Study On The Preparation And Oral Absorption Of Nanomedicine Self-assembled By Betulinic Acid-Phospholipid Derivatives

Betulinic acid(BA)is a kind of natural terpenes from betula bark.It has many pharmacological effects and is of great medical value.However,the poor water solubility and the short half-life limits its oral absorption.In order to improve the oral availability of BA,the BA-phospholipid complex 1-stearoyl-2-(3-O-succinoyl betulinic acid glycerol-3-phosphate choline)was synthesized by linking betulinic acid with stearoyl lysophosphatidylcholine via succinic acid,which can be self-assembled into a nano-formulation to promote the oral absorption of BA.The self-assembly conditions of BA-phospholipid complex were studied.The structure of the self-assembled nano-formulation was characterized.The drug release property of the nano-formulation was studied.The absorption and pharmacokinetic parameters of the nano-formulation in rats by oral adminstration were studied.The BA-derivative nano-formulation presents a liposome-like vesicle structure.The nano-formulation showed good dispersion and uniform size of about 92 nm.The nano-formulation can release BA slowly in the presence of esterase in the simulated physiological environment.When the esterase concentration was 10 U/mL and 20 U/-MI,the drug release rate was 42.8%and 61.88%,respectively.Oral absorption of BA in rats were studied.Compared with free BA,nano-formulation can improve the oral absorption of BA.The maximum serum concentration(Cmax)was 356.8±57.42 ng/mL.Parameters of half-life(T1/2)and mean residence time(MRT)was 14.82±2.31 h and 16.03±3.66 h,respectively.Oral administration of BA-derivative nano-formulation has no toxic effect on blood biochemical indexes and organs of rats.It is suggested that the nano-formulation has low toxicity.