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Self-assembled hyaluronic acid-testosterone nanocarriers for delivery of anticancer drugs
Johannes Kepler Univ Linz, Inst Polymer Chem, Altenberger Str 69, A-4040 Linz, Austria..
Univ Turku, Dept Biochem, Vatselankatu 2, SF-20500 Turku, Finland..
Univ Turku, Dept Biochem, Vatselankatu 2, SF-20500 Turku, Finland..
Univ Havana, Ctr Biomat, Ave Univ S-N Entre G & Ronda, Havana 10400, Cuba..
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2018 (English)In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 99, p. 384-393Article in journal (Refereed) Published
Abstract [en]

The present research aims at controlled delivery of anticancer drugs camptothecin and doxorubicin through encapsulation in self-assembled hyaluronic acid (HA)-testosterone conjugates. The conjugates were obtained by functionalization of either natural sodium hyaluronate or hydrazide-modified HA derivatives with testosterone hemisuccinate. From 2.0 to 7.7% of HA disaccharide units were linked to testosterone via two types of linkers of different length. Fourier transform infrared and proton nuclear magnetic resonance spectroscopies confirmed modification of HA. Conjugation of hydrophobic testosterone to hydrophilic backbone of HA resulted in the self assembly of amphiphilic HA-testosterone conjugates in aqueous medium and the formation of stable and negatively charged nanoparticles with hydrodynamic diameter ranging from 172 to 380 nm and.-potential ranging from - 37 to - 26 mV, as evidenced from dynamic light scattering measurements. Examination of the dried conjugates by transmission electron microscopy revealed almost spherical particles of 50-100 nm size. Entrapment of camptothecin and doxorubicin in the hydrophobic core of HA -testosterone nanoparticles was performed with the drugs content of ca. 2.8 wt% and 3.5 wt% respectively. The sustained release of the anticancer drugs over 96 h was observed in phosphate buffered saline at pH 7.4. Cytotoxicity of camptothecin- and doxorubicin-loaded HA -testosterone nanoparticles against MCF-7 cancer cell line was found to be similar to the cytotoxicity of the free anticancer drugs. Based on the results of the in vitro studies, we can conclude that the developed HA -testosterone nanoparticles are promising candidates in chemotherapy treatments of cancers.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD , 2018. Vol. 99, p. 384-393
Keywords [en]
Hyaluronic acid, Testosterone, Anticancer drugs, Self-assembled nanoparticles, Sustained release
National Category
Polymer Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-351026DOI: 10.1016/j.eurpolymj.2017.12.043ISI: 000427338100040OAI: oai:DiVA.org:uu-351026DiVA, id: diva2:1208726
Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2018-05-18Bibliographically approved

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Ossipov, Dmitri

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