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阿仑膦酸盐在体外介孔二氧化钛植入物/骨界面的定位。

Ex vivo alendronate localization at the mesoporous titania implant/bone interface.

作者信息

Karlsson Johan, Harmankaya Necati, Allard Stefan, Palmquist Anders, Halvarsson Mats, Tengvall Pentti, Andersson Martin

机构信息

Department of Chemical and Biological Engineering, Applied Chemistry, Chalmers University of Technology, Kemivägen 10, 412 96, Gothenburg, Sweden,

出版信息

J Mater Sci Mater Med. 2015 Jan;26(1):5337. doi: 10.1007/s10856-014-5337-7. Epub 2015 Jan 11.

Abstract

An attractive approach in implant technology is local drug delivery, and design of efficient, safe and reliable treatments. Our hitherto strategy has been to coat Ti implants with a thin mesoporous TiO2 film that in turn is loaded with an osteoporosis drug, such as Alendronate (ALN) that is known to suppress osteoclastic activity. This system has proven highly successful and results in excellent osseointegration. However, more detailed information about drug-release and distribution at the bone/implant interface is needed. In this study, (14)C-ALN loaded titanium implants were placed up to 8 weeks into rat tibia and the spatial-temporal distribution of the drug was evaluated. Autoradiography data demonstrated a sustained release of (14)C-ALN and the released drug remained bound to bone in close vicinity, within 500 micrometers, of the implants. Liquid scintillation counting experiments confirmed that the distal transport of released (14)C-ALN was extremely low. The results are favorable as they show that ALN stays for a long time in the vicinity of the implant and may therefore improve for a long time the mechanical fixation of bone anchored implants. Moreover, these findings suggest due to the low systemic spreading a minimal risk of Alendronate related systemic side effects.

摘要

植入技术中一种吸引人的方法是局部药物递送以及设计高效、安全和可靠的治疗方法。我们迄今为止的策略是在钛植入物上涂覆一层薄的介孔二氧化钛膜,该膜再负载一种骨质疏松药物,如已知可抑制破骨细胞活性的阿仑膦酸盐(ALN)。该系统已被证明非常成功,并导致了优异的骨整合。然而,需要更多关于药物在骨/植入物界面的释放和分布的详细信息。在本研究中,将负载有(14)C-ALN的钛植入物植入大鼠胫骨长达8周,并评估药物的时空分布。放射自显影数据表明(14)C-ALN持续释放,并且释放的药物在植入物周围500微米范围内仍与骨紧密结合。液体闪烁计数实验证实释放的(14)C-ALN的远端转运极低。这些结果是有利的,因为它们表明ALN在植入物附近停留很长时间,因此可能长时间改善骨锚定植入物的机械固定。此外,这些发现表明由于全身扩散较低,阿仑膦酸盐相关全身副作用的风险最小。

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