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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics

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          Abstract

          The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (C max) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model.

          Most cited references28

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          Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment.

          Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100-300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to optimize delivery of these agents. Here we analyze the functional limits of transvascular transport and its modulation by the microenvironment. One human and five murine tumors including mammary and colorectal carcinomas, hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or cranial window, and the pore cutoff size, a functional measure of transvascular gap size, was determined. The microenvironment was modulated: (i) spatially, by growing tumors in subcutaneous or cranial locations and (ii) temporally, by inducing vascular regression in hormone-dependent tumors. Tumors grown subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 1.2 microm. This pore cutoff size was reduced in tumors grown in the cranium or in regressing tumors after hormone withdrawal. Vessels induced in basic fibroblast growth factor-containing gels had a pore cutoff size of 200 nm. Albumin permeability was independent of pore cutoff size. These results have three major implications for the delivery of therapeutic agents: (i) delivery may be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery may be reduced during tumor regression induced by hormonal ablation, and (iii) permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter.
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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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              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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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2014
                24 January 2014
                : 9
                : 695-710
                Affiliations
                [1 ]Department of General Surgery, Shanghai, People’s Republic of China
                [2 ]Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China
                [3 ]Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People’s Republic of China
                [4 ]School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China
                [5 ]Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China
                Author notes
                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 7137 4413, Fax +86 278 788 0734, 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 +86 212 428 9005, Fax +86 216 430 7611, Email 2011cmr@ 123456sina.com

                *These authors contributed equally to this work

                Article
                ijn-9-695
                10.2147/IJN.S55255
                3908832
                320f3ced-733b-405d-afcf-7cb117c7d4cc
                © 2014 Cheng et al. This work is published by Dove Medical Press Limited, 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 Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                liver cancer,targeted therapy,chemotherapy,pharmacokinetics efficacy
                Molecular medicine
                liver cancer, targeted therapy, chemotherapy, pharmacokinetics efficacy

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