| Description |
In a transcatheter embolization procedure, an embolic agent is delivered locally via a microcatheter to obstruct blood flow in a blood vessel or vascular bed. These interventional radiology procedures are used to treat vascular abnormalities, hemorrhage, and neoplastic growths. Current embolization agents are plagued by toxicity and handling issues. An ideal embolic agent would be water-borne and not rely on in situ polymerization or precipitation from organic solvents for hardening. Complex coacervates represent a possible solution to these problems; they are an aqueous fluid morphology of associated polyelectrolytes that can be endowed with environmentally triggered solidification mechanisms. In this dissertation, the development of embolic coacervates (ECs) based upon an ionic strength driven setting mechanism is described. ECs are low-viscosity liquid coacervates in solutions of high ionic strength, but undergo a phase transition into a solid upon entering the low ionic strength environment of blood vessels. Early iterations were based upon the commercially available polycation protamine and an oligophosphate. These agents validated the ionic strength dependent setting mechanism and successfully occluded blood flow down to the capillary level in an acute transcatheter embolization of a rabbit kidney. Next, a synthetic polymer, poly(3-guanidinopropylmethacrylamide-co-methacrylamide), was developed to replicate the structure of protamine while offering control over the mechanical properties of the embolic both before and after solidification. ECs made from this synthetic polymer demonstrated an increase in dynamic shear modulus of nearly 4 orders of magnitude upon injection into physiological saline. In embolization of rabbit auricular arteries, these agents incited neutrophilic inflammation which began to subside at 2-4 weeks. At the endpoint of the study (4 weeks), occlusions remained stable and early signs of fibrous tissue deposition were observed. While longer-term tissue response studies are needed, embolic coacervates (ECs) represent a promising developmental embolic agent. In the final chapter, drug-releasing ECs were prepared with the antiangiogenic drug sunitinib malate. These ECs released 80% of their drug payload over the course of 14 days, displaying a linear zero order release profile. The results presented in this final chapter provide a framework for developing future embolics which prevent angiogenic revascularization resulting from post-embolization ischemia. |
