Biodistribution and pharmacokinetics of 111In-dTPA-labelled pegylated liposomes after intraperitoneal injection.
The biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated liposomes (IDLPL) and unencapsulated 111In-DTPA administered by the intraperitoneal (i.p.) and i.v. routes in non-tumour-bearing mice were compared. Mice received i.p. or i.v. injections of 0.37 MBq 111In-DTPA either encapsulated in liposomes or as an unencapsulated agent. A variety of tissues were dissected from 5 min to 192 h to determine the biodistribution and pharmacokinetics. Injection of IDLPL via the i.p. route caused a 74-fold increase in the area under the concentration (AUC) versus time curve in the peritoneum compared to unencapsulated 111In-DTPA. Similarly, the AUC for all the intra-abdominal tissues was increased significantly (20-427-fold). When i.p. IDLPLs were compared directly with i.v. IDLPLs, more modest changes were seen. There were increases in AUC for peritoneum (1.4-fold), ovary (1.3-fold), stomach (2.9-fold), pancreas (3.6-fold). small intestine (1.5-fold). colon (1.2-fold), gallbladder (5.1-fold) and adrenal gland (2.1-fold). These data support the development of i.p. liposomal chemotherapy for the treatment of intraperitoneal malignant disease.
Syrigos
Konstantinos N
KN
Cancer Research UK Targeted Therapy Laboratory, Centre for Cell and Molecular Biology, Institute of Cancer Research, London, UK.
Vile
Richard G
RG
Peters
A Michael
AM
Harrington
Kevin J
KJ
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005704:Gallbladder / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D010053:Ovary / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D004369:Pentetic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010537:Peritoneum / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014018:Tissue Distribution
D004337:Drug Carriers; D007205:Indium Radioisotopes; D008081:Liposomes; D004369:Pentetic Acid