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A novel micelle-encapsulated platinum(II) anticancer agent
- Source :
- Journal of controlled release : official journal of the Controlled Release Society. 147(1)
- Publication Year :
- 2010
-
Abstract
- A hydrophobic and water-insoluble platinum(II) compound, cis -(cha) 2 Pt(NO 3 ) 2 was encapsulated by macromolecular micelles self-assembled from an amphiphilic cyclotriphosphazene [NP(MPEG750)(GlyPheLeu) 2 Et] 3 (CP750). The micelle-encapsulated platinum(II) compound exhibited outstanding pharmacokinetics in rats by showing long blood circulation and much larger systemic exposure (AUC = 43.5 μg h/ml) compared with the free carboplatin (AUC = 4.32 μg h/ml). Biodistribution study of the micellar platinum(II) compound using male Sprague–Dawley rats has shown excellent tumor to tissue ratios of 4.03 at 2 h post injection and 4.67 at 24 h post injection. Furthermore, the micellar platinum(II) compound exhibited more than 6 times higher cellular uptake in human cervical (HeLa) and lung (A549) tumor cells compared with the free platinum compound. Also it is surprising that the micellar platinum(II) compound displayed specifically high cytotoxicity against the stomach tumor cells (SNU638), which are one of the least responsive to chemotherapeutic agents currently in clinical use. The acute toxicity study has shown that the LD 50 values of free and the micellar cis -(cha) 2 Pt(NO 3 ) 2 are approximately 70 mg/kg and 90 mg/kg, respectively. Thus the platinum compound encapsulated by cyclotriphosphazene micelles is a promising candidate for preclinical studies.
- Subjects :
- Male
Biodistribution
Organoplatinum Compounds
Stereochemistry
Cell Survival
Melanoma, Experimental
Pharmaceutical Science
chemistry.chemical_element
Biological Availability
Antineoplastic Agents
Micelle
HeLa
Lethal Dose 50
Rats, Sprague-Dawley
chemistry.chemical_compound
Mice
Cell Line, Tumor
Amphiphile
Animals
Humans
Tissue Distribution
Cytotoxicity
Micelles
Drug Carriers
biology
Chemistry
biology.organism_classification
Carboplatin
Rats
Mice, Inbred C57BL
Platinum Compound
Platinum
Hydrophobic and Hydrophilic Interactions
Nuclear chemistry
Subjects
Details
- ISSN :
- 18734995
- Volume :
- 147
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Accession number :
- edsair.doi.dedup.....877fcebafde2f5c4368e33467144cd4d