Degradable nanohydrogel with high doxorubicin loadings exhibiting controlled drug release and decreased toxicity against healthy cells

Ewelina Wałęka , Marcin Mackiewicz , Jan Romanski , Artur Dybko , Zbigniew Stojek , Marcin Karbarz

Abstract

A new nanogel/drug carrier of 100–150 nm size, based on poly(N-isopropylacrylamide-co-sodium acrylate) and degradable crosslinker (cystine derivative), was synthesized. Using the electrostatic interactions between the carboxylic groups in the polymer network and the protonated amine groups of doxorubicin it was possible to load the drug into the carrier to a very high level of 28–30% relative to the dry mass of the polymer. The presence of the -S-S- groups made the polymer network susceptible to degradation by glutathione. The size of the nanoparticles was small enough to enable them to easily penetrate the cells. The MTT assay indicated that compared to free doxorubicin the nanogel particles loaded with doxorubicin were more cytotoxic against the MCF-7 and A2780 cancer cells, while they were 150 times less toxic against the MCF-10A healthy cells. The new carrier nanoparticles appeared also to be useful for prolonged drug delivery.

Author Ewelina Wałęka (FC / CMB)
Ewelina Wałęka,,
- Chair of Medical Biotechnology
, Marcin Mackiewicz - [University of Warsaw, Biological and Chemical Research Centre]
Marcin Mackiewicz,,
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, Jan Romanski - [University of Warsaw, Biological and Chemical Research Centre]
Jan Romanski,,
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, Artur Dybko (FC / CMB)
Artur Dybko,,
- Chair of Medical Biotechnology
, Zbigniew Stojek - Faculty of Chemistry (WChUW) [University of Warsaw (UW)]
Zbigniew Stojek,,
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, Marcin Karbarz - [University of Warsaw, Biological and Chemical Research Centre]
Marcin Karbarz,,
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Journal seriesInternational Journal of Pharmaceutics, ISSN 0378-5173, e-ISSN 1873-3476
Issue year2020
Vol579
No119188
Pages119188_1-119188_8
Publication size in sheets0.3
ASJC Classification3003 Pharmaceutical Science
DOIDOI:10.1016/j.ijpharm.2020.119188
URL https://www.sciencedirect.com/science/article/pii/S0378517320301721
Languageen angielski
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 07-08-2020, ArticleFromJournal
Publication indicators Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.23; WoS Impact Factor: 2018 = 4.213 (2) - 2018=4.417 (5)
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