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胰岛素负载纳米粒子包埋于聚乙烯醇-硼酸盐水凝胶经皮给药促进大鼠皮肤创伤愈合。

Enhanced cutaneous wound healing in rats following topical delivery of insulin-loaded nanoparticles embedded in poly(vinyl alcohol)-borate hydrogels.

机构信息

School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes, Ulster University, Cromore Road, Coleraine, Co., Londonderry, BT52 1SA, UK.

Faculty of Pharmacy, Pharmaceutical Technology Department, Tanta University, Tanta, 31111, Egypt.

出版信息

Drug Deliv Transl Res. 2018 Oct;8(5):1053-1065. doi: 10.1007/s13346-018-0554-0.

Abstract

Insulin plays an important role in the wound healing process, but its method of delivery to the wound bed and subsequent effect on rate of healing is less well investigated. In this study, we evaluated the therapeutic effectiveness of topical human insulin delivery using a nanoparticulate delivery system suspended in a structured hydrogel vehicle. Poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) of 202.6 nm diameter and loaded with 33.86 μg insulin per milligram of polymer were formulated using a modified double-emulsion solvent evaporation technique and dispersed in a dilatant hydrogel (poly(vinyl alcohol)-borate). Importantly, this hydrogel formulation was used to achieve ultimate contact with the wound bed. A comparison of wound healing rates following local administration of insulin in the free and nanoencapsulated forms was performed in diabetic and healthy rats. In non-diabetic rats, there was no significant difference between healing observed in control and wounds treated with free insulin (p > 0.05), whereas treatment with insulin encapsulated within PLGA NP showed a significant difference (p < 0.001). In diabetic cohorts, both free insulin and nanoencapsulated insulin induced significant improvement in wound healing when compared to controls, with better percentage wound injury indices observed with the colloidal formulation. At day 10 of the experiment, the difference between percentage wound injury indices of insulin-PLGA NP and free insulin comparing to their controls were 29.15 and 12.16%, respectively. These results support strongly the potential of insulin-loaded colloidal carriers for improved wound healing when delivered using dilatant hydrogel formulations.

摘要

胰岛素在伤口愈合过程中起着重要作用,但它向伤口床传递的方式及其对愈合速度的影响尚未得到充分研究。在这项研究中,我们评估了使用悬浮在结构化水凝胶载体中的纳米颗粒递送系统递送人胰岛素的治疗效果。采用改良的双乳液溶剂蒸发技术,制备了直径为 202.6nm、载有 33.86μg 胰岛素/毫克聚合物的聚(乳酸-共-乙醇酸)(PLGA)纳米颗粒(NP),并将其分散在膨胀水凝胶(聚乙烯醇-硼酸盐)中。重要的是,这种水凝胶配方被用于与伤口床实现最终接触。在糖尿病和健康大鼠中,比较了局部给予游离和纳米封装胰岛素后伤口愈合率的差异。在非糖尿病大鼠中,控制组和用游离胰岛素处理的伤口之间的愈合没有显著差异(p>0.05),而用 PLGA NP 封装的胰岛素治疗则有显著差异(p<0.001)。在糖尿病队列中,与对照组相比,游离胰岛素和纳米封装胰岛素均能显著改善伤口愈合,胶体配方观察到更好的伤口损伤百分比指数。在实验的第 10 天,与对照组相比,胰岛素-PLGA NP 和游离胰岛素的伤口损伤百分比指数差异分别为 29.15%和 12.16%。这些结果强烈支持了在使用膨胀水凝胶配方递送时,载有人胰岛素的胶体载体在改善伤口愈合方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf4d/6133079/44b563314f86/13346_2018_554_Fig1_HTML.jpg

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