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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Preserved solid lipid nanoparticles (SLN) at low concentrations do cause neither direct nor indirect cytotoxic
N Schöler1, E Zimmermann, U Katzfey
1Department of Medical Microbiology, Benjamin Franklin Hospital, Free University of Berlin, Hindenburgdamm 27, D-12203, Berlin, Germany.
Abstract:
In order to investigate the interaction of preserved solid lipid nanoparticles (SLN) with murine peritoneal macrophages (Mpsi), cytotoxicity and proinflammatory effects of two different solid lipid nanoparticles (SLN) preparations consisting of either compritol (CO) or cetyl palmitate (CP) preserved with thiomersal were analyzed. Concentration-dependent cytotoxic effects were observed using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Secretion of interleukin-6 by Mpsi following incubation with CO and CP SLN did not differ from secretion by untreated cells; proinflammatory cytokines interleukin-12 and tumor-necrosis-factor-alpha as further indicators of immunomodulatory effects were not detectable. These findings paralleled our previous findings that unpreserved CO and CP SLN did not induce immunomodulatory effects but cytotoxicity at higher concentrations. There were no synergistic cytotoxic effects of preservative and SLN. Thus, preservation of SLN using thiomersal does not appear to cause increased cytotoxicity and immunomodulatory effects following incubation with Mpsi.
Insights
Thiomersal preservation of solid lipid nanoparticles (SLN) did not increase cytotoxicity or proinflammatory effects in murine peritoneal macrophages (Mpsi). The preservative did not synergize with SLN, indicating safety for Mpsi interactions.
Area of Science:
- Nanotechnology
- Biocompatibility
- Immunotoxicology
Background:
- Solid lipid nanoparticles (SLN) are increasingly used in drug delivery.
- Investigating the biocompatibility of preserved SLN with immune cells is crucial.
- Thiomersal is a common preservative with potential immunomodulatory concerns.
Purpose of the Study:
- To evaluate the cytotoxicity and proinflammatory effects of thiomersal-preserved SLN on murine peritoneal macrophages (Mpsi).
- To compare the effects of compritol (CO) and cetyl palmitate (CP) based SLN.
- To determine if thiomersal exacerbates SLN-induced effects.
Main Methods:
- Murine peritoneal macrophages (Mpsi) were incubated with CO and CP SLN preserved with thiomersal.
- Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay.
- Proinflammatory cytokine secretion (IL-6, IL-12, TNF-α) was measured.
Main Results:
- Concentration-dependent cytotoxicity was observed for both CO and CP SLN.
- No significant difference in IL-6 secretion was found compared to untreated cells.
- Key proinflammatory cytokines (IL-12, TNF-α) were undetectable, similar to unpreserved SLN.
Conclusions:
- Thiomersal preservation of SLN does not appear to increase cytotoxicity or immunomodulatory effects on Mpsi.
- No synergistic cytotoxic effects were observed between thiomersal and SLN.
- Preserved SLN demonstrate a similar safety profile to unpreserved SLN regarding Mpsi interaction.
