HPMA copolymer-based polymer conjugates for the delivery and controlled release of retinoids

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00463658" target="_blank" >RIV/61389013:_____/16:00463658 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/16:00463658

Result on the web

<a href="http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S233.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S233.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

HPMA copolymer-based polymer conjugates for the delivery and controlled release of retinoids

Original language description

In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7.4) and hydrolytically degradable in mildly acidic environments (e.g. in endosomes or lysosomes, pH5.0-6.5). Polymer-AtrHy conjugates were designed to achieve prolonged blood circulation and release of the immunomodulator intracellularly or extracellularly in solid tumor tissue. Three types of polymer precursors, differing in the structure of the keto acid-containing side chains, were synthesized. A linkage susceptible to hydrolytic cleavage was formed by the conjugation reaction of the carbonyl groupterminated side chains of the polymer precursors with the hydrazide group of a drug derivative. In vitro incubation of the conjugates in buffers resulted in much faster release of the drugs or their derivatives from the polymer at pH 5.0 than at pH 7.4, with the rate depending on the detailed structure of the spacer. Both the AtrHy derivative and its polymer conjugates showed the ability to induce the differentiation of retinoid-responsive HL-60 cells, thus demonstrating the required biological activity.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

<a href="/en/project/LQ1604" target="_blank" >LQ1604: BIOCEV: from Fundamental to Applied Research</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

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Volume of the periodical

65

Issue of the periodical within the volume

Suppl. 2

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

9

Pages from-to

"S233"-"S241"

UT code for WoS article

000386686800009

EID of the result in the Scopus database

2-s2.0-84997502422