Effective topical delivery of astaxanthin via optimized chitosan-coated nanostructured lipid carriers: A promising strategy for enhanced wound healing and tissue regeneration

The development of innovative systems with antioxidant activity and controlled release capabilities is crucial for efficient wound healing and tissue regeneration. In this study, we developed a Carbopol based gel containing astaxanthin (AST) loaded chitosan-coated nanostructured lipid carriers (CS-NLCs). This system aimed to enhance stability, biocompatibility, sustained antioxidant properties, skin permeability, and minimize AST-related side effects. AST was encapsulated in NLCs using a hot homogenization ultrasonication method. Structural and morphological characteristics of nanoparticles were analyzed through TEM, FE-SEM, DSC, DLS, and XRD, confirming successful AST encapsulation in NLCs and CS coating. SEM analysis revealed particle sizes of 80 ± 6.6 nm for AST-NLCs and 221.4 ± 39.2 nm for CS-AST-NLCs. The encapsulation efficiency was above 85.45 %, with a loading content of 4.04 % for AST-NLCs. The antioxidant activity, assessed through DPPH, hydroxyl radical inhibition, and DCFH assays, demonstrated that AST-NLC-CS and AST-NLC exhibited significantly enhanced antioxidant performance compared to free AST. MTT assay confirmed biocompatibility of CS-AST-NLC formulation, with cell viability reaching 103.6 ± 1.1 % over 72 h. In vitro cell migration studies demonstrated effectiveness of AST-NLC-CS, with 85.9 ± 4.4 % fibroblast (L929) cell migration to wound site during 24 h. In vivo studies revealed accelerated wound healing and tissue regeneration with AST-NLC-CS/gel, leaving only 9.5 ± 2.2 % of the wound area on day 11 post-treatment compared to other groups. Histopathological analyses using H&E and MT staining of incision wounds in male wistar Rats treated with CS-AST-NLC/Gel showed enhanced collagen deposition, more effective neovascularization, faster epithelialization, and reduced inflammatory cell infiltration compared to control group. This multifunctional system demonstrated great potential for improving wound healing and advancing tissue regeneration strategies.