Stable and degradable microgels linked with cystine for storing and environmentally triggered release of drugs

Marcin Mackiewicz; Klaudia Kaniewska; Jan Romanski; Ewa Augustin; Zbigniew Stojek; Marcin Karbarz

doi:10.1039/c5tb00907c

Stable and degradable microgels linked with cystine for storing and environmentally triggered release of drugs

Abstract

Environmentally sensitive, degradable microgels based on poly(N-isopropylacrylamide) (pNIPA) crosslinked with the diacryloyl derivative of cystine (BISS) were synthesized by applying surfactant-free emulsion polymerization. pNIPA contributed the sensitivity to temperature to the microgels and the cross-linker made them degradable and sensitive to pH. The morphology of the microgels was investigated by using scanning and transmission electron microscopies (SEM and TEM). The gels formed spherical particles with a narrow size distribution. The influence of temperature, pH and ionic strength on the swelling behavior and the stability of new microgels with various contents of BISS (0, 1 and 3%) were investigated by dynamic light scattering (DLS). It was found that microgels with 3% content of amino acid were highly stable over a wide range of investigated temperatures, pH values and ionic strengths, including the physiological conditions (pH = 7.4, IS = 0.15 M, and 37 1C). The reductioninduced degradation of these microgels by 0.01 M solution of dithiothreitol (DTT) or glutathione (GSH) was studied by means of SEM and TEM; the obtained micrographs showed the destruction of spherical microgel particles. The microgels containing 3% of BISS could be loaded with doxorubicin (DOX) by employing the electrostatic interactions between the DOX amine group and the ionized carboxyl group from BISS. A significant increase in the cumulative release of DOX was observed after changing pH from that characteristic to blood (B7.4) to that existing in affected cells (B5.0) and in the presence of GSH (CGSH B 10 mM). The cytotoxicity tests proved that the obtained microgels are interesting as useful carriers in directed drug delivery systems.

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Authors (6)

Marcin Mackiewicz
- University of Warsaw Faculty of Chemistry
Klaudia Kaniewska
- University of Warsaw Faculty of Chemistry
Jan Romanski
- University of Warsaw Faculty of Chemistry
Ewa Augustin dr hab.
Zbigniew Stojek
- University of Warsaw Faculty of Chemistry
Marcin Karbarz
- University of Warsaw Faculty of Chemistry

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Publication version: Accepted or Published Version
DOI:: Digital Object Identifier (open in new tab) 10.1039/c5tb00907c
License: Copyright (2015 The Royal Society of Chemistry)

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Category:: Articles
Type:: artykuł w czasopiśmie wyróżnionym w JCR
Published in:: Journal of Materials Chemistry B no. 3, edition 36, pages 7262 - 7270,
ISSN: 2050-750X
Language:: English
Publication year:: 2015
Bibliographic description:: Mackiewicz M., Kaniewska K., Romanski J., Augustin E., Stojek Z., Karbarz M.: Stable and degradable microgels linked with cystine for storing and environmentally triggered release of drugs// Journal of Materials Chemistry B. -Vol. 3, iss. 36 (2015), s.7262-7270
DOI:: Digital Object Identifier (open in new tab) 10.1039/c5tb00907c
Verified by:: Gdańsk University of Technology