Slow release properties and liver-targeting characteristics of methotrexate erythrocyte carriers.
To study the releasing properties and tissue-targeting characteristics of methotrexate-loaded red blood cells (MTX-RBCs), pharmacokinetics and tissue distributions of intravenous injected MTX-RBCs and free MTX were compared. MTX-RBCs were made from rat erythrocytes using a hypertonic method. After i.v. injection of MTX-RBCs or free MTX to rats, both plasma and tissue homogenate samples at each time-point were collected and analyzed by RP-HPLC. From this data, pharmacokinetic parameters and tissue distributions of MTX were obtained. MTX-RBCs were successfully produced by the hypertonic method. After i.v. injection, MTX-RBCs displayed more than three times longer half-life and MRT than free MTX, and the velocity of MTX clearance from plasma was much slower. The ratio of area under the concentration time curve (AUC)(tissue) to AUC(plasma) in the liver was clearly higher than that for other organs after MTX-RBCs administration; MRT in the liver was also longer. This study has demonstrated that the hypertonic method for making MTX-RBCs has led to a preparation with slow release properties as well as liver-targeting characteristics in rats. This approach offers considerable potential for the treatment of tumors in liver, which would merit further investigation.
Yuan
Sheng-Hua
SH
Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
Ge
Wei-Hong
WH
Huo
Jing
J
Wang
Xiao-Hai
XH
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000737:chemistry*; D006207:Half-Life; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008727:Methotrexate