Alginate-functionalized and PEGylated niosomes co-encapsulating letrozole and berberine for preclinical breast cancer therapy: Overcoming multidrug resistance.

In the current study, an optimum formulation of alginate-functionalized and PEGylated niosomes (Nio) co-encapsulated with letrozole (Let) and berberine (Ber) was observed for potential preclinical treatment of breast cancer to combat multidrug resistance and reduce drug doses. The incorporation of alginate (AL) and polyethylene glycol (PEG) enabled tunable network architecture, improved colloidal stability, and sustained release behavior of the formulated system. Nio-Let/Ber@PEG and Nio-Let/Ber@AL formulations showed desired entrapment efficiencies of 86.12 and 91.34 for Let and 71.32 and 75.12 for Ber, respectively. Drug release profiles showed that sustained and slower release rates were observed for coated niosomes (Nio-Let/Ber@PEG and Nio-Let/Ber@AL) compared to uncoated niosomes (Nio-Let/Ber). MTT assay showed the IC50 of coated niosomes was much lower than the uncoated formulation and free drugs for MCF-7 and MDA-MB-231 breast cancer cell lines. Moreover, coated niosomal formulations significantly increased the rate of apoptosis induction and cell cycle arrest compared to uncoated niosomes. Also, gene expressions of Bax and caspase 3/8/9 increased while the gene expression of Bcl2 (anti-apoptotic) decreased after treatment with coated niosomes compared to uncoated ones. Taken together, this preliminary research indicated that the co-delivery of Let and Ber through coated niosomal formulations (Nio-Let/Ber@PEG and Nio-Let/Ber@AL) was an efficient controlled dual-drug delivery system to increase the effectiveness of breast cancer therapy.