Formulation of chitosan coated nanoliposomes for the oral delivery of colistin sulfate: in vitro characterization, 99mTc-radiolabeling and in vivo biodistribution studies

Abstract

Colistin sulfate is a very important antibiotic for the treatment of multidrug-resistant Gram-negative infections. Unfortunately, it has low oral bioavailability and several side effects following parenteral administration. The present study aims to develop chitosan-coated colistin nanoliposomes to improve the stability in the gastrointestinal tract and to enhance the oral delivery of colistin. The chitosan-coated colistin nanoliposomes were obtained via thin-film evaporation and electrostatic deposition methods using either Span 60, Tween 65 or Tween 80 as surfactants with different cholesterol: surfactant: soya lecithin ratios. The influence of systems variables was further characterized by vesicle size analysis, zeta potential (ZP), poly dispersibility index (PDI), and also their entrapment efficiency percentage (EE %) was evaluated. Various systems were formed with vesicle sizes in the nano-range, 155.64 ± 12.53 nm to 315.64 ± 15.90 nm, and EE % of 45.2 ± 2.9% to 81.8 ± 2.9%. Moreover, the ZP value of the prepared nanoliposomes switched from a negative to a positive value after chitosan coating. To track the released colistin in vivo, technetium 99m (99mTc) was incorporated into the optimum system (S-3) system via direct coupling with colistin. Chitosan-coated 99mTc-colistin nanoliposome, 99mTc-colistin suspension, and 99mTc-chitosan-coated nanoliposomes (placebo) were administered orally into bacterial infection (Escherichia coli) bearing mice. The biodistribution results showed that chitosan-coated nanoliposome significantly enhanced the bioavailability of colistin compared to colistin suspension (the commercially available). Moreover, the system effectively improved the localization of colistin at the infected muscle. In conclusion, this approach offers a promising tool for enhanced oral delivery of colistin.