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The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates
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SYSNO ASEP 0463652 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates Author(s) Pola, Robert (UMCH-V) RID, ORCID
Janoušková, Olga (UMCH-V) RID, SAI, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCIDSource Title Physiological Research. - : Fyziologický ústav AV ČR, v. v. i. - ISSN 0862-8408
Roč. 65, Suppl. 2 (2016), S225-S232Number of pages 8 s. Language eng - English Country CZ - Czech Republic Keywords HPMA copolymers ; drug delivery system ; nucleoside analogues Subject RIV CD - Macromolecular Chemistry R&D Projects LO1507 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMCH-V - RVO:61389013 UT WOS 000386686800008 EID SCOPUS 84997419203 Annotation Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropanoyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl-phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and beta-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2017 Electronic address http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S225.pdf
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