Objective: To optimize formulation technology of betulinic acid ethosomes and investigate feasibility of ethosomes as a transdermal carrier for betulinic acid. Method: Betulinic acid ethosomes were prepared by ethanol injection method

taking entrapment efficiency as index

an orthogonal design was used to optimize formulation process of betulinic acid ethosomes with ratio of betulinic acid to phospholipid

phosphate buffer pH and ethanol concentration as factors.Shape and particle size of betulinic acid ethosomes were analyzed by transmission electron microscopy and laser particle size analyzer.In vitro transdermal delivery characteristics of betulinic acid were evaluated by using Franz diffusion cells

and compared with liposomes and 10% isopropanol solution of betulinic acid.HPLC was employed to determine the content of betulinic acid with mobile phase of acetonitrile-0.1% glacial acetic acid(70:30) and detection wavelength at 207 nm. Result: Optimal formulation process parameters for betulinic acid ethosomes were soybean lecithin-betulinic acid(19:1)

pH of phosphate buffer 7.4 and ethanol concentration of 30%.Average particle size of ethosomes under these conditions was 94.3 nm

encapsulation efficiency was 86.3%.Accumulative permeation amount of betulinic acid ethosomes within 12 h was (108.33±10.26)μg·cm-2

which was about 2.12 times of liposomes and 5.98 times of 10% isopropanol solution. Conclusion: Ethosomes

as a vector for transdermal drug delivery

could significantly promote transdermal penetration of betulinic acid better than liposomes.This study provided new ideas for anti-tumor and anti-acquired immunodeficiency syndrome treatment of pentacyclic triterpenoids.