Solid Lipid Nanoparticles as Delivery Systems for Plant-Derived Phytochemicals in Cancer Therapy: A Systematic Review

Solid lipid nanoparticles (SLNs) have been investigated as lipid-based delivery systems to improve the solubility, stability, bioavailability, and delivery of plant-derived phytochemicals to tumors for cancer therapy. However, the available evidence remains heterogeneous and predominantly preclinical. This systematic review aimed to evaluate the formulation strategies, physicochemical characteristics, and therapeutic applications of phytochemical-loaded SLNs in cancer therapy. The review followed the PRISMA 2020 guidelines. Original research articles in English investigating phytochemical-loaded SLNs for cancer therapy were included. Data on formulation composition, preparation methods, physicochemical properties, drug release, in vitro anticancer activity, pharmacokinetics, biodistribution, and in vivo antitumor efficacy were extracted. Risk of bias was assessed using the SYRCLE tool for animal studies and an adapted checklist for in vitro studies. Thirty one articles were included in the qualitative synthesis. Most SLNs had particle sizes in the nanoscale range, approximately 50-350 nm, with encapsulation efficiencies of 43-99% and sustained-release profiles. Encapsulation generally improved cellular uptake and in vitro cytotoxicity in several cancer models. However, evidence of improved bioavailability, active tumor targeting, and in vivo antitumor efficacy remained limited and heterogeneous. Surface modification enhanced cellular uptake or organ accumulation in some studies, but validated tumor-specific targeting was not consistently demonstrated. Overall, phytochemical-loaded SLNs demonstrate potential as delivery platforms; however, clinical translation requires standardized formulations, robust in vivo studies, comprehensive safety evaluations, and clinical trials.