Improving oral bioavailability of acalabrutinib using polymer-lipid hybrid nanoparticles: design, optimization, and <i>in vivo</i> pharmacokinetic evaluation.

ABSTRACT: Acalabrutinib (ACP) is one of the first-in-line treatments for hematological malignancies with minimal adverse drug reactions. However, ACP has low and variable bioavailability due to pH-dependent solubility, CYP3A4 metabolism, and P-gp efflux. This research aims to modify the dissolution behavior of ACP and improve its oral bioavailability through formulation of polymer-lipid hybrid nanoparticles (PLHNs). ACP-loaded PLHNs (ACP-PLHNs) were prepared by the emulsification-solvent evaporation method using a high shear homogenizer and optimized using a spherical and rotatable circumscribed central composite design. The optimized ACP-PLHNs exhibited a spherical morphology with an average particle size of 150.2 ± 10.7 nm, a PDI of 0.284 ± 0.06, and sufficient drug loading (20.79 ± 3.61%). In

SUBMITTER: Sinha S 

PROVIDER: S-EPMC12442105 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature