The Preparation Of Carboxymethyl Chitosan Based Micelles For Effective Anti-Angiogenesis Activity

In this article,we synthesized a series of carboxymethyl chitosan-graft-PCL(CMCS-g-PCL)polymers based on the CMCS which has good anti-angiogenesis property.It can self-assembl to a micelle and apatinib was encapsulated into cores of the micelles by hydrophobic interaction to form CPA micelles.We expected to achieve better anti-angiogenesis effect through synergistic action.In this paper,different prepared methods pf micelles were investigated,and the result showed that the emulsion/evaporation method was the best.When the dose(w/w)was 25%,the encapsulation efficiency(EE)and drug loading contents(DLC)were higher,and the best group reached 77.18%and 16.17%,respectively.The CPA micelles were the particle sizes of approximately 100-150 nm at pH 7.4,and aggregated to own bigger sizes at extracellular pH(pHe)in solid tumors(pH 6.4)that near the isoelectric point of CMCS(? pH 5.7).CPA micelles had a pH-responsive activity as the release rate at pH 6.4 was faster than that at pH 7.4 and could regulate the release rate by altering grafting ratio.In vitro cell proliferation assay and hemolysis were conducted to confirm the safety of the micelles.Besides,the micelles had significant inhibiting effect on vascular endothelial cells as indicated by CCK-8,cellular uptake,cell migration and tube formation assay.These results suggest that CPA micelles may be used as an effective drug delivery system for anti-angiogenesis cancer therapy.