Phospholipid-based nanolipid carriers for dual kinase inhibitors in triple-negative breast cancer

Aim: Current research is focused on developing phospholipid-based nanolipidic carrier (NLC) to deliver lapatinib (LNB) and imatinib (INB) to MDA-MB-231 breast cancer cells and an in vivo mammary tumor model. Materials and methods: Breast cancer (BC) was induced in female rats via the chemical carcinogen 7, 12-dimethylbenz(a)anthracene (DMBA). The dual drug-loaded phospholipid-based NLC were made via a hot microemulsion process. The developed NLC were also characterized, and tested in vitro, in vivo, and in a preclinical setting in a DMBA-induced rat model. Results: The dual drug-loaded phospholipid NLC exhibited favorable nanometric size (279.7 nm, PDI 0.323), high entrapment efficiency (94.21%), and robust loading capacity (13.11%). It achieved biphasic drug release (52.67% at 4 h; 92.12% cumulative), potent cytotoxicity with maximal IC₅₀ reduction at 48 h, and maintained stability under accelerated conditions. In vivo, it significantly reduced tumor burden, normalized hematological and biochemical markers, and demonstrated therapeutic efficacy in DMBA-induced breast cancer, highlighting its translational potential. Conclusions: The dual drug-loaded NLC not only achieved high entrapment efficiency but also enhanced cytotoxicity against MDA-MB-231 cells and significantly reduced tumor progression. The developed lipid-based nanocarrier system demonstrates strong potential as a targeted platform for the co-delivery of kinase inhibitors, addressing the therapeutic limitations associated with monotherapy and conventional drug formulations.