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HPMA-based star polymer biomaterials with tuneable structure and biodegradability tailored for advanced drug delivery to solid tumours
L. Kostka, L. Kotrchová, V. Šubr, A. Libánská, CA. Ferreira, I. Malátová, HJ. Lee, TE. Barnhart, JW. Engle, W. Cai, M. Šírová, T. Etrych
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P30 CA014520
NCI NIH HHS - United States
NV16-28600A
MZ0
CEP - Centrální evidence projektů
- MeSH
- akrylamidy MeSH
- biokompatibilní materiály * MeSH
- doxorubicin MeSH
- léčivé přípravky * MeSH
- methakryláty MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků MeSH
- polymery MeSH
- systémy cílené aplikace léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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.
Department of Biomedical Engineering University of Wisconsin Madison Madison WI United States
Department of Pharmaceutical Sciences University of Wisconsin Madison Madison WI United States
University of Wisconsin Carbone Cancer Center Madison WI United States
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- $a Kostka, Libor $u Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic
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- $a 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.
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- $a Kotrchová, Lenka $u Institute of Macromolecular Chemistry CAS, Department of Biomedical Polymers, Heyrovského Nám. 2, 162 06 Prague 6, Czech Republic
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- $a Lee, Hye Jin $u Department of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, United States
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- $a Barnhart, Todd E $u Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI, United States
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- $a Cai, Weibo $u 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
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- $a Etrych, Tomáš $u 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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