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Long circulation and cytotoxicity of PEGylated gemcitabine and its potential for the treatment of pancreatic cancer

Paper ID Volume ID Publish Year Pages File Format Full-Text
8553 597 2010 17 PDF Available
Title
Long circulation and cytotoxicity of PEGylated gemcitabine and its potential for the treatment of pancreatic cancer
Abstract

Gemcitabine [2′, 2′-difluoro-2′-deoxycytidine (dFdC)] is a low molecular weight, deoxycytidine analog inhibiting cellular DNA synthesis. Currently, it is the frontline drug approved by Food and Drug Administration (FDA) for the treatment of pancreatic cancer. However, efforts to use gemcitabine as an anti-cancer agent have been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and intracellular action. Polymer–drug conjugates, in this regard have spawned an approach to improve the cytotoxicity efficiency and bioavailability of gemcitabine by chemical modification. The present study describes the synthesis of a water soluble formulation of PEGylated gemcitabine characterized by FT IR, 1H NMR and RP-HPLC chromatography. The PEGylated gemcitabine has a prolonged circulation time in plasma as studied in an animal model. This eventually caused a marked improvement in the cytotoxicity and apoptosis-inducing activity in pancreatic cancer cell lines (MIA PaCa 2 and PANC 1). Hence, these findings demonstrate the PEGylated gemcitabine is a desirable approach for therapy by intravenous administration. Successful clinical application of this approach can significantly contribute to the treatment of pancreatic cancer.

Keywords
Gemcitabine; Pancreatic cancer; PEGylated gemcitabine; Bioavailability; Apoptosis; Cytotoxicity
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Long circulation and cytotoxicity of PEGylated gemcitabine and its potential for the treatment of pancreatic cancer
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 35, December 2010, Pages 9340–9356
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