A Review on Nanocarrier-Based Strategies for Sunitinib Delivery: Advances in Pharmacokinetic Enhancement and Targeted...

Sunitinib malate (SNB) is a multitargeted tyrosine kinase inhibitor that inhibits tumor angiogenesis and proliferation by blocking signaling through VEGFR, PDGFR, c-KIT, FLT3, and RET. SNB is currently used in the treatment of renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. The pharmacological efficacy of SNB is limited by its poor aqueous solubility, pH-dependent dissolution, poor oral bioavailability, extensive first pass metabolism, high interpatient pharmacokinetic variability, and dose-limiting toxicities such as cardiotoxicity, hypertension, and myelosuppression. Nanotechnology-based drug delivery systems have been explored as a promising strategy to overcome the limitations and improve the pharmacological efficacy of SNB. A wide variety of SNB-loaded nanocarriers, including polymeric nanoparticles, lipid-based nanocarriers, nanocapsules, polymeric micelles, dendrimers, and inorganic nanostructures, have been developed to improve solubilization, protect the drug from degradation, and provide controlled or stimulus-responsive release. These nanocarriers provide improved pharmacokinetic properties by prolonging systemic circulation, increasing tumor accumulation through enhanced permeability and retention effects, and reducing off-target exposure. Active targeting and intracellular delivery mechanisms further enhance cellular uptake and pharmacological efficacy while reducing systemic toxicity. In addition, multifunctional nanocarriers that incorporate imaging agents or microenvironment-responsive components also offer opportunities for theranostic and precision oncology applications. However, clinical adoption is currently hindered by challenges associated with large-scale nanomanufacturing, batch-to-batch reproducibility, long-term nanostability, regulatory acceptance, and limited human data. This review critically evaluates current nanocarrier platforms for SNB delivery, provides pharmacological advancements achieved through nanoformulation, and identifies key translational hurdles and future directions for clinical adoption.