Abstract:
Angiogenesis is a term used for formation of new blood vessels from pre-existing vessels. Normally, angiogenesis process is essential for wound healing yet, unregulated angiogenesis plays a pivotal role on tumor growth and metastasis. Anti-angiogenesis agents are widely used in combination therapy for cancer. Selectivity toward newly formed and disorganized blood vessels around the tumor is an attractive tool for reduced toxicity. Cell cycle inhibitors, the more commonly used anticancer agents, target fast reproducing cells: tumor cells and others such as erythrocytes and leukocytes, frequently causing hemoglobin deficiency and neutropenia, respectively. This on mechanism action of the anti-cancer agents render them less effective since the dose has to be reduced where the toxic side effects are tolerable. Many angiogenesis inhibitors entering the market in recent years, have proven successful in the clinic, with reduced side effects as well as shrunk tumor size. Polymer conjugates covalent combination of a macromolecule with a small molecule have been attractive tools for drug delivery. Conjugation of the small molecule to a polymer provides water solubility, reduced toxicity and prolonged half life owing to the slower clearance. Furthermore accumulation in the tumor due to the large size of the molecule is an important driving force for utilization of polymer therapeutics for cancer chemotherapy. This thesis will focus on modification of an anti-angiogenesis agent and conjugation to a biocompatible and biodegradable polymer.
