Abstract
Background: Dasatinib (DST), a second-generation tyrosine kinase inhibitor, suffers from poor aqueous solubility and pH-dependent absorption, limiting its oral bioavailability. Bilosomes—vesicular carriers stabilized with bile salts—offer enhanced stability in the gastrointestinal tract and improved drug encapsulation compared to conventional liposomes and niosomes. In this study, a DST-loaded bilosome (DST-LB) formulation was developed and its solubility, dissolution, and bioavailability were evaluated. Methods: Bilosomes were prepared using the reverse‑phase evaporation method and optimized via Box–Behnken design. The formulation was characterized for particle size, zeta potential, entrapment efficiency, micromeritic properties, and morphology. Capsules were evaluated for weight variation, content uniformity, dissolution, and stability. Pharmacokinetic studies were conducted in rabbits and analyzed using non-compartmental modeling. Results: The optimized bilosomes exhibited a mean particle size of 113 nm, a polydispersity index of 0.11, a zeta potential of –22 mV, and an entrapment efficiency of 81%. Capsules showed excellent flowability and uniformity. Dissolution studies showed a sustained-release profile governed by non-Fickian transport (n = 0.725), whereas the marketed tablet displayed a faster release profile following first-order kinetics (n = 0.450). In vivo, bilosomes achieved higher Cmax (477.8 ng/mL vs. 374.4 ng/mL), shorter Tmax (1 h vs. 1.5 h), and greater AUC (2886.5 ng · h/mL vs. 2107.7 ng·h/mL), indicating that the systemic exposure was 38% higher with bilosomes compared to the marketed tablet. Stability testing confirmed first-order degradation with a predicted shelf life of 2.1 years. Conclusions: DST-LB significantly enhanced dissolution, absorption, and bioavailability compared to the marketed tablet, supporting their potential as a modified-release oral delivery system for improved therapeutic outcomes.