pH-responsive carboxymethyl chitosan-derived micelles as apatinib carriers for effective anti-angiogenesis activity: Preparation and in vitro evaluation

In this study, carboxymethyl chitosan-graft-poly-(ε-caprolactone) copolymers (CMCS-g-PCL) were synthesized and used to encapsulate apatinib to prepare apatinib-loaded CMCS-g-PCL (CPA) micelles. CPA micelles' sizes were 100-150 nm at pH 7.4 while aggregated to 300-350 nm at pH 6.4, and the release rate at pH 6.4 was faster than pH 7.4, indicating CPA micelles have a pH-responsive activity. Furthermore, the release rate decreased with an increased grafting ratio of CMCS-g-PCL, which was shown by the results of release experiments from CPA-2 to CPA-10 micelles. A series of cell experiments demonstrated that blank micelles were non-toxic for human umbilical endothelial cells (HUVECs) below 0.125 mg/ml, CPA micelles had significant inhibiting effect on HUVECs as IC50 was near 3.125 μg/ml, and the drug effect could be adjusted by altering grafting ratio of CMCS-g-PCL. These results suggest that CPA micelles may be used as an effective drug delivery system for anti-angiogenesis cancer therapy.