口服聚乙二醇修饰固体脂质纳米粒的组织分布及抗肿瘤药效学研究

发布时间：2018-01-11 15:13

本文关键词：口服聚乙二醇修饰固体脂质纳米粒的组织分布及抗肿瘤药效学研究　出处：《中国现代应用药学》2016年05期 　论文类型：期刊论文

【摘要】：目的研究口服固体脂质纳米粒(solid lipid nanoparticle,SLN)和经聚乙二醇(polyethylene glycol,PEG)修饰后的SLN(p SLN)在小鼠体内的组织分布及药效。方法采用水性溶剂扩散法制备SLN,用聚乙二醇单硬脂酸酯(PEG2000-SA)修饰以提供亲水基团;测定其粒径、Zeta电位、表面元素、接触角和稳定性;以Di R为荧光标记物,测定SLN及p SLN制剂经口服给药后的体内组织分布;以阿霉素为模型药物,考察口服脂质纳米给药系统的体内抗肿瘤活性及安全性。结果SLN经PEG修饰后,得到的p SLN制剂粒径降低,Zeta电位约为?20 m V,表面亲水性及体内稳定性增加;经口服给药后,p SLN在肿瘤组织有聚集,且经PEG修饰后的纳米粒在组织中的滞留时间可显著延长;在荷瘤裸鼠模型动物上的药效学结果显示,PEG修饰口服脂质纳米给药系统在改善药效的同时,降低药物的不良反应,提高给药系统的安全性。结论 PEG修饰改善了口服纳米给药系统的生物分布及药效,提高了给药系统的安全性。
[Abstract]:Objective to study the effects of oral solid lipid nanoparticles solid lipid nanoparticlein (SLN) and polyethylene glycol polyethylene (glycol). The tissue distribution and pharmacodynamics of SLN(p modified by peg in mice were studied. Methods SLN was prepared by aqueous solvent diffusion method. Polyethylene glycol monostearate (PEG2000-SAA) was modified to provide hydrophilic groups; The particle size, Zeta potential, surface elements, contact angle and stability were determined. Using Di R as fluorescent marker, the tissue distribution of SLN and p SLN were determined after oral administration. The antitumor activity and safety of oral lipid nano-delivery system were investigated with adriamycin as model drug. Results the particle size of SLN modified with PEG decreased. The Zeta potential is about? The surface hydrophilicity and internal stability increased with 20 MV. After oral administration, SLN accumulated in tumor tissues, and the retention time of PEG modified nanoparticles in tumor tissues was significantly prolonged. The results of pharmacodynamics in nude mice showed that PEG-modified oral lipid nano-delivery system not only improved the drug efficacy, but also decreased the adverse drug reactions. Conclusion PEG modification can improve the biological distribution and efficacy of oral nano-drug delivery system and improve the safety of drug delivery system.
【作者单位】：宁波市第一医院;浙江大学;
【基金】：宁波市自然基金项目(2014A610216)
【分类号】：R943;R965
【正文快照】： 固体脂质纳米粒(solid lipid nanoparticle,SLN)是继传统的乳剂、脂质体、聚合物微粒后,近年来研究较活跃的一种缓控释靶向微粒给药统[1-2]。SLN的口服给药方式因方便、快捷、患者适应性强,已成为研究热点[3]。但SLN比表面积大,进入血液循环系统后,易受网状内皮系统吞噬作用的

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