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Open AccessArticle

A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy

1
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan
2
Center for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University, Taoyuan 333, Taiwan
3
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(8), 413; https://doi.org/10.3390/pharmaceutics11080413
Received: 11 July 2019 / Revised: 12 August 2019 / Accepted: 12 August 2019 / Published: 14 August 2019
(This article belongs to the Special Issue Designing Hydrogels for Controlled Drug Delivery)
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Abstract

Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P–Lys–Ala–PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy. View Full-Text
Keywords: allotransplantation; hydrogels; sustained delivery; tacrolimus allotransplantation; hydrogels; sustained delivery; tacrolimus
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Lin, H.-C.; Anggelia, M.R.; Cheng, C.-C.; Ku, K.-L.; Cheng, H.-Y.; Wen, C.-J.; Wang, A.Y.L.; Lin, C.-H.; Chu, I.-M. A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy. Pharmaceutics 2019, 11, 413.

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