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评估主客体系统以提高他莫昔芬的疗效。

Evaluation of host-guest system to enhance the tamoxifen efficiency.

作者信息

Heidari Majd Mostafa, Akbarzadeh Abolfazl, Sargazi Azam

机构信息

a Faculty of Pharmacy , Zabol University of Medical Sciences , Zabol , Iran.

b Stem Cell Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.

出版信息

Artif Cells Nanomed Biotechnol. 2017 May;45(3):441-447. doi: 10.3109/21691401.2016.1160916. Epub 2016 Mar 25.

DOI:10.3109/21691401.2016.1160916
PMID:27012732
Abstract

Hydrophobic drugs can absorb as guest molecules inside the cavity of cyclodextrins as host sites. So, forming the drug-cyclodextrin complex can exert a profound effect on the physicochemical and biological properties of the drugs. According to these advantages, in this study, we synthesized the tamoxifen (TMX) loaded cyclodextrin (CD)-conjugated MNPs to evaluate simultaneously the cytotoxicity and sustained release as well as hepatoprotective effect of this nanomedicine. The average size of FeO-DPA-PEG-CD-TMX NPs was approximately 31 nm. By energy-dispersive X-ray spectroscopy (EDS), it was revealed that FeO constitutes 14.34% of the composition of modified MNPs. In the other words, nearly 85% of FeO-DPA-PEG-CD NPs are made of dopamine (DPA), polyethylene glycol (PEG) and β-cyclodextrin (β-CD). The TMX loaded MNPs (with entrapment efficiency of 33 mg TMX per unit CD (mg) and loading efficiency of 87.5%) showed sustained liberation of TMX molecules (with 91% release in 120 h). Cytotoxicity assay and apoptosis assay by TUNEL analysis revealed that the engineered FeO-DPA-PEG-CD-TMX NPs were able to significantly inhibit the MCF-7 breast cancer cells. According to effect of CD on TMX sustained release, it was found that CD can decrease the hepatotoxicity induced by TMX nearly 30%. Based upon these findings, we suggest the FeO-DPA-PEG-CD-TMX NPs as an effective multifunctional nanomedicine with simultaneous therapeutic and hepatoprotective effects.

摘要

疏水性药物可以作为客体分子吸附在作为主体位点的环糊精腔内。因此,形成药物 - 环糊精复合物可对药物的物理化学和生物学性质产生深远影响。基于这些优点,在本研究中,我们合成了负载他莫昔芬(TMX)的环糊精(CD)共轭磁性纳米粒子,以同时评估这种纳米药物的细胞毒性、缓释性能以及肝保护作用。FeO - DPA - PEG - CD - TMX纳米粒子的平均尺寸约为31纳米。通过能量色散X射线光谱(EDS)分析发现,FeO占改性磁性纳米粒子组成的14.34%。换句话说,近85%的FeO - DPA - PEG - CD纳米粒子由多巴胺(DPA)、聚乙二醇(PEG)和β - 环糊精(β - CD)组成。负载TMX的磁性纳米粒子(包封效率为每单位CD(毫克)含33毫克TMX,负载效率为87.5%)显示出TMX分子的持续释放(120小时内释放91%)。细胞毒性测定和TUNEL分析的凋亡测定表明,工程化的FeO - DPA - PEG - CD - TMX纳米粒子能够显著抑制MCF - 7乳腺癌细胞。根据CD对TMX缓释的影响,发现CD可将TMX诱导的肝毒性降低近30%。基于这些发现,我们认为FeO - DPA - PEG - CD - TMX纳米粒子是一种有效的多功能纳米药物,具有同时治疗和肝保护作用。

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