Abstract
Despite advancement in the control and therapeutics of infectious diseases, antimicrobial resistance remains a global burden. Hence there is a need for novel strategies that improve and potentiate available antibiotics to prevent a regress to a pre-antibiotic era. This study aimed to co-deliver vancomycin (VCM) and 18β-glycyrrhetinic acid (GA) via pH-responsive lipid-polymer hybrid nanoparticles (VCM-GAPAH-LPHNPs) to explore its potential for enhanced activity and targeted delivery of VCM. The stability of VCM-GAPAH-LPHNPs were supported by in silico studies. Biosafe VCM-GAPAH-LPHNPs were prepared using the microemulsion technique. VCM-GAPAH-LPHNPs demonstrated size, polydispersity index, zeta potential and encapsulation efficiency of 198.4 ± 0.302 nm, 0.255 ± 0.003, −3.8 ± 0.335 mV and 69.46 ± 2.52%, respectively. In vitro drug release studies revealed that VCM-GAPAH-LPHNPs had sustained and faster release at acidic conditions compared to bare VCM. VCM-GAPAH-LPHNPs also demonstrated greater in vitro antibacterial potential against methicillin-resistant Staphylococcus aureus by 16-fold, when compared to the bare drug. Additionally, the time-killing assay indicated the ability of VCM-GAPAH-LPHNPs to eliminate 75% of MRSA in less than 12 h. Furthermore, crystal violet assay confirmed VCM-GAPAH-LPHNPs potential to eliminate biofilms. Therefore, these novel LPHNPs may serve as promising nanocarriers for enhancing antibiotic drug delivery and antibacterial activity.
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