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Low Dose Curcumin Administered in Hyaluronic Acid-Based Nanocapsules Induces Hypotensive Effect in Hypertensive Rats

Authors Czyzynska-Cichon I, Janik-Hazuka M, Szafraniec-Szczęsny J, Jasinski K, Węglarz WP, Zapotoczny S, Chlopicki S

Received 14 November 2020

Accepted for publication 24 December 2020

Published 24 February 2021 Volume 2021:16 Pages 1377—1390

DOI https://doi.org/10.2147/IJN.S291945

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster


Izabela Czyzynska-Cichon,1,* Małgorzata Janik-Hazuka,2,* Joanna Szafraniec-Szczęsny,2,3 Krzysztof Jasinski,4 Władysław P Węglarz,4 Szczepan Zapotoczny,2 Stefan Chlopicki1,5

1Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, 30-348, Poland; 2Jagiellonian University, Faculty of Chemistry, Krakow, 30-387, Poland; 3Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Krakow, 30-688, Poland; 4Institute of Nuclear Physics Polish Academy of Sciences, Department of Magnetic Resonance Imaging, Krakow, 31-342, Poland; 5Jagiellonian University Medical College, Faculty of Medicine, Department of Pharmacology, Krakow, 31-531, Poland

*These authors contributed equally to this work

Correspondence: Stefan Chlopicki; Szczepan Zapotoczny Email stefan.chlopicki@jcet.eu; zapotocz@chemia.uj.edu.pl

Background: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules.
Methods: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic – DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP.
Results: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur – based treatment changes in SBP, DBP and MAP amounted to − 2.0± 0.8 mmHg, − 3.9± 0.7 mmHg and − 3.3± 0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration.
Conclusion: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.

Keywords: nanocapsules, hyaluronic acid, 19F NMR, curcumin, hypertension, targeted vascular delivery

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