The present invention provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Retinoic acids and derivatives thereof, and paclitaxel. Also provided are methods for embolizing blood vessels, and eliminating biliary, urethral, esophageal, and tracheal/bronchial obstructions.

Anti-angiogenic compositions and methods of use

· Purpose: Methotrexate (MTX) is a folic acid antagonist used in chemotherapy regimens. Additional therapeutic applications have been suggested based on effect as an immuno-modulating drug in systemic rheumatoid disease and associated uveitis. Since chronic inflammatory disease is often associated with a neovascular response, we investigated the use of MTX for treatment of corneal angiogenesis.· Methods: Neovascularizations were induced by fibroblast growth factor in a corneal pocket model. Vessels were examined biomicroscopically. MTX was applied topically to rabbit corneas in a concentration of 0.2 mg/day. MTX level was measured in aqueous humor and plasma. · Results: On day 9 the vascularized area was 12.0±6.9 mm2 in control eyes and significantly smaller, 2.2±1.86 mm2, in treated eyes. Treated animals showed no local side effects such as epithelial defects. Although therapeutic levels were measured in the aqueous humor, MTX could not be detected in the serum of treated animals.· Conclusion: The antiangiogenic mechanism of MTX might be due to inhibition of both macrophage invasion during early angiogenesis and endothelial cell proliferation. The high levels in the aqueous humor indicate a possible application of topical MTX for inflammations of the anterior segment of the eye.

Topical application of methotrexate for inhibition of corneal angiogenesis

Neovascular diseases are the leading causes of blindness in humans. Although several promissing compounds have been isolated, pharmacological treatment remains difficult. Thalidomide has inhibitory effects on angiogenesis in the corneal micropocket assay. However, the results vary considerably depending on the administration route and animal model. The aim of this study, therefore, was to investigate thalidomide and two of its derivatives, supidimide and EM12, in the rabbit corneal micropocket assay. Using both basic fibroblast growth factor and vascular endothelial growth factor for initiation of the neovascular response, we were able to show a significant inhibition of neovascularisation with all three substances. EM12, the most teratogenic derivative analysed, was demonstrated to be the most potent inhibitor of angiogenesis in this model. Thalidomide and supidimide did not show systemic side effects in the applied dosage. An equal dosage of EM12, however, resulted in significant weight loss of the animals, but did not increase angiogenic activity compared with lower doses. Together with earlier findings, these data support a strong correlation between the antiangiogenic potential and the teratogenic activity of thalidomide and structurally related compounds.

Effect of thalidomide and structurally related compounds on corneal angiogenesis is comparable to their teratological potency

Philinopside A is a novel sulfated saponin isolated from the sea cucumber, Pentacta quadrangulari. The effects of philinopside A on angiogenesis and tumor growth were assessed in a series of models in vitro and in vivo. Our results demonstrated that philinopside A significantly inhibited the proliferation, migration and tube formation of human microvascular endothelial cells (HMECs) in a dose-dependent manner, with average IC(50) values of 1.4 +/- 0.17, 0.89 +/- 0.23 and 0.98 +/- 0.19 microM, respectively. Rat aortas culture assay provides a close imitation of in vivo angiogenesis process and 2-10 microM philinopside A suppressed the formation of new microvessels in cultured rat aortas. Philinopside A 2-10 nmol/egg obviously inhibited angiogenesis in chick embryo chorioallantoic membrane assay. In addition, philinopside A manifested strong anti-tumor activities both in vitro and in vivo. Through immunofluorescent analysis, we found the compound reduced mouse sarcoma 180 tumor volume by inducing apoptosis of tumor and tumor-associated endothelial cells. An examination of the effects of philinopside A on the angiogenesis-related receptor tyrosine kinases (RTKs) showed that philinopside A broadly inhibited all tested RTKs, including vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor (FGF) receptor-1, platelet-derived growth factor (PDGF) receptor-beta and epithelial growth factor (EGF) receptor, with IC(50) values ranging from 2.6-4.9 microM. These results suggest that philinopside A is a promising anti-cancer agent that possesses dual cytotoxic and anti-angiogenic effects that were at least partly due to its inhibitory effects on RTKs.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.20804

Philinopside a, a novel marine‐derived compound possessing dual anti‐angiogenic and anti‐tumor effects

This study describes the effects of ten clinically used cytostatics [bleomycin (BLM), cytarabine (Ara-C), cyclophosphamide (CTX), doxorubicin (DOX), etoposide (VP-16), 5-fluorouracil (5-FU), methotrexate (MTX), mitoxantrone (MXN), vincristine (VCR), and vinblastine (VLB)] on the chorioallantoic membrane vessels--especially on vessel counts--and on the weight of the chicken embryo. A significant reduction of vessel counts (VC) due both to angiocidal and an angiostatic action, was induced by DOX, MXN, VP-16, VCR, and VLB. 5-FU and BLM induced only a (weak) angiostatic effect. MTX, Ara-C, and CTX were neither angiocidal nor angiostatic. The classification of cytostatics presented here might have implications for their use in the clinical treatment of malignant tumors.

Classifying cytostatics on the basis of their angiocidal and angiostatic effects.

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Classifying cytostatics on the basis of their angiocidal and angiostatic effects.