Long-acting silk fibroin xerogel delivery systems for controlled release of estradiol

The goal of the present work was to determine and characterize the therapeutic feasibility of silk fibroin xerogels as a potential long-acting estradiol delivery system. Fibroin delivery systems were prepared by the addition of ethanol that besides dissolving the drug, served as an accelerator for the gelation of the extracted silk fibroin solution and thus for the formation of a cross-linked three-dimensional hydrogel with a measured and calculated 34% content of β-sheets. The final drug delivery system was in a form of silk fibroin xerogel, produced simply by removing the solvent from the intermediate hydrogel. Hormone estradiol was used as a pharmaceutically relevant estrogen model to assess the release from fibroin xerogels. Various parameters were considered, such as drug load, the composition of the polymer, and possible interactions between both. The material properties of fibroin xerogel delivery systems were investigated with several analytical methods (electron microscopy, infrared spectroscopy, X-ray diffraction, swelling, and degradation studies). The in vitro release of estradiol from the fibroin delivery system tested in sink conditions was sustained up to 129 days, which confirms the promising use of fibroin as a novel biopolymer for prolonged release of hydrophobic drugs.