title: In vitro and in vivo topical delivery studies of tretinoin-loaded ultradeformable vesicles.
abstract: BACKGROUND
  Ultradeformable vesicles are highly promising tools to enhance the percutaneous transport of different drugs such as tretinoin across the skin barrier and also to increase the formulation stability at absorption site and reduce the drug induced irritation.
  
  
  METHODS
  Topical delivery of tretinoin-loaded ultradeformable vesicles (tretinoin-UDV) was evaluated concerning different studies, such as: the release and permeation profiles (tape stripping); skin penetration (fluorescence analysis); induced electrical changes in skin barrier properties; cytotoxicity (Trypan Blue assay) and skin irritation in in vivo conditions (Draize test). The novel formulation performance was also compared to a commercial tretinoin formulation regarding in vivo studies.
  
  
  RESULTS
  It was obtained a sustained and controlled drug release, as expected for UDV formulation. In addition, a dermal delivery was observed regarding the permeation study since it was not detected any drug amount in the receptor phase after 24h. Nile Red-UDV stained intensively mostly in the stratum corneum, corroborating the tape stripping results. Tretinoin-UDV decreased skin resistance, suggesting its ability to induce skin barrier disruption. Finally, the formulation vehicle (empty UDV) and tretinoin-UDV were not toxic under in vitro and in vivo conditions, at least, at 5×10(-3)mg/mL and 0.5mg/mL of tretinoin, respectively.
  
  
  CONCLUSIONS
  Tretinoin-UDV is a promising delivery system for tretinoin dermal delivery without promoting skin irritation (unlike other commercial formulations), which is quite advantageous for therapeutic purpose.
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal. Electronic address: andreiaascenso@ff.ul.pt.
authors.forename: Andreia
authors.initials: A
authors.lastname: Ascenso
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Salgado
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Euletério
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Fabíola Garcia
authors.initials: FG
authors.lastname: Praça
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Maria Vitória Lopes Badra
authors.initials: MV
authors.lastname: Bentley
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Marques
authors.affiliation: Department Biology, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Oliveira
authors.affiliation: Department Biology, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Conceição
authors.initials: C
authors.lastname: Santos
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Simões
mesh_terms: D000287:Administration, Topical; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D016503:Drug Delivery Systems; D017097:Electric Impedance; D004817:Epidermis; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008027:Light; D008081:Liposomes / Q000378:metabolism; D036103:Nanotechnology; D010078:Oxazines / Q000737:chemistry; D012867:Skin / Q000187:drug effects*; D012869:Skin Absorption; D014212:Tretinoin / Q000008:administration & dosage*; D014343:Trypan Blue / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D010078:Oxazines; D014212:Tretinoin; D014343:Trypan Blue; C044808:nile red
keywords: Skin barrier function; Topical delivery; Toxicity; Transfersomes; Tretinoin; Ultradeformable vesicles