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用于姜黄素药物释放的聚(ε-己内酯)共轭聚氧乙烯脱水山梨醇油酸酯基胶束的合成与开发:对乳腺癌细胞的一项研究

The synthesis and development of poly(ε-caprolactone) conjugated polyoxyethylene sorbitan oleate-based micelles for curcumin drug release: an study on breast cancer cells.

作者信息

Shadmani Nasim, Gohari Sepehr, Kadkhodamanesh Azin, Ghaderinia Parivash, Hassani Maryam, Sharifyrad Motahare

机构信息

Trita Nanomedicine Research & Technology Development Center (TNRTC) Zanjan Health Technology Park Zanjan Iran.

Student Research Center, School of Medicine, Zanjan University of Medical Sciences Zanjan Iran.

出版信息

RSC Adv. 2023 Aug 4;13(34):23449-23460. doi: 10.1039/d3ra03660j.

Abstract

BACKGROUND

it is now known that curcumin (Cur) has a broad range of biological properties; however, photosensitivity, as well as low bioavailability and short half-life, have limited its clinical application. To overcome these problems the synthesis of poly(ε-caprolactone)-Tween 80 (PCL-T) copolymers was performed.

METHODS

the copolymers of PCL-T were created using the solvent evaporation/extraction technique. Then Cur was loaded in PCL-T micelles (PCL-T-M) by a self-assembly method. The characterization of copolymer and micelles was assessed by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (HNMR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and dynamic light scattering (DLS) methods. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to indicate the cytotoxicity of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M.

RESULTS

TEM analysis showed monodispersed and spherical shapes with a size of about 90 nm. Cur was released from PCL-T-M at pH 7.4 (45%) and 5.5 (90%) during 6 days. After 24 and 48 h, the IC50 of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M on MCF-7 cells were 80.86 and 54.45 μg mL, 278.30 and 236.19 μg mL, 45.47 and 19.05 μg mL, respectively.

CONCLUSION

this study showed that, in the same concentration, the effectiveness of the Cur-loaded PCL-T-M is more than the free Cur, and the nano-system has been able to overcome delivery obstacles of Cur drug. Thus, PCL-T-M can be a candidate as a drug carrier for the delivery of Cur and future therapeutic investigations on breast cancer.

摘要

背景

现已知道姜黄素(Cur)具有广泛的生物学特性;然而,光敏感性以及低生物利用度和短半衰期限制了其临床应用。为克服这些问题,进行了聚(ε-己内酯)-吐温80(PCL-T)共聚物的合成。

方法

采用溶剂蒸发/萃取技术制备PCL-T共聚物。然后通过自组装方法将Cur负载于PCL-T胶束(PCL-T-M)中。通过凝胶渗透色谱法(GPC)、傅里叶变换红外光谱法(FT-IR)、质子核磁共振光谱法(HNMR)、差示扫描量热法(DSC)、透射电子显微镜法(TEM)和动态光散射法(DLS)对共聚物和胶束进行表征。采用MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐] 法检测游离Cur、PCL-T-M和负载Cur的PCL-T-M的细胞毒性。

结果

TEM分析显示其呈单分散球形,大小约为90 nm。在6天内,Cur在pH 7.4时从PCL-T-M中释放45%,在pH 5.5时释放90%。24小时和48小时后,游离Cur、PCL-T-M和负载Cur的PCL-T-M对MCF-7细胞的IC50分别为80.86和54.45 μg/mL、278.30和236.19 μg/mL、45.47和19.05 μg/mL。

结论

本研究表明,在相同浓度下,负载Cur的PCL-T-M的有效性高于游离Cur,且该纳米系统能够克服Cur药物的递送障碍。因此,PCL-T-M可作为Cur递送的药物载体以及未来乳腺癌治疗研究的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ad/10401665/da9019ed18b6/d3ra03660j-f1.jpg

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