The aim of this contemporary work was to formulate a controlled release mucoadhesive nanoparticle formulation for enhancing the oral bioavailability of Ticagrelor (TG), a BCS class IV drug, having low oral bioavailability of about 36%. The nanoparticles can act as efficient carriers for hydrophobic drugs, due to having high surface area and hence can improve their aqueous solubility due to their hydrophilic nature. The nanoparticles (NPs) of TG were formulated using chitosan (CH) as polymer and sodium tripolyphosphate (TPP) as cross-linker, by ionic gelation technique with varying concentrations of polymer with respect to TG and TPP. Characterization of prepared nanoparticles was carried out to assess zeta potential, size, shape, entrapment efficiency (EE) and loading capacity (LC), using zeta sizer, surface morphology and chemical compatibility analysis. Drug release was observed using UV-Spectrophotometer. By increasing concentration of CH the desired size of particles (106.9 nm), zeta potential (22.6 mv) and poly dispersity index (0.364) was achieved. In vitro profiles showed a controlled and prolonged release of TG in both lower pH-1.2 and neutral pH-7.4 mediums, with effective protection of entrapped TG in simulated gastric conditions. X-ray diffraction patterns (XRD) showed the crystalline nature of formed NPs. Hence, this effort showed that hydrophobic drugs can be effectively encapsulated in nanoparticulate systems to enhance their solubility and stability, ultimately improving their bioavailability and effectiveness with better patient compliance by reducing dosing frequencies as well.

Background: Ticagrelor (TG), an antiplatelet drug is employed to treat patients with acute coronary syndrome, but its inadequate oral bioavailability due to poor solubility and low permeability restricts its effectiveness. Purpose: This contemporary work was aimed to design a novel pH-sensitive nanocomposite hydrogel (NCH) formulation incorporating thiolated chitosan (TCH) based nanoparticles (NPs) of Ticagrelor (TG), to enhance its oral bioavailability for effectively inhibiting platelet aggregation. Methods: NCHs were prepared by free radical polymerization technique, using variable concentrations of chitosan (CH) as biodegradable polymer, acrylic acid (AA) as a monomer, N,N-methylene bisacrylamide (MBAA) as cross-linker, and potassium persulphate (KPS) as initiator.Results: The optimum hydrogel formulation was selected for fabricating NCHs, considering porosity, sol-gel fraction, swelling studies, drug loading capacity, and TG's in vitro release as determining factors. Outcomes of the studies have shown that the extent of hydrogel swelling and drug release was comparatively greater at higher pH (7.4). Moreover, an amplifying trend was observed for drug loading and hydrogel swelling by increasing AA content, while it declined by increasing MBAA. The NCHs were evaluated by various physicochemical techniques and the selected formulation was subjected to in vivo bioavailability studies, confirming enhancement of bioavailability as indicated by prolonged half-life and multifold increase in area under the curve (AUC) as compared to pure TG. Conclusion:The results suggest that NCHs demonstrated a pH-responsive, controlled behavior along with enhanced bioavailability. Thus NCHs can be effectively utilized as efficient delivery systems for oral delivery of TG to reduce the risk of myocardial infarction.

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.