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Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing

Authors Sun T, Zhan B, Zhang W, Qin D, Xia G, Zhang H, Peng M, Li SA, Zhang Y, Gao Y, Lee WH

Received 6 November 2017

Accepted for publication 24 April 2018

Published 25 September 2018 Volume 2018:13 Pages 5771—5786

DOI https://doi.org/10.2147/IJN.S156206

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 5

Editor who approved publication: Dr Linlin Sun


Tongyi Sun,1 Bo Zhan,2,3 Weifen Zhang,2 Di Qin,1 Guixue Xia,2 Huijie Zhang,1,3 Meiyu Peng,4 Sheng-An Li,3 Yun Zhang,3 Yuanyuan Gao,2 Wen-Hui Lee1,3

1Department of Bioengineering, School of Bioscience and Technology, Weifang Medical University, Weifang 261053, Shandong, China; 2Department of Pharmaceutics, School of Pharmacy, Weifang Medical University, Weifang 261053, Shandong, China; 3Key Laboratory of Bioactive Peptide of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; 4Department of Immunology, School of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong, China

Background: Nonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing.
Purpose: To overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated.
Methods: CMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models.
Results: The release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines.
Conclusion: The prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles.

Keywords: wound healing, antimicrobial peptide, OH-CATH30, nanoparticles, skin destruction

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