Mechanistic and translational frontiers on "VEGF and TKI inhibitor axitinib": unfolding drug delivery approaches and opportunities in cancer therapy.

INTRODUCTION: Axitinib demonstrates significant promise in the field of oncology. It effectively inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis, endothelial proliferation, and tumor microvascular density. Axitinib exhibits reduced off-target kinase inhibition compared to first-generation tyrosine kinase inhibitors (TKIs), thereby minimizing broad-spectrum toxicity. However, axitinib's poor aqueous solubility, limited oral bioavailability, first-pass metabolism, and susceptibility to environmental degradation present key pharmacokinetic challenges in its translational application.

AREAS COVERED: This review integrates insights from pharmacology, clinical research, and patent literature, while delving into state-of-the-art formulation design paradigms, including lipid nanocarriers, polymeric formulations, stimuli-responsive formulations, and hydrogels. The rationale for such design paradigms is to improve solubility, controlled release, stability, and tumor targeting, thereby enhancing pharmacodynamics and ensuring a better safety profile. A literature search across major databases from 2000 to 2026 supported these findings.

EXPERT OPINION: Despite progress in targeted cancer treatment, sustained-release platforms enhance therapeutic potential while minimizing off-target effects. Studies are increasingly being conducted on axitinib combined with compatible anticancer agents after pharmacokinetic and safety considerations. These combinations may alter angiogenic signaling and delay the onset of resistance. As clinical priorities focus on minimizing toxicity, formulation innovations will be crucial to maximize the therapeutic potential of axitinib.