الفهرس 
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Abstract
Wound healing process is usually conducted through a sequence of events like inflammation, granulation and finally tissue remodeling. The ability of statins including Rosuvastatin calcium (RVS) to enhance wound healing was well reported. The current study aimed to prepare and evaluate the capacity of RVS loaded nanocubic vesicles either alone or when capped with silver nanoparticles (AgNPs) to treat wounds topically.
RVS nanocubic vesicles were developed using a thin film hydration method according to Box–Behnken design. The design investigated the effect of lecithin, poloxamer 407 (P-407) concentrations and hydration time on vesicle size, zeta potential (ZP), entrapment efficiency (EE %) and in -vitro drug release %. nanocubic formulations have shown a mean diameter between 167.2 ± 7.8 and 408 ± 18.4 nm, ZP values 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 %.Design-Expert® (version 10.0.0.3; Manugistics Inc Rockville, USA) adopted by using the desirability function to select the optimum formulation. The optimization process was designed to choose a formulation with maximum EE%, release%, ZP and minimum PS. Optimum formulation exhibited EE% about 92.2%, PS 190.5nm, ZP -39.5 mV, and released 47.5 % of RVS. AgNPs were fabricated by simple reduction method. Then, optimum RVS loaded nanocubics capped with AgNPs. The photomicrograph of optimum RVS loaded nanocubics formulation and optimum RVS loaded nanocubics capped with AgNPs were of prevalent cubic form, while AgNPs had a spherical shape. The stability of optimum RVS loaded nanocubic formulation and RVS loaded nanocubics formulation capped with AgNPs were investigated after 90 days of storage at 4 °C, based on EE%, PS, ZP and % of RVS release. No fundamental changes were detected in the measured parameters after this period. Optimum RVS loaded nanocubics and optimum RVS loaded nanocubics capped with AgNPs were incorporated into a gel base. All of the hydrogel formulations were elegant, transparent in case of plain RVS and opaque in case RVS loaded nanocubic vesicles hydrogel and RVS loaded nanocubics capped with AgNPS hydrogel. No lumps or air bubbles were observed. All of the hydrogel formulations had high spreadability and the pH was within acceptable range. Hydrogel formulations F5 released 43.1% of RVS and F9 that released 41.5 % of RVS and 77.3% of AgNPs were chosen for further in vivo study.
The optimum hydrogel formulations were examined for wound healing efficiency using different pharmacological tests in rats. The histopathological studies and serum tumor necrosis factor alpha (TNF-α) and interleukin- 1β (IL-1β) serum levels confirmed the greater efficacy of the gel containing RVS nanocubic capped with AgNPs in wound healing when compared with gentamicin ointment. The combination between RVS loaded nanocubic vesicles and AgNPs could be considered a promising nano platform to enhance the wound healing and tissue repair processes.