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Abstract
The purpose of this study was to investigate possible immunomodulatory and cytotoxic effects of solid lipid nanoparticles (SLN) on murine peritoneal macrophages. Immunomodulatory effects of SLN composed of either a lipid(glycerol-behenate) or a wax (cetylpalmitate) matrix stabilized by the surfactant Poloxamer 188 were analysed by detection of proinflammatory and downregulatory cytokines in supernatants of thioglycollate-elicited peritoneal macrophages using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity of SLN was assessed using the MTT test. Incubation of macrophages with either SLN at low concentrations did not increase production of interleukin (IL)-6, IL-12, and tumour necrosis factor (TNF)-alpha. At higher SLN concentrations, a concentration-dependent decrease in IL-6 secretion was observed compared to background production of IL-6 by untreated macrophages. IL-12 and TNF-alpha production was neither detected in supernatants of macrophages treated with SLN at any concentration nor in those of untreated cells. The decrease in IL-6 secretion was paralleled by concentration-dependent cytotoxicity of SLN on these cells. In contrast, incubation with polystyrene reference particles neither resulted in decreased IL-6 production nor in a loss of viability. SLN-treated macrophages were found to up-regulate their cytokine production following stimulation with Pansorbin, despite the concentration-dependent cytotoxicity induced by SLN. Down-regulatory effects on SLN-treated macrophages by IL-10 were not observed. In conclusion, incubation of SLN with murine peritoneal macrophages did not induce the production of proinflammatory and down-regulatory cytokines. At high concentrations of SLN, cytotoxic effects on these cells were observed. Cytotoxicity appears to be the main cause of decreased cytokine production by these cells.
