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Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2008 Jan 04; Vol. 346 (1-2), pp. 143-50. Date of Electronic Publication: 2007 Jun 16. - Publication Year :
- 2008
-
Abstract
- Oxaliplatin (trans-L-diaminocyclohexane oxalatoplatinum, L-OHP) is a novel cisplatin derivative that can improve the side effects of cisplatin such as toxicity to the kidneys and peripheral nerve system. However, L-OHP is effective only when combined with 5-Fluorouracil (5-FU) and Leucovorin. The relatively low anti-tumor index of L-OHP alone is because low levels accumulate in tumor tissues due to high partitioning to erythrocytes in vivo. A successful outcome of cancer therapy using L-OHP requires the selective delivery of a relatively high concentration of the drug to tumors. The present study examines tumor-selective delivery of L-OHP using liposomes modified with transferrin-conjugated polyethyleneglycol (TF-PEG-liposomes). Delivery using these liposomes significantly reduced L-OHP partitioning to erythrocytes and improved the circulation time of L-OHP in vivo, resulting in enhanced extravasation of liposomes into tumors. The TF-PEG-liposomes maintained a high L-OHP concentration in tumors for over 72 h after intravenous injection, which was longer than that of the liposomes modified with PEG (PEG-liposomes). Intravenously administered L-OHP encapsulated within TF-PEG-liposomes (L-OHP: 5 mg/kg) suppressed tumor growth more effectively than PEG-liposomes, Bare-liposomes and free L-OHP. Although L-OHP is usually combined with 5-FU and Leucovorin, our results suggest that L-OHP encapsulated within TF-PEG-liposomes has potential for cancer therapy.
- Subjects :
- Animals
Antineoplastic Agents blood
Antineoplastic Agents pharmacokinetics
Antineoplastic Agents therapeutic use
Cell Line, Tumor
Erythrocytes metabolism
Kidney metabolism
Liposomes
Liver metabolism
Lung metabolism
Mice
Mice, Inbred BALB C
Neoplasms, Experimental drug therapy
Neoplasms, Experimental metabolism
Organoplatinum Compounds blood
Organoplatinum Compounds pharmacokinetics
Organoplatinum Compounds therapeutic use
Oxaliplatin
Spleen metabolism
Tissue Distribution
Antineoplastic Agents administration & dosage
Organoplatinum Compounds administration & dosage
Polyethylene Glycols chemistry
Polyethylene Glycols pharmacokinetics
Polyethylene Glycols therapeutic use
Transferrin chemistry
Transferrin pharmacokinetics
Transferrin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0378-5173
- Volume :
- 346
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 17640835
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2007.06.010