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      Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells

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          Abstract

          Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma.

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          Most cited references 40

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          Targeted delivery of low molecular drugs using chitosan and its derivatives.

          Chitosan has prompted the continuous impetus for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical properties. When the hydrophobic moiety is conjugated to a chitosan molecule, the resulting amphiphile may form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site of action. Chemical attachment of the drug to the chitosan throughout the functional linker may produce useful prodrugs, exhibiting the appropriate biological activity at the target site. Mucoadhesive and absorption enhancement properties of chitosan increase the in vivo residence time of the dosage form in the gastrointestinal tract and improve the bioavailability of various drugs. The main objective of this review is to provide an insight into various target-specific carriers, based on chitosan and its derivatives, towards low molecular weight drug delivery. The first part of the review is concerned with the organ-specific delivery of low molecular drugs using chitosan and its derivatives. The subsequent section considers the recent developments of drug delivery carriers for cancer therapy with special focus on various targeting strategies. 2009 Elsevier B.V. All rights reserved.
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            Nanosuspensions: a promising drug delivery strategy.

            Nanosuspensions have emerged as a promising strategy for the efficient delivery of hydrophobic drugs because of their versatile features and unique advantages. Techniques such as media milling and high-pressure homogenization have been used commercially for producing nanosuspensions. Recently, the engineering of nanosuspensions employing emulsions and microemulsions as templates has been addressed in the literature. The unique features of nanosuspensions have enabled their use in various dosage forms, including specialized delivery systems such as mucoadhesive hydrogels. Rapid strides have been made in the delivery of nanosuspensions by parenteral, peroral, ocular and pulmonary routes. Currently, efforts are being directed to extending their applications in site-specific drug delivery.
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              Chitosan Based Polyelectrolyte Complexes as Potential Carrier Materials in Drug Delivery Systems

              Chitosan has been the subject of interest for its use as a polymeric drug carrier material in dosage form design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. However, one drawback of using this natural polysaccharide in modified release dosage forms for oral administration is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pKa value), it spontaneously associates with negatively charged polyions in solution to form polyelectrolyte complexes. These chitosan based polyelectrolyte complexes exhibit favourable physicochemical properties with preservation of chitosan’s biocompatible characteristics. These complexes are therefore good candidate excipient materials for the design of different types of dosage forms. It is the aim of this review to describe complexation of chitosan with selected natural and synthetic polyanions and to indicate some of the factors that influence the formation and stability of these polyelectrolyte complexes. Furthermore, recent investigations into the use of these complexes as excipients in drug delivery systems such as nano- and microparticles, beads, fibers, sponges and matrix type tablets are briefly described.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                25 October 2013
                : 7
                : 1287-1299
                Affiliations
                [1 ]Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China
                [2 ]Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China
                [3 ]Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China
                [4 ]School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China
                [5 ]Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People’s Republic of China
                [6 ]Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China
                Author notes

                *These authors contributed equally to this work

                Correspondence: Yong Wang, School of Materials Science and Engineering, Wuhan University of Technology, Youyi Ave, Wuchang, Wuhan 430070, People’s Republic of China, Tel +86 189 713 74 413, Fax +86 27 878 807 34, Email wangyong@ 123456whut.edu.cn
                Bing He, Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, 128 Ruili Rd, Minhang, Shanghai 200240, People’s Republic of China, Tel +86 21 24 289 005, Fax +86 21 64 307 611, Email 2011cmr@ 123456sina.com
                Article
                dddt-7-1287
                10.2147/DDDT.S52809
                3810199
                © 2013 Cheng et al. This work is published by Dove Medical Press Ltd, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Ltd, provided the work is properly attributed.

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                Original Research

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