Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice.

OBJECTIVE: Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side effects proposed considerable problems to the patients.

SIGNIFICANCE: Polymeric nanoparticles (NPs) of poly (butylene adipate-co-butylene terephthalate) (Ecoflex® ), a biodegradable and biocompatible polymer, were prepared for the first time by the upgradeable electrospraying technique.

METHODS: The formulation and procedure variables were optimized using Design Expert software, and effect of each variable on particle size, particle size distribution, drug entrapment efficiency, and drug release of the NPs were evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction pattern, and morphological characteristics of the optimized NPs were evaluated. Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing nude mice.

RESULTS: The optimum condition for production of NPs included voltage of 20 kV, 12 cm distance between electrodes, feeding rate of 1 mL/hr, polymer to drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test confirmed no cytotoxic effect caused by blank NPs, while cell viability of the DTX loaded NPs was significantly lower than the free DTX (p < .05). The NPs significantly enhanced anti-tumor efficacy of the drug in nude mice (p < .05).

CONCLUSION: The Ecoflex® NPs could potentially provide a suitable alternative for currently available formulations of DTX.