Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.
Int J Mol Sci. 2021 Apr 29;22(9):4708. doi: 10.3390/ijms22094708.
For decades, local bone drug delivery systems have been investigated in terms of their application in regenerative medicine. Among them, inorganic polymers based on amorphous silica have been widely explored. In this work, we combined two types of amorphous silica: bioglass and doxycycline-loaded mesoporous silica MCM-41 into the form of spherical granules (pellets) as a bifunctional bone drug delivery system. Both types of silica were obtained in a sol-gel method. The drug adsorption onto the MCM-41 was performed via adsorption from concentrated doxycycline hydrochloride solution. Pellets were obtained on a laboratory scale using the wet granulation-extrusion-spheronization method and investigated in terms of physical properties, drug release, antimicrobial activity against , mineralization properties in simulated body fluid, and cytotoxicity towards human osteoblasts. The obtained pellets were characterized by satisfactory mechanical properties which eliminated the risk of pellets cracking during further investigations. The biphasic drug release from pellets was observed: burst stage (44% of adsorbed drug released within the first day) followed by prolonged release with zero-order kinetics (estimated time of complete drug release was 19 days) with maintained antimicrobial activity. The progressive biomimetic apatite formation on the surface of the pellets was observed. No cytotoxic effect of pellets towards human osteoblasts was noticed.
几十年来，人们一直在研究局部骨药物输送系统在再生医学中的应用。其中，基于无定形二氧化硅的无机聚合物得到了广泛的探索。在这项工作中，我们将两种类型的无定形硅：生物玻璃和载多西环素的介孔硅 MCM-41 组合成球形颗粒（颗粒）的形式作为双功能骨药物输送系统。这两种类型的硅都是通过溶胶-凝胶法获得的。通过从高浓度盐酸多西环素溶液中吸附来实现 MCM-41 上的药物吸附。使用湿法制粒-挤出-滚圆法在实验室规模上获得颗粒，并对其物理性质、药物释放、对 的抗菌活性、模拟体液中的矿化性能以及对人成骨细胞的细胞毒性进行了研究。所得到的颗粒具有令人满意的机械性能，消除了在进一步研究中颗粒开裂的风险。从颗粒中观察到双相药物释放：突释阶段（吸附药物的 44%在第一天内释放），随后以零级动力学进行延长释放（估计完全释放药物的时间为 19 天），同时保持抗菌活性。在颗粒表面观察到渐进的仿生磷灰石形成。颗粒对人成骨细胞没有细胞毒性作用。
