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.

Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma

“…Our one step thiolation reaction yielded 787 µmol of thiol groups present per Gram of polymer. These results are in line with findings of who reported that thiolation of chitosan yielded 465 μmol/G of polymer (Shahid et al, 2022).…”

Fabrication of PEGylated Chitosan Nanoparticles Containing Tenofovir Alafenamide: Synthesis and Characterization

“…This interaction ultimately resulted in the preparation of highly entrapped drug nanoparticles. In a previous study conducted by Shahid et al, they prepared ticagrelor-loaded simple chitosan and ticagrelor-loaded thiolated chitosan nanoparticles and reported EE values of 84.1% and 94.3%, respectively [ 39 ]. In another study, Bo Fan et al reported an EE of 98% in thiolated chitosan nanoparticles [ 40 ].…”

Crosslinked PVA-g-poly(AMPS) Nanogels for Enhanced Solubility and Dissolution of Ticagrelor: Synthesis, Characterization, and Toxicity Evaluation

“…The peculiar peaks at 1105.23 and 1055.08 cm –1 suggested −C–O stretching vibrations. 22c 36 The presence of nearly unchanged peaks of TGR at 3409.25, 3289.70, 2910.63, 1611.55, 1532.47, 1441.81, 1200.70, and 1050.25 cm –1 in the drug-loaded nanogels confirm that there was no chemical interaction among drugs and excipients, and the drug was efficiently loaded in the synthesized nanogels. Our findings showed consensus with results previously described by Maria et al, who designed a copolymeric hydrogel by using gelatin, PVA, and AMPS for prolonged sitagliptin and metformin release.…”