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

Tomalová, Barbora; Šírová, Milada; Rossmann, Pavel; Pola, Robert; Strohalm, Jiří; Chytil, Petr; Černý, Viktor; Tomala, Jakub; Kabešová, Martina; Říhová, Blanka; Ulbrich, Karel; Etrych, Tomáš; Kovář, Marek

doi:https://dx.doi.org/10.1016/j.jconrel.2015.12.023

Number of the records: 1

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

1.

SYSNO ASEP	0463915
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia
Author(s)	Tomalová, Barbora (MBU-M)_ORCID Šírová, Milada (MBU-M)_{RID, ORCID} Rossmann, Pavel (MBU-M) Pola, Robert (UMCH-V)_{RID, ORCID} Strohalm, Jiří (UMCH-V) Chytil, Petr (UMCH-V)_{RID, ORCID} Černý, Viktor (MBU-M) Tomala, Jakub (MBU-M)_{RID, ORCID} Kabešová, Martina (MBU-M)_RID Říhová, Blanka (MBU-M)_RID Ulbrich, Karel (UMCH-V)_RID Etrych, Tomáš (UMCH-V)_{RID, ORCID} Kovář, Marek (MBU-M)_{RID, ORCID}
Source Title	Journal of Controlled Release. - : Elsevier - ISSN 0168-3659 Roč. 223, 10 February (2016), s. 1-10
Number of pages	10 s.
Language	eng - English
Country	NL - Netherlands
Keywords	HPMA ; Doxorubicin ; Structure
Subject RIV	EE - Microbiology, Virology
Subject RIV - cooperation	Institute of Macromolecular Chemistry - Macromolecular Chemistry
R&D Projects	GAP301/11/0325 GA ČR - Czech Science Foundation (CSF)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013
UT WOS	000368788900001
EID SCOPUS	84961346074
DOI	10.1016/j.jconrel.2015.12.023
Annotation	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.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2017

Number of the records: 1