delivery. Stearic acid and oleic acid that showed the highest solubility for MXD were selected as solid lipid and liquid lipid, respectively, and the NLCs were prepared by hot high pressure homogenization method. The minoxidil loaded NLCs prepared accordingly to the optimal formulation exhibited spherical shape with a mean diameter of 281.4 ± 7.4 nm, polydispersity of 0.207 ± 0.009, zeta potential of -32.90 ± 1.23 mV, drug entrapment efficiency of 92.48 ± 0.31%, and drug loading of 13.85 ± 0.47%. Storage stability studies demonstrated that the particle size and entrapment efficiency of the MXD-NLCs were not changed during 3 months both at 4°C and room temperature. Moreover, the release of MXD from the NLCs was faster than drug release from SLNs. In vitro skin permeability test demonstrated that MXD-NLCs had a more pronounced permeation and retention profile than MXD-SLNs. Furthermore, no erythema was observed after administration of MXD-NLCs. All these results indicated that the developed MXD-NLCs could be a promising and effective nanocarrier for topical delivery of MXD.

Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier.

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Keith D Miller

Full Text Available Tobacco addiction represents one of the largest public health problems in the world and is the leading cause of cancer and heart disease, resulting in millions of deaths a year. Vaccines for smoking cessation have shown considerable promise in preclinical models, although functional antibody responses induced in humans are only modestly effective in preventing nicotine entry into the brain. The challenge in generating serum antibodies with a large nicotine binding capacity is made difficult by the fact that this drug is non-immunogenic and must be conjugated as a hapten to a protein carrier. To circumvent the limitations of traditional carriers like keyhole limpet hemocyanin (KLH, we have synthesized a short trimeric coiled-coil peptide (TCC that creates a series of B and T cell epitopes with uniform stoichiometry and high density. Here we compared the relative activities of a TCC-nic vaccine and two control KLH-nic vaccines using Alum as an adjuvant or GLA-SE, which contains a synthetic TLR4 agonist formulated in a stable oil-in-water emulsion. The results showed that the TCC's high hapten density correlated with a better immune response in mice as measured by anti-nicotine Ab titer, affinity, and specificity, and was responsible for a reduction in anti-carrier immunogenicity. The Ab responses achieved with this synthetic vaccine resulted in a nicotine binding capacity in serum that could prevent >90% of a nicotine dose equivalent to three smoked cigarettes (0.05 mg/kg from reaching the brain.

Strategy for selecting nanotechnology carriers to overcome immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics.

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Dobrovolskaia, Marina A; McNeil, Scott E

2015-07-01

Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation. This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents. NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.

Doxorubicin loaded PEG-b-poly(4-vinylbenzylphosphonate) coated magnetic iron oxide nanoparticles for targeted drug delivery

Energy Technology Data Exchange (ETDEWEB)

Hałupka-Bryl, Magdalena, E-mail: magdalenahalupka@op.pl [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Division of Medical Physics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba (Japan); Bednarowicz, Magdalena [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Division of Medical Physics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba (Japan); Dobosz, Bernadeta; Krzyminiewski, Ryszard [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Division of Medical Physics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Zalewski, Tomasz [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Wereszczyńska, Beata [Department of Macromolecular Physics, Adam Mickiewicz University, Poznań (Poland); Nowaczyk, Grzegorz; Jarek, Marcin [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Nagasaki, Yukio [Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba (Japan); Master’s School of Medicinal Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba (Japan); International Centre for Materials Nanoarchitectonics Satellite (WPI-MANA), National Institute For Materials Sciences (NIMS) and University of Tsukuba (Japan)

2015-06-15

Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles with chemiotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer. The aim of this work is to characterize physical and magnetic properties of synthesized nanoparicles. Characterization was carried out using EPR, HRTEM, X-ray diffraction, SQUID and NMR methods. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery. - Highlights: • Synthesized PEG-PIONs/DOX have excellent physical properties. • PEG-PIONs/DOX have a potential to in vivo application. • PEG-PIONs/DOX could be used as drug delivery system as well as contrast agents.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

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Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

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Mohammad Barzegar-jalali

2014-09-01

Full Text Available Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD, particle size analyzer and differential scanning calorimetry (DSC. Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models.

Design of in situ dispersible and calcium cross-linked alginate pellets as intestinal-specific drug carrier by melt pelletization technique.

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Nurulaini, Harjoh; Wong, Tin Wui

2011-06-01

Conventional alginate pellets underwent rapid drug dissolution and loss of multiparticulate characteristics such as aggregation in acidic medium, thereby promoting oral dose dumping. This study aimed to design sustained-release dispersible alginate pellets through rapid in situ matrix dispersion and cross-linking by calcium salts during dissolution. Pellets made of alginate and calcium salts were prepared using a solvent-free melt pelletization technique that prevented reaction between processing materials during agglomeration and allowed such a reaction to occur only in dissolution phase. Drug release was remarkably retarded in acidic medium when pellets were formulated with water-soluble calcium acetate instead of acid-soluble calcium carbonate. Different from calcium salt-free and calcium carbonate-loaded matrices that aggregated or underwent gradual erosion, rapid in situ solvation of calcium acetate in pellets during dissolution resulted in burst of gas bubbles, fast pellet breakup, and dispersion. The dispersed fragments, though exhibiting a larger specific surface area for drug dissolution than intact matrix, were rapidly cross-linked by Ca(2+) from calcium acetate and had drug release retarded till a change in medium pH from 1.2 to 6.8. Being dispersible and pH-dependent in drug dissolution, these pellets are useful as multiparticulate intestinal-specific drug carrier without exhibiting dose dumping tendency of a "single-unit-like" system via pellet aggregation. Copyright © 2011 Wiley-Liss, Inc.

Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

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Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

2016-01-01

Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting.

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Å Urga, Simon; Nanut, Milica Perišić; Kos, Janko; Sabotič, Jerica

2017-04-18

Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus.

State-of-the-Art Materials for Ultrasound-Triggered Drug Delivery

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Sirsi, Shashank; Borden, Mark

2014-01-01

Ultrasound is a unique and exciting theranostic modality that can be used to track drug carriers, trigger drug release and improve drug deposition with high spatial precision. In this review, we briefly describe the mechanisms of interaction between drug carriers and ultrasound waves, including cavitation, streaming and hyperthermia, and how those interactions can promote drug release and tissue uptake. We then discuss the rational design of some state-of-the-art materials for ultrasound-triggered drug delivery and review recent progress for each drug carrier, focusing on the delivery of chemotherapeutic agents such as doxorubicin. These materials include nanocarrier formulations, such as liposomes and micelles, designed specifically for ultrasound-triggered drug release, as well as microbubbles, microbubble-nanocarrier hybrids, microbubble-seeded hydrogels and phase-change agents. PMID:24389162

Aerodynamic Factors Responsible for the Deaggregation of Carrier-Free Drug Powders to form Micrometer and Submicrometer Aerosols

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Longest, P. Worth; Son, Yoen-Ju; Holbrook, Landon; Hindle, Michael

2013-01-01

Purpose The objective of this study was to employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. Methods Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler. Results For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1μm. Conclusions The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications. PMID:23471640

Metal oxide nanoparticles as antimicrobial agents: a promise for the future.

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Raghunath, Azhwar; Perumal, Ekambaram

2017-02-01

Microbial infectious diseases are a global threat to human health. Excess and improper use of antibiotics has created antimicrobial-resistant microbes that can defy clinical treatment. The hunt for safe and alternate antimicrobial agents is on in order to overcome such resistant micro-organisms, and the birth of nanotechnology offers promise to combat infectious organisms. Over the past two decades, metal oxide nanoparticles (MeO-NPs) have become an attractive alternative source to combat microbes that are highly resistant to various classes of antibiotics. Their vast array of physicochemical properties enables MeO-NPs to act as antimicrobial agents through various mechanisms. Apart from exhibiting antimicrobial properties, MeO-NPs also serve as carriers of drugs, thus barely providing a chance for micro-organisms to develop resistance. These immense multiple properties exhibited by MeO-NPs will have an impact on the treatment of deadly infectious diseases. This review discusses the mechanisms of action of MeO-NPs against micro-organisms, safety concerns, challenges and future perspectives. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers.

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Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

2016-07-01

Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma

Cytoplasmic fungal lipases release fungicides from ultra-deformable vesicular drug carriers.

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Gero Steinberg

Full Text Available The Transfersome® is a lipid vesicle that contains membrane softeners, such as Tween 80, to make it ultra-deformable. This feature makes the Transfersome® an efficient carrier for delivery of therapeutic drugs across the skin barrier. It was reported that TDT 067 (a topical formulation of 15 mg/ml terbinafine in Transfersome® vesicles has a much more potent antifungal activity in vitro compared with conventional terbinafine, which is a water-insoluble fungicide. Here we use ultra-structural studies and live imaging in a model fungus to describe the underlying mode of action. We show that terbinafine causes local collapse of the fungal endoplasmic reticulum, which was more efficient when terbinafine was delivered in Transfersome® vesicles (TFVs. When applied in liquid culture, fluorescently labeled TFVs rapidly entered the fungal cells (T(1/2~2 min. Entry was F-actin- and ATP-independent, indicating that it is a passive process. Ultra-structural studies showed that passage through the cell wall involves significant deformation of the vesicles, and depends on a high concentration of the surfactant Tween 80 in their membrane. Surprisingly, the TFVs collapsed into lipid droplets after entry into the cell and the terbinafine was released from their interior. With time, the lipid bodies were metabolized in an ATP-dependent fashion, suggesting that cytosolic lipases attack and degrade intruding TFVs. Indeed, the specific monoacylglycerol lipase inhibitor URB602 prevented Transfersome® degradation and neutralized the cytotoxic effect of Transfersome®-delivered terbinafine. These data suggest that (a Transfersomes deliver the lipophilic fungicide Terbinafine to the fungal cell wall, (b the membrane softener Tween 80 allows the passage of the Transfersomes into the fungal cell, and (c fungal lipases digest the invading Transfersome® vesicles thereby releasing their cytotoxic content. As this mode of action of Transfersomes is independent of the

Simultaneous tracking of drug molecules and carriers using aptamer-functionalized fluorescent superstable gold nanorod-carbon nanocapsules during thermo-chemotherapy

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Wang, Xue-Wei; Gao, Wei; Fan, Huanhuan; Ding, Ding; Lai, Xiao-Fang; Zou, Yu-Xiu; Chen, Long; Chen, Zhuo; Tan, Weihong

2016-04-01

Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core-shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through π-π interactions, a useful tool for cancer-targeted cellular imaging and therapy. Moreover, such a stable and intrinsic fluorescence effect of the AuNR@carbon enabled simultaneous tracking of released therapeutic molecules and nanocarriers under thermo-chemotherapy. The AuNR@carbons had high surface areas and stable shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core-shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through π-π interactions, a useful tool for cancer-targeted cellular imaging and

Stacking dependence of carrier transport properties in multilayered black phosphorous

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Sengupta, A.; Audiffred, M.; Heine, T.; Niehaus, T. A.

2016-02-01

We present the effect of different stacking orders on carrier transport properties of multi-layer black phosphorous. We consider three different stacking orders AAA, ABA and ACA, with increasing number of layers (from 2 to 6 layers). We employ a hierarchical approach in density functional theory (DFT), with structural simulations performed with generalized gradient approximation (GGA) and the bandstructure, carrier effective masses and optical properties evaluated with the meta-generalized gradient approximation (MGGA). The carrier transmission in the various black phosphorous sheets was carried out with the non-equilibrium green’s function (NEGF) approach. The results show that ACA stacking has the highest electron and hole transmission probabilities. The results show tunability for a wide range of band-gaps, carrier effective masses and transmission with a great promise for lattice engineering (stacking order and layers) in black phosphorous.

Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

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Yang L

2016-03-01

Full Text Available Liang Yang, Yating Shao, Hyo-Kyung Han BK Plus Project Team, College of Pharmacy, Dongguk University, Goyang, South Korea Abstract: This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC. The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w, krill oil to fenofibrate of 2:1 (w/w, and antisolvent to solvent of 6:4 (v/v. The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax and area under the curve (AUC of fenofibric acid (an active metabolite in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. Keywords: aminoclay, omega-3 phospholipids, fenofibrate, drug release, oral absorption 

The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells.

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Daniel Pan

Full Text Available Red blood cells (RBCs can be used for vascular delivery of encapsulated or surface-bound drugs and carriers. Coupling to RBC prolongs circulation of nanoparticles (NP, 200 nm spheres, a conventional model of polymeric drug delivery carrier enabling their transfer to the pulmonary vasculature without provoking overt RBC elimination. However, little is known about more subtle and potentially harmful effects of drugs and drug carriers on RBCs. Here we devised high-throughput in vitro assays to determine the sensitivity of loaded RBCs to osmotic stress and other damaging insults that they may encounter in vivo (e.g. mechanical, oxidative and complement insults. Sensitivity of these tests is inversely proportional to RBC concentration in suspension and our results suggest that mouse RBCs are more sensitive to damaging factors than human RBCs. Loading RBCs by NP at 1:50 ratio did not affect RBCs, while 10-50 fold higher NP load accentuated RBC damage by mechanical, osmotic and oxidative stress. This extensive loading of RBC by NP also leads to RBCs agglutination in buffer; however, addition of albumin diminished this effect. These results provide a template for analyses of the effects of diverse cargoes loaded on carrier RBCs and indicate that: i RBCs can tolerate carriage of NP at doses providing loading of millions of nanoparticles per microliter of blood; ii tests using protein-free buffers and mouse RBCs may overestimate adversity that may be encountered in humans.

Luminescent GdVO4:Eu3+ functionalized mesoporous silica nanoparticles for magnetic resonance imaging and drug delivery.

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Huang, Shanshan; Cheng, Ziyong; Ma, Ping'an; Kang, Xiaojiao; Dai, Yunlu; Lin, Jun

2013-05-14

Luminescent GdVO4:Eu(3+) nanophosphor functionalized mesoporous silica nanoparticles (MSN) were prepared (denoted as GdVO4:Eu(3+)@MSN). The in vitro cytotoxicity tests show that the sample has good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. Flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 ovarian cancer cells and A549 lung adenocarcinoma cells. It was also shown that the GdVO4:Eu(3+)@MSN brightened the T1-weighted images and enhanced the r1 relaxivity of water protons, which suggested that they could act as T1 contrast agents for magnetic resonance (MR) imaging. It was found that the carriers present a pH-dependent drug release behavior for doxorubicin (DOX). The composites show a red emission under UV irradiation due to the GdVO4:Eu(3+) nanophosphors. Furthermore, the PL intensity of the composite shows correlation with the cumulative release of DOX. These results suggest that the composite can potentially act as a multifunctional drug carrier system with luminescent tagging, MR imaging and pH-controlled release property for DOX.

Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo.

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Deng, Wentao; Qiu, Juhui; Wang, Shaoting; Yuan, Zhi; Jia, Yuefeng; Tan, Hailin; Lu, Jiru; Zheng, Ruqiang

2018-01-01

In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.

Hot carrier dynamics in plasmonic transition metal nitrides

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Habib, Adela; Florio, Fred; Sundararaman, Ravishankar

2018-06-01

Extraction of non-equilibrium hot carriers generated by plasmon decay in metallic nano-structures is an increasingly exciting prospect for utilizing plasmonic losses, but the search for optimum plasmonic materials with long-lived carriers is ongoing. Transition metal nitrides are an exciting class of new plasmonic materials with superior thermal and mechanical properties compared to conventional noble metals, but their suitability for plasmonic hot carrier applications remains unknown. Here, we present fully first principles calculations of the plasmonic response, hot carrier generation and subsequent thermalization of all group IV, V and VI transition metal nitrides, fully accounting for direct and phonon-assisted transitions as well as electron–electron and electron–phonon scattering. We find the largest frequency ranges for plasmonic response in ZrN, HfN and WN, between those of gold and silver, while we predict strongest absorption in the visible spectrum for the VN, NbN and TaN. Hot carrier generation is dominated by direct transitions for most of the relevant energy range in all these nitrides, while phonon-assisted processes dominate only below 1 eV plasmon energies primarily for the group IV nitrides. Finally, we predict the maximum hot carrier lifetimes to be around 10 fs for group IV and VI nitrides, a factor of 3–4 smaller than noble metals, due to strong electron–phonon scattering. However, we find longer carrier lifetimes for group V nitrides, comparable to silver for NbN and TaN, while exceeding 100 fs (twice that of silver) for VN, making them promising candidates for efficient hot carrier extraction.

Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

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Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

2017-02-25

Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Protein-based nanostructures as carriers for photo-physically active molecules in biosystems

OpenAIRE

Delcanale, Pietro

2017-01-01

In nature, many proteins function as carriers, being able to bind, transport and possibly release a ligand within a biological system. Protein-based carriers are interesting systems for drug delivery, with the remarkable advantage of being water-soluble and, as inherent components of biosystems, highly bio-compatible. This work focuses on the use of protein-based carriers for the delivery of hydrophobic photo-physically active molecules, whose structure and chemical properties lead to spontan...

A Promising Approach to Provide Appropriate Colon Target Drug Delivery Systems of Vancomycin HCL: Pharmaceutical and Microbiological Studies

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Kadria A. Elkhodairy

2014-01-01

Full Text Available Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6 were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20 were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested.

A promising approach to provide appropriate colon target drug delivery systems of vancomycin HCL: pharmaceutical and microbiological studies.

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Elkhodairy, Kadria A; Afifi, Samar A; Zakaria, Azza S

2014-01-01

Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10-60% of tablet weight of guar gum (F1-F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6-F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6-8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested.

Nanostructures for protein drug delivery.

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Pachioni-Vasconcelos, Juliana de Almeida; Lopes, André Moreni; Apolinário, Alexsandra Conceição; Valenzuela-Oses, Johanna Karina; Costa, Juliana Souza Ribeiro; Nascimento, Laura de Oliveira; Pessoa, Adalberto; Barbosa, Leandro Ramos Souza; Rangel-Yagui, Carlota de Oliveira

2016-02-01

Use of nanoscale devices as carriers for drugs and imaging agents has been extensively investigated and successful examples can already be found in therapy. In parallel, recombinant DNA technology together with molecular biology has opened up numerous possibilities for the large-scale production of many proteins of pharmaceutical interest, reflecting in the exponentially growing number of drugs of biotechnological origin. When we consider protein drugs, however, there are specific criteria to take into account to select adequate nanostructured systems as drug carriers. In this review, we highlight the main features, advantages, drawbacks and recent developments of nanostructures for protein encapsulation, such as nanoemulsions, liposomes, polymersomes, single-protein nanocapsules and hydrogel nanoparticles. We also discuss the importance of nanoparticle stabilization, as well as future opportunities and challenges in nanostructures for protein drug delivery.

Comparison of pharmaceutical nanoformulations for curcumin: Enhancement of aqueous solubility and carrier retention.

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Allijn, Iris E; Schiffelers, Raymond M; Storm, Gert

2016-06-15

Curcumin, originally used in traditional medicine and as a spice, is one of the most studied and most popular natural products of the past decade. It has been described to be an effective anti-inflammatory and anti-cancer drug and protects against chronic diseases such as rheumatoid arthritis and atherosclerosis. Despite these promising pharmacological properties, curcumin is also very lipophilic, which makes its formulation challenging. Ideally the nanocarrier should additionally also retain the encapsulated curcumin to provide target tissue accumulation. In this study we aimed to tackle this aqueous solubility and carrier retention challenge of curcumin by encapsulating curcumin in different nanoparticles. We successfully loaded LDL (30nm), polymeric micelles (80nm), liposomes (180nm) and Intralipid (280nm) with curcumin. The relative loading capacity was inversely related to the size of the particle. The stability for all formulations was determined in fetal bovine serum over a course of 24h. Although all curcumin-nanoparticles were stable in buffer solution, all leaked more than 70% of curcumin under physiological conditions. Altogether, tested nanoparticles do solve the aqueous insolubility problem of curcumin, however, because of their leaky nature, the challenge of carrier retention remains. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanodiamond and its application to drug delivery

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Eiji Osawa

2012-08-01

Full Text Available Quasi-spherical diamond crystals having an average diameter of 3.7±0.6 nm are attracting much attention as an ideal material in carbon nanotechnology. In contrast to the other popular nanocarbons including fullerenes, carbon nanotubes and graphenes, our single-nanodiamond can be produced in uniform shape/size on industrial scale. Thus, the most serious problem in nanocarbon industry that persisted in the past 25 years, namely the technical failure to produce highly crystalline nanocarbons in narrow shape/size range does not exist in our diamond from the beginning. Among potential applications of the single-nanodiamond under development, this review concentrates on its highly promising role as a drug carrier, especially for therapeutic-resistant cancer. An interesting possibility of intercalation is proposed as the mechanism of drug transport through blood, which takes into accounts of the spontaneous formation of nanographene layer on the [111] facets, which is then extensively oxidized during oxidative soot removal process to give nanographene oxide partial surface, capable of intercalating drug molecules to prevent them from leaking and causing undesirable side effects during transportation to target malignant cells. A perspective of quantifying the drug delivery process by anticipating orders of magnitude in the number of administered detonation nanodiamond (DND particles is suggested.

Side-chain amino-acid-based pH-responsive self-assembled block copolymers for drug delivery and gene transfer.

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Kumar, Sonu; Acharya, Rituparna; Chatterji, Urmi; De, Priyadarsi

2013-12-10

Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

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Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

2017-02-28

Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic Devices for Drug Delivery Systems and Drug Screening

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Kompella, Uday B.; Damiati, Safa A.

2018-01-01

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

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Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

2016-06-14

With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

Carrier multiplication in silicon nanocrystals: ab initio results

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Ivan Marri

2015-02-01

Full Text Available One of the most important goals in the field of renewable energy is the development of original solar cell schemes employing new materials to overcome the performance limitations of traditional solar cell devices. Among such innovative materials, nanostructures have emerged as an important class of materials that can be used to realize efficient photovoltaic devices. When these systems are implemented into solar cells, new effects can be exploited to maximize the harvest of solar radiation and to minimize the loss factors. In this context, carrier multiplication seems one promising way to minimize the effects induced by thermalization loss processes thereby significantly increasing the solar cell power conversion. In this work we analyze and quantify different types of carrier multiplication decay dynamics by analyzing systems of isolated and coupled silicon nanocrystals. The effects on carrier multiplication dynamics by energy and charge transfer processes are also discussed.

The Research Progress of Targeted Drug Delivery Systems

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Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites.

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Liu, Huinan; Webster, Thomas J

2010-06-01

Pharmaceutical agents are often used to stimulate new bone formation for the treatment of bone injuries or diseases (such as osteoporosis). However, there are several problems associated with current orthopedic drug delivery methods. First, conventional systemic administration of pharmaceutical agents may not effectively reach targeted sites and, thus, they can cause nonspecific bone formation in areas not affected by injury or disease. Second, even if intentionally delivered or implanted locally to the damaged bone tissue, these agents tend to rapidly diffuse into adjacent tissues due to weak physical bonding to their drug carriers, which limits their potential to promote prolonged bone formation in targeted areas of bone disease. Therefore, in this study, biodegradable ceramic/polymer nanocomposites were explored as novel drug carriers for orthopedic applications to prolong local drug release and, thus, improve drug effectiveness at bone disease sites. Specifically, a bone morphogenetic protein (BMP-7) derived peptide (DIF-7c) was used as a model drug in this study and was first loaded onto nanocrystalline hydroxyapatite (nano-HA) by either covalent chemical attachment or physical adsorption. These drug-carrying nano-HA particles were then dispersed into a degradable polymer (poly-lactide-co-glycolide or PLGA) matrix to create an implantable system capable of long-term drug release. The aminophase silane covalent chemical immobilization process was utilized in this study. These nanocomposite-based drug delivery systems were then characterized for drug loading efficiency and in vitro drug release. Results demonstrated that DIF-7c was successfully immobilized onto nano-HA placed in PLGA. Moreover, a greater prolonged two-phase release profile (of more than 3 months) was achieved when using aminophase silane chemical immobilization to nano-HA particles. Since previous studies have demonstrated greater in vivo bone growth on nano- compared with micron-HA particles

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.

Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

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Gao, Lin; Sun, Jihong; Li, Yuzhen

2011-08-01

The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.

Science.gov (United States)

Hemmati, Mohammad; Kazemi, Bahram; Najafi, Farhood; Zarebkohan, Amir; Shirkoohi, Reza

2016-01-01

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.

Magnetically modified bacterial cellulose: A promising carrier for immobilization of affinity ligands, enzymes, and cells

Energy Technology Data Exchange (ETDEWEB)

Baldikova, Eva [Global Change Research Institute, CAS, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic); Pospiskova, Kristyna [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 27, 783 71 Olomouc (Czech Republic); Ladakis, Dimitrios; Kookos, Ioannis K. [Department of Chemical Engineering, University of Patras, 26504 Patras, Rio (Greece); Koutinas, Apostolis A. [Department of Food Science and Human Nutrition, Agricultural University of Athens, Iera Odos 75, Athens 11855 (Greece); Safarikova, Mirka [Global Change Research Institute, CAS, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic); Department of Nanobiotechnology, Biology Centre, ISB, CAS, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic); Safarik, Ivo, E-mail: safarik@nh.cas.cz [Global Change Research Institute, CAS, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic); Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 27, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Biology Centre, ISB, CAS, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

2017-02-01

Bacterial cellulose (BC) produced by Komagataeibacter sucrofermentans was magnetically modified using perchloric acid stabilized magnetic fluid. Magnetic bacterial cellulose (MBC) was used as a carrier for the immobilization of affinity ligands, enzymes and cells. MBC with immobilized reactive copper phthalocyanine dye was an efficient adsorbent for crystal violet removal; the maximum adsorption capacity was 388 mg/g. Kinetic and thermodynamic parameters were also determined. Model biocatalysts, namely bovine pancreas trypsin and Saccharomyces cerevisiae cells were immobilized on MBC using several strategies including adsorption with subsequent cross-linking with glutaraldehyde and covalent binding on previously activated MBC using sodium periodate or 1,4-butanediol diglycidyl ether. Immobilized yeast cells retained approximately 90% of their initial activity after 6 repeated cycles of sucrose solution hydrolysis. Trypsin covalently bound after MBC periodate activation was very stable during operational stability testing; it could be repeatedly used for ten cycles of low molecular weight substrate hydrolysis without loss of its initial activity. - Highlights: • Bacterial cellulose was magnetically modified with magnetic fluid. • Magnetic cellulose is an efficient carrier for affinity ligands. • Enzymes and cells can be efficiently immobilized to magnetic cellulose.

Drug Carrier for Photodynamic Cancer Therapy

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Tilahun Ayane Debele

2015-09-01

Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

Drug- not carrier-dependent haematological and biochemical changes in a repeated dose study of cyclosporine encapsulated polyester nano- and micro-particles: Size does not matter

International Nuclear Information System (INIS)

Venkatpurwar, V.P.; Rhodes, S.; Oien, K.A.; Elliott, M.A.; Tekwe, C.D.; Jørgensen, H.G.; Kumar, M.N.V. Ravi

2015-01-01

Highlights: • The particulate delivery allows an increase in dose range without accrual of toxicities. • The altered haematological and biochemical changes are drug, but not particle dependent. • PLGA nano/microparticles are safe on subacute peroral dosing over 28 days. • Nano-toxicology, drug needs to be considered. - Abstract: Biodegradable nanoparticles are being considered more often as drug carriers to address pharmacokinetic/pharmacodynamic issues, yet nano-product safety has not been systematically proven. In this study, haematological, biochemical and histological parameters were examined on 28 day daily dosing of rats with nano- or micro-particle encapsulated cyclosporine (CsA) to confirm if any changes observed were drug or carrier dependent. CsA encapsulated poly(lactide-co-glycolide) [PLGA] nano- (nCsA) and micro-particles (mCsA) were prepared by emulsion techniques. CsA (15, 30, 45 mg/kg) were administered by oral gavage to Sprague Dawley (SD) rats over 28 days. Haematological and biochemical metrics were followed with tissue histology performed on sacrifice. Whether presented as nCsA or mCsA, 45 mg/kg dose caused significant loss of body weight and lowered food consumption compared to untreated control. Across the doses, both nCsA and mCsA produce significant decreases in lymphocyte numbers compared to controls, commensurate with the proprietary product, Neoral ® 15. Dosing with nCsA showed higher serum drug levels than mCsA presumably owing to the smaller particle size facilitating absorption. The treatment had no noticeable effects on inflammatory/oxidative stress markers or antioxidant enzyme levels, except an increase in ceruloplasmin (CP) levels for high dose nCsA/mCsA group. Further, only subtle, sub-lethal changes were observed in histology of nCsA/mCsA treated rat organs. Blank (drug-free) particles did not induce changes in the parameters studied. Therefore, it is extremely important that the encapsulated drug in the nano-products is

Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

Science.gov (United States)

Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

2016-04-01

Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

Science.gov (United States)

Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

2016-03-11

Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

Directory of Open Access Journals (Sweden)

Giovana Maria Fioramonti Calixto

2016-03-01

Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

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

Directory of Open Access Journals (Sweden)

Fu-Heng Yang

2015-03-01

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

Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery.

Science.gov (United States)

Yu, Yuan; Pang, Zhiqing; Lu, Wei; Yin, Qi; Gao, Huile; Jiang, Xinguo

2012-01-01

To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized. Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-β(25-35) was investigated by immunohistochemical analysis. The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood-brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls. These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration.

Enhanced Dissolution of a Porous Carrier-Containing Ternary Amorphous Solid Dispersion System Prepared by a Hot Melt Method.

Science.gov (United States)

Hanada, Masataka; Jermain, Scott V; Williams, Robert O

2018-01-01

The focus of our study was to employ a solvent-free, thermal process to evaluate the use of a porous carrier in a drug-polymer-porous carrier ternary formulation containing a high drug load (e.g., ≥50% w/w). The purpose of the study was to improve the dissolution properties of the biopharmaceutical classification system class II drug, indomethacin, in the ternary formulation. The effect that the selected polymer has on properties of the formulation was studied, and the formulation characteristics of hypromellose (AF15), copovidone (VA64), and polyvinyl alcohol-polyethylene glycol graft copolymer was evaluated to understand differences in dissolution rates and drug adsorption onto the porous carrier. The ternary formulations were manufactured using a thermal technique that relied on heating and mixing, without the necessity of mechanical shear. All thermally processed granules that employed the porous carrier exhibited immediate release compared with crystalline indomethacin and physical mixtures. In addition, the ternary formulations maintained supersaturation compared with the binary formulations without polymer. The results of this study indicated that the thermally processed ternary formulations containing a porous carrier demonstrated a much improved dissolution profile in nonsink conditions. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Gelucire Based In Situ Gelling Emulsions: A Potential Carrier for Sustained Stomach Specific Delivery of Gastric Irritant Drugs

Directory of Open Access Journals (Sweden)

Ashwin Saxena

2013-01-01

Full Text Available Non steroidal anti-inflammatory drugs (NSAIDs are commonly prescribed medications to the geriatric patients for the treatment of arthritis and other painful disorders. The major side effects of NSAIDs are related to their effects on the stomach and bowels. The present study concerns assessment of the potential of liquid in situ gelling emulsion formulations (emulgels as patient compliant stomach specific sustained release carrier for the delivery of highly gastric irritant drug, Piroxicam. Emulgels were prepared, without using any emulgent, by mixing different concentrations of molten Gelucire 39/01 with low viscosity sodium alginate solution prepared in deionized water at 50°C. CaCO3 was used as buoyancy imparting as well as crosslinking agent. Emulgels so prepared were homogenous, physically stable, and rapidly formed into buoyant gelled mass when exposed to simulated gastric fluid (SGF, pH 1.2. Drug release studies carried out in SGF revealed significant retardation (P<0.05 of Piroxicam release from emulgels compared to conventional in situ gelling formulations prepared without Gelucire 39/01. Pharmacodynamic studies carried out in albino rats revealed significantly increased analgesic/anti-inflammatory response from in situ emulgels compared to conventional in situ gelling formulations. Further, in vivo toxicity studies carried out in albino rats revealed no signs of gastric ulceration upon prolonged dosing.

Charge-reversal nanoparticles: novel targeted drug delivery carriers.

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Chen, Xinli; Liu, Lisha; Jiang, Chen

2016-07-01

Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

Polymer brush hexadecyltrimethylammonium bromide (CTAB) modified poly (propylene-g-styrene sulphonic acid) fiber (ZB-1): CTAB/ZB-1 as a promising strategy for improving the dissolution and physical stability of poorly water-soluble drugs.

Science.gov (United States)

Cao, Jinxu; Yang, Baixue; Wang, Yumei; Wei, Chen; Wang, Hongyu; Li, Sanming

2017-11-01

The feasibility of polymer brush as drug delivery vehicle was demonstrated with the goal of improving the dissolution and physical stability of poorly water-soluble drugs. Polymer brush CTAB/ZB-1 was synthesized by electrostatic interaction using a physical modification method with anionic poly (propylene-g-styrene sulphonic acid) fiber (ZB-1) as the substrate and cationic hexadecyltrimethylammonium bromide (CTAB) as the modifier. The polymer brush structure of CTAB/ZB-1 was validated by atomic force microscopy (AFM) and the channels of brush provided the drug loading sites. Flurbiprofen (FP), a BCS class II representative drug, was selected as the model poorly water-soluble drug to be loaded into this polymer brush. Then the drug loading and release were systematically investigated. Besides, the transformation from crystalline FP to amorphous state was observed by differential scanning calorimeter (DSC). In vitro dissolution in pure water and pH1.2 HCl media with/without 0.1% sodium dodecyl sulfate (SDS) was tested. Moreover, the optimal formulations (namely carrier/drug ratios) were determined. The results demonstrated prominent improvement of dissolution when FP was released from CTAB/ZB-1. After a long time storage, FP remained amorphous in CTAB/ZB-1 according to DSC determinations and performed an approximately equivalent dissolution compared with fresh samples, suggesting the advantage of CTAB/ZB-1 as carrier in enhancing the physical stability of drugs. The study introduced the versatile easily formulated polymer brush CTAB/ZB-1 and demonstrated the potential of polymer brush as an alternative approach for improving the dissolution and physical stability of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Subcutaneous administration of carrier erythrocytes: slow release of entrapped agent

International Nuclear Information System (INIS)

DeLoach, J.R.; Corrier, D.E.

1988-01-01

Carrier erythrocytes administered subcutaneously in mice release encapsulated molecules at the injection site and through cells that escape the injection site. One day postinjection, the efflux of encapsulated [ 14 C]sucrose, [ 3 H]inulin, and 51 Cr-hemoglobin from the injection site was 45, 55, and 65%, respectively. Intact carrier erythrocytes escaped the injection site and entered the blood circulation carrying with them the encapsulated molecules. Most of the encapsulated [ 3 H]inulin that reached whole blood circulated within erythrocytes. Small but measurable numbers of encapsulated molecules were trapped within lymph nodes. Subcutaneous injection of carrier erythrocytes may allow for limited extravascular tissue targeting of drugs

Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs

International Nuclear Information System (INIS)

Maeda, Noriyuki; Miyazawa, Souichiro; Shimizu, Kosuke; Asai, Tomohiro; Yonezawa, Sei; Oku, Naoto; Kitazawa, Sadaya; Namba, Yukihiro; Tsukada, Hideo

2006-01-01

We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG-PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular therapy (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2- 18 F]2-fluoro-2-deoxy- D -glucose ([2- 18 F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this liposome was quite similar to that of non-targeted long-circulating liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both liposomes was performed by use of fluorescence-labeled liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer drug in the tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for cancer treatment. (author)

Mesoporous silica as carrier of antioxidant for food packaging materials

Science.gov (United States)

Buonocore, Giovanna Giuliana; Gargiulo, Nicola; Verdolotti, Letizia; Liguori, Barbara; Lavorgna, Marino; Caputo, Domenico

2014-05-01

Mesoporous silicas have been long recognized as very promising materials for the preparation of drug delivery systems. In this work SBA-15 mesoporous silica has been functionalized with amino-silane to be used as carrier of antioxidant compound in the preparation of active food packaging materials exhibiting tailored release properties. Active films have been prepared by loading the antioxidant tocopherol, the purely siliceous SBA-15 and the aminofunctionalized SBA-15 loaded with tocopherol into LDPE matrix trough a two-step process (mixing+extrusion). The aim of the present work is the study of the effect of the pore size and of the chemical functionality of the internal walls of the mesophase on the migration of tocopherol from active LDPE polymer films. Moreover, it has been proved that the addition of the active compound do not worsen the properties of the film such as optical characteristic and water vapor permeability, thus leading to the development of a material which could be favorably used mainly, but not exclusively, in the sector of food packaging.

Polylactic acid (PLA) controlled delivery carriers for biomedical applications.

Science.gov (United States)

Tyler, Betty; Gullotti, David; Mangraviti, Antonella; Utsuki, Tadanobu; Brem, Henry

2016-12-15

Polylactic acid (PLA) and its copolymers have a long history of safety in humans and an extensive range of applications. PLA is biocompatible, biodegradable by hydrolysis and enzymatic activity, has a large range of mechanical and physical properties that can be engineered appropriately to suit multiple applications, and has low immunogenicity. Formulations containing PLA have also been Food and Drug Administration (FDA)-approved for multiple applications making PLA suitable for expedited clinical translatability. These biomaterials can be fashioned into sutures, scaffolds, cell carriers, drug delivery systems, and a myriad of fabrications. PLA has been the focus of a multitude of preclinical and clinical testing. Three-dimensional printing has expanded the possibilities of biomedical engineering and has enabled the fabrication of a myriad of platforms for an extensive variety of applications. PLA has been widely used as temporary extracellular matrices in tissue engineering. At the other end of the spectrum, PLA's application as drug-loaded nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities. The clinical translation of these technologies from preclinical experimental settings is an ever-evolving field with incremental advancements. In this review, some of the biomedical applications of PLA and its copolymers are highlighted and briefly summarized. Copyright © 2016 Elsevier B.V. All rights reserved.

Zn-based porous coordination solid as diclofenac sodium carrier

Science.gov (United States)

Lucena, Guilherme Nunes; Alves, Renata Carolina; Abuçafy, Marina Paiva; Chiavacci, Leila Aparecida; da Silva, Isabel Cristiane; Pavan, Fernando Rogério; Frem, Regina Célia Galvão

2018-04-01

Drug delivery systems produced with biocompatible components can be used to reduce adverse effects and improve therapy efficacy. Most of the carrier materials reported in the literature show poor drug loading and rapid release. However, porous hybrid solids, such as metal-organic frameworks, are well suited to serve as carriers for delivery and imaging applications. In this work, a luminescent and nontoxic porous Zn(II) coordination polymer with 4,4‧-biphenyl-dicarboxylic acid (BPDC) and adenine linkers (BioMOF-Zn) was synthesized by a solvothermal process and characterized by PXRD, TGA, SEM-FEG, and FTIR. Nitrogen adsorption measurements revealed the presence of micropores as well as mesopores in the framework after activation of the material. The blue-emitting BioMOF-Zn exhibited an outstanding loading capacity (1.72 g g-1) and satisfactory release capability (56% after two days) for diclofenac sodium.

Antiprotozoal Activity of α,β-Unsaturated δ-Lactones: Promising ...

African Journals Online (AJOL)

The parasite resistance and side effects of drugs used to treat protozoal diseases have led to the search for new therapies, both natural and synthetic. Studies have shown that various α,β-unsaturated δ-lactones displayed high antiprotozoal activity and thus are promising compounds for new drug discovery and ...

Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

Science.gov (United States)

Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

2017-05-01

In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO 4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO 4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD 10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD 10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Sustained ophthalmic delivery of highly soluble drug using pH-triggered inner layer-embedded contact lens.

Science.gov (United States)

Zhu, Qiang; Cheng, Hongbo; Huo, Yingnan; Mao, Shirui

2018-06-10

In the present work the feasibility of using inner layer-embedded contact lenses (CLs) to achieve sustained release of highly water soluble drug, betaxolol hydrochloride (BH) on the ocular surface was investigated. Blend film of cellulose acetate and Eudragit S100 was selected as the inner layer, while silicone hydrogel was used as outer layer to construct inner layer-embedded contact lenses. Influence of polymer ratio in the blend film on in vitro drug release behavior in phosphate buffered solution or simulated tear fluid was studied and drug-polymer interaction, erosion and swelling of the blend film were characterized to better understand drug-release mechanism. Storage stability of the inner layer-embedded contact lenses in phosphate buffer solution was also conducted, with ignorable drug loss and negligible change in drug release pattern within 30 days. In vivo pharmacokinetic study in rabbits showed sustained drug release for over 240 h in tear fluid, indicating prolonged drug precorneal residence time. In conclusion, cellulose acetate/Eudragit S100 inner layer-embedded contact lenses are quite promising as controlled-release carrier of highly water soluble drug for ophthalmic delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

Directory of Open Access Journals (Sweden)

Warangkana Lohcharoenkal

2014-01-01

Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

Protein nanoparticles as drug delivery carriers for cancer therapy.

Science.gov (United States)

Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie; Rojanasakul, Yon

2014-01-01

Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

Amine-modified magnetic iron oxide nanoparticle as a promising carrier for application in bio self-healing concrete.

Science.gov (United States)

Seifan, Mostafa; Ebrahiminezhad, Alireza; Ghasemi, Younes; Samani, Ali Khajeh; Berenjian, Aydin

2018-01-01

Self-healing mechanisms are a promising solution to address the concrete cracking issue. Among the investigated self-healing strategies, the biotechnological approach is distinguished itself by inducing the most compatible material with concrete composition. In this method, the potent bacteria and nutrients are incorporated into the concrete matrix. Once cracking occurs, the bacteria will be activated, and the induced CaCO 3 crystals will seal the concrete cracks. However, the effectiveness of a bio self-healing concrete strictly depends on the viability of bacteria. Therefore, it is required to protect the bacteria from the resulted shear forces caused by mixing and drying shrinkage of concrete. Due to the positive effects on mechanical properties and the high compatibility of metallic nanoparticles with concrete composition, for the first time, we propose 3-aminopropyltriethoxy silane-coated iron oxide nanoparticles (APTES-coated IONs) as a biocompatible carrier for Bacillus species. This study was aimed to investigate the effect of APTES-coated IONs on the bacterial viability and CaCO 3 yield for future application in the concrete structures. The APTES-coated IONs were successfully synthesized and characterized by transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The results show that the presence of 100 μg/mL APTES-coated IONs could increase the bacterial viability. It was also found that the CaCO 3 -specific yield was significantly affected in the presence of APTES-coated IONs. The highest CaCO 3 -specific yield was achieved when the cells were decorated with 50 μg/mL of APTES-coated IONs. This study provides new insights for the application of APTES-coated IONs in designing bio self-healing strategies.

Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.

Science.gov (United States)

Lukyanov, Anatoly N; Torchilin, Vladimir P

2004-05-07

Polymeric micelles have a whole set of unique characteristics, which make them very promising drug carriers, in particular, for poorly soluble drugs. Our review article focuses on micelles prepared from conjugates of water-soluble polymers, such as polyethylene glycol (PEG) or polyvinyl pyrrolidone (PVP), with phospholipids or long-chain fatty acids. The preparation of micelles from certain polymer-lipid conjugates and the loading of these micelles with various poorly soluble anticancer agents are discussed. The data on the characterization of micellar preparations in terms of their morphology, stability, longevity in circulation, and ability to spontaneously accumulate in experimental tumors via the enhanced permeability and retention (EPR) effect are presented. The review also considers the preparation of targeted immunomicelles with specific antibodies attached to their surface. Available in vivo results on the efficiency of anticancer drugs incorporated into plain micelles and immunomicelles in animal models are also discussed.

Formic Acid as a Hydrogen Energy Carrier

KAUST Repository

Eppinger, Jö rg; Huang, Kuo-Wei

2016-01-01

The high volumetric capacity (S3 g H-2/L) and its low toxicity and flammability under ambient conditions make formic acid a promising hydrogen energy carrier. Particularly, in the past decade, significant advancements have been achieved in catalyst development for selective hydrogen generation from formic acid. This Perspective highlights the advantages of this approach with discussions focused on potential applications in the transportation sector together with analysis of technical requirements, limitations, and costs.

Formic Acid as a Hydrogen Energy Carrier

KAUST Repository

Eppinger, Jorg

2016-12-15

The high volumetric capacity (S3 g H-2/L) and its low toxicity and flammability under ambient conditions make formic acid a promising hydrogen energy carrier. Particularly, in the past decade, significant advancements have been achieved in catalyst development for selective hydrogen generation from formic acid. This Perspective highlights the advantages of this approach with discussions focused on potential applications in the transportation sector together with analysis of technical requirements, limitations, and costs.

Clinical relevance of drug binding to plasma proteins

Science.gov (United States)

Ascenzi, Paolo; Fanali, Gabriella; Fasano, Mauro; Pallottini, Valentina; Trezza, Viviana

2014-12-01

Binding to plasma proteins highly influences drug efficacy, distribution, and disposition. Serum albumin, the most abundant protein in plasma, is a monomeric multi-domain macromolecule that displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds, such as fatty acids and most acidic drugs. α-1-Acid glycoprotein, the second main plasma protein, is a glycoprotein physiologically involved in the acute phase reaction and is the main carrier for basic and neutral drugs. High- and low-density lipoproteins play a limited role in drug binding and are natural drug delivery system only for few lipophilic drugs or lipid-based formulations. Several factors influence drug binding to plasma proteins, such as pathological conditions, concurrent administration of drugs, sex, and age. Any of these factors, in turn, influences drug efficacy and toxicity. Here, biochemical, biomedical, and biotechnological aspects of drug binding to plasma proteins are reviewed.

Dual responsive PNIPAM–chitosan targeted magnetic nanopolymers for targeted drug delivery

Energy Technology Data Exchange (ETDEWEB)

Yadavalli, Tejabhiram, E-mail: tejabhiram@gmail.com [Nanotechnology Research Centre, SRM University, Chennai 603203 (India); Ramasamy, Shivaraman [Nanotechnology Research Centre, SRM University, Chennai 603203 (India); School of Physics, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 (Australia); Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal [Nanotechnology Research Centre, SRM University, Chennai 603203 (India); Chennakesavulu, Ramasamy [Department of Pharmacy practice, SRM College of Pharmacy, Chennai 603203 (India)

2015-04-15

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation. - Highlights: • The use of gadolinium doped nickel ferrite with the suggested doping level. • The use of PNIPMA–chitosan polymer with folic acid and fluorescein as a drug carrier complex. • Magnetic hyperthermia studies of gadolinium doped nickel ferrites are being reported for the first time. • Proton relaxivity studies which indicate the MRI contrasting properties on the reported system are new. • Use of curcumin, a hydrophobic Indian spice as a cancer killing agent inside the reported magnetic polymer complex.

Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.

Science.gov (United States)

Qi, Dingqing; Gong, Feirong; Teng, Xin; Ma, Mingming; Wen, Huijing; Yuan, Weihao; Cheng, Yi; Lu, Chong

2017-10-01

Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB) 2 ) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB) 2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI PLA-Lys(FB) 2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB) 2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.

A review on target drug delivery: magnetic microspheres

Directory of Open Access Journals (Sweden)

Amit Chandna

2013-01-01

Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional radiation methods which use highly penetrating radiation that is absorbed throughout the body. Its use is limited by toxicity and side effects. The aim of the specific targeting is to enhance the efficiency of drug delivery & at the same time to reduce the toxicity & side effects. This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. magnetic microspheres can be prepared from a variety of carrier material. One of the most utilized is serum albumin from human or other appropriate species. Drug release from albumin microspheres can be sustained or controlled by various stabilization procedures generally involving heat or chemical cross-linking of the protein carrier matrix.

Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.

Science.gov (United States)

Zhao, Jiacheng; Lai, Haiwang; Lu, Hongxu; Barner-Kowollik, Christopher; Stenzel, Martina H; Xiao, Pu

2016-09-12

Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 μg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.

Disease-responsive drug delivery: the next generation of smart delivery devices.

Science.gov (United States)

Wanakule, Prinda; Roy, Krishnendu

2012-01-01

With the advent of highly potent and cytotoxic drugs, it is increasingly critical that they be targeted and released only in cells of diseased tissues, while sparing physiologically normal neighbors. Simple ligand-based targeting of drug carriers, although promising, cannot always provide the required specificity to achieve this since often normal cells also express significant levels of the targeted receptors. Therefore, stimuli-responsive delivery systems are being explored to allow drug release from nano- and microcarriers and implantable devices, primarily in the presence of physiological or disease-specific pathophysiological signals. Designing smart biomaterials that respond to temperature or pH changes, protein and ligand binding, disease-specific degradation, e.g. enzymatic cleavage, has become an integral part of this approach. These strategies are used in combination with nano- and microparticle systems to improve delivery efficiency through several routes of administration, and with injectable or implantable systems for long term controlled release. This review focuses on recent developments in stimuli-responsive systems, their physicochemical properties, release profiles, efficacy, safety and biocompatibility, as well as future perspectives.

Sodium tetra-hydro-borate as energy/hydrogen carrier, its history

International Nuclear Information System (INIS)

Demirci, U.B.; Miele, Ph.

2009-01-01

Sodium tetra-hydro-borate NaBH 4 is considered as being a promising energy/hydrogen carrier. NaBH 4 is not a new compound. It has been discovered in 1940's by Prof. H.C. Brown, Nobel Laureate in Chemistry in 1979. NaBH 4 has thus a history and this history distinguishes the NaBH 4 utilisation as hydrogen carrier from that as energy carrier. In fact, the history of NaBH 4 (for both utilizations) can be divided into three periods, each period being characterised by specific societal challenges. Whereas during the first period the challenges were military and political, the challenges in the third period (i.e. at present) are energetic, environmental, civilian, social and political. The second period was rather calm for NaBH 4 even if it was intensively used as a reducing agent in organic chemistry. (authors)

Thermal and mechanical behaviour of oxygen carrier materials for chemical looping combustion in a packed bed reactor

International Nuclear Information System (INIS)

Jacobs, M.; Van Noyen, J.; Larring, Y.; Mccann, M.; Pishahang, M.; Amini, S.; Ortiz, M.; Galluci, F.; Sint-Annaland, M.V.; Tournigant, D.; Louradour, E.; Snijkers, F.

2015-01-01

Highlights: • Ilmenite-based oxygen carriers were developed for packed-bed chemical looping. • Addition of Mn_2O_3 increased mechanical strength and microstructure of the carriers. • Oxygen carriers were able to withstand creep and thermal cycling up to 1200 °C. • Ilmenite-based granules are a promising shape for packed-bed reactor conditions. - Abstract: Chemical looping combustion (CLC) is a promising carbon capture technology where cyclic reduction and oxidation of a metallic oxide, which acts as a solid oxygen carrier, takes place. With this system, direct contact between air and fuel can be avoided, and so, a concentrated CO_2 stream is generated after condensation of the water in the exit gas stream. An interesting reactor system for CLC is a packed bed reactor as it can have a higher efficiency compared to a fluidized bed concept, but it requires other types of oxygen carrier particles. The particles must be larger to avoid a large pressure drop in the reactor and they must be mechanically strong to withstand the severe reactor conditions. Therefore, oxygen carriers in the shape of granules and based on the mineral ilmenite were subjected to thermal cycling and creep tests. The mechanical strength of the granules before and after testing was investigated by crush tests. In addition, the microstructure of these oxygen particles was studied to understand the relationship between the physical properties and the mechanical performance. It was found that the granules are a promising shape for a packed bed reactor as no severe degradation in strength was noticed upon thermal cycling and creep testing. Especially, the addition of Mn_2O_3 to the ilmenite, which leads to the formation of an iron–manganese oxide, seems to results in stronger granules than the other ilmenite-based granules.

Overview of biopolymers as carriers of antiphlogistic agents for treatment of diverse ocular inflammations

International Nuclear Information System (INIS)

Sharma, Anil Kumar; Arya, Amit; Sahoo, Pravat Kumar; Majumdar, Dipak Kanti

2016-01-01

Inflammation of the eye is a usual clinical condition that can implicate any part of the eye. The nomenclature of variety of such inflammations is based on the ocular part involved. These diseases may jeopardize normal functioning of the eye on progression. In general, corticosteroids, antihistamines, mast cell stabilizers and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammatory diseases/disorders of the eye. There have been several attempts via different approaches of drug delivery to overcome the low ocular bioavailability resulting from shorter ocular residence time. The features like safety, ease of elimination and ability to sustain drug release have led to application of biopolymers in ocular therapeutics. Numerous polymers of natural origin such as gelatin, collagen, chitosan, albumin, hyaluronic acid, alginates etc. have been successfully employed for preparation of different ocular dosage forms. Chitosan is the most explored biopolymer amongst natural biopolymers because of its inherent characteristics. The emergence of synthetic biopolymers (like PVP, PACA, PCL, POE, polyanhydrides, PLA, PGA and PLGA) has also added new dimensions to the drug delivery strategies meant for treatment of ophthalmic inflammations. The current review is an endeavor to describe the utility of a variety of biomaterials/polymers based drug delivery systems as carrier for anti-inflammatory drugs in ophthalmic therapeutics. - Highlights: • Numerous eye inflammations pose troubles in vision functions. • Low bioavailability by conventional drug delivery systems due to eye constraints • Drug carriers ensuring improved bioavailability to the eye are need of the hour. • Chitosan - most explored amongst all biomaterials for ocular delivery. • Emergence of novel synthetic carriers in ophthalmology

Overview of biopolymers as carriers of antiphlogistic agents for treatment of diverse ocular inflammations

Energy Technology Data Exchange (ETDEWEB)

Sharma, Anil Kumar, E-mail: sharmarahul2004@gmail.com [Delhi Institute of Pharmaceutical Sciences and Research, Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi 110017,India (India); Arya, Amit; Sahoo, Pravat Kumar [Delhi Institute of Pharmaceutical Sciences and Research, Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi 110017,India (India); Majumdar, Dipak Kanti [School of Pharmaceutical Sciences, Apeejay Stya University, Sohna-Palwal Road, Gurgaon 122103 (India)

2016-10-01

Inflammation of the eye is a usual clinical condition that can implicate any part of the eye. The nomenclature of variety of such inflammations is based on the ocular part involved. These diseases may jeopardize normal functioning of the eye on progression. In general, corticosteroids, antihistamines, mast cell stabilizers and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammatory diseases/disorders of the eye. There have been several attempts via different approaches of drug delivery to overcome the low ocular bioavailability resulting from shorter ocular residence time. The features like safety, ease of elimination and ability to sustain drug release have led to application of biopolymers in ocular therapeutics. Numerous polymers of natural origin such as gelatin, collagen, chitosan, albumin, hyaluronic acid, alginates etc. have been successfully employed for preparation of different ocular dosage forms. Chitosan is the most explored biopolymer amongst natural biopolymers because of its inherent characteristics. The emergence of synthetic biopolymers (like PVP, PACA, PCL, POE, polyanhydrides, PLA, PGA and PLGA) has also added new dimensions to the drug delivery strategies meant for treatment of ophthalmic inflammations. The current review is an endeavor to describe the utility of a variety of biomaterials/polymers based drug delivery systems as carrier for anti-inflammatory drugs in ophthalmic therapeutics. - Highlights: • Numerous eye inflammations pose troubles in vision functions. • Low bioavailability by conventional drug delivery systems due to eye constraints • Drug carriers ensuring improved bioavailability to the eye are need of the hour. • Chitosan - most explored amongst all biomaterials for ocular delivery. • Emergence of novel synthetic carriers in ophthalmology.

Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs.

Science.gov (United States)

Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Chougule, Mahavir Bhupal; Shoyele, Sunday A; Alexander, Amit

2018-05-23

According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found

Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

Science.gov (United States)

Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2017-01-01

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanoscale drug delivery for targeted chemotherapy.

Science.gov (United States)

Xin, Yong; Huang, Qian; Tang, Jian-Qin; Hou, Xiao-Yang; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

2016-08-28

Despite significant improvements in diagnostic methods and innovations in therapies for specific cancers, effective treatments for neoplastic diseases still represent major challenges. Nanotechnology as an emerging technology has been widely used in many fields and also provides a new opportunity for the targeted delivery of cancer drugs. Nanoscale delivery of chemotherapy drugs to the tumor site is highly desirable. Recent studies have shown that nanoscale drug delivery systems not only have the ability to destroy cancer cells but may also be carriers for chemotherapy drugs. Some studies have demonstrated that delivery of chemotherapy via nanoscale carriers has greater therapeutic benefit than either treatment modality alone. In this review, novel approaches to nanoscale delivery of chemotherapy are described and recent progress in this field is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

Science.gov (United States)

Jang, Yong-Man; Yu, Chol-Jun; Kim, Jin-Song; Kim, Song-Un

2018-04-01

Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes containing the interior cavity can enhance the affinity and specificity of the osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the suitability of nine different calix[4]-arenes and -resorcinarenes based macrocycles as hosts for the ZOD guest molecule by conducting {\\it ab initio} density functional theory calculations for structures and energetics of eighteen different host-guest complexes. For the optimized molecular structures of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the geometric sizes of their interior cavities are measured and compared with those of the host-guest complexes in order to check the appropriateness for host-guest complex formation. Our calculations of binding energies indicate that in gaseous states some of the complexes might be unstable but in aqueous states almost all of the complexes can be formed spontaneously. Of the two different docking ways, the insertion of ZOD with the \\ce{P-C-P} branch into the cavity of host is easier than that with the nitrogen containing heterocycle of ZOD. The work will open a way for developing effective drug delivering systems for the ZOD drug and promote experimentalists to synthesize them.

Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design.

Science.gov (United States)

Andalib, Sare; Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi, Hojjat

2012-01-01

Nanostructured lipid carriers (NLC) are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol), lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of -25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

Synthesis of stimuli-responsive chitosan-based hydrogels by Diels-Alder cross-linking `click´ reaction as potential carriers for drug administration.

Science.gov (United States)

Guaresti, O; García-Astrain, C; Aguirresarobe, R H; Eceiza, A; Gabilondo, N

2018-03-01

Stimuli-responsive chitosan-based hydrogels for biomedical applications using the Diels-Alder reaction were prepared. Furan modified chitosan (Cs-Fu) was cross-linked with polyetheramine derived bismaleimide at different equivalent ratios in order to determine the effect in the swelling and release properties on the final CsFu:BMI hydrogels. The Diels Alder cross-linking reaction was monitored by UV-vis spectroscopy and rheological measurements. Both the sol-gel transition value and the final storage modulus for the different formulations were similar and close to 40 min and 400 Pa, respectively. On the contrary, the swelling degree was found to be strongly dependent on the amount of bismaleimide, mainly in acidic medium, where the increased cross-linking reduced the swelling value in 25%, but maintaining the sustained drug release in the simulated gastrointestinal environment. Our study suggested that these DA-cross-linked chitosan hydrogels could be potential carriers for targeted drug administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Halopentacenes: Promising Candidates for Organic Semiconductors

International Nuclear Information System (INIS)

Gong-He, Du; Zhao-Yu, Ren; Ji-Ming, Zheng; Ping, Guo

2009-01-01

We introduce polar substituents such as F, Cl, Br into pentacene to enhance the dissolubility in common organic solvents while retaining the high charge-carrier mobilities of pentacene. Geometric structures, dipole moments, frontier molecule orbits, ionization potentials and electron affinities, as well as reorganization energies of those molecules, and of pentacene for comparison, are successively calculated by density functional theory. The results indicate that halopentacenes have rather small reorganization energies (< 0.2 eV), and when the substituents are in position 2 or positions 2 and 9, they are polarity molecules. Thus we conjecture that they can easily be dissolved in common organic solvents, and are promising candidates for organic semiconductors. (condensed matter: electronicstructure, electrical, magnetic, and opticalproperties)

Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

Directory of Open Access Journals (Sweden)

Hadjira Rabti

2014-06-01

Full Text Available Elementary osmotic pump (EOP is a unique extended release (ER drug delivery system based on the principle of osmosis. It has the ability to minimize the amount of the drug, accumulation and fluctuation in drug level during chronic uses. Carbamazepine (CBZ, a poorly water-soluble antiepileptic drug, has serious side effects on overdoses and chronic uses. The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance. Firstly, a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug. Then, designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance (ANOVA, respectively. The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone (PVP K30 and sodium lauryl sulfate (SLS. The plasticizer amount and molecular weight (MW together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane (SPM thickness inversely influence the release rate. In addition, the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core. Further, orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm. In this study we report the successful formulation of CBZ-EOP tablets, which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80% of CBZ at a rate of approximately zero order for up to 12 h.

High-throughput bioscreening system utilizing high-performance affinity magnetic carriers exhibiting minimal non-specific protein binding

International Nuclear Information System (INIS)

Hanyu, Naohiro; Nishio, Kosuke; Hatakeyama, Mamoru; Yasuno, Hiroshi; Tanaka, Toshiyuki; Tada, Masaru; Nakagawa, Takashi; Sandhu, Adarsh; Abe, Masanori; Handa, Hiroshi

2009-01-01

For affinity purification of drug target protein we have developed magnetic carriers, narrow in size distribution (184±9 nm), which exhibit minimal non-specific binding of unwanted proteins. The carriers were highly dispersed in aqueous solutions and highly resistant to organic solvents, which enabled immobilization of various hydrophobic chemicals as probes on the carrier surfaces. Utilizing the carriers we have automated the process of separation and purification of the target proteins that had been done by manual operation previously.

Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

Energy Technology Data Exchange (ETDEWEB)

Lv, Ouyang; Tao, Yongxin; Qin, Yong [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China); Chen, Chuanxiang [School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003 (China); Pan, Yan; Deng, Linhong [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China); Liu, Li [School of pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164 (China); Kong, Yong, E-mail: yzkongyong@126.com [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China)

2016-10-01

Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH{sub 2} groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH{sub 2} on CS result in a pH-dependent drug delivery.

Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

International Nuclear Information System (INIS)

Lv, Ouyang; Tao, Yongxin; Qin, Yong; Chen, Chuanxiang; Pan, Yan; Deng, Linhong; Liu, Li; Kong, Yong

2016-01-01

Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH_2 groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH_2 on CS result in a pH-dependent drug delivery.

Exploitation of 3D face-centered cubic mesoporous silica as a carrier for a poorly water soluble drug: Influence of pore size on release rate

Energy Technology Data Exchange (ETDEWEB)

Zhu, Wenquan; Wan, Long; Zhang, Chen; Gao, Yikun; Zheng, Xin; Jiang, Tongying; Wang, Siling, E-mail: silingwang@syphu.edu.cn

2014-01-01

The purposes of the present work were to explore the potential application of 3D face-centered cubic mesoporous silica (FMS) with pore size of 16.0 nm as a delivery system for poorly soluble drugs and investigate the effect of pore size on the dissolution rate. FMS with different pore sizes (16.0, 6.9 and 3.7 nm) was successfully synthesized by using Pluronic block co-polymer F127 as a template and adjusting the reaction temperatures. Celecoxib (CEL), which is a BCS class II drug, was used as a model drug and loaded into FMS with different pore sizes by the solvent deposition method at a drug–silica ratio of 1:4. Characterization using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transformation infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), nitrogen adsorption, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) was used to systematically investigate the drug loading process. The results obtained showed that CEL was in a non-crystalline state after incorporation of CEL into the pores of FMS-15 with pore size of 16.0 nm. In vitro dissolution was carried out to demonstrate the effects of FMS with different pore sizes on the release of CEL. The results obtained indicated that the dissolution rate of CEL from FMS-15 was significantly enhanced compared with pure CEL. This could be explained by supposing that CEL encountered less diffusion resistance and its crystallinity decreased due to the large pore size of 16.0 nm and the nanopore channels of FMS-15. Moreover, drug loading and pore size both play an important role in enhancing the dissolution properties for the poorly water-soluble drugs. As the pore size between 3.7 and 16.0 nm increased, the dissolution rate of CEL from FMS gradually increased. - Highlights: • Exploitation of 3D cubic mesoporous silica (16 nm) as a carrier was completed. • The release rate of CEL increased on increasing the pore size of carriers. • The crystallinity

Montmorillonite-lipid hybrid carriers for ionizable and neutral poorly water-soluble drugs: Formulation, characterization and in vitro lipolysis studies.

Science.gov (United States)

Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

2017-06-30

Lipid-based formulations (LBFs) are a popular strategy for enhancing the gastrointestinal solubilization and absorption of poorly water-soluble drugs. In light of this, montmorillonite-lipid hybrid (MLH) particles, composed of medium-chain triglycerides, lecithin and montmorillonite clay platelets, have been developed as a novel solid-state LBF. Owing to the unique charge properties of montmorillonite, whereby the clay platelet surfaces carry a permanent negative charge and the platelet edges carry a pH-dependent charge, three model poorly water-soluble drugs with different charge properties; blonanserin (weak base, pKa 7.7), ibuprofen (weak acid, pKa 4.5) and fenofibrate (neutral), were formulated as MLH particles and their performance during biorelevant in vitro lipolysis at pH 7.5 was investigated. For blonanserin, drug solubilization during in vitro lipolysis was significantly reduced 3.4-fold and 3.2-fold for MLH particles in comparison to a control lipid solution and silica-lipid hybrid (SLH) particles, respectively. It was hypothesized that strong electrostatic interactions between the anionic montmorillonite platelet surfaces and cationic blonanserin molecules were responsible for the inferior performance of MLH particles. In contrast, no significant influence on drug solubilization was observed for ibuprofen- and fenofibrate-loaded MLH particles. The results of the current study indicate that whilst MLH particles are a promising novel formulation strategy for poorly water-soluble drugs, drug ionization tendency and the potential for drug-clay interactions must be taken into consideration to ensure an appropriate performance. Copyright © 2017 Elsevier B.V. All rights reserved.

The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol.

Science.gov (United States)

Wang, Yanzhu; Sun, Lizhang; Jiang, Tongying; Zhang, Jinghai; Zhang, Chen; Sun, Changshan; Deng, Yihui; Sun, Jin; Wang, Siling

2014-06-01

To explore the suitable application of MCM-41 (Mobil Composition of Matter number forty-one)-type and MCM-48-type mesoporous silica in the oral water insoluble drug delivery system. Cilostazol (CLT) as a model drug was loaded into synthesized MCM-48 (Mobil Composition of Matter number forty-eight) and commercial MCM-41 by three common methods. The obtained MCM-41, MCM-48 and CLT-loaded samples were characterized by means of nitrogen adsorption, thermogravimetric analysis, ultraviolet-visible spectrophotometry, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and powder X-ray diffractometer. It was found that solvent evaporation method was preferred according to the drug loading efficiency and the maximum percent cumulative drug dissolution. MCM-48 with 3D cubic pore structure and MCM-41 with 2D long tubular structure are nearly spherical particles in 300-500 nm. Nevertheless, the silica carriers with similar large specific surface areas and concentrating pore size distributions (978.66 m(2)/g, 3.8 nm for MCM-41 and 1108.04 m(2)/g, 3.6 nm for MCM-48) exhibited different adsorption behaviors for CLT. The maximum percent cumulative drug release of the two CLT/silica solid dispersion (CLT-MCM-48 and CLT-MCM-41) was 63.41% and 85.78% within 60 min, respectively; while in the subsequent 12 h release experiment, almost 100% cumulative drug release were both obtained. In the pharmacokinetics aspect, the maximum plasma concentrations of CLT-MCM-48 reached 3.63 mg/L by 0.92 h. The AUC0-∞ values of the CLT-MCM-41 and CLT-MCM-48 were 1.14-fold and 1.73-fold, respectively, compared with the commercial preparation. Our findings suggest that MCM-41-type and MCM-48-type mesoporous silica have great promise as solid dispersion carriers for sustained and immediate release separately.

PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril.

Science.gov (United States)

Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

2014-10-01

Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA-PEG-PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.

Mucosal delivery of liposome-chitosan nanoparticles complexes

OpenAIRE

Carvalho, Edison Samir Mascarelhas; 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...

Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

Science.gov (United States)

Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

2009-02-01

Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

Preparation and anti-tumor efficiency evaluation of doxorubicin-loaded bacterial magnetosomes: magnetic nanoparticles as drug carriers isolated from Magnetospirillum gryphiswaldense.

Science.gov (United States)

Sun, Jian-Bo; Duan, Jin-Hong; Dai, Shun-Ling; Ren, Jun; Guo, Lin; Jiang, Wei; Li, Ying

2008-12-15

Bacterial magnetosomes (BMs) are commonly used as vehicles for certain enzymes, nucleic acids and antibodies, although they have never been considered drug carriers. To evaluate the clinical potential of BMs extracted from Magnetospirillum gryphiswaldense in cancer therapy, doxorubicin (DOX) was loaded onto the purified BMs at a ratio of 0.87 +/- 0.08 mg/mg using glutaraldehyde. The DOX-coupled BMs (DBMs) and BMs exhibited uniform sizes and morphology evaluated by TEM. The diameters of DBMs and BMs obtained by AFM were 71.02 +/- 6.73 and 34.93 +/- 8.24 nm, respectively. The DBMs released DOX slowly into serum and maintained at least 80% stability following 48 h of incubation. In vitro cytotoxic tests showed that the DBMs were cytotoxic to HL60 and EMT-6 cells, manifested as inhibition of cell proliferation and suppression in c-myc expression, consistent with DOX. These observations depicted in vitro antitumor property of DBMs similar to DOX. The approach of coupling DOX to magnetosomes may have clinical potential in anti-tumor drug delivery.

Mesoporous silica formulation strategies for drug dissolution enhancement: a review.

Science.gov (United States)

McCarthy, Carol A; Ahern, Robert J; Dontireddy, Rakesh; Ryan, Katie B; Crean, Abina M

2016-01-01

Silica materials, in particular mesoporous silicas, have demonstrated excellent properties to enhance the oral bioavailability of poorly water-soluble drugs. Current research in this area is focused on investigating the kinetic profile of drug release from these carriers and manufacturing approaches to scale-up production for commercial manufacture. This review provides an overview of different methods utilized to load drugs onto mesoporous silica carriers. The influence of silica properties and silica pore architecture on drug loading and release are discussed. The kinetics of drug release from mesoporous silica systems is examined and the manufacturability and stability of these formulations are reviewed. Finally, the future prospects of mesoporous silica drug delivery systems are considered. Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future.

Controlled Fabrication of Gelatin Nanoparticles as Drug Carriers

Science.gov (United States)

Jahanshahi, M.; Sanati, M. H.; Minuchehr, Z.; Hajizadeh, S.; Babaei, Z.

2007-08-01

In recent years, significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes by either localized or targeted delivery to the tissue of interest. Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as nanoparticles, nanocapsules, micellar systems, and conjugates. Protein nanoparticles (BSA, HAS and gelatin) generally vary in size from 50-300 nm and they hold certain advantages such as greater stability during storage, stability in vivo, non-toxicity, non-antigen and ease to scale up during manufacture over the other drug delivery systems. The primary structure of gelatin offers many possibilities for chemical modification and covalent drug attachment. Here nanoparticles of gelatin type A were prepared by a two-step desolvation method as a colloidal drug delivery system and the essential parameters in fabrication were considered. Gelatin was dissolved in 25 mL distilled water under room temperature range. Then acetone was added to the gelatin solution as a desolvating agent to precipitate the high molecular weight (HMW) gelatin. The supernatant was discarded and the HMW gelatin re-dissolved by adding 25 mL distilled water and stirring at 600 rpm. Acetone were added drop-wise to form nanoparticles. At the end of the process, glutaraldehyde solution was used for preparing nanoparticles as a cross-linking agent, and stirred for 12h at 600 rpm. For purification stage we use centrifuge with 600rpm for 3 times. The objective of the present study is consideration of some factors such as temperature, gelatin concentration, agitation speed and the amount of acetone and their effects on size and distribution of nanoparticles. Among the all conditions, 60° C, 50 mg/ml gelatin concentration, 75 ml acetone had the best result and the nanoparticle size was under 170 nm. The effect

Poly(glycerol adipate)-fatty acid esters as versatile nanocarriers

DEFF Research Database (Denmark)

Weiss, Verena M; Naolou, Toufik; Hause, Gerd

2012-01-01

Poly(glycerol adipate) (PGA) is a biodegradable polymer with promising features for nanoparticulate drug carrier systems. By acylation of PGA with fatty acids, composite systems with amphiphilic properties can be obtained. Variation of the fatty acid (laurate, stearate and behenate) and their sub...... and the nanoparticles. With their diverse particle shapes and internal structures as well as their different thermal behavior, aggregate states and polarities, the systems offer promising possibilities as delivery systems for lipophilic, amphiphilic and water soluble drugs.......Poly(glycerol adipate) (PGA) is a biodegradable polymer with promising features for nanoparticulate drug carrier systems. By acylation of PGA with fatty acids, composite systems with amphiphilic properties can be obtained. Variation of the fatty acid (laurate, stearate and behenate...

Dissolution Enhancement of Drugs. Part II: Effect of Carriers ...

African Journals Online (AJOL)

Recent high throughput screening and combinatorial and parallel synthesis are increasing the number of drug molecules which are highly lipophilic. The oral route is the most preferred route of drug administration due to its convenience, good patient compliance and low medicine production costs. The challenges to ...

Recent progress on fabrication and drug delivery applications of nanostructured hydroxyapatite.

Science.gov (United States)

Mondal, Sudip; Dorozhkin, Sergy V; Pal, Umapada

2018-07-01

Through this brief review, we provide a comprehensive historical background of the development of nanostructured hydroxyapatite (nHAp), and its application potentials for controlled drug delivery, drug conjugation, and other biomedical treatments. Aspects associated with efficient utilization of hydroxyapatite (HAp) nanostructures such as their synthesis, interaction with drug molecules, and other concerns, which need to be resolved before they could be used as a potential drug carrier in body system, are discussed. This review focuses on the evolution of perceptions, practices, and accomplishments in providing improved delivery systems for drugs until date. The pioneering developments that have presaged today's fascinating state of the art drug delivery systems based on HAp and HAp-based composite nanostructures are also discussed. Special emphasis has been given to describe the application and effectiveness of modified HAp as drug carrier agent for different diseases such as bone-related disorders, carriers for antibiotics, anti-inflammatory, carcinogenic drugs, medical imaging, and protein delivery agents. As only a very few published works made comprehensive evaluation of HAp nanostructures for drug delivery applications, we try to cover the three major areas: concepts, practices and achievements, and applications, which have been consolidated and patented for their practical usage. The review covers a broad spectrum of nHAp and HAp modified inorganic drug carriers, emphasizing some of their specific aspects those needed to be considered for future drug delivery applications. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Nanotechnology Approaches to Biology > Cells at the Nanoscale. © 2017 Wiley Periodicals, Inc.

Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs.

Science.gov (United States)

Tian, Ye; Mao, Shirui

2012-06-01

Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo. In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed. During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.

Supramolecular Drug Delivery Systems Based on Water-Soluble Pillar[n]arenes.

Science.gov (United States)

Wu, Xuan; Gao, Lei; Hu, Xiao-Yu; Wang, Leyong

2016-06-01

Supramolecular drug delivery systems (SDDSs), including various kinds of nanostructures that are assembled by reversible noncovalent interactions, have attracted considerable attention as ideal drug carriers owing to their fascinating ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, which provides a flexible and robust platform for designing and developing functional and smart supramolecular nano-drug carriers. Pillar[n]arenes represent a new generation of macrocyclic hosts, which have unique structures and excellent properties in host-guest chemistry. This account describes recent progress in our group to develop pillararene-based stimuli-responsive supramolecular nanostructures constructed by reversible host-guest interactions for controllable anticancer drug delivery. The potential applications of these supramolecular drug carriers in cancer treatment and the fundamental questions facing SDDSs are also discussed. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

International Nuclear Information System (INIS)

Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

2010-01-01

Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

Exploiting Specific Interactions toward Next-Generation Polymeric Drug Transporters

NARCIS (Netherlands)

Wieczorek, Sebastian; Krause, Eberhard; Hackbarth, Steffen; Roeder, Beate; Hirsch, Anna K. H.; Boerner, Hans G.

2013-01-01

A generic method describes advanced tailoring of polymer drug carriers based on polymer-block-peptides. Combinatorial means are used to select suitable peptide segments to specifically complex small-molecule drugs. The resulting specific drug formulation agents render insoluble drugs water-soluble

Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy.

Science.gov (United States)

Menjoge, Anupa R; Rinderknecht, Amber L; Navath, Raghavendra S; Faridnia, Masoud; Kim, Chong J; Romero, Roberto; Miller, Richard K; Kannan, Rangaramanujam M

2011-03-30

Dendrimers offer significant potential as nanocarriers for targeted delivery of drugs and imaging agents. The objectives of this study were to evaluate the transplacental transport, kinetics and biodistribution of PAMAM dendrimers ex-vivo across the human placenta in comparison with antipyrine, a freely diffusible molecule, using dually perfused re-circulating term human placental lobules. The purpose of this study is to determine if dendrimers as drug carriers can be used to design drug delivery systems directed at selectively treating either the mother or the fetus. The transplacental transfers of fluorescently (Alexa 488) tagged PAMAM dendrimer (16 kDa) and antipyrine (188 Da) from maternal to fetal circulation were measured using HPLC/dual UV and fluorescent detector (sensitivity of 10 ng/mL for dendrimer and 100 ng/mL for antipyrine respectively). C(max) for the dendrimer-Alexa (DA) in maternal perfusate (T(max)=15 min) was 18 times higher than in the fetal perfusate and never equilibrated with the maternal perfusate during 5.5 h of perfusion (n=4). DA exhibited a measurable but low transplacental transport of 2.26±0.12 μg/mL during 5.5h, where the mean transplacental transfer was 0.84±0.11% of the total maternal concentration and the feto-maternal ratio as percent was 0.073%±0.02. The biochemical and physiological analysis of the placentae perfused with DA demonstrated normal function throughout the perfusion. The immunofluorescence histochemistry confirmed that the biodistribution of DA in perfused placenta was sparsely dispersed, and when noted was principally seen in the inter-villous spaces and outer rim of the villous branches. In a few cases, DA was found internalized and localized in nuclei and cytoplasm of syncytiotrophoblast and inside the villous core; however, DA was mostly absent from the villous capillaries. In conclusion, the PAMAM dendrimers exhibited a low rate of transfer from maternal to the fetal side across the perfused human placenta

Modelling the encapsulation of the anticancer drug cisplatin into carbon nanotubes

International Nuclear Information System (INIS)

Hilder, Tamsyn A; Hill, James M

2007-01-01

The proposed use of nanocapsules in drug delivery systems promises many advantages over current procedures. The major advantage is the potential for patients to have significantly reduced side effects from taking the drug, especially for highly toxic drugs such as those used for cancer treatments. Nanotubes have been suggested as one such carrier to deliver a drug to a specific site, giving rise to the notion of the 'magic bullet'. The aim of this paper is to determine whether a particular nanotube would accept a particular drug, and to determine the radius of the nanotube that provides the maximum uptake of the drug molecule. In particular, this paper looks at the drug cisplatin, a platinum based anticancer drug widely used in the treatment of tumours. Three orientations of cisplatin, a polar molecule, are investigated as it enters the nanotube. It is shown that, for all three orientations of cisplatin to be accepted into the carbon nanotube, the minimum radius must be at least 4.785 A, which is slightly smaller than a (9, 5) nanotube and that the maximum suction energy occurs when the carbon nanotube radius is approximately 5.3 A, which is approximately equivalent to a (11, 4) nanotube. This paper presents for the first time a calculation of this nature, and although the model represents only a first approximation, it constitutes a necessary preliminary calculation which might provide medical scientists with some overall guidelines

[Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

Science.gov (United States)

Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

2010-01-01

The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

Solid dispersions: a strategy for poorly aqueous soluble drugs and technology updates.

Science.gov (United States)

Alam, Mohd Aftab; Ali, Raisuddin; Al-Jenoobi, Fahad Ibrahim; Al-Mohizea, Abdullah M

2012-11-01

Present article reviews solid dispersion (SD) technologies and other patented inventions in the area of pharmaceutical SDs, which provide stable amorphous SDs. The review briefly compiles different techniques for preparing SDs, their applications, characterization of SDs, types of SDs and also elaborates the carriers used to prepare SDs. The advantages of recently introduced SD technologies such as RightSize(™), closed-cycle spray drying (CSD), Lidose® are summarized. Stability-related issues like phase separation, re-crystallization and methods to curb these problems are also discussed. A patented carrier-screening tool for predicting physical stability of SDs on the basis of drug-carrier interaction is explained. Applications of SD technique in controlled drug delivery systems and cosmetics are explored. Review also summarizes the carriers such as Soluplus®, Neusilin®, Solumer(TM) used to prepare stable amorphous SD. Binary and ternary SDs are found to be more stable and provide better enhancement of solubility or dissolution of poorly water-soluble drugs. The use of surfactants in the carrier system of SD is a recent trend. Surfactants and polymers provide stability against re-crystallization of SDs, surfactants also improve solubility and dissolution of drug.

Promising cardiovascular and blood pressure effects of the SGLT2 inhibitors: a new class of antidiabetic drugs.

Science.gov (United States)

Chrysant, S G

2017-03-01

Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of cardiovascular (CV) events. Treatment of these patients with traditional as well as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes compared to placebo, despite effective control of diabetes. However, the recently FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of T2DM have demonstrated promising CV-protecting and blood pressure-lowering effects in addition to their effectiveness in glucose lowering, making them a novel class of drugs for the treatment of T2DM. So far, there are three SGLT2 inhibitors approved by the FDA and EMA for the treatment of T2DM: canagliflozin, dapagliflozin and empagliflozin. They exert their antihyperglycemic effect through inhibition of SGLT2 in the kidney and significantly reduce glucose reabsorption from the proximal renal tubule. By blocking glucose reabsorption, they lead to loss of calories, weight, abdominal and total body fat, blood pressure and CV complications. One CV outcomes randomized trial and several short-term studies have shown reductions in CV events and blood pressure in patients with T2DM. It is the hope that large ongoing long-term outcome studies will provide further much-needed information, when they are completed. Copyright 2017 Clarivate Analytics.

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer.

Science.gov (United States)

Liang, Yan; Tian, Baocheng; Zhang, Jing; Li, Keke; Wang, Lele; Han, Jingtian; Wu, Zimei

2017-01-01

Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl-d-glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl-d-galactopyranose)-GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

Acoustic manipulation: Bessel beams and active carriers

Science.gov (United States)

Rajabi, Majid; Mojahed, Alireza

2017-10-01

In this paper, we address the interaction of zero-order acoustic Bessel beams as an acoustic manipulation tool, with an active spherical shell, as a carrier in drug, agent, or material delivery systems, in order to investigate the controllability of exerted acoustic radiation force as the driver. The active body is comprised of a spherical elastic shell stimulated in its monopole mode of vibrations with the same frequency as the incident wave field via an internally bonded and spatially uniformly excited piezoelectric actuator. The main aim of this work is to examine the performance of a nondiffracting and self-reconstructing zero-order Bessel beam to obtain the full manipulability condition of active carriers in comparison with the case of a plane wave field. The results unveil some unique potentials of the Bessel beams in the company of active carriers, with emphasis on the consumed power of the actuation system. This paper will widen the path toward the single-beam robust acoustic manipulation techniques and may lead to the prospect of combined tweezers and fields, with applications in delivery systems, microswimmers, and trapper designs.

Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

Directory of Open Access Journals (Sweden)

Sare Andalib

2012-01-01

Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

Drug delivery's quest for polymers: Where are the frontiers?

Science.gov (United States)

Merkle, Hans P

2015-11-01

Since the legendary 1964 article of Folkman and Long entitled "The use of silicone rubber as a carrier for prolonged drug therapy" the role of polymers in controlled drug delivery has come a long way. Today it is evident that polymers play a crucial if not the prime role in this field. The latest boost owes to the interest in drug delivery for the purpose of tissue engineering in regenerative medicine. The focus of this commentary is on a selection of general and personal observations that are characteristic for the current state of polymer therapeutics and carriers. It briefly highlights selected examples for the long march of synthetic polymer-drug conjugates from bench to bedside, comments on the ambivalence of selected polymers as inert excipients versus biological response modifiers, and on the yet unsolved dilemma of cationic polymers for the delivery of nucleic acid therapeutics. Further subjects are the complex design of multifunctional polymeric carriers including recent concepts towards functional supramolecular polymers, as well as observations on stimuli-sensitive polymers and the currently ongoing trend towards natural and naturally-derived biopolymers. The final topic is the discovery and early development of a novel type of biodegradable polyesters for parenteral use. Altogether, it is not the basic and applied research in polymer therapeutics and carriers, but the translational process that is the key hurdle to proceed towards an authoritative approval of new polymer therapeutics and carriers. Copyright © 2015 Elsevier B.V. All rights reserved.

Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

Science.gov (United States)

Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

2015-07-05

Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

Microbial Tyrosinases: Promising Enzymes for Pharmaceutical, Food Bioprocessing, and Environmental Industry

Directory of Open Access Journals (Sweden)

Kamal Uddin Zaidi

2014-01-01

Full Text Available Tyrosinase is a natural enzyme and is often purified to only a low degree and it is involved in a variety of functions which mainly catalyse the o-hydroxylation of monophenols into their corresponding o-diphenols and the oxidation of o-diphenols to o-quinones using molecular oxygen, which then polymerizes to form brown or black pigments. The synthesis of o-diphenols is a potentially valuable catalytic ability and thus tyrosinase has attracted a lot of attention with respect to industrial applications. In environmental technology it is used for the detoxification of phenol-containing wastewaters and contaminated soils, as biosensors for phenol monitoring, and for the production of L-DOPA in pharmaceutical industries, and is also used in cosmetic and food industries as important catalytic enzyme. Melanin pigment synthesized by tyrosinase has found applications for protection against radiation cation exchangers, drug carriers, antioxidants, antiviral agents, or immunogen. The recombinant V. spinosum tryosinase protein can be used to produce tailor-made melanin and other polyphenolic materials using various phenols and catechols as starting materials. This review compiles the recent data on biochemical and molecular properties of microbial tyrosinases, underlining their importance in the industrial use of these enzymes. After that, their most promising applications in pharmaceutical, food processing, and environmental fields are presented.