International Journal of Nanomedicine (Sep 2018)
Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing
Abstract
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
