RESUMEN
Bisphosphonate drugs constitute the primary treatment for bone diseases such as Paget's disease and osteoporosis. Despite their effectiveness, they also exhibit severe drawbacks, such as rapid excretion and limited oral bioavailability. High doses are usually administered to counterbalance these drawbacks. Subsequently, side effects are triggered, such as osteonecrosis of the lower jaw and esophageal cancer. Controlled drug release systems may be viable candidates to overcome those issues. Herein, we present novel functionalized silica-based hydrogels loaded with the osteoporosis drug etidronate (1,1-hydroxyethylidene-diphosphonate) used to control the release profile of the drug. Various methodologies were evaluated to control the initial release rate and the final released concentration of the drug. These included the gel density, by systematically increasing the initial concentration of silicate used to prepare the hydrogels, the presence of metal cations (Ca2+ and Cu2+), and the internal surface functionalization of the gel with silane-based grafting agents (with anionic, cationic, and neutral groups). This study also contributes to our continuous effort to develop new a priori programmable drug-loaded gels for the controlled release of osteoporosis drugs.