University of Kashan Journal of Nanostructures 2251-7871 16 1 2026 01 01 Design, Optimization, and in‑Vitro Evaluation of Dasatinib‑Loaded Bilosomes Using Response Surface Methodology 109 133 115166 10.22052/JNS.2026.01.012 EN Ahmed Hamed Salman Department of Pharmacetics, College of Pharmacy, Al-Bayan University, Baghdad, Iraq Shaimaa Nazar Abd Alhammid Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq Journal Article 2025 09 03 Dasatinib, a potent second‑generation tyrosine kinase inhibitor for chronic myeloid leukemia (CML), exhibits pH‑dependent solubility and poor oral bioavailability due to precipitation in the intestinal pH and extensive first‑pass metabolism. Bilosomes, bile salt‑stabilized nanovesicles, offer enhanced stability in the gastrointestinal tract and potential for improved oral delivery of poorly soluble drugs. To formulate and characterize an optimized oral bilosomal dasatinib system with improved physicochemical stability, dissolution behavior, and selective anticancer activity. Dasatinib-loaded bilosomes were prepared using reverse-phase evaporation and optimized via a Box–Behnken design, varying Span 60, Tween 60, cholesterol, sodium deoxycholate, and Soluplus. The optimized formulation underwent characterization (particle size, PDI, zeta potential, entrapment efficiency, TEM), and solid‑state analysis (FTIR, DSC, XRD). In vitro release studies at pH 1.2, 6.8, and 7.4 were fitted to kinetic models. Cytotoxicity was assessed in K562 CML cells and normal human lymphocytes using the MTT assay. The optimized bilosomes (113.2 nm, PDI 0.109, zeta potential –22.36 mV, EE 81.02%) showed spherical morphology and amorphous drug dispersion. Compared to pure drug, release was sustained with significantly higher dissolution at intestinal pH, best fitting the Korsmeyer‑Peppas model at pH 6.8/7.4. Cytotoxicity studies revealed potent activity against K562 cells (IC₅₀ = 1.308 ng/mL) with ~17.6‑fold selectivity over normal lymphocytes. The developed bilosomal system effectively encapsulated dasatinib, enhanced stability, modulated release, and achieved selective in vitro anticancer activity, supporting its potential as a promising oral delivery platform for CML therapy. https://jns.kashanu.ac.ir/article_115166_aaea597dfed7fe57a1b3eb2521dc2021.pdf