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

PURPOSE: 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.

METHODS

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.

RESULTS

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.

CONCLUSION

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