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载厄洛替尼纳米结构脂质载体与脂质体对A549肺癌细胞系的比较评价

Comparative of Evaluation between Erlotinib Loaded Nanostructured Lipid Carriers and Liposomes against A549 Lung Cancer Cell Line.

作者信息

Abedi Gaballu Fereydoon, Abbaspour-Ravasjani Soheil, Mansoori Behzad, Yekta Reza, Hamishehkar Hamed, Mohammadi Ali, Dehghan Gholamreza, Shokouhi Behrooz, Ghahremani Dehbokri Shaho, Baradaran Behzad

机构信息

Immounology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Iran J Pharm Res. 2019 Summer;18(3):1168-1179. doi: 10.22037/ijpr.2019.1100775.

Abstract

Erlotinib (ELT) as a small molecule with poor solubility, poor bioavailability, and instability in gastrointestinal environment, has been considered as a therapeutic agent for Non-Small-Cell Lung Cancer (NSCLC) therapy through oral administration. In the present study, ELT-liposome and ELT-NLCs were successfully prepared and characterized by assessment of the particle size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (EE), and drug loading (DL). DAPI staining and Flow cytometry techniques were employed to probe anticancer activities of the optimal formulations. The obtained results indicated that the average size of optimized ELT-NLCs was 109 ± 2 nm, while the optimal formulation of ELT-liposome was 130 ± 4 nm. In addition, the values of EE, DL, and cellular uptake were higher in ELT-NLCs than ELT-liposome. Moreover, the stability of ELT-NLCs and ELT-liposome were not significantly changed ( > 0.05) within storage time. The results of anti-cancer assessment indicated that ELT-NLCs caused more cell viability reduction than ELT-liposome and free ELT. According to the Flow cytometry and DAPI staining results, the exposed A549 cells with ELT-NLCs had more rates of apoptosis than ELT-liposome. The obtained data from this study clearly showed that ELT-NLCs had better anti-cancer activity than ELT-liposome, which may be related to the effective nano particle size, PDI, EE, and DL of ELT-NLCs.

摘要

厄洛替尼(ELT)作为一种小分子,具有溶解度差、生物利用度低以及在胃肠道环境中不稳定的特点,一直被视为通过口服给药治疗非小细胞肺癌(NSCLC)的治疗剂。在本研究中,成功制备了ELT脂质体和ELT纳米脂质载体,并通过评估粒径、zeta电位(ZP)、多分散指数(PDI)、包封率(EE)和载药量(DL)对其进行了表征。采用DAPI染色和流式细胞术技术探究最佳制剂的抗癌活性。所得结果表明,优化后的ELT纳米脂质载体的平均粒径为109±2nm,而ELT脂质体的最佳制剂为130±4nm。此外,ELT纳米脂质载体的EE、DL和细胞摄取值均高于ELT脂质体。而且,ELT纳米脂质载体和ELT脂质体在储存时间内的稳定性没有显著变化(>0.05)。抗癌评估结果表明,ELT纳米脂质载体比ELT脂质体和游离ELT导致更多的细胞活力降低。根据流式细胞术和DAPI染色结果,用ELT纳米脂质载体处理的A549细胞的凋亡率高于ELT脂质体。本研究获得的数据清楚地表明,ELT纳米脂质载体比ELT脂质体具有更好的抗癌活性,这可能与ELT纳米脂质载体有效的纳米粒径、PDI、EE和DL有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac90/6934956/b166d4a0aed1/ijpr-18-1168-g001.jpg

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