Assessment of Oral Bioavailability and In-vivo Anti-leukemic Efficacy of Dasatinib-Loaded Solid Lipid Nanoparticles

Due to its oral administration and antiproliferative properties against chronic myeloid leukaemia (CML), dasatinib has been identified as a second-generation tyrosine kinase inhibitor (TKI). Central-composite designs (CCD) was followed to optimise dasatinib and hesperidin loaded solid lipid nanoparticles (SLNs), which were made in-house using a high-shear homogenisation approach. After leukaemia cells were injected intravenously into a mouse model, the produced SLNs' oral administring in vivo anti-leukemic activity and bioavailability (PK) were evaluated. In the leukemic mice, dasatinib was given as an SLN formulation in addition to a pure drug suspension. liquid chromatography (HPLC) system was used to analyse and compare the pharmacokinetic parameters to those of the drug suspension. For the pure drug and SLN formulations, the mean half-lives were calculated to be 4.62hours and 8.76hours, respectively; the mean maximum plasma concentrations (Cmax) were found to be 184.12µg/L and 390.53µg/L; and the mean Tmax values were recorded at 2 and 4hours. The suspension's mean area under the curve (AUClast) was 1080.95 hr•ng/mL, while the SLN formulation's was 3669.50hr•ng/mL. The group treated with the SLN formulation showed a statistically drastinc increase in survival. When compared to the free medication, the SLN showed increased cytotoxic efficacy. Thus, it was discovered that dasatinib's double drug-targeted SLN formulation improved cellular sensitivity to the encapsulated medication more successfully than the non-encapsulated formulation.