Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin

Alicja Karabasz , Dorota Lachowicz , Anna Karewicz , Renata Mezyk-Kopec , Krystyna Stalińska , Ewa Werner , Agnieszka Cierniak , Grzegorz Dyduch , Joanna Bereta , Monika Bzowska

Abstract

Background: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models. Method: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur. Results: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas. Conclusion: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.
Author Alicja Karabasz
Alicja Karabasz,,
-
, Dorota Lachowicz
Dorota Lachowicz,,
-
, Anna Karewicz
Anna Karewicz,,
-
, Renata Mezyk-Kopec
Renata Mezyk-Kopec,,
-
, Krystyna Stalińska
Krystyna Stalińska,,
-
, Ewa Werner (FoAS / DoARaA)
Ewa Werner,,
- Department of Animal Reproduction and Anatomy
, Agnieszka Cierniak
Agnieszka Cierniak,,
-
, Grzegorz Dyduch
Grzegorz Dyduch,,
-
, Joanna Bereta
Joanna Bereta,,
-
, Monika Bzowska
Monika Bzowska,,
-
Journal seriesInternational journal of nanomedicine, ISSN 1176-9114, e-ISSN 1178-2013, (N/A 140 pkt)
Issue year2019
Vol14
Pages7249-7262
Publication size in sheets0.65
Keywords in Englishcurcumin, alginate conjugates, in vivo toxicity, antitumor activity
ASJC Classification2700 General Medicine; 1304 Biophysics; 3002 Drug Discovery; 1502 Bioengineering; 1605 Organic Chemistry; 2502 Biomaterials
DOIDOI:10.2147/IJN.S213942
URL https://www.dovepress.com/getfile.php?fileID=52602
Languageen angielski
LicenseJournal (articles only); author's original; Uznanie Autorstwa - Użycie Niekomercyjne (CC-BY-NC); after publication
File
Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin of 09-10-2019
9,23 MB
Score (nominal)140
Score sourcejournalList
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.16; WoS Impact Factor: 2018 = 4.471 (2) - 2018=5.029 (5)
Citation count*
Additional fields
FinansowanieThis work was supported by the Grant for employees over 35 – “Program 35+” no. 35p/4/2016 to MB and The Grant for Young Researchers no. BMN 9/2018 to AK funded by the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Kraków. The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Kraków was partner of the Leading National Research Center (KNOW) supported by the Polish Ministry of Science and Higher Education.
Cite
Share Share

Get link to the record


* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
Back
Confirmation
Are you sure?