Aina Valentina, Malavasi Gianluca, Magistris Claudio, Cerrato Giuseppina, Martra Gianmario, Viscardi Guido, Menabue Ledi, Lusvardi Gigliola
Department of Chemistry, Interdepartmental NIS (Nanostructured Interfaces and Surfaces); INSTM (Italian National Consortium for Materials Science and Technology), University of Torino, Via P. Giuria 7, 10125, Turin, Italy,
J Mater Sci Mater Med. 2014 Oct;25(10):2243-53. doi: 10.1007/s10856-014-5206-4. Epub 2014 Apr 11.
Bioceramics, such as silica-based glasses, are widely used in bone and teeth restoration. Nowadays, the association between nanotechnology and pharmacology is one of the most promising research fields in cancer therapy. The advanced processing methods and new chemical strategies allow the incorporation of drugs within them or on their functionalized surfaces. Bioceramics can act as local drug delivery systems to treat bone and teeth diseases. The present paper reports data related to the development of a pH-stimuli responsive bioactive glass. The glass conjugation with 5-aminofluorescein (5-AF), through a pH-sensitive organic spacer, allows to produce a pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favour the release of 5-AF directly at the target site. 5-AF has been chosen as a simple, low cost, non toxic model to simulate doxorubicin, an anticancer drug. As doxorubicin, 5-AF contains an amino group in its structure in order to form an amide bond with the carboxylic functionalities of the glass. Raman spectroscopy and thermal analysis confirm the glass conjugation of 5-AF by means of an amide bond; the amount of 5-AF loaded was very high (≈ 65 and 44 wt%). The release tests at two different pH (4.2 and 7.4) show that the amount of released 5-AF is higher at acid pH with respect to physiological one. This preliminary datum evidenced that a pH-sensitive drug delivery system has been developed. The low amount of 5-AF released (<1 wt% of the total 5-AF) is due to the very low solubility of 5-AF in aqueous medium. This disadvantage, may be overcome in a dynamic environment (physiological conditions), where it is possible to obtain a drug release system ensuring an effective therapeutic dose for long times and, at the same time, avoiding the drug toxicity.
生物陶瓷,如二氧化硅基玻璃,被广泛应用于骨骼和牙齿修复。如今,纳米技术与药理学之间的关联是癌症治疗中最具前景的研究领域之一。先进的加工方法和新的化学策略使得药物能够被包封在生物陶瓷内部或其功能化表面。生物陶瓷可作为局部药物递送系统用于治疗骨骼和牙齿疾病。本文报道了与一种pH响应性生物活性玻璃的研发相关的数据。通过一个pH敏感的有机间隔基将玻璃与5-氨基荧光素(5-AF)共轭,能够制备出一种pH响应性生物活性生物材料:当它暴露于特定的pH变化时,它可以促进5-AF直接在靶位点释放。5-AF被选作一种简单、低成本、无毒的模型来模拟抗癌药物阿霉素。与阿霉素一样,5-AF在其结构中含有一个氨基,以便与玻璃的羧基官能团形成酰胺键。拉曼光谱和热分析证实了5-AF通过酰胺键与玻璃共轭;5-AF的负载量非常高(约65和44 wt%)。在两种不同pH(4.2和7.4)下的释放测试表明,相对于生理pH,在酸性pH下释放的5-AF量更高。这一初步数据证明已开发出一种pH敏感的药物递送系统。释放的5-AF量较低(<总5-AF的1 wt%)是由于5-AF在水性介质中的溶解度非常低。在动态环境(生理条件)中,这一缺点可能会被克服,在这种环境下有可能获得一种药物释放系统,该系统能长时间确保有效治疗剂量,同时避免药物毒性。