Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Department of Neurology, Cangzhou Central Hospital, Cangzhou, 061000, People's Republic of China.
Int J Nanomedicine. 2023 Jul 19;18:3951-3972. doi: 10.2147/IJN.S410996. eCollection 2023.
Drug-resistant bacterial infections and biofilm formation play important roles in the pathogenesis of diabetic refractory wounds. Tea tree oil (TTO) exhibits antimicrobial, antimycotic, and antiviral activities, especially against common clinically resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making it a potential natural antimicrobial for the treatment of acute and chronic wounds. However, TTO is insoluble in water, volatile, light-sensitive, and cytotoxic. While previous macroscopic studies have focused on sterilization with TTO, none have sought to alter its structure or combine it with other materials to achieve sustained release.
Electrospun TTO nanoliposomes (TTO-NLs), arranged linearly via high-pressure homogenization, could stabilize the structure and performance of TTO to achieve slow drug release. Herein, we established a composite nano-sustained release system, TTO-NL/polyvinyl alcohol/chitosan (TTO-NL@PCS), using high-voltage electrospinning.
Compared with the control, TTO-NL@PCS exhibits higher concentrations of the active TTO drug components, terpinen-4-ol and 1,8-cineole. Owing to its increased stability and slow release, early exposure to TTO-NL@PCS increases the abundance of reactive oxygen species in vitro, ultimately causing the biofilm to disperse and completely killing MRSA without inducing cytotoxic effects to the host. Moreover, in BKS-Lepr/Gpt mice with a whole-layer skin infection, untargeted metabolomics analysis of wound exudates reveals upregulated PGF2α/FP receptor signaling and interleukin (IL)-1β and IL-6 expression following application of the composite system. The composite also ameliorates the chemotaxis disorder in early treatment and attenuates the wound inflammatory response during the repair stage of diabetic inflammatory wounds, and upregulates VEGF expression in the wound bed.
TTO-NL@PCS demonstrates the remarkable potential for accelerating diabetic and MRSA-infected wound healing.
耐药细菌感染和生物膜形成在糖尿病难治性创面的发病机制中起着重要作用。茶树油（TTO）具有抗菌、抗真菌和抗病毒活性，尤其对常见的临床耐药菌株如耐甲氧西林金黄色葡萄球菌（MRSA）具有抗菌作用，因此是治疗急性和慢性创面的潜在天然抗菌剂。然而，TTO 不溶于水，易挥发，对光敏感，具有细胞毒性。虽然之前的宏观研究侧重于 TTO 的杀菌作用，但没有研究试图改变其结构或与其他材料结合以实现药物持续释放。
通过高压匀质线性排列的电纺 TTO 纳米脂质体（TTO-NL）可以稳定 TTO 的结构和性能，实现药物缓慢释放。在此，我们使用高压静电纺丝技术构建了一种复合纳米缓释系统 TTO-NL/聚乙烯醇/壳聚糖（TTO-NL@PCS）。
与对照组相比，TTO-NL@PCS 具有更高浓度的活性 TTO 药物成分萜品-4-醇和 1,8-桉叶油醇。由于其稳定性增加和释放缓慢，早期暴露于 TTO-NL@PCS 会增加体外活性氧的丰度，最终导致生物膜分散，完全杀死 MRSA，而不会对宿主产生细胞毒性作用。此外，在具有全层皮肤感染的 BKS-Lepr/Gpt 小鼠中，对伤口渗出物进行非靶向代谢组学分析表明，复合体系应用后，PGF2α/FP 受体信号和白细胞介素（IL）-1β 和 IL-6 的表达上调。该复合物还改善了早期治疗中的趋化作用障碍，并减轻了糖尿病炎症性创面修复阶段的伤口炎症反应，同时上调了伤口床中的 VEGF 表达。
TTO-NL@PCS 具有加速糖尿病和 MRSA 感染性创面愈合的显著潜力。
