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      Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals

      review-article
      , , *
      Pharmaceutics
      MDPI
      oral delivery, biological barriers, co-delivery, throughput, sustained delivery

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          Abstract

          Routes of drug administration and the corresponding physicochemical characteristics of a given route play significant roles in therapeutic efficacy and short term/long term biological effects. Each delivery method has favorable aspects and limitations, each requiring a specific delivery vehicles design. Among various routes, oral delivery has been recognized as the most attractive method, mainly due to its potential for solid formulations with long shelf life, sustained delivery, ease of administration and intensified immune response. At the same time, a few challenges exist in oral delivery, which have been the main research focus in the field in the past few years. The present work concisely reviews different administration routes as well as the advantages and disadvantages of each method, highlighting why oral delivery is currently the most promising approach. Subsequently, the present work discusses the main obstacles for oral systems and explains the most recent solutions proposed to deal with each issue.

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          Most cited references203

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          Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism

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            Designing hydrogels for controlled drug delivery

            Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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              Transdermal drug delivery.

              Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                19 March 2019
                March 2019
                : 11
                : 3
                : 129
                Affiliations
                Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada; homayun@ 123456ualberta.ca (B.H.); xueting2@ 123456ualberta.ca (X.L.)
                Author notes
                [* ]Correspondence: hyojick@ 123456ualberta.ca ; Tel.: +1-780-248-1666
                Author information
                https://orcid.org/0000-0001-8233-5864
                Article
                pharmaceutics-11-00129
                10.3390/pharmaceutics11030129
                6471246
                30893852
                39727b8b-f53e-4b1d-996a-ecbb6d2704ce
                © 2019 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 (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 February 2019
                : 14 March 2019
                Categories
                Review

                oral delivery,biological barriers,co-delivery,throughput,sustained delivery

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