Le Uyen M, Cui Zhengrong
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
Int J Pharm. 2006 Apr 7;312(1-2):105-12. doi: 10.1016/j.ijpharm.2006.01.002. Epub 2006 Feb 2.
Gadolinium neutron capture therapy (Gd-NCT) is a promising cancer therapy modality. One of the key factors for a successful Gd-NCT is to deliver and maintain a sufficient amount of Gd in tumor tissues during neutron irradiation. We proposed to prepare a Gd delivery system by complexing a Gd-containing compound, diethylenetriaminepentaacetic acid (Gd-DTPA), with a polycationic peptide, poly-L-lysine (pLL), and then encapsulate the complexed Gd-DTPA into PEGylated liposomes. Complexation of Gd-DTPA with pLL not only enhanced the encapsulation efficiency of Gd-DTPA in liposomes, but also significantly limited the release of Gd-DTPA from the liposomes. A Gd-DTPA-encapsulated liposome formulation that contained 6.8+/-0.3 mg/mL of pure encapsulated Gd was prepared. The blood half-life of the Gd encapsulated into the liposome formulation was estimated to be about 24 h in healthy tumor-free mice. About 12 h after the Gd-encapsulated liposomes were intravenously injected into mice with pre-established model tumors, the Gd content in the tumors reached an average of 159 microg/g of wet tumor tissue. This Gd-DTPA encapsulated liposome may be used to deliver Gd into solid tumors for NCT and tumor imaging.
钆中子俘获疗法（Gd-NCT）是一种很有前景的癌症治疗方式。成功进行Gd-NCT的关键因素之一是在中子辐照期间在肿瘤组织中递送并维持足够量的钆。我们提议通过将含钆化合物二乙烯三胺五乙酸（Gd-DTPA）与聚阳离子肽聚-L-赖氨酸（pLL）络合来制备钆递送系统，然后将络合后的Gd-DTPA包封到聚乙二醇化脂质体中。Gd-DTPA与pLL的络合不仅提高了Gd-DTPA在脂质体中的包封效率，还显著限制了Gd-DTPA从脂质体中的释放。制备了一种包封有Gd-DTPA的脂质体制剂，其中纯包封的钆含量为6.8±0.3mg/mL。在健康无肿瘤的小鼠中，包封在脂质体制剂中的钆的血液半衰期估计约为24小时。将包封有钆的脂质体静脉注射到预先建立模型肿瘤的小鼠中约12小时后，肿瘤中的钆含量平均达到159μg/g湿肿瘤组织。这种包封有Gd-DTPA的脂质体可用于将钆递送至实体瘤以进行中子俘获疗法和肿瘤成像。
