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

      review-article
      1 , 2 , 3 , 1 , 1 , 2
      Drug Delivery
      Taylor & Francis
      pH-Responsive, oral delivery, controlled release, bioavailability, drug delivery

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          Abstract

          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.

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          Most cited references166

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          Stimuli-responsive nanocarriers for drug delivery.

          Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).
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            Hydrogels in pharmaceutical formulations.

            N. Peppas (2000)
            The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.
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              Long-circulating and target-specific nanoparticles: theory to practice.

              The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.
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                Author and article information

                Journal
                Drug Deliv
                Drug Deliv
                Drug Delivery
                Taylor & Francis
                1071-7544
                1521-0464
                14 February 2017
                2017
                : 24
                : 1
                : 569-581
                Affiliations
                [1 ]The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, PR China,
                [2 ]Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou, PR China, and
                [3 ]College of Pharmaceutical Sciences, Zhejiang Chinese Medical University , Hangzhou, PR China
                Author notes
                [*]

                These authors contributed to this work equally and should be considered as co-corresponding authors.

                Address for correspondence: Dr. JianQing Gao, Professor, Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , 866 Yuhangtang Road, Hangzhou 310058, PR China. Tel: +86 57188208436. Fax: +86 57188208436. E-mail: gaojianqing@ 123456zju.edu.cn
                Article
                1279238
                10.1080/10717544.2017.1279238
                8241197
                28195032
                f1ab99a6-4b8d-45d0-95cc-bc8b15a46f05
                © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 1, Pages: 13
                Categories
                Review
                Review Article

                Pharmacology & Pharmaceutical medicine
                ph-responsive,oral delivery,controlled release,bioavailability,drug delivery

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