PDF(Pubmed)
Abstract：
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.
摘要：
双膦酸盐药物是治疗骨病如Paget病和骨质疏松症的主要药物。尽管他们的有效性，它们也表现出严重的缺点，如快速排泄和有限的口服生物利用度。通常施用高剂量以抵消这些缺点。随后，副作用被触发，如下颌骨坏死和食道癌。受控的药物释放系统可能是克服这些问题的可行候选物。在这里，我们提出了新型的功能化硅基水凝胶，其中装载了骨质疏松症药物依替膦酸盐（1,1-羟基亚乙基二膦酸盐），用于控制药物的释放曲线。评价各种方法以控制药物的初始释放速率和最终释放浓度。这些包括凝胶密度，通过系统地增加用于制备水凝胶的硅酸盐的初始浓度，金属阳离子（Ca2+和Cu2+）的存在，以及用硅烷基接枝剂(用阴离子，阳离子,和中立组)。这项研究也有助于我们不断努力开发新的先验可编程载药凝胶，以控制骨质疏松症药物的释放。
