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头孢羟氨苄壳聚糖纳米粒原位凝胶的潜在抗菌伤口敷料:制备、体外优化及体内评价。

A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel: Fabrication, in vitro optimization and in vivo evaluation.

机构信息

Pharmaceutical Technology Department, National Research Centre, Cairo 12311, Egypt.

Pharmaceutical Technology Department, National Research Centre, Cairo 12311, Egypt.

出版信息

Int J Pharm. 2018 Jun 10;544(1):129-140. doi: 10.1016/j.ijpharm.2018.04.021. Epub 2018 Apr 12.

Abstract

Wound healing following skin injury is a natural phenomenon that usually lacks quality, rapidity, and aesthetics. Thus, the purpose of this study was to fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting the possible accompanying bacterial infection. The nanoparticles were prepared by double emulsion technique and the influence of formulation parameters on drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were investigated using a full factorial design. The results show that the optimized CDX-CSNP1 composed of low molecular weight chitosan (0.2%w/v) was spherical with EE%, PS, PDI and ZP of 84.25 ± 0.02, 408.30 ± 53.17 nm, 0.458 ± 0.048 and 22.80 ± 0.57 mV, respectively. DSC and XRD studies confirmed the amorphous nature of the drug. After ensuring the safety and non toxicity of CDX-CSNP1 in situ gel through cytotoxic study, the antibacterial activity was evaluated using a rat skin infection model against Staphylococcus aureus. Compared to the rats treated with free CDX, the CDX-CSNP1 treated group revealed a remarkable accelerated wound healing process and bacterial clearance which was further confirmed by the histopathological examination of skin biopsies.

摘要

皮肤损伤后的伤口愈合是一种自然现象,但通常缺乏质量、速度和美感。因此,本研究的目的是制备一种新的易应用于原位的载头孢羟氨苄(CDX)壳聚糖纳米粒(CDX-CSNPs)的原位凝胶,以促进伤口愈合,并能抑制可能伴随的细菌感染。采用复乳技术制备纳米粒,并通过完全析因设计考察制剂参数对药物包封率(EE%)、粒径(PS)、多分散指数(PDI)和Zeta 电位(ZP)的影响。结果表明,由低分子量壳聚糖(0.2%w/v)组成的优化 CDX-CSNP1 呈球形,EE%、PS、PDI 和 ZP 分别为 84.25±0.02、408.30±53.17nm、0.458±0.048 和 22.80±0.57mV。DSC 和 XRD 研究证实了药物的无定形性质。通过细胞毒性研究确保 CDX-CSNP1 原位凝胶的安全性和非毒性后,采用金黄色葡萄球菌大鼠皮肤感染模型评估其抗菌活性。与用游离 CDX 治疗的大鼠相比,CDX-CSNP1 治疗组表现出明显加速的伤口愈合过程和细菌清除,皮肤活检的组织病理学检查进一步证实了这一点。

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