title: Targeting of sebaceous glands by δ-aminolevulinic acid-based photodynamic therapy: An in vivo study.
abstract: OBJECTIVE
  Wide application of ALA-PDT for acne is limited due to relative strong side effects, such as pain and erythema. The objective of this study was to establish a protocol for ALA-PDT that would provide specific destruction of sebaceous glands at the lowest concentrations and shortest contact times of ALA.
  
  
  METHODS
  The rhino (hr(rh) hr(rh) ) murine model, an experimental acne model, was used in this study. A freshly prepared hydrophilic ALA hydrochloride ointment (2.5%, 5%, and 20%) was applied to the backs of 16-week-old male rhino mice. The fluorescence intensity (FI) of ALA-induced protoporphyrin IX (ALA-PpIX) on the skin was measured by spectrofluorometry. Skin samples were taken at 1, 2, and 4 hours after ALA application to determine the tissue distribution of ALA-PpIX by fluorescence microscopy. Light irradiation was also performed with a broadband light source (600-1100 nm, 15 J/cm² , 60 mW/cm²) with subsequent histological examination 1 day after treatment.
  
  
  RESULTS
  Prominent increases of ALA-PpIX were observed 1 hour after application of 5% and 20% ALA, while no increase was observed with 2.5% ALA until 2 hours. A direct correlation was found between ALA concentration and ALA-PpIX FI. While no fluorescence was detected 1 hour after application of 2.5% or 5% ALA, 20% ALA produced a strong fluorescence in the epidermis, utricle walls, and sebaceous glands. Histological evaluation showed no damage to skin treated with 2.5% ALA-PDT incubated for 1 hour. Damage was still focused within the sebaceous glands with longer incubation times. Increased ALA concentrations resulted in more prominent damage to the epidermis and sebaceous glands, with deeper damage to the dermis when longer incubation times were used.
  
  
  CONCLUSIONS
  Focused damage of sebaceous glands can be achieved with ALA-PDT when low concentrations of ALA (2.5-5.0%) and short incubation times (to 2 hours) were used.
authors.affiliation: Department of Dermatology, Nippon Medical School, Tokyo 113-8603, Japan. p-chan@nms.ac.jp
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kosaka
authors.forename: Norio
authors.initials: N
authors.lastname: Miyoshi
authors.forename: Oleg E
authors.initials: OE
authors.lastname: Akilov
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawana
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy*; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011524:Protoporphyrins / Q000032:analysis; D012627:Sebaceous Glands / Q000187:drug effects* / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013050:Spectrometry, Fluorescence
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX