Nanotechnology-Driven Enhancement Of Diffusion For Poorly Water-Soluble Anticancer Drugs: Formulation And Characterization

Abstract

This study was undertaken to develop and characterize nanoparticle-based formulations of Venetoclax, a poorly water-soluble anticancer agent and selective inhibitor of the B-cell lymphoma 2 (BCL-2) protein, widely used in the treatment of hematologic malignancies including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML). Poor aqueous solubility and the need for toxic co-solvents in conventional delivery limit the clinical potential of Venetoclax. To address this, Liposomes were prepared using the thin-film hydration method and evaluated for physicochemical and functional parameters. Particle size analysis revealed nanoscale dimensions ranging from 200.01 nm to 251.12 nm, while zeta potential values (–19 to –30 mV) and entrapment efficiency (60–75%) confirmed the formation of stable nanosystems with effective drug loading. Transmission Electron Microscopy (TEM) analysis further confirmed the formation of discrete, spherical nanoparticles with smooth surfaces and uniform morphology, corroborating the particle size data obtained by dynamic light scattering. In vitro release studies demonstrated a sustained release profile with cumulative drug release reaching up to 99.2% within 24 h, in contrast to incomplete release from free drug suspension. Among all formulations, F10 and F17 emerged as optimized systems, exhibiting high entrapment efficiency (~75%), adequate colloidal stability (–29 to –30 mV), and nearly complete release (~99%). These results highlight the potential of nanoparticulate carriers to enhance solubility, diffusion, and dissolution rates of hydrophobic anticancer drugs. Overall, the study demonstrates that nanoformulation of Venetoclax can serve as a promising strategy to improve its bioavailability and therapeutic efficacy while minimizing the drawbacks of conventional delivery system.