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Enhanced immunosuppressive effects of 3,5-bis[4(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one, an α, β-unsaturated carbonyl-based compound as PLGA-b-PEG nanoparticles

Authors Arshad L, Jantan I, Bukhari SNA

Received 28 November 2018

Accepted for publication 5 March 2019

Published 30 April 2019 Volume 2019:13 Pages 1421—1436

DOI https://doi.org/10.2147/DDDT.S185191

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Manfred Ogris


Laiba Arshad,1 Ibrahim Jantan,2 Syed Nasir Abbas Bukhari3

1Department of Pharmacy, Forman Christian College (A Chartered University), Lahore, Pakistan; 2School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Selangor, Malaysia; 3Department of Pharmaceutical Chemistry, College of Pharmacy, Al Jouf University, Aljouf, Sakaka, Saudi Arabia

Background: 3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has been revealed to possess strong in vitro and in vivo immunosuppressive effects.
Purpose: The aim of present study was to prepare and characterize BBP-encapsulated polylactic-co-glycolic acid-block-polyethylene glycol (PLGA-b-PEG) nanoparticles and to evaluate its in vivo efficacy against innate and adaptive immune responses.
Methods: Male BALB/c mice were orally administered with BBP alone and BBP- encapsulated nanoparticles equivalent to 5, 10 and 20 mg/kg of BBP in distilled water for a period of 14 days. The immunomodulatory potential was appraised by determining its effects on non-specific and specific immune parameters.
Results: The results showed that BBP was successfully encapsulated in PLGA-b-PEG polymer with 154.3 nm size and high encapsulation efficiency (79%) while providing a sustained release for 48 hours. BBP nanoparticles showed significant enhanced dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity, reactive oxygen species (ROS) production, serum levels of ceruloplasmin and lysozyme, immunoglobulins and myloperoxidase (MPO) plasma levels when compared to unencapsulated BBP. Enhanced dose-dependent inhibition was also observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines, and reduction in rat paw oedema in BBP nanoparticles treated mice. At higher doses the suppressive effects of the BBP nanoparticles on various cellular and humoral parameters of immune responses were comparable to that of cyclosporine-A at 20 mg/kg.
Conclusion: These findings suggest that the immunosuppressive effects of BBP were enhanced as PLGA-b-PEG nanoparticles.

Keywords: αβ-unsaturated carbonyl-based compound, curcumin analogue, PLGA-b-PEG nanoparticles, immunosuppression, innate immune response, humoral immune response

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