# Foamable pluroleosomes system loaded with amlodipine as a repurposed antibacterial topical formulation against MRSA-induced infection; optimization, in-vitro, ex-vivo, and in-vivo studies

## TL;DR

This study develops a foam-based drug delivery system using amlodipine to treat MRSA infections, showing promising in vitro and in vivo antibacterial effects.

## Contribution

A novel foamable pluroleosome system for amlodipine is developed and optimized for topical antibacterial applications.

## Key findings

- The optimized AML-PLOs formulation showed 71.25% drug entrapment and a controlled release over 48 hours.
- The foam system demonstrated effective antibacterial activity against MRSA in both in vitro and in vivo models.
- Confocal microscopy confirmed efficient penetration of the drug through skin layers.

## Abstract

Amlodipine besylate (AML) is a renowned antihypertensive drug currently acknowledged for having antibacterial activity. AML repositioning can be helpful in the defeat of microbial-resistant strains. Loading amlodipine in the pluroleosomes (PLOs) foam system is desired to approach innovative remedies with a convenient application capable of targeting deep infections. The mixture design was employed to generate different pluroleosomes formulations consisting of various ratios of Pluronic F-127, oleic acid, and soya lecithin loaded with amlodipine. Based on the desirability function, the selected optimized formula (AML-PLOs), consisting of 4.875 for lecithin, one for oleic acid, and 1.125 for pluronic, exhibits a particle size of 320.56 ± 15.5 nm, a polydispersity index of 0.4461 ± 0.03, a surface charge of 15.261 ± 0.62 mV, and AML entrapment of 71.25 ± 3.52 %. The morphological image displayed a uniform spherical shape at the nanoscale. In addition, thermal analysis and infrared spectroscopy (IR) proved the suitability of AML-pluroleosome vesicles. Tween 20, the selected nonionic surfactant in foam preparation, achieved the demand values of foam parameters and showed adequate stability upon storage for up to 90 days. The selected AML-PLO foam showed complete AML release after 48 h in a controlled manner, and the cumulative amount permeated after 24 h was about 45 %. Efficient penetration through dermal strata was affirmed by utilizing a confocal microscope. In vitro microbiological assay, besides the in vivo microbiological and histopathological studies employing a wound healing model, validated the antibacterial efficacy of amlodipine. Those outcomes demonstrated that the prepared pluroleosome foam system of AML is a competent candidate for combating topical bacterial infection.

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