RESUMO
Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.
RESUMO
During ischemic stroke, higher glucose level linked worse outcomes were reported even in patients without pre-existing diabetes. Evidence suggest that such worse stroke outcomes were mainly due to production of reactive, toxic glucose metabolites that expands oxidative damage inside the brain. As a consequence of high oxidative stress, microvasculature structures and tight junctions compromised their functionally, infarct volume expands and brain edema exacerbates. In a mouse model of ischemic stroke with induced acute hyperglycaemia, Lauric acid (LA) as a natural saturated fatty acid demonstrated neuroprotection by attenuating infarct volume and brain edema. In addition, in the ipsilateral hyperglycaemic brain, the LA significantly increased the expression of tight junction representative protein (occludin) as well as anti-oxidative markers; Manganese superoxide dismutase (Mn) SOD, Extracellular superoxide dismutase (Ec-SOD) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in the ipsilateral region against hyperglycemic ischemic stroke. LA treated animals showed a significant reduction in the production of lipid peroxidation products (4-HNE) in the microvascular structures, maintained the blood brain barrier (BBB) integrity. LA linked neuroprotective outcomes were further confirmed by behavioral tests, where functional outcomes and motor coordination were improved significantly. Furthermore, LA treatment enhanced food intake, decreased mortality rate, and net body weight loss. Conclusively, LA modulated ischemic insult exacerbated by hyperglycemia and provided neuroprotection.
