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经鼻途径给予吉西他滨和表没食子儿茶素-3-没食子酸酯负载的固体脂质纳米粒对苯并芘诱导的肺癌模型的评价:改善的药代动力学和安全性概况。

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

作者信息

Mishra Mohini, Verma Rinki, Sharma Aditya, Kumar Krishan, Chawla Ruchi

机构信息

Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India.

Department of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India.

出版信息

AAPS PharmSciTech. 2024 Jul 31;25(6):176. doi: 10.1208/s12249-024-02892-w.

Abstract

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

摘要

本研究的目的是利用负载吉西他滨(GEM)和表没食子儿茶素-3-没食子酸酯(EGCG)的固体脂质纳米粒(SLNs)开发一种可经鼻给药的肺癌新疗法。我们在苯并芘诱导的瑞士白化小鼠肺癌模型中,从粉体学、药物释放和抗癌活性方面分析了该制剂的有效性。我们还评估了GEM-EGCG SLNs的药代动力学、生物分布、生物相容性和血液相容性。GEM-EGCG SLNs的平均粒径为93.54±11.02nm,多分散指数为0.146±0.05,ζ电位为-34.7±0.4mV。GEM和EGCG的包封率分别为93.39±4.2%和89.49±5.1%,两种药物均具有缓释特性。GEM-EGCG SLNs的药代动力学比其他治疗方法更好,GEM的药物靶向指数值为17.605,EGCG为2.118,表明它们对肺部具有靶向有效性。空白SLNs在肝脏、肾脏和鼻腔区域未显示病理损伤,证实了SLNs的安全性。GEM-EGCG SLNs也比其他治疗方法显示出更少的病理损伤,溶血率更低,为1.62±0.10%。这些结果表明,GEM-EGCG SLNs可以有效治疗肺癌。

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