title: Surfactant dependent toxicity of lipid nanocapsules in HaCaT cells.
abstract: Lipid nanocapsules (LNC) have been suggested for a variety of pharmaceutical applications. Among them approaches for drug delivery to the skin appear particularly interesting. The current standard composition has been modified to better understand their properties by selecting a variety of different surfactants. LNC have been prepared using different non-ionic surfactants (Solutol(®) HS15: Polyoxyl 15 Hydroxystearate; Cremophor(®) EL: Polyoxyl 35 Castor Oil; Simulsol(®) 4000: Polyoxyl 40 Hydrogenated Castor Oil; Vitamin E TPGS(®): alpha-tocopheryl poly(ethylene glycol) succinate; Polysorbate 20 and 80) and analysed for their size, stability, drug release and toxicity on keratinocytes in cell culture. The feasibility of LNC using different surfactant was surprisingly easy and led to a variety of stable formulations that were selected for further investigations. Surfactants led to a variability of the release kinetics (t50% release varied from Polysorbate 20: 2.5h to Simulsol(®) 4000: 5.0h), however different formulations from the same surfactant did not differ significantly. In vitro toxicity of LNC was surfactant type dependent and a correlation between LNC and the pure respective surfactant was found. This toxicity was found to be mainly independent from the surface active properties. The surfactant type in LNC is easily interchangeable from formulation point of view. LNC appear to be appropriate as carrier for cutaneous delivery however toxicity can vary distinctly depending on the surfactant used for the preparation.
authors.affiliation: Laboratory of Pharmaceutical Engineering, University Franche-Comté, Besançon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Maupas
authors.forename: Brice
authors.initials: B
authors.lastname: Moulari
authors.forename: Arnaud
authors.initials: A
authors.lastname: Béduneau
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
authors.forename: Yann
authors.initials: Y
authors.lastname: Pellequer
mesh_terms: D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008055:Lipids / Q000737:chemistry / Q000633:toxicity*; D053769:Nanocapsules / Q000737:chemistry / Q000633:toxicity*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012867:Skin / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D004364:Pharmaceutical Preparations; D013501:Surface-Active Agents; D014810:Vitamin E; D011092:Polyethylene Glycols