Integration of terpesomes loaded Levocetrizine dihydrochloride gel as a repurposed cure for Methicillin-Resistant Staphylococcus aureus (MRSA)-Induced skin infection; D-optimal optimization, ex-vivo, in-silico, and in-vivo studies

Moaz M El-Naggar; Mohamed A El-Nabarawi; Mahmoud H Teaima; Mariam Hassan; Mohammed I A Hamed; Ahmed A Elrashedy; Rofida Albash

doi:10.1016/j.ijpharm.2023.122621

Integration of terpesomes loaded Levocetrizine dihydrochloride gel as a repurposed cure for Methicillin-Resistant Staphylococcus aureus (MRSA)-Induced skin infection; D-optimal optimization, ex-vivo, in-silico, and in-vivo studies

Int J Pharm. 2023 Feb 25:633:122621. doi: 10.1016/j.ijpharm.2023.122621. Epub 2023 Jan 21.

Authors

Moaz M El-Naggar¹, Mohamed A El-Nabarawi², Mahmoud H Teaima², Mariam Hassan³, Mohammed I A Hamed⁴, Ahmed A Elrashedy⁵, Rofida Albash⁶

Affiliations

¹ Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Egypt.
² Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
³ Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala City, Suez, Egypt.
⁴ Organic and Medicinal Chemistry Department, Faculty of Pharmacy, Fayoum University, Egypt.
⁵ Natural and Microbial Products Department, National Research Center (NRC), Egypt.
⁶ Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Egypt. Electronic address: rofida.albash@must.edu.eg.

PMID: 36693486
DOI: 10.1016/j.ijpharm.2023.122621

Abstract

The intention of this work is to assess the repurposed antimicrobial impact of Levocetirizine dihydrochloride (LVC), which is a well-known antihistaminic drug, in addition, to augment the antimicrobial effect by using terpene-enriched vesicles (TPs). To investigate how various parameters affect TPs aspects, TPs were made employing the ethanol-injection-method and optimized d-optimal design. The TPs were characterized based on their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum TP was submitted to more examinations. The optimum TP (TP12) showed a spherical vesicle having an EE% of 66.39 ± 0.12%, PS of 243.3 ± 4.60 nm, PDI of 0.458 ± 0.003, and ZP of 24.2 ± 0.55 mV. The in-vitro release study results demonstrated that LVC is sustainedly liberated from the optimum TP compared to LVC-solution. The ex-vivo assessment showed that LVC was released in a more sustained manner from TPs-gel related to LVC solution, optimum TP, and LVC gel. Ex-vivo visualization by confocal laser scanning microscopy showed good deposition of the fluorescein-labeled TP. Further, the in-vitro anti-bacterial effect and biofilm inhibition and detachment assessment confirmed the potency of LVC against Methicillin-resistant-Staphylococcus-aureus (MRSA). The in-silico study demonstrated that the LVC has excellent stability with other ingredients combined with it in the TPs, further, it proved that LVC is a potential candidate for treating MRSA. In-vivo assessments revealed a good antimicrobial effect toward MRSA infection. Moreover, the histopathological evaluation confirmed the safety of using TPs-gel topically. In conclusion, MRSA-related skin infections may be treated using the LVC loaded TPs-gel as a promising system.

Keywords: Biofilm; Confocal laser scanning microscope; In-silico study; In-vivo study; Levocetrizine dihydrochloride; MRSA infection.

MeSH terms

Anti-Bacterial Agents / pharmacology
Methicillin-Resistant Staphylococcus aureus*
Research Design

Substances

levocetirizine
Anti-Bacterial Agents