不同链长聚乙二醇修饰的香豆素6脂质纳米粒对口服吸收的影响

Effects of polyethylene glycol length on oral absorption of coumarin 6-loaded nanostructured lipid carrier

通过制备不同链长聚乙二醇(PEG)修饰的纳米脂质载体(NLCs)考察PEG链长对其口服吸收的影响。使用聚乙二醇(100)单硬脂酸酯(S100)、聚乙二醇(55)单硬脂酸酯(S55)、聚乙二醇(40)单硬脂酸酯(S40)3种不同链长的PEG通过薄膜分散法制备NLCs,以香豆素6(coumarin 6)作为荧光探针,对修饰不同链长PEG的NLCs进行理化性质表征。考察了不同链长PEG修饰的NLCs在模拟缓冲液中的稳定性以及体外释药行为。同时对NLCs的细胞毒性、细胞摄取动力学以及摄取机制进行了考察。结果表明,随着PEG链段长度的增加,其水化层厚度不断增大。与其他NLCs相比,S100修饰的NLCs(pNLC-EG100)具有更好的细胞摄取效率,证明S100的链段长度是用于口服NLCs给药的最佳长度。

Polyethylene glycol(PEG)of different lengths were prepared to investigate their effects on oralabsorption of nanostructured lipid carrier(NLCs).Three kinds of PEG-modified NLCs with different chainlengths,including polyethylene glycol(100)monostearate(S100),polyethylene glycol(55)monostearate(S55),polyethylene glycol(40)monostearate(S40),were prepared by film dispersion method.Coumarin 6 was chosen asa fluorescent probe to characterize the physicochemical properties of NLCs with different lengths.Meanwhile,thestability of NLCs in simulate buffer,the release behavior,cytotoxicity of NLCs,the uptake kinetics and cellularuptake mechanisms were evaluated.This work demonstrated that the thickness of the hydrated layer increasedwith the increase of PEG length.Of note,S100-modified NLCs(p NLC-EG100)exhibited higher cellular uptakeefficiency compared with other formulations.Thus,S100 was optimized as the best molecular weight for PEGmodified NLCs on oral drug delivery system.