Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle

Authors

  • Refaat Omar College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
  • Jiaqi Yang College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
  • Samaa Alrushaid College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
  • Frank J. Burczynski College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. Department of Pharmacology & Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
  • Gerald Y. Minuk College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. Section of Hepatology, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
  • Yuewen Gong College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. Section of Hepatology, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.

DOI:

https://doi.org/10.18433/jpps29584

Abstract

Purpose: To develop and characterize vitamin A (VA)-coupled liposomes for the targeted delivery of BMP4-siRNA to hepatic stellate cells (HSC). VA was selected to increase the uptake by HSC based on their function in the storage of VA. Methods: DOTAP/DOPE liposomes were prepared by film hydration method and their surfaces were decorated with VA. The cytotoxicity of VA-conjugated liposomes was evaluated by the WST-1 assay. Inhibition of BMP4 and α-SMA was determined by PCR and ELISA. Results: VA-coated lipoplexes exhibited an average particle sizes less than 200 nm and zeta potential around +25 mV both determined using ZetaPALS. Inclusion of VA to liposomal surfaces significantly enhanced their cellular uptake without affecting cytotoxicity. VA-coupled liposomes carrying BMP4-siRNA resulted in a significant reduction in BMP4 and α-SMA at both mRNA and protein levels.  Conclusion: VA-coated liposomes were successfully designed to deliver BMP4-siRNA to specifically target HSC. The novel delivery system discussed herein may serve as a potential therapeutic strategy for the treatment of liver fibrosis in the future.

 

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Published

2018-03-30

How to Cite

Omar, R., Yang, J., Alrushaid, S., Burczynski, F. J., Minuk, G. Y., & Gong, Y. (2018). Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle. Journal of Pharmacy & Pharmaceutical Sciences, 21, 119–134. https://doi.org/10.18433/jpps29584

Issue

Vol. 21 (2018): Pages 1-142

Section

Pharmaceutical Sciences; Original Research Articles

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