Dual drug loaded liposome bearing apigenin and 5-Fluorouracil for synergistic therapeutic efficacy in colorectal cancer

This study reports the synthesis and production of a relatively robust dual drug-loaded liposomal formulation by modified thin film hydration method which substantially entraps both the drugs. Even though there have been reports of the combinatorial regimen involving apigenin and 5-Flurouracil our study reports the optimal molar ratio for effective synergistic therapeutic application of this drug combination to alleviate colorectal cancer. The cytotoxicity and cellular effects of individual, combinatorial free drugs and their liposomal counterparts tested against two human colon cancer cell lines revealed significantly higher cytotoxicity of the dual-drug liposomes. The dual-drug liposomes demonstrated enhanced inhibition of angiogenesis, better reduction in cell proliferation and increased apoptotic potential. Cell signaling studies indicating a significant upregulation of pAMPK and activity against downstream targets by dual drug liposomes suggested its role in the reversal of Warburg effect. The formulation was tested in a preclinical setting in nude mice tumor xenograft model and was found to have greater anti-neoplastic and anti-tumorigenic effect. The study indicated that the increased chemotherapeutic potential in vivo was due to the passive targeting achieved by the liposomal drug loaded nano-carrier and the synergistic effect of apigenin in 5-Fluorouracil treatment offers a new attractive alternative to enhance the therapeutic potency of drugs and paves way for poten...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research