Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
Int J Mol Sci. 2013 Jan 29;14(2):2862-74. doi: 10.3390/ijms14022862.
In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, 99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of liposomes was enhanced by PEGylation which was not an ideal brain delivery system for crossing the blood brain barrier (BBB). With the modification of a brain-targeting ligand, lactoferrin (Lf), the PEGylated liposome (PL) might become a potential brain delivery vehicle. In order to test the hypothesis in vitro and in vivo, 99mTc-BMEDA was loaded into the liposomes as a reporter with or without Lf-conjugation. The mouse brain endothelia cell line, bEnd.3 cells, was cultured to investigate the potential uptake of liposomes in vitro. The in vivo uptake by the mouse brain of the liposomes was detected by tissue biodistribution study. The results indicated that Lf-conjugated PEGylated liposome showed more than three times better uptake efficiency in vitro and two-fold higher of brain uptake in vivo than PEGlyated liposome. With the success of loading the potential Single Photon Emission Tomography (SPECT) imaging probe, 99mTc-BMEDA, Lf-PL might serve as a promising brain delivery system for loading diagnostics or therapeutics of various brain disorders.
在这项研究中，乳铁蛋白偶联聚乙二醇化脂质体（PL）作为一种潜在的脑内递药载体，负载放射性同位素复合物 99mTc 标记的 N,N-双（2-巯基乙基）-N'，N'-二乙基亚乙基二胺（99mTc-BMEDA）进行体外和体内评价。聚乙二醇化提高了脂质体的亲水性，但它并不是穿越血脑屏障（BBB）的理想脑内递药系统。通过修饰脑靶向配体乳铁蛋白（Lf），聚乙二醇化脂质体（PL）可能成为一种有前途的脑递药载体。为了在体外和体内验证这一假说，将 99mTc-BMEDA 作为报告分子负载到脂质体中，有无 Lf 偶联。培养小鼠脑内皮细胞系 bEnd.3 细胞，以研究脂质体在体外的潜在摄取情况。通过组织生物分布研究检测脂质体在小鼠脑中的体内摄取情况。结果表明，Lf 偶联聚乙二醇化脂质体在体外的摄取效率比聚乙二醇化脂质体高 3 倍以上，体内脑摄取也高 2 倍。由于成功负载了潜在的单光子发射计算机断层扫描（SPECT）成像探针 99mTc-BMEDA，Lf-PL 可能成为一种有前途的脑内递药系统，用于装载各种脑疾病的诊断或治疗药物。
