Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft
gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new
excipients exploration are needed to improve the water-solubility and comfort of the
drug administration. In the present study, novel
etoposide-loaded submicron
emulsions (ESE) with the biosurfactants of acidic
sophorolipid (ASL) and
lactonic sophorolipid (LSL) instead of the chemical
surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain
triglyceride: long-chain
triglyceride (MCT:LCT),
lecithin concentration, homogenization pressure and cycle, and type and concentration of
surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher
drug loading capacity, slower release rate, and significantly increased antitumor activity against
ovarian cancer cell line A2780 via apoptosis than
Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and
Tween-ESE caused no
hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the
hemolysis test, making ASL more reliable for
drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to
Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement.