Abstract

Chronic wounds are a serious problem that could cause severe morbidity and even death. The ability of statins including rosuvastatin calcium (RVS) to enhance wound healing was well reported. However, RVS is poorly soluble and has low bioavailability. Thus, this study aimed to prepare and evaluate RVS-loaded nanocubics to enhance its skin performance. In addition, silver nanoparticles (AgNPs) exhibited potent antimicrobial activity, thus, the optimum RVS-loaded nanocubics was capped with AgNPs to evaluate its effect in wound management. Box–Behnken design was adopted to prepare RVS nanocubics. The design investigated the effect of lecithin, poloxamer 407 concentrations and hydration time on vesicle size, zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release%. Optimum formulation capped with AgNPs was incorporated into a gel base and examined for wound healing efficiency using different pharmacological tests in rats. Nanocubics have shown a mean diameter between 167.2 ± 7.8 and 408 ± 18.4 nm, ZP values ranging from −20.9 ± 1.9 to −53.5 ± 4 mV, EE% equivocated between 31.6 ± 1.4 and 94.4 ± 8.6 and drug release after 12 h between 17.9 ± 1.9 and 68.0 ± 4.0%. The histopathological studies and serum tumour necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels confirmed the greater efficacy of RVS nanocubics capped with AgNPs gel in wound healing when compared with gentamicin ointment. RVS-loaded nanocubic vesicles and AgNPs-loaded hydrogel could be considered as a promising platform to enhance the wound healing and tissue repair processes.

摘要

慢性伤口是一个严重的问题，可能导致严重的发病率甚至死亡。包括瑞舒伐他汀钙 (RVS) 在内的他汀类药物促进伤口愈合的能力已得到充分报道。然而，RVS 溶解性差，生物利用度低。因此，本研究旨在制备和评估负载 RVS 的纳米立方体以增强其皮肤性能。此外，银纳米粒子 (AgNPs) 表现出强大的抗菌活性，因此，最佳的 RVS 负载纳米立方体被 AgNPs 封顶，以评估其在伤口管理中的效果。采用 Box-Behnken 设计制备 RVS 纳米立方体。该设计研究了卵磷脂、泊洛沙姆 407 浓度和水合时间对囊泡大小、zeta 电位 (ZP)、包封率 (EE%) 和体外的影响药物释放％。将用 AgNPs 封端的最佳配方掺入凝胶基质中，并在大鼠中使用不同的药理学试验检查伤口愈合效率。Nanocubics 的平均直径在 167.2 ± 7.8 和 408 ± 18.4 nm 之间，ZP 值在 -20.9 ± 1.9 到 -53.5 ± 4 mV 之间，EE% 在 31.6 ± 1.4 和 94.4 ± 8.6 之间模棱两可，12 小时后的药物释放在 17.9 之间± 1.9 和 68.0 ± 4.0%。与庆大霉素软膏相比，组织病理学研究和血清肿瘤坏死因子 α (TNF-α) 和白细胞介素 1β (IL-1β) 水平证实了用 AgNPs 凝胶封端的 RVS 纳米立方体在伤口愈合中的更大功效。负载 RVS 的纳米立方囊泡和负载 AgNPs 的水凝胶可以被认为是增强伤口愈合和组织修复过程的有前途的平台。