Open AccessInhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle
Author(s) -
Refaat Omar,
Jiaqi Yang,
Samaa Alrushaid,
Frank J. Burczynski,
Gerald Y. Minuk,
Yuewen Gong
Publication year - 2018
Publication title -
journal of pharmacy and pharmaceutical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.497
H-Index - 78
ISSN - 1482-1826
DOI - 10.18433/jpps29584
Subject(s) - liposome , hepatic stellate cell , cytotoxicity , chemistry , zeta potential , in vitro , biochemistry , microbiology and biotechnology , biophysics , nanotechnology , nanoparticle , biology , medicine , materials science , pathology
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. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.