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

Pharm Res. 2010 Oct;27(10):2213-20. doi: 10.1007/s11095-010-0227-2. Epub 2010 Jul 31.

Abstract

Purpose: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives*
  • Aminolevulinic Acid / therapeutic use
  • Erythema / prevention & control*
  • Female
  • Humans
  • Light
  • Male
  • Needles
  • Pain / prevention & control*
  • Photochemotherapy / adverse effects
  • Photochemotherapy / instrumentation
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / therapeutic use
  • Protoporphyrins / biosynthesis*
  • Punctures* / instrumentation
  • Silicon
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / radiation effects
  • Skin Absorption

Substances

  • Photosensitizing Agents
  • Protoporphyrins
  • delta-aminolevulinic acid methyl ester
  • Aminolevulinic Acid
  • protoporphyrin IX
  • Silicon