Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 37, Issue 3-4, Pages 405-412Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2009.03.011
Keywords
HPMA copolymer; Drug carriers; Doxorubicin; Dexamethason; Combination therapy; Anti-tumor activity; Carboxyesterase
Categories
Funding
- Academy of Sciences of the Czech Republic [KAN 200200651, IAAX 00500803]
- Agency of Academy of Sciences of the Czech Republic [IAA 400500806]
Ask authors/readers for more resources
Synthesis and physico-chemical behavior of new polymer-drug conjugates intended for the treatment of cancer were investigated. In the polymer conjugate with the expected dual therapeutic activity, two drugs, a cytostatic agent doxorubicin (DOX) and anti-inflammatory drug dexamethason (DEX) were covalently attached to the same polymer backbone via hydrolytically labile pH-sensitive hydrazone bonds. The precursor, a copolymer of N-(2-hyroxypropyl)methacrylamide (HPMA) bearing hydrazide groups randomly distributed along the polymer chain, was conjugated with DOX (through its C13 keto group) or with a keto ester (DEX). Two derivatives of DEX, 4-oxopentanoate and 4-(2-oxopropyl)benzoate esters, were synthesized and employed for conjugation reaction. As a control, also a few polymer conjugates containing only a single drug (DOX or DEX) attached to the polymer carrier were synthesized. Physicochemical properties of the polymer conjugates strongly depend on the attached drug, spacer structure and the drug content. Polymer-drug conjugates incubated in buffers modeling intracellular environment released the drug (DOX) or a drug derivatives (DEX) at the rate significantly exceeding the release rate observed under conditions mimicking Situation in the blood stream. Incubation of the DEX conjugates in a buffer containing carboxyesterase resulted in complete ester hydrolysis thus demonstrating susceptibility of the system to release free active drug in the two-step release profile. (C) 2009 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available