title: A comparative study on the possible cytotoxic effects of different nanostructured lipid carrier (NLC) compositions in human dermal fibroblasts.
abstract: Nanostructured lipid carriers (NLC) are widely used for topical delivery of active ingredients into the skin for both local and systemic treatment. But concerns have been raised regarding their potential nanotoxicity. To understand the role of NLC composition in terms of cytotoxicity and pro-oxidant effects, we investigated cell viability and intracellular levels of ROS (reactive oxygen species) production in human dermal fibroblasts (HDF) incubated with five NLC formulations differing in their solid lipid composition. HDF and NLC were also exposed to UVA irradiation in order to evaluate the behavior of NLC under realistic environmental conditions which might promote their instability. Using the Guava via-count assay, all nanoparticles, except for those formulated with Compritol 888 ATO, showed a significant decrease in live cells and a parallel increase in apoptotic or dead cells compared to the control, either before and/or after UVA irradiation (18 J/cm(2)). NLC formulated with Geleol™ Mono Diglycerides resulted the most cytotoxic. A similar trend was also observed when intracellular ROS levels were measured in HDF incubated with NLC: there was increased ROS content compared to the control, further exacerbated following UVA. NLC formulated with Dynasan 118 were particularly susceptible to UVA exposure. The results indicate which could be the most suitable candidates for formulating NLC that are biocompatible and non-cytotoxic even when exposed to UVA and hence help direct future choices during the formulation strategies of these delivery systems. Of those tested, Compritol 888 ATO appears to be the best choice.
authors.affiliation: Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Universitá Politecnica delle Marche, Via Brecce Bianche,60131 Ancona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Brugè
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy. Electronic address: e.damiani@univpm.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Damiani
authors.affiliation: Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Universitá Politecnica delle Marche, Via Brecce Bianche,60131 Ancona, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marcheggiani
authors.affiliation: Dipartimento di Scienza del Farmaco, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Offerta
authors.affiliation: Dipartimento di Scienza del Farmaco, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Puglia
authors.affiliation: Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Universitá Politecnica delle Marche, Via Brecce Bianche,60131 Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tiano
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003603:Cytotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry*; D004355:Drug Stability; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D014466:Ultraviolet Rays
chemical_list: D003603:Cytotoxins; D004337:Drug Carriers; D008055:Lipids; D017382:Reactive Oxygen Species
keywords: Cytotoxicity; Lipid composition; Nanostructured lipid carriers (NLC); Reactive oxygen species; UVA