Preparation and in vitro evaluation of pro-mixed docetaxel micelles

This paper prepared a pro-mixed docetaxel micelles(MM) formulation intended for the parenteral administration of docetaxel.Docetaxel bile salt(BS)/phospholipid(PC) pro-MM were prepared by thin-film dispersion and could be diluted to form MM spontaneously.Encapsulation efficiency was determined by HPLC.The morphology and diameter were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS).In vitro release was observed by the dialysis.Compatibility with 0.9% saline and 5% glucose injections was assessed after dilution.Micelles stimulation to blood vessel and the potential of hemolysis relating to the micelles were evaluated in rabbits.Abnormal toxicity of the micelles was investigated using mice.The encapsulation efficiency of docetaxel MM after 50-fold dilution by saline was more than 96% with an average particle size of 65 nm.The accumulated release ratio was 96.02% in 24 h.The stability of docetaxel MM infusion solutions after dilution by normal saline was better than that by glucose injection.In rabbit vessel stimulation test，it showed that there were no obviously pathological changes in the injection site examined by naked eyes and microscope.There was no hemolysis or agglomeration on vitro-body red cells of rabbit.LD₅₀ of MM was more than 20 mg/kg.Therefore，it could be concluded that pro-mixed docetaxel micelles has the potential of clinical applications.