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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。
Objective To study the tissue distribution and pharmacodynamics of oral solid lipid nanoparticle (SLN) and polyethylene glycol (PEG) modified SLN (p SLN) in mice. Methods SLN was prepared by aqueous solvent diffusion method and modified with polyethylene glycol monostearate (PEG2000-SA) to provide hydrophilic groups. The particle size, Zeta potential, surface element, contact angle and stability were determined by Di R is a fluorescent marker to determine the in vivo tissue distribution of SLN and pSLN preparations after oral administration. Adriamycin was used as a model drug to investigate the in vivo anti-tumor activity and safety of the oral lipid nano-drug delivery system. Results After SLN was modified by PEG, the particle size of pSLN preparation was decreased, the zeta potential was about 20 mV, the surface hydrophilicity and the stability in vivo were increased. After oral administration, pSLN accumulated in the tumor tissue, and PEG-modified nanoparticles in the tissue retention time can be significantly prolonged; in nude mice bearing tumor model of pharmacodynamics results show that PEG-modified oral lipid nano-drug delivery system to improve efficacy while reducing the drug Adverse reactions, improve the safety of the drug delivery system. Conclusion PEG modification improves the biodistribution and pharmacodynamics of oral nano-drug delivery system and improves the safety of drug delivery system.