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Poly(γ,l-glutamic acid)–cisplatin conjugate effectively inhibits human breast tumor xenografted in nude mice

Paper ID Volume ID Publish Year Pages File Format Full-Text
11727 755 2006 8 PDF Available
Title
Poly(γ,l-glutamic acid)–cisplatin conjugate effectively inhibits human breast tumor xenografted in nude mice
Abstract

An easily administered cis-dichlorodiammineplatinum (II) (CDDP) formulation with less toxicity and greater antitumor effect would be extremely valuable. We describe PGA–CDDP, a water-soluble CDDP derivative. The hydrolyzed γ-PGA has a molecular weight between 45 and 60 kDa, and is a water-soluble, biodegradable, and nontoxic polymer produced by microbial fermentation. CDDP can be released from the resulting conjugate in PBS: there was initially a burst release during the first 6 h, followed by sustained release. In vitro, PGA–CDDP was less potent than free CDDP at inhibiting cell growth in the Bcap-37 cell line. PGA–CDDP was given as 3 doses at an equivalent CDDP dose of 4 or 12 mg/kg with 2-day intervals between injections to Bcap-37-grafted mice. This treatment showed stronger antitumor activity and was less toxic than CDDP in vivo. Antitumor activity assays demonstrated that the PGA–CDDP conjugate treatment had significantly higher antitumor activity than control PBS treatment (P<0.01P<0.01). PGA–CDDP also increased the survival of mice bearing Bcap-37 cells with reference to PBS treatment or free CDDP treatment. Furthermore, mice treated with PGA–CDDP (4 mg/kg, administered on day 0 and 5) showed no body weight loss (P>0.05P>0.05 with respect to PBS treatment), whereas free CDDP treatment at the same dose caused a body weight loss of 20–30% (P<0.001P<0.001). These findings suggest that PGA produced by microbial fermentation may be used as an effective drug carrier for CDDP and that PGA–CDDP may have potential applications in the treatment of human breast cancer.

Keywords
Cis-dichlorodiammineplatinum(II); Poly(γ-glutamic acid); Drug carriers; Antitumor efficacy
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Poly(γ,l-glutamic acid)–cisplatin conjugate effectively inhibits human breast tumor xenografted in nude mice
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 35, December 2006, Pages 5958–5965
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us