title: Microneedle pre-treatment of human skin improves 5-aminolevulininc acid (ALA)- and 5-aminolevulinic acid methyl ester (MAL)-induced PpIX production for topical photodynamic therapy without increase in pain or erythema.
abstract: OBJECTIVE
  To determine the impact of skin pretreatment with microneedles (MNs) on ALA- and MAL-induced protoporphyrin IX (PpIX) production, as well as MN impact on pain sensations during light exposure and erythema after PDT.
  
  
  METHODS
  The skin of 14 healthy volunteers was preteated with MNs. Equal amounts of creams containing 2%, 8% and 16% (w/w) ALA and MAL were applied on 1 cm(2) areas for 4 h. Additionally, 16% ALA and MAL creams were applied for 24 h. Afterwards, PpIX fluorescence spectra were measured. Sixteen percent ALA and MAL spots were exposed to red light (632 nm, 77 mW/cm(2)). Time for pain to occur was measured in seconds, and erythemal response was monitored up to 6 h after the end of the light exposure.
  
  
  RESULTS
  Use of MNs increased the PpIX fluorescence after 4 h incubation time with 2% and 8% ALA or MAL, but not with 16% ALA or MAL. Pretreatment with MNs did not increase the pain sensations during light exposure, nor did it influence erythema occurrence.
  
  
  CONCLUSIONS
  MNs are a promising tool for improving the efficiency of topical PDT by improving the cutaneous delivery of ALA and MAL, without increase in side effects.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway. patrycja.mikolajewska@rr-research.no
authors.forename: Patrycja
authors.initials: P
authors.lastname: Mikolajewska
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Garland
authors.forename: Desmond I J
authors.initials: DI
authors.lastname: Morrow
authors.forename: Thakur Raghu Raj
authors.initials: TR
authors.lastname: Singh
authors.forename: Vladimir
authors.initials: V
authors.lastname: Iani
authors.forename: Johan
authors.initials: J
authors.lastname: Moan
authors.forename: Asta
authors.initials: A
authors.lastname: Juzeniene
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004890:Erythema / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D009339:Needles; D010146:Pain / Q000517:prevention & control*; D010778:Photochemotherapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D011524:Protoporphyrins / Q000096:biosynthesis*; D011677:Punctures / Q000295:instrumentation; D012825:Silicon; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D012869:Skin Absorption
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; C114767:delta-aminolevulinic acid methyl ester; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D012825:Silicon