Functionalized chitosan based nanotherapeutics to combat emerging antimicrobial resistance in bacterial pathogen

Abstract

Ineffectiveness of conventional antibiotics due to antimicrobial resistance and microbial adaptations has led to the exploration of alternative or complementary therapeutics. In the present study, surface engineered nanosystems (SENS) were developed by conjugation of chitosan with rhamnolipids (RL) through amide linkage. Subsequently, FTIR and NMR analyses affirmed covalent immobilization of RL. SENS exhibited an increase in the particle size and reduction in zeta potential as compared to chitosan nanosystems (CNS). In parallel, first-line antibiotic (ciprofloxacin) was encapsulated in SENS and CNS for augmenting their antimicrobial potential against drug-resistant Salmonella enterica subsp. enterica serotype Typhi. Drug entrapment efficiency for AB-SENS (64 ± 2 %) was higher than AB-CNS. Furthermore, bacterial growth kinetics assay along with colony forming unit (CFU) assay revealed that AB-SENS inhibited the growth of Salmonella sp. even at ½ MIC with restoration of the antibiotic activity. Due to enhanced biofilm penetration ability, the diffusion of entrapped drug from AB-SENS resulted in an effective biofilm disruption to control drug-resistant Salmonella sp. Release kinetics study demonstrated a pH dependent drug release from AB-SENS in simulated gastric fluid (14.2 ± 2 %) and simulated intestinal fluid (28.4 ± 3 %). Hence, our findings suggest that void or drug-loaded SENS can be a versatile synergistic tool to revive the conventional antibiotics for improved treatment outcomes against resistant pathogens.