An Experimental Study Of Anti-Angiogenesis With Polyethylene Glycol Modified Endostatin

ObjectiveEndostatin is a widely-known endogenous angiogenesis inhibitor. It can strongly inhibit the proliferation and migration of endothelial cells. It also causes apoptosis of endothelial cells. However, recent phase I clinical trial indicates that its half-life is short and its bioavailability is poor. If we can improve its bioavailability and prolong its half-life to reduce the dose and prolong the drug cycle, the therapy effect of endostatin will be greatly improved and thus promote its clinical application. Our study will use polyethylene glycol to modify endostatin's structure and use the modified endostatin on the retinal neovarscularization of mice. Materials and Methods1. Preparation of PEG-endostatinUse oxidation method to preparation dioic acid PEG, then use it to block actived PEG (molecular mass 10ku) in one end. Then modify endostatin with the blocked PEG , and segregate and purificate the modified product with CTLL22 cell short term culture combined with 3H2TDR penetration method which reported by Gillis.2. Animal experimentMice RNV model was induced by hyper-oxygen. PEG-ES was injected into vitreous cavity. Pathologic study was used to observe the number of new retinal vessels. And the expression of VEGF, PEDF was studied with immunochemistry.3. ResultsEndostatin was successfully modified with PEG The neovascularization in group A...