Aboelazayem Samar, Nasra Maha, Ebada Heba, Abdallah Ossama
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Central Lab, Faculty of Pharmacy, Damanhour University, Damanhour, 22511, Egypt.
AAPS PharmSciTech. 2025 May 6;26(5):126. doi: 10.1208/s12249-025-03114-7.
Novel topical nanosponges were implemented to improve the skin availability of simvastatin (SV) for treating full-thickness wounds while controlling the scarring process. SV exhibits great potential in treating various skin diseases owing to its antibacterial, antioxidant, anti-inflammatory, and immunomodulatory properties. However, its poor oral bioavailability and systemic side effects have hindered its clinical application in dermatology. For the first time, nanosponges were utilized to target injured skin, creating an SV reservoir within the wound bed to enhance therapeutic efficacy while minimizing adverse effects. Herein, SV-loaded ethyl-cellulose nanosponges (SV-NS) were prepared using the emulsion solvent evaporation technique, optimizing organic solvents, SV concentration, and stabilizer concentration. The selected SV-NS (20 mg SV) exhibited nanoporous particles (786.2 ± 50 nm), a specific surface area of 10.3 m/g, and a total pore volume of 0.016 cm/g, offering sustained release and enhanced skin retention capacity. In vivo studies on full-thickness rat wounds confirmed that topical SV-NS (5 mg SV, applied every 5 days) significantly accelerated wound closure (P < 0.0001), achieving 76.23 ± 3.20% closure by day 8, a 47% improvement over free SV. Consequently, SV-NS facilitated wound closure exceeding 90% by day 11, whereas free SV required 16 days to attain a comparable level, representing a 31.2% faster healing rate. Histological analysis further revealed that SV-NS promoted optimal epidermal layer formation and well-organized collagen deposition, with collagen expression significantly (P < 0.0001) reaching 59.85 ± 3.17% by day 16. Conclusively, SV-NS enhances SV's dermal availability, improving wound healing and minimizing side effects, demonstrating a promising approach for wound restoration.
新型局部纳米海绵被用于提高辛伐他汀（SV）的皮肤可及性，以治疗全层伤口并控制瘢痕形成过程。由于其抗菌、抗氧化、抗炎和免疫调节特性，SV在治疗各种皮肤疾病方面具有巨大潜力。然而，其口服生物利用度差和全身副作用阻碍了它在皮肤科的临床应用。首次利用纳米海绵靶向受损皮肤，在伤口床内形成SV储库，以提高治疗效果并将不良反应降至最低。在此，采用乳液溶剂蒸发技术制备了载SV的乙基纤维素纳米海绵（SV-NS），优化了有机溶剂、SV浓度和稳定剂浓度。所选的SV-NS（20mg SV）呈现出纳米多孔颗粒（786.2±50nm），比表面积为10.3m/g，总孔体积为0.016cm/g，具有缓释和增强的皮肤保留能力。对大鼠全层伤口的体内研究证实，局部应用SV-NS（5mg SV，每5天应用一次）显著加速了伤口闭合（P<0.0001），到第8天实现了76.23±3.20%的闭合，比游离SV提高了47%。因此，SV-NS在第11天时促进伤口闭合超过90%，而游离SV需要16天才能达到可比水平，愈合速度快31.2%。组织学分析进一步表明，SV-NS促进了最佳表皮层形成和组织良好的胶原蛋白沉积，到第16天时胶原蛋白表达显著（P<0.0001）达到59.85±3.17%。总之，SV-NS提高了SV在皮肤中的可及性，改善了伤口愈合并减少了副作用，展示了一种有前景的伤口修复方法。
