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双膦酸盐-多壁碳纳米管缀合物的合成、表征、控释动力学和抗癌活性。

Synthesis, characterization, kinetic drug release and anticancer activity of bisphosphonates multi-walled carbon nanotube conjugates.

机构信息

Department of Applied Chemistry; Faculty of Science; University of Johannesburg, Doornfontein Campus, P.O. Box 17011, Johannesburg, South Africa.

Pharmacology Division, Department of Pharmacy and Pharmacology; WITS Institute for Malaria (WRIM), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Nov;104:109967. doi: 10.1016/j.msec.2019.109967. Epub 2019 Jul 10.

Abstract

The statistical proof that most forms of cancer metastasize to bone tissue has redirected research focus to the development of efficient secondary bone cancer treatment regimens. Bisphosphonates (BPs) have been earmarked as a drug of choice for bone metastasis. However, they have a shortcoming of being released before reaching targeted sites due to their low molecular weight. In haste to attain increased efficacy, there is a tendency for drug overdose to occur, resulting in systemic toxicity. One way to curb this is by employing drug delivery systems for targeted and controlled release of the drugs. Having been explored as versatile and innovative drug carriers, multi-walled carbon nanotubes (MWCNTs) have emerged as potential drug delivery systems. Hence, in the present study, alendronate, neridronate and pamidronate are three classes of bisphosphonates that were conjugated onto multi-walled carbon nanotubes. Conjugation was confirmed by characterization techniques including SEM, TEM, EDX, FTIR, Raman and TGA. Drug release studies were also conducted at pH 1.2, 5.5 and 7.4 to study the mechanism of release for neridronate. Results obtained were fitted into Zero order (42.6%), Higuchi (26%) and Korsmeyer-Peppas (22%). The best models describing the release of neridronate from MWCNTs were Zero order, Higuchi and Korsmeyer-Peppas at pH 1.2, 5.5 and 7.4, respectively. A tetrazolium cell viability assay was performed to assess the anticancer activity of the MWCNTs conjugated BPs.

摘要

统计证据表明,大多数形式的癌症都会转移到骨组织,这使得研究重点转向开发有效的继发性骨癌治疗方案。双膦酸盐(BPs)已被指定为治疗骨转移的首选药物。然而,由于其分子量低,它们在到达靶向部位之前就会释放出来,这是它们的一个缺点。为了提高疗效,往往会出现药物过量的情况,导致全身毒性。一种抑制这种情况的方法是使用药物传递系统来靶向和控制药物的释放。多壁碳纳米管(MWCNTs)作为多功能和创新的药物载体已经得到了探索,它们已经成为潜在的药物传递系统。因此,在本研究中,阿仑膦酸盐、奈立膦酸盐和帕米膦酸盐这三种双膦酸盐被共轭到多壁碳纳米管上。通过 SEM、TEM、EDX、FTIR、Raman 和 TGA 等表征技术证实了共轭。还在 pH 1.2、5.5 和 7.4 进行了药物释放研究,以研究奈立膦酸盐的释放机制。得到的结果拟合到零级(42.6%)、Higuchi(26%)和 Korsmeyer-Peppas(22%)。描述奈立膦酸盐从 MWCNTs 释放的最佳模型分别是 pH 1.2、5.5 和 7.4 时的零级、Higuchi 和 Korsmeyer-Peppas。进行了四唑细胞活力测定以评估 MWCNTs 共轭 BPs 的抗癌活性。

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