This study investigates the ability of hybrid polymer-lipid nanoparticles (PLN) containing ceftriaxone sodium (CTX) drug to enhance the mortality rate of Escherichia coli (E. coli), as gram-negative, and Enterococcus faecium (E-faecium), as gram-positive bacteria. PLN samples were prepared using a self-assembly method with different lipid-polymer mass ratios (L/P) ranging from 0.2 to 0.7. PLNs consisted of chitosan as a biocompatible polymer, glycerol monostearate as a lipid and Tween 80 as a stabilizer. Characterization results based on FESEM, FTIR, DSC and XRD analyses confirmed the successful formation of a polymer-lipid matrix. In vitro drug release showed that L/P ratio could significantly control the rate and amount of drug released from nanoparticles (NPs), including burst release and sustained release, in which PLN with an L/P ratio of 0.5 had desirable sustained drug release. This sample had a positive effect on the mortality rate of E. Coli bacteria compared to other PLN samples. In addition, compared to other conventional forms of antibiotics, the resistance of E. faecium bacteria in patients with cellulitis was reduced to half by applying these NPs. In conclusion, results confirmed that hybrid PLN provides an appropriate nanostructure for the delivery of hydrophilic antibiotics such as CTX with lower bacteria resistance.

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