Micelle-forming HPMA copolymer conjugates of ritonavir bound via a pH-sensitive spacer with improved cellular uptake designed for enhanced tumor accumulation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00466223" target="_blank" >RIV/61389013:_____/16:00466223 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1039/C6TB02225A" target="_blank" >http://dx.doi.org/10.1039/C6TB02225A</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/C6TB02225A" target="_blank" >10.1039/C6TB02225A</a>

Result language

angličtina

Original language name

Micelle-forming HPMA copolymer conjugates of ritonavir bound via a pH-sensitive spacer with improved cellular uptake designed for enhanced tumor accumulation

Original language description

We describe design, synthesis, physico-chemical characterization and preliminary biological evaluation of micelle-forming polymer drug conjugates with controlled drug release intended for tumor treatment. The structure of the conjugates was designed to enable tumor tissue- and cell-specific drug release and micelle disassembly to avoid side effects accompanying classic chemotherapy and guarantee safe elimination of the drug-free carrier from the organisms. The amphiphilic polymer conjugates consisted of a hydrophobic hexaleucine block and a hydrophilic block based on the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer with an antiviral and cytostatic drug, ritonavir, bound through a pH-sensitive spacer. Diblock copolymers with low dispersity (Đ ∼ 1.1) were prepared via reversible addition-fragmentation chain transfer (RAFT) copolymerization using a hexaleucine derivative as a chain transfer agent. The associative properties of the copolymers depend on the hydrophilic polymer block length and the hydrophobic ritonavir content. The micelles dissociated under mild acidic conditions mimicking the environment inside tumor tissue/cells, because of the decrease in polymer hydrophobicity after the rapid release of the hydrophobic drug from the polymer carrier. Unexpectedly, the polymer–ritonavir conjugates internalized into HeLa cells significantly more than the polymers without ritonavir. The enhanced cell penetration and pH-triggered micelle disassembly predetermine the polymer–ritonavir conjugates to become promising tumor-targeted drug carriers.

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

CD - Macromolecular chemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

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

Journal of Materials Chemistry B

ISSN

2050-750X

e-ISSN

—

Volume of the periodical

4

Issue of the periodical within the volume

47

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

7620-7629

UT code for WoS article

000391777800012

EID of the result in the Scopus database

2-s2.0-85001022714