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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

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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 cm2 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/cm2). 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.

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ACKNOWLEDGEMENTS

The volunteer aspect of this work was supported by the Norwegian Cancer Society (Det Norske Kreftforening). The microneedles aspect of this work was supported by BBSRC grant number BB/E020534/1 and Invest Northern Ireland Proof of Concept grant number POC21A.

CONFLICT OF INTEREST

The manuscript contains original data which are not published or intended to publish elsewhere. We state no conflicts of interests or of financial nature or others.

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Authors and Affiliations

  1. Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310, Oslo, Norway

    Patrycja Mikolajewska, Vladimir Iani, Johan Moan & Asta Juzeniene

  2. School of Pharmacy, Queen’s University, Medical Biology Centre, 97 Lisburn Road, Belfast, UK

    Ryan F. Donnelly, Martin J. Garland, Desmond I. J. Morrow & Thakur Raghu Raj Singh

  3. Institute of Physics, University of Oslo, Postboks 1048, Blindern, 0316, Oslo, Norway

    Johan Moan

  4. Department of Radiation Biology, Oslo University Hospital, Montebello, 0310, Oslo, Norway

    Patrycja Mikolajewska

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  1. Patrycja Mikolajewska
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  2. Ryan F. Donnelly
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  3. Martin J. Garland
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  5. Thakur Raghu Raj Singh
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  6. Vladimir Iani
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Correspondence to Patrycja Mikolajewska.

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Mikolajewska, P., Donnelly, R.F., Garland, M.J. et al. 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 27, 2213–2220 (2010). https://doi.org/10.1007/s11095-010-0227-2

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