Nanoparticles of thiolated chitosan for controlled delivery of moxifloxacin: In-vitro and in-vivo evaluation

Abstract

Controlled release drug delivery system of moxifloxacin produces better therapeutic effects and maintain the plasma concentration for prolong period of time. The objective of this work was to formulate nanoparticles of thiolated chitosan (TC) having enhanced mucoadhesion and controlled release behaviour of drug. The chitosan (CS) was thiolated by conjugation with thiourea. Ionic gelation method using TC was used for the preparation of the nanoparticles. FTIR, DSC, TGA and 1H NMR were used to characterize the CS and TC. The measurement of particle size and zeta potential of the developed nanoparticles confirmed that the formulation was stable. The CS, TC and nanoparticles were evaluated for mucoadhesion and swelling. The toxicity of developed nanoparticles was evaluated by Caco-2 cell line. The release of drug from nanoparticles of non-thiolated (NT) and TC was studied using simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and phosphate buffer pH 7.4. The albino rats were used to investigate the moxifloxacin pharmacokinetics from nanoparticles of TC. The thiol group showed peak at 2122 cm−1 which was confirmed by FTIR. The thermal stability of NT and TC was confirmed by DSC and TGA. The thiolation of CS was confirmed by 1H NMR. The nanoparticle of TCN3 showed 105 nm average particle size and zeta potential of TCN1 to TCN5 was range from −18 to + 29. The TC show better mucoadhesion as compare to the CS. The drug, CS, TC and nanoparticles of TCN3 did not exhibit any effect on the viability of Caco-2 cells. In SGF, the drug release from nanoparticles was 5 to 10 %. TCN3 formulation showed 97.84% and 99.43% release of moxifloxacin in SIF and phosphate buffer pH 7.4 within 24 h. The nanoparticles of TCN3 showed 97.13% release of moxifloxacin within 8 h. The TCN3 formulation showed greater bioavailability and improved pharmacokinetic parameters of moxifloxacin as compare to the marketed formulation. Our findings proved that the thiolation of CS with thiourea is an easy and reproducible method to improve the mucoadhesion and the controlled release pattern of the drug over an extended period of time.