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      Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements

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          Abstract

          Colon targeted drug delivery systems have gained a great deal of attention as potential carriers for the local treatment of colonic diseases with reduced systemic side effects and also for the enhanced oral delivery of various therapeutics vulnerable to acidic and enzymatic degradation in the upper gastrointestinal tract. In recent years, the global pharmaceutical market for biologics has grown, and increasing demand for a more patient-friendly drug administration system highlights the importance of colonic drug delivery as a noninvasive delivery approach for macromolecules. Colon-targeted drug delivery systems for macromolecules can provide therapeutic benefits including better patient compliance (because they are pain-free and can be self-administered) and lower costs. Therefore, to achieve more efficient colonic drug delivery for local or systemic drug effects, various strategies have been explored including pH-dependent systems, enzyme-triggered systems, receptor-mediated systems, and magnetically-driven systems. In this review, recent advancements in various approaches for designing colon targeted drug delivery systems and their pharmaceutical applications are covered with a particular emphasis on formulation technologies.

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          Most cited references105

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          Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease.

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            Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

            Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research.
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              Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells.

              In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                15 January 2020
                January 2020
                : 12
                : 1
                : 68
                Affiliations
                College of Pharmacy, Dongguk University-Seoul, Dongguk-ro 32, Ilsan-Donggu, Goyang 10326, Korea; sh_lee@ 123456dongguk.edu (S.H.L.); rajivbajra@ 123456hotmail.com (R.B.); jyin14@ 123456naver.com (J.Y.M.); hjw0868@ 123456naver.com (J.-W.H.); bjpark@ 123456dongguk.edu (B.J.P.)
                Author notes
                [* ]Correspondence: hkhan@ 123456dongguk.edu ; Tel.: +82-31-961-5217
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-4929-1972
                Article
                pharmaceutics-12-00068
                10.3390/pharmaceutics12010068
                7022598
                31952340
                a160bb5a-87f8-4d9d-a825-a7a9facf14b1
                © 2020 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
                : 29 November 2019
                : 10 January 2020
                Categories
                Review

                colon,noninvasive drug delivery,inflammatory bowel diseases,colorectal cancer,protein drugs

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