title: Optimization of photodynamic therapy using negative pressure.
abstract: OBJECTIVE
  The goal of this study is to demonstrate an alternative procedure to perform topical photodynamic therapy (PDT). Here, we propose the combined use of negative pressure and a 5-Aminolevulinic acid (5-ALA) cream occlusion to increase protoporphyrin IX (PPIX) formation.
  
  
  BACKGROUND
  PDT using topical 5-ALA as a prodrug and precursor of PPIX has been used in the treatment and diagnosis of different types of cancer and skin diseases. The use of 5-ALA offers many advantages as a localized and non-systemic application, but it shows limitations in relation to skin penetration. Many authors have discussed the limitations of 5-ALA penetration through the skin. The skin penetration of 5-ALA can be optimized using mechanical devices associated with typical PDT procedure.
  
  
  METHODS
  For this study, 20% 5-ALA cream was applied to a 9 cm(2) area of skin, and an occlusive dressing was placed. The PPIX production was collected at the skin surface, using fluorescence spectroscopy and widefield fluorescence imaging, for 7 h, and after 24 h.
  
  
  RESULTS
  We observed that in the presence of negative pressure therapy, the PPIX production, distribution, and elimination are greater and faster than in the control group. The PPIX formation was ∼30% in deeper skin layers, quantified by fluorescence spectroscopy analysis, and ∼20% in surface skin layers, quantified by widefield fluorescence imaging analysis.
  
  
  CONCLUSIONS
  Negative pressure induction can also help PDT application in the case of inefficient PPIX production. These results can be useful for optimizing the PDT.
authors.affiliation: Instituto de Física de São Carlos (IFSC), University of São Paulo (USP) , São Carlos - SP, Brazil .
authors.forename: Priscila Fernanda Campos
authors.initials: PF
authors.lastname: Menezes
authors.forename: Michelle Barreto
authors.initials: MB
authors.lastname: Requena
authors.forename: Vanderlei Salvador
authors.initials: VS
authors.lastname: Bagnato
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage; D006801:Humans; D054843:Negative-Pressure Wound Therapy; D010778:Photochemotherapy / Q000379:methods*; D011524:Protoporphyrins / Q000096:biosynthesis; D063465:Skin Cream
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX