title: A study of the enhanced sensitizing capacity of a contact allergen in lipid vesicle formulations.
abstract: The growing focus on nanotechnology and the increased use of nano-sized structures, e.g. vesicles, in topical formulations has led to safety concerns. We have investigated the sensitizing capacity and penetration properties of a fluorescent model compound, rhodamine B isothiocyanate (RBITC), when administered in micro- and nano-scale vesicle formulations. The sensitizing capacity of RBITC was studied using the murine local lymph node assay (LLNA) and the skin penetration properties were compared using diffusion cells in combination with two-photon microscopy (TPM). The lymph node cell proliferation, an indicator of a compounds sensitizing capacity, increased when RBITC was applied in lipid vesicles as compared to an ethanol:water (Et:W) solution. Micro-scale vesicles showed a slightly higher cell proliferative response compared to nano-scale vesicles. TPM imaging revealed that the vesicle formulations improved the skin penetration of RBITC compared to the Et:W solution. A strong fluorescent region in the stratum corneum and upper epidermis implies elevated association of RBITC to these skin layers when formulated in lipid vesicles. In conclusion, the results indicate that there could be an elevated risk of sensitization when haptens are delivered in vehicles containing lipid vesicles. Although the size of the vesicles seems to be of minor importance, further studies are needed before a more generalized conclusion can be drawn. It is likely that the enhanced sensitizing capacity is a consequence of the improved penetration and increased formation of hapten-protein complexes in epidermis when RBITC is delivered in ethosomal formulations.
authors.affiliation: Department of Chemistry, University of Gothenburg, SE-412 96, Gothenburg, Sweden. carl.simonsson@chem.gu.se
authors.forename: Carl
authors.initials: C
authors.lastname: Simonsson
authors.forename: Jakob Torp
authors.initials: JT
authors.lastname: Madsen
authors.forename: Annette
authors.initials: A
authors.lastname: Graneli
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Andersen
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Jonsson
authors.forename: Marica B
authors.initials: MB
authors.lastname: Ericson
mesh_terms: D000279:Administration, Cutaneous; D000485:Allergens / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023441:Local Lymph Node Assay; D051379:Mice; D010316:Particle Size; D012235:Rhodamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000502:physiology*
chemical_list: D000485:Allergens; D008081:Liposomes; D012235:Rhodamines; C027755:rhodamine isothiocyanate