Crystal Engineering, Growth and Design Laboratory, Department of Chemistry, University of Crete, 71003 Heraklion, Greece.
School of Pharmacy, University of Eastern Finland, Biocenter Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.
Molecules. 2022 Sep 21;27(19):6212. doi: 10.3390/molecules27196212.
Bisphosphonates (BPs) are common pharmaceutical treatments used for calcium- and bone-related disorders, the principal one being osteoporosis. Their antiresorptive action is related to their high affinity for hydroxyapatite, the main inorganic substituent of bone. On the other hand, the phosphonate groups on their backbone make them excellent ligands for metal ions. The combination of these properties finds potential application in the utilization of such systems as controlled drug release systems (CRSs). In this work, the third generation BP drug zoledronate (ZOL) was combined with alkaline earth metal ions (e.g., Sr and Ba) in an effort to synthesize new materials. These metal-ZOL compounds can operate as CRSs when exposed to appropriate experimental conditions, such as the low pH of the human stomach, thus releasing the active drug ZOL. CRS networks containing Sr or Ba and ZOL were physicochemically and structurally characterized and were evaluated for their ability to release the free ZOL drug during an acid-driven hydrolysis process. Various release and kinetic parameters were determined, such as initial rates and release plateau values. Based on the drug release results of this study, there was an attempt to correlate the ZOL release efficiency with the structural features of these CRSs.
双膦酸盐（BPs）是一种常用于治疗钙和骨骼相关疾病的药物，其中主要的是骨质疏松症。它们的抗吸收作用与其对羟磷灰石（骨骼的主要无机成分）的高亲和力有关。另一方面，其主链上的膦酸基团使它们成为金属离子的优良配体。这些特性的结合在利用此类系统作为控制药物释放系统（CRSs）方面具有潜在的应用。在这项工作中，第三代 BP 药物唑来膦酸（ZOL）与碱土金属离子（例如 Sr 和 Ba）结合，以合成新材料。当这些金属-ZOL 化合物暴露于适当的实验条件下，例如人体胃部的低 pH 值时，它们可以作为 CRSs 运作，从而释放出活性药物 ZOL。含有 Sr 或 Ba 和 ZOL 的 CRS 网络进行了物理化学和结构表征，并评估了它们在酸驱动的水解过程中释放游离 ZOL 药物的能力。确定了各种释放和动力学参数，例如初始速率和释放平台值。基于这项研究的药物释放结果，尝试将 ZOL 释放效率与这些 CRSs 的结构特征相关联。
