Dasatinib Pharmacokinetics and Advanced Nanocarrier Strategies: from Systemic Limitations to Targeted Success

Abstract

Dasatinib (DSB) is a second-generation tyrosine kinase inhibitor widely used for treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Though clinically effective, DSB has some pharmacokinetic drawbacks evidenced by rapid systemic clearance, low oral bioavailability, and poor aqueous solubility requiring high doses for therapeutic action. Novel formulation strategies like solid dispersions, liposomal formulations, and PEGylated and hybrid nanoparticles enhance DSB's pharmacokinetic and pharmacodynamic profiles by enhancing drug solubility, stability, and controlled release. In addition, through these targeted drug-delivery systems based on ligand-functionalized nanoparticles and antibody-drug conjugates-the tumor-targeted DSB is allowed selective accumulation at the tumor site, causing fewer off-target effects and lessening systemic toxicity while maximizing effectiveness. These approaches are geared toward utilizing nanotechnology to improve intracellular drug uptake and extend the circulation time to optimize antitumor efficacy. Overall, those advances in drug delivery systems could greatly boost the therapeutic efficacy of DSB by providing better bioavailability, controlled release, and targeted distribution. Such advances would increase treatment success in CML and Ph + ALL and expand DSB's potential clinical applications toward other malignancies. Research concerning the delivery of DSB with nanocarriers and ligand-mediated targeting strategies should bear further fruits to augment DSB therapy in oncology.

Keywords: BCR-ABL kinase; Dasatinib; Nanocarriers; Tumor targeting; Tyrosine kinase.