本文關(guān)鍵詞： 脂質(zhì)體 穿膜肽 血腦屏障 腦腫瘤　出處：《藥學(xué)學(xué)報(bào)》2015年01期 　論文類型：期刊論文

【摘要】：本文旨在制備T7肽和穿膜肽TAT雙修飾的脂質(zhì)體(T7 and TAT dual modified liposomes,T7-TAT-LIP)用于血腦屏障和腦腫瘤細(xì)胞雙級(jí)靶向藥物遞送。研究以CFPE為熒光探針,T7修飾的PEG-DSPE、TAT修飾的PEG-DSPE、卵磷脂、PEG-DSPE和膽固醇為材料,采用成膜水化法制備脂質(zhì)體,對(duì)T7濃度、TAT濃度、連接T7和TAT的PEG長度進(jìn)行優(yōu)化,表征其粒徑、zeta電位、形態(tài)和穩(wěn)定性。以b End.3細(xì)胞和C6細(xì)胞為模型,考察T7-TAT-LIP的細(xì)胞攝取能力,表征其穿過血腦屏障和腦腫瘤細(xì)胞靶向能力。結(jié)果表明,T7用量為脂質(zhì)的6%、修飾T7所用PEG鏈長為2000、TAT用量為脂質(zhì)的0.5%、修飾TAT所用PEG鏈長為1000時(shí)所得到的雙修飾脂質(zhì)體被C6細(xì)胞攝取能力最強(qiáng)。優(yōu)化后T7-TAT-LIP粒徑為118 nm,zeta電位為-6.32 m V,透射電鏡下形態(tài)圓整。脂質(zhì)體在PBS中較為穩(wěn)定,37℃放置24 h,濁度和粒徑無明顯變化;4~8℃放置1個(gè)月,粒徑和PDI無明顯變化。在不同時(shí)間點(diǎn),b End.3和C6細(xì)胞攝取T7-TAT-LIP的強(qiáng)度均高于單配體修飾脂質(zhì)體,且隨著孵育時(shí)間提高,攝取濃度逐漸提高。這些結(jié)果說明,雙修飾脂質(zhì)體具有血腦屏障和腦腫瘤細(xì)胞雙級(jí)靶向能力,且效果優(yōu)于單配體修飾脂質(zhì)體。
[Abstract]:The aim of this study was to prepare T7 and TAT dual modified liposomes (T7 and dual modified liposomes) modified by T7 peptide and transmembrane peptide TAT. T7-TAT-LIPs were used for the delivery of dual-level targeted drugs in blood-brain barrier and brain tumor cells. The PEG-DSPE modified with CFPE as fluorescence probe was studied. TAT modified PEG-DSPE, phosphatidylcholine PEG-DSPE and cholesterol were used to prepare liposomes by membrane hydration. The length of PEG connecting T7 and TAT was optimized to characterize the particle size, morphology and stability of T7 and TAT. The model was b End.3 cells and C6 cells. The cell uptake ability of T7-TAT-LIP was investigated, and the targeting ability of T7-TAT-LIP through the blood-brain barrier and brain tumor cells was characterized. The results showed that the dosage of T7-TAT-LIP was 6% of lipid. The PEG chain length of modified T7 was 0.5% of that of lipid. When the PEG chain length of modified TAT was 1000, the double modified liposomes were the most capable of uptake by C6 cells. The optimized T7-TAT-LIP particle size was 118nm. The zeta potential was -6.32 MV, and the morphology of liposomes was round under transmission electron microscope. The turbidity and particle size of liposomes remained stable at 37 鈩，

本文編號(hào)：1442931