Polymer-Lipid Hybrid Nanoparticles for Enhanced Gentamicin Efficacy Against Drug-Resistant Bacteria

Antibiotic resistance is a critical global health concern, exacerbated by biofilm formation and the declining effectiveness of conventional therapies. This study investigates polymer-lipid hybrid nanoparticles (PLNs) as an innovative nanocarrier system to enhance the antibacterial efficacy of gentamicin (Gen) while overcoming its inherent hydrophilicity and poor encapsulation efficiency.

Using an optimized double-emulsification/solvent-evaporation technique, PLNs were designed to improve drug encapsulation efficiency (EE%) and loading capacity (DL%). The resulting formulations (F0, f1, F2, F3, F4) were characterized for particle size, polydispersity index (PDI), zeta potential, and EE%. Transmitted electron microscopy (TEM) provided insights into particle morphology, while antibacterial activity was tested against multiple bacterial strains, including resistant isolates.

The optimized formulation (F4) demonstrated favorable characteristics (p≤0.05) including, EE% of 42.1±3.8%, a DL% of 8.0±0.7%, and uniform small average particle size (143.4±3.69 nm) and zeta potential -37.9±3.1 mV. TEM analysis confirmed Gen encapsulation within the lipid-polymer matrix. In vitro antibacterial assays demonstrated that F4 significantly enhanced antibacterial activity (p ≤ 0.05), achieving up to a 160-fold reduction in minimum inhibitory and bactericidal concentrations (MIC/MBC) against Methicillin-resistant Staphylococcus aureus (MRSA-59) and Pseudomonas aeruginosa (PA-78) compared with free Gen.

These findings underscore the potential of PLNs as a robust platform for targeted drug delivery, offering a promising strategy to combat antimicrobial resistance.