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https://ptsldigital.ukm.my/jspui/handle/123456789/485641| Title: | Immunosuppressive effects of alpha, beta-unsaturated carbonyl based compounds and curcumin analogue encapsulated polylactic acid-co-glycolic acid-poly ethylene glycol based nanoparticles |
| Authors: | Laiba Arshad (P85373) |
| Supervisor: | Ibrahim Jantan, Prof. Dato' Dr. |
| Keywords: | Therapeutic potential Curcumin Chalcones Nanoparticles Dissertations, Academic -- Malaysia |
| Issue Date: | 28-Sep-2018 |
| Description: | Compounds containing α, β-unsaturated carbonyl based moieties such as curcumin and chalcones including their analogues and derivatives possess diverse pharmacological activities. Curcumin has low therapeutic potential due to its physicochemical limitations when administered orally. The present study was aimed to enhance the immunomodulatory activity of curcumin and chalcones through structural modification and provision of a drug delivery system. A series of α, β-unsaturated carbonyl based compounds (curcumin analogues and chalcone derivatives) and their pyrazoline derivatives were investigated for their modulatory effects on chemotactic migration, Mac-1 expression, phagocytic activity and reactive oxygen species production by human whole blood cells and isolated human polymorphonuclear neutrophils. Among all compounds tested, 3,5-bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP) was the most potent in suppressing the sequential steps of phagocytosis. BBP was further investigated for its immunosuppressive effects on various cellular and humoral immune responses in Balb/c mice. Its effects on immune responses in the mice were determined by measuring phagocytosis, serum levels of ceruloplasmin and lysozyme, myeloperoxidase (MPO) plasma level, proliferation of T and B lymphocytes, T lymphocytes subsets (CD4+ and CD8+) and secretion of Th1 and Th2 cytokines as well as serum immunoglobulins (IgG and IgM) and delayed type hypersensitivity reaction (DTHR). BBP significantly and dose-dependently reduced the migration of neutrophils, phagocytic activity and serum levels of ceruloplasmin and lysozyme, suppressed lymphocyte proliferation along with the downregulation of effector cells expression and release of Th1/Th2 cytokines. Reduction in DTHR and serum immunoglobulins was also observed. BBP encapsulated in polylactic-co-glycolic acid-b-polyethylene glycol (PLGA-b-PEG) nanoparticles was prepared through nanoprecipitation technique and characterized for its physicochemical properties. BBP was successfully encapsulated in PLGA-b-PEG polymer with high encapsulation efficiency (79%) while providing a controlled release. The BBP encapsulated PLGA-b-PEG nanoparticles and unencapsulated BBP were investigated against aforementioned specific and nonspecific innate and adaptive immune responses in male Balb/c mice. The in vivo responses produced by BBP encapsulated nanoparticles when compared to unencapsulated BBP, showed an enhanced and significant suppressive effects on the specific and non-specific immune responses mediated by various cellular and humoral parameters. In conclusion, these findings suggest that the novel curcumin analogue, BBP possessed strong immunosuppressive effects and its potency was raised by providing the carrier system.,Doktor Falsafah |
| Pages: | 238 |
| Call Number: | QV785.L185i 2018 9 |
| Publisher: | UKM, Kuala Lumpur |
| Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
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