Sustained release of small molecules from carbon nanotube-reinforced monetite calcium phosphate cement.
Sustained release of small molecules from carbon nanotube-reinforced monetite calcium phosphate cement.
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DOI：
10.1016/j.msec.2014.06.027
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Boren Lin;H. Zhou;D. Leaman;V. Goel;A. Agarwal;S. Bhaduri
中科院分区：
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作者：
Boren Lin;H. Zhou;D. Leaman;V. Goel;A. Agarwal;S. Bhaduri
人们对开发磷酸钙骨水泥(CPC)作为药物输送系统的兴趣与日俱增，因为它能够实现对骨病部位的局部和可控治疗。本研究的目的是研究载药羧酸功能化多壁碳纳米管(MWCNT)增强单硝酸酯(DCPA，CaHPO4)基骨水泥的释药规律。以抑制核因子-κB介导的破骨细胞吸收的小肽分子Z-亮氨酸(MG132)为模型药物。在固化过程中将MG132添加到水泥中，释放到用于培养指示细胞的培养液中。在MG132负载CPC的培养液中，成骨细胞MC3T3-E1细胞出现明显的细胞死亡；然而，当MWCNTs存在于骨水泥中时，其毒性作用并不明显。在人胚胎肾293细胞中，使用一个由核因子-κB启动子驱动的荧光素酶报告来定量检测核因子-κB的激活。与含或不含多壁碳纳米管的含药CPC孵育后收集的培养液均可抑制肿瘤坏死因子α诱导的NF-κB活化，表明MG132的有效释放量被释放。CPC/药物复合体在24小时内迅速释放，而多壁碳纳米管的加入减弱了这种突释效应。此外，在RAW 264.7细胞培养中抑制肿瘤坏死因子α诱导的破骨细胞分化也证实了多壁碳纳米管/骨水泥/药物的持续释放。我们的数据证明了这种水泥复合材料的药物输送能力，它可以潜在地用于携带治疗分子，以结合其骨折稳定功能来促进骨再生。此外，它还提出了一种新的方法，通过引入功能化的多壁碳纳米管来降低基于CPC的药物递送系统的突释效应。
The interest in developing calcium phosphate cement (CPC) as a drug delivery system has risen because of its capability to achieve local and controlled treatment to the site of the bone disease. The purpose of this study was to investigate the release pattern of drug-carrying carboxylic acid-functionalized multi-walled carbon nanotube (MWCNT)-reinforced monetite (DCPA, CaHPO4)-based CPC. Z-Leu-Leu-Leu-al (MG132), a small peptide molecule inhibiting NF-κB-mediated osteoclastic resorption, was used as a model drug. MG132 was added into the cement during setting and released into the medium used to culture indicator cells. Significant cell death was observed in osteoblast MC3T3-E1 cells cultured in the medium incubated with MG132-loaded CPC; however, with the presence of MWCNTs in the cement, the toxic effect was not detectable. NF-κB activation was quantified using a NF-κB promoter-driving luciferase reporter in human embryonic kidney 293 cells. The medium collected after incubation with drug-incorporated CPC with or without MWCNT inhibited TNFα-induced NF-κB activation indicating that the effective amount of MG132 was released. CPC/drug complex showed a rapid release within 24 h whereas incorporation of MWCNTs attenuated this burst release effect. In addition, suppression of TNFα-induced osteoclast differentiation in RAW 264.7 cell culture also confirmed the sustained release of MWCNT/CPC/drug. Our data demonstrated the drug delivery capability of this cement composite, which can potentially be used to carry therapeutic molecules to improve bone regeneration in conjunction with its fracture stabilizing function. Furthermore, it suggested a novel approach to lessen the burst release effect of the CPC-based drug delivery system by incorporating functionalized MWCNTs.