The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00463915" target="_blank" >RIV/61389013:_____/16:00463915 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/16:00463915

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.jconrel.2015.12.023" target="_blank" >http://dx.doi.org/10.1016/j.jconrel.2015.12.023</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2015.12.023" target="_blank" >10.1016/j.jconrel.2015.12.023</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia

Popis výsledku v původním jazyce

Polymer drug carriers that are based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (M-w similar to 27 kDa, Rh similar to 4 nm) and non-degradable star (M-w similar to 250 kDa, R-h similar to 13 nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85 mg DOX/kg) and lower for the star conjugate (22.5 mg DOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate.

Název v anglickém jazyce

The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia

Popis výsledku anglicky

Polymer drug carriers that are based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (M-w similar to 27 kDa, Rh similar to 4 nm) and non-degradable star (M-w similar to 250 kDa, R-h similar to 13 nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85 mg DOX/kg) and lower for the star conjugate (22.5 mg DOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CD - Makromolekulární chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Journal of Controlled Release

ISSN

0168-3659

e-ISSN

—

Svazek periodika

223

Číslo periodika v rámci svazku

10 February

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

1-10

Kód UT WoS článku

000368788900001

EID výsledku v databázi Scopus

2-s2.0-84961346074