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Breast cancer conventional therapeutics are effective; however, they encounter some limitations including multidrug resistance, the presence of pharmacological barriers, and non-selectivity which hinder their optimal therapeutic efficacy. Overcoming such drawbacks necessitates the development of efficient drug vehicles including lipid-based nanoparticles. This study aimed to quantitatively investigate  in-vitro  the synergistic therapeutic effect of the novel combination of capsaicin and 5-fluorouracil (5-FU) encapsulated in lipid nanocapsules (LNCs). To this end, thorough physicochemical and  in-vitro  assessments on the breast cancer cell line (MCF-7) were done. The drug-loaded LNCs were characterized using DLS, TEM imaging, stability study, and  in-vitro  release study. Furthermore, the biological activity of the prepared LNCs was assessed by implementing comparative cytotoxicity studies as well as apoptosis, and cell cycle flow cytometric analyses. The developed nanoformulations were monodisperse with average particle size (PS) of 31, 43.8, and 127.3 nm for empty LNCs, Cap-LNCs, and 5-FU-LNCs, respectively, and with a surface charge of −35.4, −21.7 and −31.4 mV, respectively, reflecting good physical stability. The TEM micrographs revealed the spherical morphology of the drugs-loaded LNCs with comparable PS to that obtained by DLS. on the other hand, all the biological assessments confirmed the superior antiproliferative effect of the combined drug-loaded LNCs over their free drug counterparts. Intriguingly, the study findings highlighted the potential synergistic activity of the drugs (capsaicin and 5-FU) and the extensive enhancement of their biological activity through incorporation into LNCs. Such promising results will pave the way to further novel combined nanoformulation in preclinical and clinical studies on breast cancer patients.

drug development and industrial pharmacy

An  in-vitro  quantitative investigation on the synergistic effect of capsaicin and 5-fluorouracil encapsulated into lipid nanocapsules to treat breast cancer