Preparation and evaluation of a novel anticancer drug delivery carrier for 5-Fluorouracil using synthetic bola-amphiphile based on lysine as polar heads

Abstract A novel bolaamphiphile surfactant N , N ′-(dodecane-1, 12-diyl) bis (2,6-diaminohexanamide) (DADL) was designed and synthesized using l -lysine and 1,12-diaminododecane as the hydrophilic and hydrophobic part, respectively. After separation and purification, the structure of the synthetic bolaamphiphile surfactant was verified by FTIR, MS and 1 H NMR. The synthetic bolaamphiphile was able to self-assemble to form vesicles. After formulation screening, vesicles loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by sonication and were examined by dynamic light scattering and transmission electron microscopy. Micro-FTIR was applied to investigate the conformation of the bola molecules within the vesicle membrane. The release profile of the vesicles showed a pH-sensitive and sustained release. No significant toxicity was observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu-loaded vesicles on H 22 tumor-bearing mice was remarkably high due to the EPR effects. These results show that our novel bolaamphiphile derived from lysine has excellent potential as a pH-sensitive drug carrier.