RESUMO
After intravenous (i.v.) injection, solid lipid nanoparticles (SLN) interact with mononuclear cells. Murine peritoneal macrophages were incubated with SLN formulations consisting of Dynasan 114 coated with different surfactants. The present study was performed to examine the impact of surfactants, which are important surface defining components of SLN, on viability and cytokine production by macrophages. Cytotoxicity, as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test, was strongly influenced by the surfactant used being marked with cetylpyridinium chloride- (CPC-) coated SLN at a concentration of 0.001% and further increased at SLN concentrations of 0.01 and 0.1%. All other SLN formulations -- containing Poloxamine 908 (P908), Poloxamer 407 (P407), Poloxamer 188 (P188), Solutol HS15 (HS15), Tween 80 (T80), Lipoid S75 (S75), sodium cholate (SC), or sodium dodecylsulfate (SDS) -- when used at the same concentrations reduced cell viability only slightly. None of the SLN formulations tested induced cytokine production but a concentration-dependent decrease of IL-6 production was observed, which appeared to be associated with cytotoxic effects. IL-12 and TNF-alpha were detected neither in supernatants of macrophages treated with SLN at any concentration nor in those of untreated cells. In contrast to the type of surfactant, the size of SLN was found neither to affect cytotoxicity of SLN nor to result in induction or digression of cytokine production by macrophages. In conclusion, testing the effects of surfactants on SLN on activity of macrophages is a prerequisite prior to in vivo use of SLN.
Assuntos
Citocinas/biossíntese , Lipídeos/farmacologia , Macrófagos Peritoneais/metabolismo , Tensoativos , Animais , Sobrevivência Celular , Células Cultivadas , Química Farmacêutica , Feminino , Lipídeos/administração & dosagem , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Tamanho da PartículaRESUMO
Lactation was found to be significantly inhibited by greater than or equal to 2.0 mg methylergometrin-bimaleinate administered during the early postpartal period, particularly when the treatment was started as early as on the first or second day of puerperium. Therefore, such ergometrin treatment should be avoided as far as possible in order to improve breast-feeding, which was shown to be of great importance for the mental, psychic and physical development of the newborn.