Khosravian Pegah, Mardani Reza, Boldaji Zahra Khaksar, Javdani Moosa, Hashemnia Mohammad
Medical Plants Research Center, Shahrekord University of Medical Science, Shahrekord, Iran.
Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 12. doi: 10.1007/s00210-025-04417-z.
Effective wound healing requires materials that modulate inflammation, enhance tissue regeneration, and promote re-epithelialization. In this study, we developed and evaluated the wound healing efficacy of controlled-release chitosan-based transdermal patches loaded with ciprofloxacin and zinc nanoparticles in rats. Full-thickness excisional wounds (2 cm diameter) were created on 75 Wistar rats, assigned to five groups: chitosan (Cs), Cs-ciprofloxacin (CsCi), Cs-zinc (CsZn), Cs-ciprofloxacin-zinc (Cs/Zn@Ci), and untreated control. Tissue samples were collected on days 7, 14, and 21 for histopathological, immunohistochemical, and biochemical analysis. The Cs/Zn@Ci group exhibited significantly enhanced wound closure, approximately 1.8-, 1.54-, and 1.19-fold greater than the control at each respective time point (P < 0.05). The Cs/Zn@Ci-treated group showed marked modulation of inflammation, enhanced fibroplasia and angiogenesis, and improved scar tissue formation in the early phase. Long-term treatment resulted in improved collagen alignment, reduced scar formation, and enhanced epithelial regeneration. Gene expression analysis showed significantly elevated CK14 and EGFR levels in the Cs/Zn@Ci group compared to control, with fold increases ranging from 1.1 to 1.6 across time points (P < 0.05). Additionally, collagen and glycosaminoglycan content were markedly higher in the Cs/Zn@Ci groups throughout the healing phases. These findings demonstrate that Cs/Zn@Ci patches act synergistically to enhance healing through antimicrobial activity, immunomodulation, and matrix regeneration. This novel formulation holds strong clinical potential for improving outcomes in cutaneous wound management.
有效的伤口愈合需要能够调节炎症、促进组织再生和上皮再形成的材料。在本研究中，我们开发并评估了负载环丙沙星和锌纳米颗粒的壳聚糖基控释透皮贴剂在大鼠中的伤口愈合效果。在75只Wistar大鼠身上制造直径为2厘米的全层切除伤口，将其分为五组：壳聚糖（Cs）、壳聚糖-环丙沙星（CsCi）、壳聚糖-锌（CsZn）、壳聚糖-环丙沙星-锌（Cs/Zn@Ci）和未处理的对照组。在第7天、14天和21天采集组织样本进行组织病理学、免疫组织化学和生化分析。Cs/Zn@Ci组的伤口闭合显著增强，在各个时间点分别比对照组大1.8倍、1.54倍和1.19倍（P < 0.05）。Cs/Zn@Ci处理组在早期显示出明显的炎症调节、增强的纤维增生和血管生成，以及改善的瘢痕组织形成。长期治疗导致胶原排列改善、瘢痕形成减少和上皮再生增强。基因表达分析显示，与对照组相比，Cs/Zn@Ci组的CK14和EGFR水平显著升高，在各个时间点的倍数增加范围为1.1至1.6（P < 0.05）。此外，在整个愈合阶段，Cs/Zn@Ci组的胶原蛋白和糖胺聚糖含量明显更高。这些发现表明，Cs/Zn@Ci贴剂通过抗菌活性、免疫调节和基质再生协同作用来促进愈合。这种新型制剂在改善皮肤伤口管理结果方面具有强大的临床潜力。
