Fumagillin Nanoparticle Therapy for Angiogenesis

Example 13

As shown in FIG. 19, fumagillin dissolved in a lipid membrane rapidly releases in vivo, making it practically ineffective in vivo. FIG. 20 shows, however, the in vivo effectiveness of a fumagillin prodrug administered in a nanoparticle of the invention. In particular, the figure shows the in vivo MR signal enhancement post treatment with targeted fumagillin nanoparticles (a-b) and control (no drug, c-d); Reduced Matrigel implant volume (%) in rats treated with αvβ3-integrin-targeted nanoparticles with 2.28 mole % fumagillin-PD vs. αvβ3-integrin-targeted nanoparticles with 2.28% fumagillin, αvβ3-integrin-targeted nanoparticles without drug, nontargeted nanoparticles with 2.28 mole % fumagillin-PD.

FIG. 21 shows the effect of the fumagillin prodrug in an in vitro cell proliferation assay. The left panel shows the effects of fumagillin prodrug incorporated nanoparticles and control nanoparticles (targeted no drug, non targeted and targeted fumagillin) on human umbilical vein endothelial cells (HUVEC) for cell proliferation by CyQuant NF assay and the right panel shows cell metabolic activity by Alamar Blue assay.