Summary of Research Activities
The general goal of this study was to develop and study bioresorbable composite core/ shell fiber structures loaded with the antiproliferative drug Farnesylthiosalicylate (FTS, Salirasib). These structures are composed of a dense core and porous bioresorbable shell, so as to combine good mechanical properties together with effective local drug release. Such composite fibers can be used as basic elements of biomedical devices. When releasing antiproliferative drugs, such fibers can build endovascular stents that in addition to their support function, they will also help to prevent of in-stent restenosis. The porous drug-loaded coating can actually be applied on any type of core fiber, polymer or metal, and hence, be used in both types of stents, stable and biodegradable. Such fibers can also be used for local treatment of cancer, especially in the case of glioblastoma multiforme, where local drug release is of high importance. FTS is a new drug which was developed lately by Prof. Yoel Kloog, Tel-Aviv University. It acts on specific oncogenic proteins and was found effective and safe for prevention of ISR and for treatment of cancer.
Our novel coating technique utilizes the freeze drying of "water in oil" emulsion where the emulsion's organic phase contains the FTS molecules. The effect of the emulsion's composition and processing parameters on the coating’s nanostructure and on the resulting FTS controlled release profile have been extensively studied. The nanostructure of the coating ("shell") was studied using scanning electron microscopy and the in-vitro FTS release from the fibers has been studied using HPLC analysis for determining the drug contents within the release medium. Degradation and erosion profiles of the porous biodegradable shell are studied as well using Gel Permeation Chromatography (GPC) and weight loss measurements.
Our results till now show that all FTS release profiles exhibited diffusion-controlled pattern and all released quantities are in the therapeutic range. The shell's structure is affected mainly by the homogenization rate and addition of surface active agents (surfactants) for stabilizing the emulsion. The resulting FTS release profiles are affected mainly by the drug and polymer contents, emulsion's aqueous to organic phase ratio and homogenization rate. The degradation study (GPC results) show that the porous shell losses approximately 85% of its initial molecular weight during the first month of degradation, while the polymer shell's weight loss starts only after one month of degradation. We have demonstrated that proper selection of processing conditions, based on kinetics and thermodynamic considerations, can yield core/shell fiber structures with desired microstructure, FTS release and degradation behavior.
