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Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers

Paper ID Volume ID Publish Year Pages File Format Full-Text
10304 678 2009 10 PDF Available
Title
Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers
Abstract

Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. To demonstrate that polymers, as liposomes, can be used for simultaneously delivering multiple chemotherapeutic agents to tumors in vivo, we have synthesized and evaluated an HPMA-based polymer–drug conjugate carrying 6.4 wt% of gemcitabine, 5.7 wt% of doxorubicin and 1.0 mol% of tyrosinamide (to allow for radiolabeling). The resulting construct, i.e. poly(HPMA-co-MA-GFLG-gemcitabine-co-MA-GFLG-doxorubicin-co-MA-TyrNH2), was termed P-Gem-Dox, and was shown to effectively kill cancer cells in vitro, to circulate for prolonged period of time, to localize to tumors relatively selectively, and to inhibit tumor growth. As compared to control regimens, P-Gem-Dox increased the efficacy of the combination of gemcitabine and doxorubicin without increasing its toxicity, and it more strongly inhibited angiogenesis and induced apoptosis. These findings demonstrate that passively tumor-targeted polymeric drug carriers can be used for delivering two different chemotherapeutic agents to tumors simultaneously, and they thereby set the stage for more elaborate analyses on the potential of polymer-based multi-drug targeting.

Keywords
Chemotherapy; Copolymer; Drug delivery; Gamma irradiation; In vivo test
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Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 20, July 2009, Pages 3466–3475
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