Lipid nanocapsules containing the non-ionic surfactant Solutol HS15 inhibit the transport of calcium through hyperforin-activated channels in neuronal cells.
Hyperforin is described as a natural antidepressant inhibiting the reuptake of neurotransmitters and also activating cation channels. However the blood-brain barrier limits the access to the brain of this biomolecule. To circumvent this problem it was envisaged to encapsulate hyperforin into biomimetic lipid nano-carriers like lipid nanocapsules (LNCs). When testing the safety of 25 nm LNCs it appeared that they strongly blocked hyperforin-activated Ca2+ channels of cultured cortical neurons. This inhibition was due to one of their main component: solutol HS15 (polyoxyethylene-660-12-hydroxy stearate), a non-ionic soluble surfactant. Solutol HS15 rapidly depresses in a concentration-dependent manner the entry of Ca2+ through hyperforin-activated channels without influencing store-operated channels. This effect is mimicked by Brij58 but not by PEG600, indicating that the lipid chain of Solutol HS15 is important in determining its effects on the channels. The inhibition of the Ca2+ fluxes depends on the cellular cholesterol content; it is stronger after depleting cholesterol with methyl-β-cyclodextrin and is nearly absent on cells cultured in a cholesterol-rich medium. When chronically applied for 24 h, Solutol HS15 slightly up-regulates the entry of Ca2+ through hyperforin-activated channels. Similar observations were made when testing 25 nm lipid nanocapsules containing the surfactant Solutol HS15. Altogether, this study shows that Solutol HS15 perturbs in a cholesterol-dependent manner the activity of some neuronal channels. This is the first demonstration that LNCs containing this surfactant can influence cellular calcium signaling in the brain, a finding that can have important clinical implications.
Univ Grenoble Alpes, iRTSV-LCBM, F-38000 Grenoble, France; CNRS, iRTSV-LCBM, F-38000 Grenoble, France; CEA, iRTSV-LCBM, F-38000 Grenoble, France.
Sylvain
S
Chauvet
Institut d'Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS 8520, Université Lille 1, Avenue Poincaré - BP 60069, 59652 Villeneuve d'Ascq, France.
Alexandre
A
Barras
Institut d'Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS 8520, Université Lille 1, Avenue Poincaré - BP 60069, 59652 Villeneuve d'Ascq, France.
Rabah
R
Boukherroub
Univ Grenoble Alpes, iRTSV-LCBM, F-38000 Grenoble, France; CNRS, iRTSV-LCBM, F-38000 Grenoble, France; CEA, iRTSV-LCBM, F-38000 Grenoble, France. Electronic address: alexandre.bouron@cea.fr.
Alexandre
A
Bouron
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002592:Cetomacrogol / Q000008:administration & dosage; D002784:Cholesterol / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D008810:Mice, Inbred C57BL; D053769:Nanocapsules; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D013229:Stearic Acids / Q000008:administration & dosage*; D013501:Surface-Active Agents / Q000008:administration & dosage*; D013729:Terpenes / Q000378:metabolism*
D003470:Culture Media; D053769:Nanocapsules; D013229:Stearic Acids; D013501:Surface-Active Agents; D013729:Terpenes; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D002592:Cetomacrogol; D002784:Cholesterol; D010696:Phloroglucinol; C001654:hyperforin; D002118:Calcium
Calcium channels; Hyperforin; Lipid nanocapsules; Nanoparticles; Solutol HS15; Store-operated channels