Skip to main content
Journal cover image

Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension.

Publication ,  Journal Article
Lee, Y; Pai, SB; Bellamkonda, RV; Thompson, DH; Singh, J
Published in: The Journal of pharmacology and experimental therapeutics
July 2018

In this study we investigated nanoliposome as an approach to tailoring the pharmacology of cerivastatin as a disease-modifying drug for pulmonary arterial hypertension (PAH). Cerivastatin encapsulated liposomes with an average diameter of 98 ± 27 nm were generated by a thin film and freeze-thaw process. The nanoliposomes demonstrated sustained drug-release kinetics in vitro and inhibited proliferation of pulmonary artery (PA) smooth muscle cells with significantly less cellular cytotoxicity as compared with free cerivastatin. When delivered by inhalation to a rat model of monocrotaline-induced PAH, cerivastatin significantly reduced PA pressure from 55.13 ± 9.82 to 35.56 ± 6.59 mm Hg (P < 0.001) and diminished PA wall thickening. Echocardiography showed that cerivastatin significantly reduced right ventricle thickening (monocrotaline: 0.34 ± 0.02 cm vs. cerivastatin: 0.26 ± 0.02 cm; P < 0.001) and increased PA acceleration time (monocrotaline: 13.98 ± 1.14 milliseconds vs. cerivastatin: 21.07 ± 2.80 milliseconds; P < 0.001). Nanoliposomal cerivastatin was equally effective or slightly better than cerivastatin in reducing PA pressure (monocrotaline: 67.06 ± 13.64 mm Hg; cerivastatin: 46.31 ± 7.64 mm Hg vs. liposomal cerivastatin: 37.32 ± 9.50 mm Hg) and improving parameters of right ventricular function as measured by increasing PA acceleration time (monocrotaline: 24.68 ± 3.92 milliseconds; cerivastatin: 32.59 ± 6.10 milliseconds vs. liposomal cerivastatin: 34.96 ± 7.51 milliseconds). More importantly, the rate and magnitude of toxic cerivastatin metabolite lactone generation from the intratracheally administered nanoliposomes was significantly lower as compared with intravenously administered free cerivastatin. These studies show that nanoliposome encapsulation improved in vitro and in vivo pharmacologic and safety profile of cerivastatin and may represent a safer approach as a disease-modifying therapy for PAH.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

The Journal of pharmacology and experimental therapeutics

DOI

EISSN

1521-0103

ISSN

0022-3565

Publication Date

July 2018

Volume

366

Issue

1

Start / End Page

66 / 74

Related Subject Headings

  • Safety
  • Rats
  • Pyridines
  • Pharmacology & Pharmacy
  • Nanostructures
  • Liposomes
  • Lactones
  • Hypertension, Pulmonary
  • Humans
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lee, Y., Pai, S. B., Bellamkonda, R. V., Thompson, D. H., & Singh, J. (2018). Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension. The Journal of Pharmacology and Experimental Therapeutics, 366(1), 66–74. https://doi.org/10.1124/jpet.118.247643
Lee, Young, S Balakrishna Pai, Ravi V. Bellamkonda, David H. Thompson, and Jaipal Singh. “Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension.The Journal of Pharmacology and Experimental Therapeutics 366, no. 1 (July 2018): 66–74. https://doi.org/10.1124/jpet.118.247643.
Lee Y, Pai SB, Bellamkonda RV, Thompson DH, Singh J. Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension. The Journal of pharmacology and experimental therapeutics. 2018 Jul;366(1):66–74.
Lee, Young, et al. “Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension.The Journal of Pharmacology and Experimental Therapeutics, vol. 366, no. 1, July 2018, pp. 66–74. Epmc, doi:10.1124/jpet.118.247643.
Lee Y, Pai SB, Bellamkonda RV, Thompson DH, Singh J. Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension. The Journal of pharmacology and experimental therapeutics. 2018 Jul;366(1):66–74.
Journal cover image

Published In

The Journal of pharmacology and experimental therapeutics

DOI

EISSN

1521-0103

ISSN

0022-3565

Publication Date

July 2018

Volume

366

Issue

1

Start / End Page

66 / 74

Related Subject Headings

  • Safety
  • Rats
  • Pyridines
  • Pharmacology & Pharmacy
  • Nanostructures
  • Liposomes
  • Lactones
  • Hypertension, Pulmonary
  • Humans
  • Animals