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

Moaz A Eltabeeb; Raghda Rabe Hamed; Mohamed A El-Nabarawi; Mahmoud H Teaima; Mohammed I A Hamed; Khaled M Darwish; Mariam Hassan; Menna M Abdellatif

doi:10.1007/s13346-024-01611-z

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

Drug Deliv Transl Res. 2024 May 18. doi: 10.1007/s13346-024-01611-z. Online ahead of print.

Authors

Moaz A Eltabeeb¹, Raghda Rabe Hamed², Mohamed A El-Nabarawi³, Mahmoud H Teaima³, Mohammed I A Hamed⁴, Khaled M Darwish⁵, Mariam Hassan^{6

7}, Menna M Abdellatif²

Affiliations

¹ Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt. [email protected].
² Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
³ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁴ Organic and Medicinal Chemistry Department, Faculty of Pharmacy, Fayoum University, Faiyum, Egypt.
⁵ Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt.
⁶ Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala City, Suez, 43511, Egypt.
⁷ Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.

PMID: 38762697
DOI: 10.1007/s13346-024-01611-z

Abstract

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 1³. 2² 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.

Keywords: MRSA skin infection; Alginate nanocomposite; Antibacterial; Biofilm; Confocal laser microscopy; In-silico study; In-vivo study; Propranolol hydrochloride; Topical drug delivery.