Nanocomposite alginate hydrogel loaded with propranolol hydrochloride kolliphor ® based cerosomes as a repurposed platform for Methicillin-Resistant Staphylococcus aureus-(MRSA)-induced skin infection; in-vitro, ex-vivo, in-silico, and in-vivo evaluation.

Nanocomposite alginate hydrogel containing Propranolol hydrochloride (PNL) cerosomes (CERs) was prepared as a repurposed remedy for topical skin Methicillin-Resistant Staphylococcus aureus (MRSA) infection. CERs were formed via an ethanol injection technique using different ceramides, Kolliphores ® as a surfactant, and Didodecyldimethylammonium bromide (DDAB) as a positive charge inducer. CERs were optimized utilizing 1 3 . 2 2 mixed-factorial design employing Design-Expert ® software, the assessed responses were entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimum CER, composed of 5 mg DDAB, ceramide VI, and Kolliphor ® RH40 showed tubular vesicles with EE% of 92.91 ± 0.98%, PS of 388.75 ± 18.99 nm, PDI of 0.363 ± 0.01, and ZP of 30.36 ± 0.69 mV. Also, it remained stable for 90 days and manifested great mucoadhesive aspects. The optimum CER was incorporated into calcium alginate to prepare nanocomposite hydrogel. The ex-vivo evaluation illustrated that PNL was permeated in a more prolonged pattern from PNL-loaded CERs nanocomposite related to PNL-composite, optimum CER, and PNL solution. Confocal laser scanning microscopy revealed a perfect accumulation of fluorescein-labeled CERs in the skin. The in-silico investigation illustrated that the PNL was stable when mixed with other ingredients in the CERs and confirmed that PNL is a promising candidate for curing MRSA. Moreover, the PNL-loaded CERs nanocomposite revealed superiority over the PNL solution in inhibiting biofilm formation and eradication. The PNL-loaded CERs nanocomposite showed superiority over the PNL-composite for treating MRSA infection in the in-vivo mice model. Histopathological studies revealed the safety of the tested formulations. In conclusion, PNL-loaded CERs nanocomposite provided a promising, safe cure for MRSA bacterial skin infection.