Alatzoglou Fanouria-Eirini G, Vassaki Maria, Nirgianaki Kalliopi, Tripodianos Eleftherios, Turhanen Petri, Demadis Konstantinos D, Papathanasiou Konstantinos E
Crystal Engineering, Growth and Design Laboratory, Department of Chemistry, University of Crete, 71003 Heraklion, Crete, Greece.
Biocenter Kuopio, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Materials (Basel). 2023 Apr 26;16(9):3379. doi: 10.3390/ma16093379.
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 (Ca and Cu), 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.
双膦酸盐药物是治疗佩吉特病和骨质疏松症等骨病的主要药物。尽管它们有效，但也存在严重缺点，如排泄迅速和口服生物利用度有限。通常需要服用高剂量药物来抵消这些缺点。随后，会引发副作用，如下颌骨坏死和食道癌。可控药物释放系统可能是克服这些问题的可行选择。在此，我们展示了负载骨质疏松症药物依替膦酸（1,1-羟基亚乙基二膦酸）的新型功能化二氧化硅基水凝胶，用于控制药物的释放曲线。评估了各种方法来控制药物的初始释放速率和最终释放浓度。这些方法包括通过系统地增加用于制备水凝胶的硅酸盐的初始浓度来控制凝胶密度、金属阳离子（钙和铜）的存在以及用硅烷类接枝剂（带有阴离子、阳离子和中性基团）对凝胶进行内表面功能化。这项研究也有助于我们持续努力开发新的用于骨质疏松症药物控释的先验可编程载药凝胶。
