Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity.

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan.

METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method.

RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs.

CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.