Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays

Iman M.N. Hamdan, Ismaiel A. Tekko, Kyle B Matchett, Luis G. Arnaut, Claudia S. Silva, Helen O. McCarthy, Ryan F. Donnelly

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin™) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 μm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 1010 ± 2.5 × 1010 and 3.8 × 109 ± 1.6 × 109 p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.
LanguageEnglish
Pages2439-2450
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume107
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

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Photosensitizing Agents
Skin
Fluorescence
Photochemotherapy
Nude Mice
Basal Cell Carcinoma
Pharmaceutical Preparations
Control Groups

Keywords

  • intradermal
  • microneedles
  • nodular basal cell carcinoma
  • photodynamic therapy

Cite this

Hamdan, I. M. N., Tekko, I. A., Matchett, K. B., Arnaut, L. G., Silva, C. S., McCarthy, H. O., & Donnelly, R. F. (2018). Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays. Journal of Pharmaceutical Sciences, 107(9), 2439-2450. https://doi.org/10.1016/j.xphs.2018.05.017
Hamdan, Iman M.N. ; Tekko, Ismaiel A. ; Matchett, Kyle B ; Arnaut, Luis G. ; Silva, Claudia S. ; McCarthy, Helen O. ; Donnelly, Ryan F. / Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays. In: Journal of Pharmaceutical Sciences. 2018 ; Vol. 107, No. 9. pp. 2439-2450.
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Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays. / Hamdan, Iman M.N.; Tekko, Ismaiel A.; Matchett, Kyle B; Arnaut, Luis G.; Silva, Claudia S.; McCarthy, Helen O.; Donnelly, Ryan F.

In: Journal of Pharmaceutical Sciences, Vol. 107, No. 9, 01.09.2018, p. 2439-2450.

Research output: Contribution to journalArticle

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AU - Hamdan, Iman M.N.

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AU - Matchett, Kyle B

AU - Arnaut, Luis G.

AU - Silva, Claudia S.

AU - McCarthy, Helen O.

AU - Donnelly, Ryan F.

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AB - Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin™) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 μm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 1010 ± 2.5 × 1010 and 3.8 × 109 ± 1.6 × 109 p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.

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