Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), Av. Diagonal 647, 08028 Barcelona, Spain.
Acta Biomater. 2013 Sep;9(9):8403-12. doi: 10.1016/j.actbio.2013.05.016. Epub 2013 May 23.
Calcium phosphate cements (CPCs) have great potential as carriers for controlled release and vectoring of drugs in the skeletal system. However, a lot of work still has to be done in order to obtain reproducible and predictable release kinetics. A particular aspect that adds complexity to these materials is that they cannot be considered as stable matrices, since their microstructure evolves during the setting reaction. The aims of the present work were to analyze the effect of the microstructural evolution of the CPC during the setting reaction on the release kinetics of the antibiotic doxycycline hyclate and to assess the effect of the antibiotic on the microstructural development of the CPC. The incorporation of the drug in the CPC modified the textural and microstructural properties of the cements by acting as a nucleating agent for the heterogeneous precipitation of hydroxyapatite crystals, but did not affect its antibacterial activity. In vitro release experiments were carried out on readily prepared cements (fresh CPCs), and compared to those of pre-set CPCs. No burst release was found in any formulation. A marked difference in release kinetics was found at the initial stages; the evolving microstructure of fresh CPCs led to a two-step release. Initially, when the carrier was merely a suspension of α-TCP particles in water, a faster release was recorded, which rapidly evolved to a zero-order release. In contrast, pre-set CPCs released doxycycline following non-Fickian diffusion. The final release percentage was related to the total porosity and entrance pore size of each biomaterial.
磷酸钙骨水泥 (CPCs) 作为在骨骼系统中控制药物释放和导向的载体具有很大的潜力。然而，为了获得可重复和可预测的释放动力学，仍有许多工作要做。这些材料的一个特别之处在于，它们不能被视为稳定的基质，因为它们的微观结构在凝固反应过程中会发生变化。本工作的目的是分析 CPC 在凝固反应过程中的微观结构演变对抗生素盐酸多西环素释放动力学的影响，并评估抗生素对 CPC 微观结构发展的影响。药物的掺入通过充当羟基磷灰石晶体异质沉淀的成核剂，改变了水泥的结构和微观结构性质，但不影响其抗菌活性。在体外释放实验中，对易于制备的水泥（新鲜 CPCs）进行了实验，并与预设定的 CPCs 进行了比较。在任何配方中都没有发现爆发性释放。在初始阶段发现了明显的释放动力学差异；新鲜 CPCs 的演变微观结构导致了两步释放。最初，当载体仅仅是在水中的 α-TCP 颗粒的悬浮液时，记录到更快的释放，该释放迅速演变为零级释放。相比之下，预设定的 CPCs 按照非菲克扩散释放多西环素。最终的释放百分比与每个生物材料的总孔隙率和入口孔径有关。
