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      Exploring Polymeric Micelles for Improved Delivery of Anticancer Agents: Recent Developments in Preclinical Studies

      review-article
      * , ,
      Pharmaceutics
      MDPI
      block polymer, EPR effect, tumor-targeting ligand, pharmacokinetics, targeted cancer therapy

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          Abstract

          As versatile drug delivery systems, polymeric micelles have demonstrated particular strength in solubilizing hydrophobic anticancer drugs while eliminating the use of toxic organic solvents and surfactants. However, the true promise of polymeric micelles as drug carriers for cancer therapy resides in their potential ability to preferentially elevate drug exposure in the tumor and achieve enhanced anticancer efficacy, which still remains to be fully exploited. Here, we review various micellar constructs that exhibit the enhanced permeation and retention effect in the tumor, the targeting ligands that potentiate the anticancer efficacy of micellar drugs, and the polyplex micelle systems suitable for the delivery of plasmid DNA and small interference RNA. Together, these preclinical studies in animal models help us further explore polymeric micelles as emerging drug carriers for targeted cancer therapy.

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          Most cited references52

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          Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery.

          The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that (i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and biotherapeutics (e.g. peptide and protein drugs, and siRNA) exert therapeutical effects only inside cells like the cytosol and cell nucleus, and (ii) several intracellular compartments such as cytosol, mitochondria, and cell nucleus contain a high concentration of glutathione (GSH) tripeptides (about 2-10 mM), which is 100 to 1000 times higher than that in the extracellular fluids and circulation (about 2-20 μM). Glutathione has been recognized as an ideal and ubiquitous internal stimulus for rapid destabilization of nano-carriers inside cells to accomplish efficient intracellular drug release. In this paper, we will review recent results on GSH-responsive nano-vehicles in particular micelles, nanoparticles, capsules, polymersomes, nanogels, dendritic and macromolecular drug conjugates, and nano-sized nucleic acid complexes for controlled delivery of anti-cancer drugs (e.g. doxorubicin and paclitaxel), photosensitizers, anti-oxidants, peptides, protein drugs, and nucleic acids (e.g. DNA, siRNA, and antisense oligodeoxynucleotide). The unique disulfide chemistry has enabled novel and versatile designs of multifunctional delivery systems addressing both intracellular and extracellular barriers. We are convinced that GSH-responsive nano-carrier systems have enormous potential in targeted cancer therapy. Copyright © 2011 Elsevier B.V. All rights reserved.
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            Current prospects for RNA interference-based therapies

            Key Points RNA interference (RNAi) is a powerful approach for reducing expression of endogenously expressed proteins for biological applications, or targeting the expression of pathological proteins for therapy. Several delivery methods are available to achieve RNAi in ex vivo and in vivo settings for therapeutic results. The development of RNAi-based therapeutics has advanced sufficiently to allow human clinical trials to begin. Here we outline the broad range of cell-, tissue- and disease-specific approaches under investigation for RNAi therapeutics. The barriers posed by certain cells and tissues are described, as are issues with off-target silencing.
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              Polymeric micelles drug delivery system in oncology.

              Polymeric micelles (PM) system, as an efficient drug carrier, has received growing scientific attention in recent years owing to its solubilization, selective targeting, P-glycoprotein inhibition and altered drug internalization route and subcellular localization properties. Seven PM formulations of anti-tumor drugs being evaluated in clinical trials are reviewed in this paper, in terms of formulation study, in vitro cytotoxicity, in vivo pharmacokinetics, anti-tumor efficacy and safety as well as clinical trials, to shed new light on the discovery of novel PM formulations. In these seven PM formulations, PM system was employed to overcome the issues of low water solubility, high toxicity and (or) multidrug resistance accompanied with the conventional formulation, which greatly hampered their clinical application. Those promising preclinical and clinical results combined with rapid advancement and intense multidisciplinary collaboration enable the extension of the PM system to traditional Chinese medicine, imaging agents, gene and combination agent deliveries as well as some other administration routes, which facilitate the clinical translation of the PM drug delivery system. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                22 March 2013
                March 2013
                : 5
                : 1
                : 201-219
                Affiliations
                Cancer Nanomedicine Laboratory, Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA 30341, USA; E-Mails: Yingzhe.Wang@ 123456live.mercer.edu (Y.W.); stojkovic@ 123456163.com (W.F.)
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: tan_c@ 123456mercer.edu ; Tel.: +1-678-547-6240; Fax: +1-678-547-6423.
                Article
                pharmaceutics-05-00201
                10.3390/pharmaceutics5010201
                3834940
                24300405
                831bccd6-cb35-4bb5-8f90-f13d4c5a9ca4
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 21 December 2012
                : 28 February 2013
                : 13 March 2013
                Categories
                Review

                block polymer,epr effect,tumor-targeting ligand,pharmacokinetics,targeted cancer therapy

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