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      Design and development of hydrogel nanoparticles for mercaptopurine

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          Abstract

          Hydrogel nanoparticles have gained attention in recent years as they demonstrate the features and characters of hydrogels and nanoparticles at the same time. In the present study chitosan and carrageenan have been used, as hydrogel nanoparticles of mercaptopurine are developed using natural, biodegradable, and biocompatible polymers like chitosan and carrageenan. As these polymers are hydrophilic in nature, the particles will have a long life span in systemic circulation. Hydrogel nanoparticles with mercaptopurine is form an antileukemia drug by the counter polymer gelation method. Fourier-Transform Infrared (FT-IR) studies have shown a compatibility of polymers with the drug. The diameter of hydrogel nanoparticles was about 370 – 800 nm with a positive zeta potential of 26 – 30 mV. The hydrogel nanoparticles were almost spherical in shape, as revealed by scanning electron microscopy (SEM). Drug loading varied from 9 to 17%. Mercaptopurine released from the nanoparticles at the end of the twenty-fourth hour was about 69.48 – 76.52% at pH 7.4. The drug release from the formulation was following zero order kinetics, which was evident from the release kinetic studies and the mechanism of drug release was anomalous diffusion, which indicated that the drug release was controlled by more than one process.

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          Hydrogel nanoparticles in drug delivery.

          Hydrogel nanoparticles have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique potentials via combining the characteristics of a hydrogel system (e.g., hydrophilicity and extremely high water content) with a nanoparticle (e.g., very small size). Several polymeric hydrogel nanoparticulate systems have been prepared and characterized in recent years, based on both natural and synthetic polymers, each with its own advantages and drawbacks. Among the natural polymers, chitosan and alginate have been studied extensively for preparation of hydrogel nanoparticles and from synthetic group, hydrogel nanoparticles based on poly (vinyl alcohol), poly (ethylene oxide), poly (ethyleneimine), poly (vinyl pyrrolidone), and poly-N-isopropylacrylamide have been reported with different characteristics and features with respect to drug delivery. Regardless of the type of polymer used, the release mechanism of the loaded agent from hydrogel nanoparticles is complex, while resulting from three main vectors, i.e., drug diffusion, hydrogel matrix swelling, and chemical reactivity of the drug/matrix. Several crosslinking methods have been used in the way to form the hydrogel matix structures, which can be classified in two major groups of chemically- and physically-induced crosslinking.
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            Dual agents loaded PLGA nanoparticles: systematic study of particle size and drug entrapment efficiency.

            PLGA nanoparticles simultaneously loaded with vincristine sulfate (VCR) and quercetin (QC) were prepared via O/W emulsion solvent evaporation. Six independent processing parameters and PLGA characteristics were assessed systematically to enhance the incorporation of the dual agents with different properties (VCR and QC, hydrophilic and hydrophobic molecule, respectively) into PLGA nanoparticles and control particle size. Approaches investigated for the enhancement of drug entrapment efficiencies and the controlling of particle size included the influence of the molecular weight (MW) of PLGA and the lactide-to-glycolide (L:G) ratio of PLGA, PLGA concentration, PVA concentration, initial QC content, acetone-to-dichloromethane (A/D) volume ratio, aqueous phase pH and aqueous to organic phase (W/O) volume ratio. The nanoparticles produced by optimal formulation were submicron size (139.5+/-4.3 nm, n=3) with low polydispersity index (0.095+/-0.031, n=3). Nanoparticles observed by transmission electron microscopy (TEM) showed extremely spherical shape. The entrapment efficiencies determined by high performance liquid chromatography (HPLC) by ultracentrifuge method were 92.84+/-3.37% for VCR and 32.66+/-2.92% for QC (n=3). The drug loadings were 0.0037+/-0.0001% for VCR and 1.36+/-0.12% for QC (n=3).
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              Development of new chitosan/carrageenan nanoparticles for drug delivery applications.

              The use of polymeric nanoparticles, especially those composed of natural polymers, has become a very interesting approach in drug delivery, mainly because of the advantages offered by their small dimensions. The aim of this work was to develop a novel formulation of nanoparticles comprised of two natural marine-derived polymers, namely chitosan and carrageenan, and to evaluate their potential for the association and controlled release of macromolecules. Nanoparticles were obtained in a hydrophilic environment, under very mild conditions, avoiding the use of organic solvents or other aggressive technologies for their preparation. The developed nanocarriers presented sizes within 350-650 nm and positive zeta potentials of 50-60 mV. Polymeric interactions between nanoparticles' components were evaluated by Fourier transform infrared spectroscopy. Using ovalbumin as model protein, nanoparticles evidenced loading capacity varying from 4% to 17% and demonstrated excellent capacity to provide a controlled release for up to 3 weeks. Furthermore, nanoparticles have demonstrated to exhibit a noncytotoxic behavior in biological in vitro tests performed using L929 fibroblasts, which is critical regarding the biocompatibility of those carriers. In summary, the developed chitosan-carrageenan nanoparticles have shown promising properties to be used as carriers of therapeutic macromolecules, with potential application not only strictly in drug delivery, but also in broader areas, such as tissue engineering and regenerative medicine. (c) 2009 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                J Adv Pharm Technol Res
                JAPTR
                Journal of Advanced Pharmaceutical Technology & Research
                Medknow Publications & Media Pvt Ltd (India )
                2231-4040
                0976-2094
                Jul-Sep 2010
                : 1
                : 3
                : 334-337
                Affiliations
                [1]Department of Pharmaceutics, JSS College of Pharmacy, Ooty, JSS University, Mysore, India.
                Author notes
                Address for correspondence: Dr. V. Senthil, Assistant Professor, Department of Pharmaceutics, JSS College of Pharmacy, Ooty 643 001, Tamilnadu. E-mail: senthil.v@ 123456rediffmail.com
                Article
                JAPTR-1-334
                10.4103/0110-5558.72431
                3255408
                22247867
                fbea1b87-3479-4758-84af-e47dfa8a94b2
                Copyright: © Journal of Advanced Pharmaceutical Technology & Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                chitosan,counter polymer gelation,hydrogel nanoparticles,carrageenan and mercaptopurine

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