title: Cytotoxicity studies of Dynasan 114 solid lipid nanoparticles (SLN) on RAW 264.7 macrophages-impact of phagocytosis on viability and cytokine production.
abstract: Solid lipid nanoparticles (SLN) based on Dynasan 114 (D114) were tested using RAW 264.7 cells. The influence of different surfactants on the cytotoxicity of this type of SLN was examined, expressed as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) viability and the production of cytokines such as interleukin 6 (IL-6), IL-12 and tumour necrosis factor-alpha (TNF-alpha). Results were compared with previously obtained data when peritoneal mouse macrophages were used. SLN produced with stabilizers/surfactants such as poloxamer 188, sodium cholate, Lipoid S75, Tween 80, Poloxamine 908 and sodium dodecylsulfate were shown to be nontoxic towards RAW 264.7 cells. Cytokine production was reduced and stimulation, expressed in elevated cytokine levels, could not be found. Using cetylpyridinium chloride (CPC) as stabilizing surfactant, SLN became cytotoxic in a concentration-dependent manner. Not only were the viabilities reduced but also cytokine production. Cytotoxic effects of CPC stabilized SLN could be antagonized using cytochalasin B to block phagocytosis. D114-SLN produced with pharmaceutically accepted surfactants for intravenous injection (poloxamer 188, Lipoid S75, sodium cholate, Tween 80) were very well tolerated by the cells. Even sodium dodecylsulfate-stabilized D114-SLN did not exert toxic effects. Comparison of the RAW 264.7 data with previously obtained data from toxicity studies of D114-SLN towards peritoneal mouse macrophages showed similar results. This offers the possibility of using the RAW 264.7 cell line for cytotoxicity studies of colloidal drug carrier systems, rather than using laboratory animals as source of macrophages for these kinds of studies.
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics and Biotechnology, The Free University of Berlin, Kelchstr. 31, D-12169 Berlin, Germany; Schering AG, Research Laboratories, D 13342 Berlin. carsten.olbrich@schering.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Olbrich
authors.forename: Nadja
authors.initials: N
authors.lastname: Schöler
authors.forename: Kerstin
authors.initials: K
authors.lastname: Tabatt
authors.forename: Oliver
authors.initials: O
authors.lastname: Kayser
authors.forename: Rainer Helmut
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D036103:Nanotechnology; D010587:Phagocytosis; D013501:Surface-Active Agents; D018675:Toxicity Tests / Q000379:methods; D014280:Triglycerides / Q000737:chemistry / Q000633:toxicity*
chemical_list: D016207:Cytokines; D008081:Liposomes; D013501:Surface-Active Agents; D014280:Triglycerides; C036694:trimyristin