[In vivo imaging in tumor-bearing animals and pharmacokinetics of PEGylated liposomes modified with RGD cyclopeptide].
The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Liu-Xiao
LX
Tu
Yue-Hong
YH
Xu
Chen-Yi
CY
Tang
Li-He
LH
Deng
Chuan-Bin
CB
Wu
D000818:Animals; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D005260:Female; D005456:Fluorescent Dyes; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000175:diagnosis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution
D005456:Fluorescent Dyes; D008081:Liposomes; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; C120029:homocamptothecin; D002166:Camptothecin