Objective: pH responsive polymer micelles loaded with cantharidin were prepared to increase the solubility of cantharidin in water.The pH responsive property of the micelles was verified by the controlled drug release under tumoral mimic mild acidic environment. Method: Cantharidin micelles were prepared by thin film hydration method with amphiphilic methoxy poly(ethylene glycol)-b-polylactide (PELA) block copolymer and methoxy poly(ethylene glycol)-b-polylactide-b-poly(β-amino ester) (PELA-PBAE) as carriers.The structure and morphology of the micelles was characterized by transmission electron microscopy.The particle size of the micelles was measured by laser light scattering analyzer.HPLC was employed to determine drug loading and encapsulation efficiency of the micelles.In vitro release of the micelles was performed in phosphate buffered saline (pH of 7.4

6.5 and 5.5

respectively) by permeation diffusion method. Result: The micelles of PELA-cantharidin (PELA-C) and PELA-PBAE-C exhibited spherical shape with particle size of 21.6 nm and 21.2 nm

respectively;they were at least stable within 5 d.Drug loading and encapsulation efficiency of PELA-C micelles were 1.68% and 92.0%

while these of PELA-PBAE-C micelles were 1.72% and 88.8%

respectively.The cumulative release rates of PELA-C micelles and PELA-PBAE-C micelles in 8 h were 24.7% and 79.1% under pH of 5.5

13.6% and 50.0% under pH of 6.5

10.2% and 13.9% under pH of 7.4

respectively. Conclusion: The solubility of cantharidin is significantly improved with PELA-PBAE as nanocarrier

in vitro release of PELA-PBAE-C micelles has significant pH responsive performance.