Abstract No. 514 Injectable thermo-sensitive hydrogels as chemoembolic drug delivery agents for interventional applications

Abstract

Controversy exist when discussing disease control of hepatocellular carcinoma in regards to bland embolization verses drug loaded microspheres. While the reasons for the absence of convincing data supporting the use of embolic microspheres in combination with chemotherapy are multiple, the importance of achieving complete vascular occlusion and sustained drug release are clear. Therefore, the development of biodegradable injectable drug loaded materials that can “cast” the tumor capillary bed would be advantageous. Chitosan is an FDA approved biocompatible and biodegradable polysaccharide derived from the crustacean exoskeleton. It can be used as a delivery vehicle for small molecules. Chitosan was dissolved in 0.25% acetic acid solution (1.44%w/v) under magnetic stirring for approximately 12 hours at room temperature. The solution was sterilized by autoclaving at 121ºC for 30 min. Chitosan (5 mL) was mixed with 200μL of ammonium hydrogen phosphate (AHP) solution (60% aqueous solution) via two syringe vigorous mixing method. The pH of the mixture was in the range of 7-7.2. Doxorubicin (5 mg/ml) was loaded into chitosan solution during magnetic stirring for release studies. The drug released from the hydrogel was determined by measuring the concentrations of the doxorubicin after set time points with a UV-vis spectrophotometer at 483 nm with a standard curve constructed with known concentrations of doxorubicin. The resulting solution can be injected through a microcatheter with gelation times range from 1-3 minutes at 37 degrees. In vitro degradation and release studies were performed with doxorubin from the hydrogel. It was determined that the hydrogels are stable in an aqueous environment for up to 90 days. Additionally, when loaded with 5 mg/ml doxorubicin, drug release profiles demonstrated up to 70% delivery of the drug at 28 days. We hypothesized that the development of a chitosan hydrogel to enable casting and drug release can be used as an intravascular chemoembolic agent. These gels demonstrate controlled, sustained release of doxorubicin and can be injected through a microcatheter in preparation for in-vivo trials.