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磁性介孔硅纳米颗粒作为一种乳腺癌治疗策略:疏水性药物依西美坦的载药与释放

Magnetic mesoporous silica nanoparticles as a theranostic approach for breast cancer: Loading and release of the poorly soluble drug exemestane.

机构信息

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Faculdade de Engenharia, Universidade do Porto, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal.

出版信息

Int J Pharm. 2022 May 10;619:121711. doi: 10.1016/j.ijpharm.2022.121711. Epub 2022 Apr 1.

Abstract

Exemestane has a limited aqueous solubility that leads to a very high variability in absorption when administrated orally. It is crucial to develop strategies to increase the solubility and bioavailability of this drug. To overcome these issues, the aim of the present work was the development of magnetic silica mesoporous nanoparticles (IOMSNs) to carry and release exemestane. Furthermore, these nanoparticles could be also used as Magnetic Resonance Imaging (MRI) contrast agents for treatment monitorization and tumor detection. MRI analysis showed that IOMSNs present a concentration dependent contrast effect, revealing their potential for MRI applications. Also, IOMSNs present a very good polydispersity (0.224) and nanometric range size (137.2 nm). It was confirmed that the nucleus is composed by magnetite and the silica coating presents tubes with MCM-41-like hexagonal structure. Both iron oxide nanoparticles and iron oxide mesoporous silica nanoparticles were not toxic in cell culture for 24 h. Exemestane was successful released for 72 h following a typical sustained release pattern, achieving a very high loading capacity (37.7%) and in vitro release of 98.8%. Taking into account the results it is possible to conclude that IOMSNs have a high potential to be used as theranostic for intravenous breast cancer treatment with exemestane.

摘要

依西美坦的水溶性有限,口服给药时吸收的变异性很大。因此,开发提高药物溶解度和生物利用度的策略至关重要。为了克服这些问题,本工作的目的是开发磁性硅介孔纳米粒子(IOMSNs)来携带和释放依西美坦。此外,这些纳米粒子还可以用作磁共振成像(MRI)造影剂,用于治疗监测和肿瘤检测。MRI 分析表明,IOMSNs 具有浓度依赖性的对比效果,揭示了它们在 MRI 应用中的潜力。此外,IOMSNs 具有非常好的分散性(0.224)和纳米级尺寸(137.2nm)。证实核由磁铁矿组成,二氧化硅涂层呈现出具有 MCM-41 类似六方结构的管。在细胞培养 24 小时内,氧化铁纳米粒子和氧化铁介孔硅纳米粒子均无毒性。依西美坦按照典型的持续释放模式成功释放了 72 小时,达到了非常高的载药量(37.7%)和体外释放 98.8%。考虑到这些结果,可以得出结论,IOMSNs 具有作为静脉内乳腺癌治疗用依西美坦的治疗诊断的巨大潜力。

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