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

• Published in: Drug delivery and translational research 2025-02, Vol.15 (2), p.556-576
• Main Authors: Eltabeeb, Moaz A., Hamed, Raghda Rabe, El-Nabarawi, Mohamed A., Teaima, Mahmoud H., Hamed, Mohammed I. A., Darwish, Khaled M., Hassan, Mariam, Abdellatif, Menna M.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Original; Original Article; Pharmaceutical Sciences/Technology
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-024-01611-z

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. Graphical Abstract