Long-circulating gadolinium-encapsulated liposomes for potential application in tumor neutron capture therapy.
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.
Le
Uyen M
UM
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
Cui
Zhengrong
Z
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism; D017247:Neutron Capture Therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D003692:Delayed-Action Preparations; D008081:Liposomes; D019275:Radiopharmaceuticals; D011107:Polylysine; D011092:Polyethylene Glycols; D019786:Gadolinium DTPA