Preparation of a controlled release chitosan transdermal patch loaded by ciprofloxacin/zinc oxide nanoparticles for cutaneous wound healing in rat.

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.