Enhancement of rifaximin bioavailability and antibacterial efficacy through mPEG-b-PCL micelles and chitosan-coated systems

Abstract

Rifaximin (RFX) is a BCS Class IV antibiotic characterized by low water solubility and limited bioavailability, although it possesses broad-spectrum antibacterial activity. To overcome the limitations of RFX use, RFX was encapsulated in methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-b-PCL) micelles within the scope of this study and subsequently coated with chitosan (CS) to improve structural stability. The micelles were synthesized via nanoprecipitation. The optimized RFX-loaded micelles (OPT-M) had an average size of 75.18 + 0.62 nm, a polydispersity index (PDI) of 0.08 + 0.014, and an encapsulation efficiency of 85.19 + 2.76 %. The CS-coated micelles (OPT-C-M) exhibited an increase in size to 213.95 + 6.26 nm, a PDI of 0.250 + 0.002, and a zeta potential shift to +28.4 + 2.46 mV. Morphological analyses confirmed the spherical shape of the micelles, and colloidal stability studies verified the enhanced stability. Both formulations significantly enhanced the antioxidant activity compared to free RFX. Antibacterial studies indicated substantial reductions in minimum inhibitory concentration (MIC) values against S. aureus and E. coli. OPT-M and OPT-C-M showed 8-fold and 4-fold MIC reductions for S. aureus, and 4-fold and 8-fold MIC reductions for E. coli, respectively. Furthermore, both formulations maintained high biocompatibility, exceeding 70 % viability in L929 fibroblast cells at effective concentrations. These findings highlight the potential of CS-coated micelles to enhance RFX's therapeutic efficacy, demonstrating promise for advanced antibiotic delivery applications.