HPMA-based star polymer biomaterials with tuneable structure and biodegradability tailored for advanced drug delivery to solid tumours.


Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
03 2020
Historique:
received: 26 09 2019
revised: 27 11 2019
accepted: 22 12 2019
pubmed: 12 2 2020
medline: 15 5 2021
entrez: 12 2 2020
Statut: ppublish

Résumé

Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N-(2-hydroxypropyl)methacrylamide copolymers onto a 2,2-bis(hydroxymethyl)propionic acid (bisMPA)-based polyester dendritic core of various structures. The hydrodynamic diameter of the star copolymer biomaterials can be tuned from 13 to 31 nm and could be adjusted to a given purpose by proper selection of the bisMPA dendritic core type and generation and by considering the sL copolymer molecular weight and polymer-to-core molar ratio. The hydrolytic degradation was proved for both the star copolymers containing either dendron or dendrimer core, showing the spontaneous hydrolysis in duration of few weeks. Finally, it was shown that the therapy with the biodegradable star conjugate with attached doxorubicin strongly suppresses the tumour growth in mice and is fully curative in most of the treated animals at dose corresponding approximately to one fourth of maximum tolerated dose (MTD) value. Both new biodegradable systems show superior efficacy and tumour accumulation over the first generation of star copolymers containing non-degradable PAMAM core.

Identifiants

pubmed: 32044514
pii: S0142-9612(19)30846-4
doi: 10.1016/j.biomaterials.2019.119728
pmc: PMC7123463
mid: NIHMS1558552
pii:
doi:

Substances chimiques

Acrylamides 0
Biocompatible Materials 0
Drug Carriers 0
Methacrylates 0
Pharmaceutical Preparations 0
Polymers 0
Doxorubicin 80168379AG
N-(2-hydroxypropyl)methacrylamide R3F262Z4E0
hydroxypropyl methacrylate UKW89XAX2X

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

119728

Subventions

Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Auteurs

Libor Kostka (L)

Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic.

Lenka Kotrchová (L)

Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic.

Vladimír Šubr (V)

Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic.

Alena Libánská (A)

Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic.

Carolina A Ferreira (CA)

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States.

Iva Malátová (I)

Institute of Microbiology CAS, Laboratory of Tumour Immunology, Vídeňská 1083, 142 20 Prague 4, Czech Republic.

Hye Jin Lee (HJ)

Department of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, United States.

Todd E Barnhart (TE)

Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI, United States.

Jonathan W Engle (JW)

Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI, United States.

Weibo Cai (W)

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States; Department of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, United States; Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI, United States; University of Wisconsin, Carbone Cancer Center, Madison, WI, United States.

Milada Šírová (M)

Institute of Microbiology CAS, Laboratory of Tumour Immunology, Vídeňská 1083, 142 20 Prague 4, Czech Republic.

Tomáš Etrych (T)

Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic. Electronic address: etrych@imc.cas.cz.

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Classifications MeSH