| Description |
Globally, hepatocellular carcinoma (HCC) of the liver is diagnosed in over 700,000 people annually and trends indicate increasing prevalence. The majority of cases, >80%, are detected at advanced stages where systemic chemotherapies have little efficacy. The primary curative treatment is liver transplant, but if a donor liver is not available, only palliative care such as transarterial chemoembolization (TACE) is possible. TACE targets the tumor blood supply. An embolic containing a chemotherapeutic agent is injected into the tumor's vasculature via an endovascular catheter, subsequently shutting down blood flow while delivering localized chemotherapy. A presently approved product, Lipiodol, is an oily emulsion mixed with a chemotherapeutic used in conjunction with gelatin particles or synthetic polymer beads that act as emboli. Calibrated spherical drug eluting beads are now gaining favor for this procedure, replacing the multistep oil emulsion system. These beads, however, have shortcomings: aggregation of smaller diameter beads, fracturing of beads while under strain in the catheter, off target embolization particularly in pulmonary circulation, elution of only charged small molecule therapeutics, nondegradability, limited tumor depth penetration, and revascularization induced by a hypoxic state. To address these limitations, a genetically engineered silk-elastinlike protein polymer (SELP) system was developed to create a liquid-to-solid embolic agent capable of retaining and releasing a wider range of therapeutics, controlled degradation into nontoxic amino acids, and soluble until injected into the body where they transition irreversibly to a solid hydrogel network. This provides potential for ideal injectability as a low viscosity fluid at room temperature followed by optimal embolization by a highly stable hydrogel at body temperature. The proposed research involved engineering a SELP formulation with suitable viscosity for injection into the tumor vasculature via a microcatheter and a suitable gelation rate and gel strength for stable embolization. The drug release properties of the polymer matrix were determined for small molecule chemotherapeutics such as doxorubicin and anti-angiogenic sorafenib. Preliminary in vivo performance of the novel system for TACE was evaluated using a rodent model. Future directions include expansion of in vivo studies, particularly in an animal model for HCC and TACE to study therapeutic efficacy and longterm biocompatibility. |
