Coated Zein Polymeric Nanoparticles Loaded with Amlodipine as a Repurposed Antibacterial Ocular Cure for MRSA-Induced Infection: Optimization, In Vitro, Ex Vivo, and In Vivo Assessments

<b>Background:</b> Amlodipine besylate (AML) is recognized as a calcium channel blocker curative for hypertension. However, the drug emerged recently as an antibacterial cure that competently prevails over resistant strains. <b>Methods:</b> Incorporating amlodipine into zein nanoparticles was employed to innovate a suitable carrier for loading and targeting deep corneal infection. The Box-Behnken design was adopted to produce various formulations of amlodipine-loaded zein nanoparticles (AML-ZNs) with diversity in composition concentration (% <i>w</i>/<i>v</i>), comprising zein, Labrafac, and poloxamer 407. <b>Results:</b> Relying on the optimization criterion, the chosen preference formulation concentration (% <i>w</i>/<i>v</i>) consists of 2.068 for zein, 0.75 for Labrafac, and 1.0 for Poloxamer. Morphological micrography of AML-ZNs showed regular spherical particles in the nanometric scale, and physicochemical characterization procedures confirmed system suitability. While tracking eyedrop optimum features, sodium alginate was selected for coating nanoparticles to improve stability and system viscosity. Both pH and sterility were also considered and maintained. Comparative studies were conducted pre- and post-coating, and the assessed features for the final selected formulation were 349.9 ± 5.8 nm, 0.2186 ± 0.0271, -55.45 ± 1.84 mV, 81.293 ± 0.9%, and 19.3 ± 0.19 cp for size, PDI, surface charge, entrapment, and viscosity, respectively. The AML-ZNs-Alg formulation demonstrates a more controlled pattern of release of roughly 40% of the drug released after 48 h, while the permeation profile shows 37 ± 3.52% permeated after 24 h, confirmed visually. In vitro microbial assay alongside the corneal in vivo microbial and histological pathology evaluation proved the efficacy of amlodipine as an antibacterial agent. <b>Conclusions:</b> These findings highlighted that the prepared AML-ZNs-Alg eyedrop can be a promising system as an antibacterial therapy.