Non-small cell lung carcinoma (NSCLC), accounting for nearly 85% of lung cancer cases, remains a leading cause of cancer-related deaths despite advances in chemotherapy, targeted agents, and immunotherapy. Limitations such as systemic toxicity, acquired resistance, and inadequate tumor selectivity continue to challenge current treatments. Flavonoids, particularly fisetin and flavokawain A (FKA), have shown promise through multiple mechanisms including induction of apoptosis, suppression of proliferation and migration, and modulation of multidrug resistance. Preclinical studies indicate that fisetin enhances the anticancer activity of paclitaxel, while FKA sensitizes resistant NSCLC cells by inhibiting P-glycoprotein. However, their therapeutic application is constrained by poor solubility and bioavailability. Nanostructured lipid carriers (NLCs), especially when surface-functionalized with hyaluronic acid (HA) and bovine serum albumin (BSA), improve stability, circulation, and CD44-mediated tumor targeting, thereby enhancing efficacy and reducing off-target effects. Evidence from in vitro and in vivo models supports that flavonoid-based nanocarriers provide stronger anticancer activity and synergistic effects with standard chemotherapy compared to free drugs. Collectively, fisetin and FKA, when incorporated into HA-BSA coated NLCs, represent a promising strategy to overcome current therapeutic limitations, offering potential for safer, more effective, and targeted management of NSCLC.
Keywords: hyaluronic acid (HA), Nanostructured lipid carriers (NLCs), NSCLC
How to cite this article: Hasnain AN, Zanwar SM, Patel V, Mantri SM, Sambhaji AS, Tanaji MP.., Systematic Review of Flavonoids in NSCLC: Comparative Efficacy, Synergy with Chemotherapy, and Nanocarrier Innovations".Int J Drug Deliv Technol. 2026;16(1s): 420-428; DOI: 10.25258/ijddt.16. 420-428