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

Title:

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

Creator:

Lidický, O., Milada Šírová, and Tomáš Etrych

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:3f9bfbd2-eb41-4c3e-bf98-e8803275a5b0
uuid:3f9bfbd2-eb41-4c3e-bf98-e8803275a5b0
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, retinoidy, retinoids, polymer conjugate, HPMA, controlled release, myeloid-derived suppressor cells, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

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, pH~5.0-6.5). 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., O. Lidický, M. Šírová, T. Etrych., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2016 Volume:65 | Number:Suppl 2

Harvested from:

CDK

Metadata only:

false