Surface Modification of PLGA Nanoparticles with Chitosan or Eudragit® RS 100: Characterization, prolonged release, cytotoxicity, and enhanced antimicrobial activity

Abstract Cefpodoxime proxetil (CEF) is a third-generation cephalosporin that is situated in BCS Class II with poor oral bioavailability. In current work, poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs) with chitosan (CS)/Eudragit® RS 100 (ERS 100) were designed to be used as efficient and prolonged released antimicrobial drug delivery systems by modified nanoprecipitation method. The rational for this approach is to bring a new aspect to antimicrobial treatment with modification of CEF loaded PLGA NPs with CS/ERS 100 by means of smaller particle size (PS), cationic surface, biocompatible nature, prolonged release, and enhanced antimicrobial activity. The PS of CEF loaded NPs were between 181 and 382 nm. The zeta potential of NPs was achieved cationic character with the modification of NPs with CS/ERS 100. EE% values ranged from 36% to 64%. The surface modification and structures of NPs were confirmed with solid state analyses (DSC, FT-IR and 1H-NMR). In vitro release profiles of NPs demonstrated extended release pattern which followed Peppas-Sahlin model. The safety and biocompatibility of NPs with higher cell viability values than CEF on CCD-19-Lu cell line. Antimicrobial efficacy of the NPs was analysed against Staphylococcus aureus and Escherichia Coli by microdilution method. ERS 100 modified NPs were more effective on bacterial cells (4-8 fold) than CS modified and unmodified PLGA NPs both two organisms. Moreover, all NPs designed exhibited enhanced antimicrobial activity compared to free CEF. These findings indicate that surface modification with CS/ERS 100 were significantly effective on NPs characteristics like PS, ZP, EE%, cytotoxicity, release behavior and antimicrobial activity.