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

Int J Nanomedicine. 2021 Feb 24:16:1377-1390. doi: 10.2147/IJN.S291945. eCollection 2021.

Abstract

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: 19F NMR; curcumin; hyaluronic acid; hypertension; nanocapsules; targeted vascular delivery.

MeSH terms

  • Administration, Oral
  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Blood Pressure / drug effects
  • Curcumin / administration & dosage*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Diastole / drug effects
  • Dose-Response Relationship, Drug
  • Fluorine / chemistry
  • Heart Rate / drug effects
  • Hyaluronic Acid / chemistry*
  • Hydrodynamics
  • Hydrophobic and Hydrophilic Interactions
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Magnetic Resonance Spectroscopy
  • Male
  • Nanocapsules / chemistry*
  • Particle Size
  • Rats
  • Static Electricity
  • Systole / drug effects

Substances

  • Nanocapsules
  • Fluorine
  • Hyaluronic Acid
  • Curcumin

Grants and funding

This work was supported by the National Science Centre (Grant No. DEC-2015/16/W/NZ4/00070) and the Ministry of Science and Higher Education of the Republic of Poland (Grant No. DI2015 015445). The open-access publication of this article was funded by the Priority Research Area BioS under the program “Excellence Initiative –Research University” at the Jagiellonian University in Krakow.