Formulation development and in vitro evaluation of gentamicin sulfate-loaded PLGA nanoparticles based film for the treatment of surgical site infection by Box-Behnken design.

Objective: Gentamicin sulfate (GS)-loaded poly lactic-co-glycolic acid (PLGA) polymeric nanoparticles (PNPs) were developed and incorporated in film for the treatment of surgical site infection (SSI).

Method: PNPs were prepared by double emulsification solvent removal technique using ethyl acetate solution containing PLGA and polyvinyl alcohol (PVA) as an emulsifier. The emulsion was re-emulsified using Gum Kondagogu (GKK). PNPs loaded film was prepared with 5% w/v solution of pullulan in PNPs using solvent casting technique. Design of Experiment (DoE) study using Box-Behnken design was performed for the optimization of PNPs. Drug release study was carried out for PNPs at phosphate buffer saline (PBS) pH 6.4 and simulated wound fluid (SWF) pH 7.4.

Result: PNPs were found to have average particle size 280 ± 12.04 nm, polydispersity index (PDI) 0.15 ± 0.01 and zeta potential - 4.9 ± 0.84 mV. Scanning electron microscopy (SEM) showed spherical nature of PNPs along with particle size of 160 ± 35.30 nm confirmed with transmission electron microscopy (TEM). PNPs were found to be effective against Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). Optimized batch of film showed in vitro disintegration time below 8 min with tensile strength (TS) 0.06 ± 0.03 N/cm and percentage elongation (% E) 70.95 ± 4.29. X-ray diffraction study (XRD) confirmed amorphous nature of GS, PLGA, pullulan, GKK and film.

Conclusion: PNPs showed controlled release of GS after an initial burst release. Developed film can be an effective approach for management of SSI and control of antibiotic induced drug resistance.