An overview of advanced nanocarrier systems for Ibrutinib delivery: overcoming pharmacokinetic barriers and enabling targeted cancer therapy.

Ibrutinib (IBR), a covalent inhibitor of Bruton's tyrosine kinase (BTK), has transformed the treatment of B-cell malignancies like chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. With its clinical success, IBR is faced with enormous challenges like low aqueous solubility, low oral bioavailability, extensive first-pass metabolism, off-target toxicities, and resistance development. Nanotechnology-based drug delivery systems have been reported to be effective solutions for these issues. This review offers a comprehensive and critical examination of new trends in IBR-loaded nanocarriers, including PEGylated liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, nanostructured lipid carriers, and hybrid nanoplatforms. These nanocarriers showed improved drug solubility, prolonged circulation, controlled release, cancer-specific targeting, and reduced systemic toxicity. Emphasis on advanced approaches such as ligand-mediated targeting, stimuli-sensitive release, and co-delivery systems designed to optimize therapeutic effects and avoid resistance mechanisms. Preclinical models demonstrated improved bioavailability, improved tumor accumulation, and improved safety profiles of the IBR nanocarriers. This review covers the translational hurdles, regulatory aspects, and commercial tractability of nanocarrier-mediated inhibition of BTK. In summary, nanotechnology provides a revolutionary pathway for maximizing IBR therapy that could facilitate more efficient, safer, and targeted care for patients with hematologic cancers.