Document Detail


Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits.
MedLine Citation:
PMID:  18778907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. MATERIALS AND METHODS: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. RESULTS: The renal parenchymal platinum concentrations (microg/ml) with 4.51+/-2.25 (day 0), 1.59+/-0.70 (day 1), 0.72+/-0.10 (day 3) and 0.20+/-0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99+/-0.55, 0.08+/-0.03, 0.18+/-0.01 and 0.10+/-0.07, respectively. Relative tumor growth rates resulted in 84.5%+/-26.4 (group I); 241.4%+/-145.1 (II); 331.9%+/-72.2 (III), and 413.6%+/-103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. CONCLUSIONS: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an increased and prolonged anti-cancer effect compared to cisplatin alone or controls. Moreover this proves indirectly the breakdown and release of cisplatin from the GMSs which is of primary importance for drug delivery systems.
Authors:
Shinichi Ohta; Norihisa Nitta; Akinaga Sonoda; Ayumi Seko; Toyohiko Tanaka; Masashi Takahashi; Shizuki Takemura; Yasuhiko Tabata; Kiyoshi Murata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-07
Journal Detail:
Title:  European journal of radiology     Volume:  72     ISSN:  1872-7727     ISO Abbreviation:  Eur J Radiol     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2010-02-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8106411     Medline TA:  Eur J Radiol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  534-40     Citation Subset:  IM    
Affiliation:
Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192, Japan. junryuhei@yahoo.co.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / administration & dosage*
Chemoembolization, Therapeutic / methods*
Cisplatin / administration & dosage*,  pharmacokinetics*
Gelatin / chemistry
Liver Neoplasms / drug therapy*,  metabolism*
Metabolic Clearance Rate
Microspheres
Rabbits
Tissue Distribution
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 15663-27-1/Cisplatin; 9000-70-8/Gelatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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