Rosuvastatin calcium-based novel nanocubic vesicles capped with silver nanoparticles-loaded hydrogel for wound healing management: optimization employing Box-Behnken design: in vitro and in vivo assessment

Chronic wounds are a serious problem that could cause severe morbidity and even death. The ability of statins including rosuvastatin calcium (RVS) to enhance wound healing was well reported. However, RVS is poorly soluble and has low bioavailability. Thus, this study aimed to prepare and evaluate RVS-loaded nanocubics to enhance its skin performance. In addition, silver nanoparticles (AgNPs) exhibited potent antimicrobial activity, thus, the optimum RVS-loaded nanocubics was capped with AgNPs to evaluate its effect in wound management. Box-Behnken design was adopted to prepare RVS nanocubics. The design investigated the effect of lecithin, poloxamer 407 concentrations and hydration time on vesicle size, zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release%. Optimum formulation capped with AgNPs was incorporated into a gel base and examined for wound healing efficiency using different pharmacological tests in rats. Nanocubics have shown a mean diameter between 167.2 +/- 7.8 and 408 +/- 18.4 nm, ZP values ranging from -20.9 +/- 1.9 to -53.5 +/- 4 mV, EE% equivocated between 31.6 +/- 1.4 and 94.4 +/- 8.6 and drug release after 12 h between 17.9 +/- 1.9 and 68.0 +/- 4.0%. The histopathological studies and serum tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels confirmed the greater efficacy of RVS nanocubics capped with AgNPs gel in wound healing when compared with gentamicin ointment. RVS-loaded nanocubic vesicles and AgNPs-loaded hydrogel could be considered as a promising platform to enhance the wound healing and tissue repair processes.