PLGA-Lipid Hybrid (PLH) Microparticles Enhance the Intracellular Uptake and Anti-Bacterial Activity of Rifampicin

An urgent demand exists for the development of effective carrier systems that systematically enhance the cellular uptake and localization of antibiotic drugs for the treatment of intracellular pathogens. Commercially available antibiotics suffer from poor cellular penetration, restricting their efficacy against pathogens hosted and protected within phagocytic cells. In this study, the potency of the antibiotic, rifampicin, against intracellular small colony variants (SCV) of Staphylococcus aureus was improved through encapsulation within a strategically engineered cell-penetrant delivery system, composed of lipid nanoparticles encapsulated within a poly(lactic-co¬-glycolic) acid (PLGA) nanoparticle matrix. PLGA-lipid hybrid (PLH) microparticles were synthesized through the process of spray drying, whereby rifampicin was loaded within both the polymer and lipid phase, to create a nanoparticle-in-microparticle system capable of efficient redispersion in aqueous biorelevant media and with programmable releas...