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

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. <i>In vitro</i> microbiological assay, besides the <i>in vivo</i> 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.