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Rgd Peptide Grafted Polybutylene Adipate-Co-Terephthalate/Gelatin Electrospun Nanofibers Loaded With a Matrix Metalloproteinase Inhibitor Drug for Alleviating of Wounds: An In Vitro/In Vivo Study Publisher Pubmed



Varshosaz J1 ; Arabloo K1 ; Sarrami N1 ; Ghassami E1 ; Yazdani Kachouei E2 ; Kouhi M1 ; Jahaniannajafabadi A3
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  3. 3. Department of Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Drug Development and Industrial Pharmacy Published:2020


Abstract

The objective of the present study was the fabrication of a wound dressing membrane based on RGD modified polybutylene adipate-co-terephthalate (PBAT)/gelatin nanofibrous structures loaded with doxycycline (DOX). This type of nanofiber for wound healing has not been reported so far and is quite novel. PBAT and gelatin nanofibers were separately electrospun using double needles electrospinning setup. Electrospinning variables were optimized to obtain bead-free thin nanofibers. The amount of drug loaded and release were measured in different concentrations of DOX and PBAT. MMPs inhibition was studied by polyacrylamide gel-zymography. Then, surface of the nanofibers was modified with RGD peptide, and their antimicrobial effect was investigated on Staphylococcus aureus and Pseudomonas aeruginosa. Effect of developed nanofibrous membranes on L929 fibroblast cells proliferation, adhesion and closure of excised wounds in rat were also studied. PBAT/gelatin nanofibrous structures with average fiber diameter of 75–529 nm were developed successfully. Drug release study revealed that about 65% of DOX was released from the optimized formulation (P17D1.6) after 20 h. The developed DOX loaded membrane inhibited the MMPs activity and showed no cytotoxicity. RGD surface-modified PBAT/gelatin nanofibers significantly improved the wound closure and histopathological results (re-epithelialization, collagen deposition, and angiogenesis) in rats compared to the control groups. Overall, RGD immobilized PBAT/gelatin nanofibrous membrane may have a potential application for wound healing. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
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