The present work is focused on the development of novel surface-functionalized poly(lactic-co-glycolic acid) nanoparticles loaded with thymol (TH-NPs) for topical administration enhancing thymol anti-inflammatory, antioxidant and wound healing activities against acne. TH-NPs were prepared by solvent evaporation method using different surface functionalization strategies and obtaining suitable physicochemical parameters and a good short-term stability at 4 °C. Moreover, TH-NPs skin penetration and antioxidant activity were assessed in ex vivo pig skin models. Skin penetration of TH-NPs followed the follicular route, independently of the surface charge and they were able to enhance antioxidant capacity. Furthermore, antimicrobial activity against Cutibacterium acnes was evaluated in vitro by the suspension test showing improved antibacterial performance. Using human keratinocyte cells (HaCat), cytotoxicity, cellular uptake, antioxidant, anti-inflammatory and wound healing activities were studied. TH-NPs were non-toxic and efficiently internalized inside the cells. In addition, TH-NPs displayed significant anti-inflammatory, antioxidant and wound healing activities, which were highly influenced by TH-NPs surface modifications. Moreover, a synergic activity between TH-NPs and their surface functionalization was demonstrated. To conclude, surface-modified TH-NPs had proven to be suitable to be used as anti-inflammatory, antioxidant and wound healing agents, constituting a promising therapy for treating acne infection and associated inflammation.

中文翻译：

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用于局部痤疮治疗的表面改性多功能百里酚负载生物可降解纳米颗粒

目前的工作重点是开发负载百里酚 (TH-NPs) 的新型表面功能化聚（乳酸 - 共 - 乙醇酸）纳米粒子，用于局部给药，增强百里酚对痤疮的抗炎、抗氧化和伤口愈合活性。TH-NPs 是通过溶剂蒸发法使用不同的表面功能化策略制备的，并获得合适的理化参数和在 4°C 下良好的短期稳定性。此外，在离体猪皮肤模型中评估了 TH-NPs 皮肤渗透和抗氧化活性。TH-NPs 的皮肤渗透遵循毛囊途径，与表面电荷无关，并且它们能够增强抗氧化能力。此外，对痤疮皮肤杆菌的抗菌活性通过悬浮试验进行体外评估，显示出改善的抗菌性能。使用人类角质形成细胞 (HaCat)，研究了细胞毒性、细胞摄取、抗氧化、抗炎和伤口愈合活性。TH-NPs 无毒且有效地内化在细胞内。此外，TH-NPs 显示出显着的抗炎、抗氧化和伤口愈合活性，这受到 TH-NPs 表面修饰的高度影响。此外，证明了 TH-NPs 与其表面功能化之间的协同活性。总之，表面修饰的 TH-NPs 已被证明适合用作抗炎、抗氧化剂和伤口愈合剂，构成治疗痤疮感染和相关炎症的有前途的疗法。