In vitro Anti-cancer Efficacy and Cellular Interaction of Cubic Phases Containing Cinnamic Acid, Poly(ethyleneimine), and Doxorubicin

Folate-decorated monoolein (MO) cubosomes containing poly(ethyleneimine) (PEI), cinnamic acid (CA), and doxorubicin (DOX) were prepared to deliver the anti-cancer drug specifically to cancer cells (KB cells) and boost the anti-cancer efficacy without causing an acute toxicity. Hydrophobically modified (Hm) gelatin (Gel)-folate (FA) conjugate (HmGel-FA) was prepared through amidation reaction among Gel, decanoyl chloride, and FA. HmGel-FA and Pluronic F127 were used as stabilizers for the cubosomal particles. According to the measurement of air/water interfacial tension, the surface activity was greater in the order of HmGel > HmGel-FA > Gel. Since it was reported that PEI and CA formed a self-assembly in the water channel of cubosomes and the dissolving property of the self-assembly was dependent on the pH value of medium, they were included in the water channel as a controller for DOX release. On the TEM micrographs of the cubosomes, water channels were surrounded by MO bilayers, and the payload (i.e. PEI, CA, DOX) had little effect on the structure. The in vitro anti-cancer efficacy of folate-decorated cubosomes containing PEI, CA, and DOX was higher than that of folate-free ones. According to flow cytometric analysis and confocal laser scanning microscopy, DOX fluorescence intensity was greater in the order of KB cells treated with folate-decorated cubosomes containing PEI, CA, and DOX > folate-free ones > free DOX. The folate-decorated cubosomes would be able to target the cancer cells and subsequently the receptor-mediated endocytosis would take place.