Biomimetic hydroxyapatite-drug nanocrystals as potential bone substitutes with antitumor drug delivery properties
Biomimetic hydroxyapatite-drug nanocrystals as potential bone substitutes with antitumor drug delivery properties
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DOI：
10.1002/adfm.200600361
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发表时间：
2007-09-03
影响因子：
19
通讯作者：
Roveri, Norberto
中科院分区：
文献类型：
--
作者：
Palazzo, Barbara;Iafisco, Michele;Roveri, Norberto
本文研究了抗癌药物顺铂(CDDP，cisplatin)和新型铂(II)络合物二(乙二胺铂)甲磺酸(DPM)以及临床上相关的双膦酸阿伦磷酸酯对两种仿生合成羟基磷灰石纳米晶材料的吸附和解吸性能。吸附和解吸动力学取决于药物的特性和HA纳米颗粒的形貌。铂络合物的吸附随着氮配体的保留而发生，但顺铂的氯配体被置换。尽管它们的电荷相反，但带负电的阿伦磷酸双膦酸盐和带正电的水合顺铂被强吸附，而中性的DPM络合物对带负电的磷灰石表面的亲和力较低。结果表明，两种铂配合物的吸附是由静电吸引驱动的，而阿伦磷酸钠与HA表面的相互作用是通过配体交换进行的，药物分子中的两个膦酸基取代了表面的两个磷酸基团。值得注意的是，顺铂的正电水解物种在富磷表面更有利于吸附，而负电的阿伦磷酸钠在富钙表面更有利于吸附。后一种类型的短程静电相互作用似乎也主导了解吸动力学；因此，中性DPM的药物释放比带电的阿伦磷酸钠和含水顺铂更大。此外，虽然两种HAS的单位面积带电物种的释放相同，但表面钙含量较低的HANS释放DPM的速度比HAPS快。总体而言，这项工作表明，HA纳米晶体的性质可以通过这种方式进行调节，以产生针对特定治疗应用而量身定做的HA/生物分子结合物。
This Full Paper investigates the adsorption and desorption of the anticancer drugs cis-diamminedichloroplatinum(II) (CDDP, cisplatin) and the new platinum(II) complex di(ethylenediamineplatinum)medronate (DPM), as well as the clinically relevant bisphosphonate alendronate, towards two biomimetic synthetic HA nanocrystalline materials with either plate-shaped (HAps) or needle-shaped (HAns) morphologies and different chemico-physical properties. The adsorption and desorption kinetics are dependent on the specific properties of the drugs and the morphology of the HA nanoparticles. Adsorption of the platinum complexes occurs with retention of the nitrogen ligands but the chloride ligands of cisplatin are displaced. Despite their opposite charges, the negatively charged alendronate bisphosphonate and the positively charged aquated cisplatin are strongly adsorbed, while the neutral DPM complex shows lower affinity towards the negatively charged apatitic surface. The data suggest that adsorption of the two platinum complexes is driven by electrostatic attractions, while interaction between the alendronate and the HA surface takes place by ligand exchange in which the two phosphonate groups of the drug molecule replace two surface phosphate groups. Significantly, adsorption of positively charged hydrolysis species of cisplatin is more favored on the phosphate-rich HAns surface while adsorption of negatively charged alendronate is more favored on the calcium-rich HAps surface. The latter type of short-range electrostatic interactions also appear to dominate the desorption kinetics; consequently, drug release is greater for neutral DPM than for charged alendronate and aquated cisplatin. Moreover, while the release per unit area of charged species is the same for the two types of HAs, the release of DPM is faster from HAns, which is lower in surface calcium, than for HAps. Overall, this work demonstrates that the properties of HA nanocrystals can be modulated in such a way to produce HA/biomolecule conjugates tailored for specific therapeutic applications.