Fabrication of thiolated chitosan based biodegradable nanoparticles of ticagrelor and their pharmacokinetics

Abstract

The current study was aimed to design a thiolated chitosan (TC) based mucoadhesive nanoparticle (NP) formulation for enhancing the oral bioavailability of an anti-coagulant, Ticagrelor (TG). Nanoparticles (NPs) containing naturally occurring biodegradable polymers have been revealed as promising carriers for the controlled delivery of various therapeutic agents through the oral route. Ionic gelation technique was adopted to prepare thiolated chitosan nanoparticles of TG (TCNPs/TG) and chitosan (CH) nanoparticles of TG (CHNPs/TG) by varying the concentration of polymers with respect to TG and cross-linker i.e. tripolyphosphate (TPP). The prepared CHNPs/TG and TCNPs/TG were subjected to assessment for their particle size, the zeta potential, shape and morphology along with loading capacity (LC) and entrapment efficiency (EE). Formed TCNPs/TG showed a particle size of 190.3 nm, zeta potential of 16 mv along with the polydispersity index (PDI) of 0.375 as compared to CHNPs/TG, displaying particle size of 147.3 nm, zeta potential of 22.6 mv and PDI of 0.364. Likewise, during Fourier transform infrared spectroscopy (FTIR) analysis, the emergence of a characteristic peak at 2495 cm−1 in TC, has confirmed the successful modification of CH. Moreover, in-vitro drug release studies have disclosed a good sustained release behavior of the drug, both from CHNPs/TG and TCNPs/TG. However, the in-vivo pharmacokinetics have illustrated the superiority ( p < .05) of the TCNPs/TG (494.96 ng/mL) over the CHNPs/TG (438.73 ng/mL) in terms of bioavailability. Ultimately, the findings have indicated that TCNPs/TG might help to improve the oral bioavailability of TG and hence, its therapeutic effects.