A Repurposed Olmesartan-Loaded Hyaluronic Acid-Functionalized Lecithin-Chitosan Nanoparticle Hydrogel for Enhanced...

A novel topical nanocarrier-based hydrogel system incorporating olmesartan medoxomil (OLM) was designed to enhance diabetic wound healing through targeted skin delivery. OLM was efficiently encapsulated within lecithin-chitosan hybrid nanoparticles (LCNPs), which were subsequently functionalized with hyaluronic acid (HA) to improve dermal adhesion, biocompatibility, and sustained release. The optimized OLM-HA-LCNPs exhibited a nanoscale size of 324.28 ± 5.71 nm, a negative zeta potential (-39.64 ± 3.2 mV), and a high entrapment efficiency of 89.86 ± 3.15%. In vitro release studies demonstrated a controlled, biphasic OLM release pattern over 24 h following Weibull kinetics, confirming diffusion erosion-controlled release behavior. Incorporation into a hydrogel base preserved pseudoplastic rheology, optimal pH (6.3 ± 0.2), and superior spreadability (35.26 cm²). In streptozotocin-induced diabetic rats, the OLM-HA-LCNP hydrogel produced 93.5% wound closure after 14 days, compared with 87.6%, 77.1%, and 90.8% for the marketed reference, plain HA-LCNPs, and OLM-pure treatments, respectively. OLM-HA-LCNP hydrogel also increased CAT, SOD, and GSH levels by 2.7, 1.45, and 2.16 fold, respectively, and reduced MDA levels by 77% compared with diabetic controls. Histological and immunohistochemical findings further demonstrated improved epidermal regeneration, collagen deposition, and normalization of VEGF and MMP-9 expression. Collectively, these findings demonstrate that HA-functionalized lecithin-chitosan nanoparticles incorporated into a hydrogel provide an effective platform for sustained topical OLM delivery and enhanced therapeutic performance in diabetic wound healing.