Hydrogel-forming and dissolving microneedles for enhanced delivery of photosensitizers and precursors

Ryan F. Donnelly*, Desmond I.J. Morrow, Maelíosa T.C. McCrudden, Ahlam Zaid Alkilani, Eva M. Vicente-Pérez, Conor O'Mahony, Patricia González-Vázquez, Paul A. McCarron, A. David Woolfson

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We present "one-step application" dissolving and hydrogel-forming microneedle arrays (MN) for enhanced delivery of photosensitizers/precursors. MN (280 μm) prepared from 20% w/w poly(methylvinylether/maelic acid) and cross-linked with glycerol by esterification to form hydrogels upon skin insertion, or allowed to dissolve rapidly in skin, were combined with patches containing 19 mg cm-2 of 5-aminolevulinic acid (ALA) or meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) for drug delivery. Both MN types were mechanically robust, with compression forces of 20.0 N only causing height reductions of 14%. Application forces as low as 8.0 N per array allowed >95% of the MN in each array type to penetrate excised porcine skin, with the MN penetrating to approximately 220 μm. MN significantly enhanced transdermal delivery of ALA and TMP in vitro, with the hydrogel-forming system comparable with the dissolving system for ALA delivery (approximately 3000 nmol cm-2 over 6 h), but superior for delivery of the much larger TMP molecule (approximately 14 nmol cm-2 over 24 h, compared to 0.15 nmol cm-2). As this technology clearly has potential in enhanced photodynamic therapy of neoplastic skin lesions, we are currently planning animal studies, to be followed by preliminary human evaluations. GMP manufacturing scale-up is ongoing. We present novel dissolving and hydrogel-forming microneedle arrays (MN) that can be applied in a one-step fashion and are intended to enhance delivery of photosensitizers and photosensitizer precursors. Both dissolving and hydrogel-forming MN proved effective in in vitro studies and we are now proceeding with animal investigations prior to preliminary human evaluation of technology with the potential to improve therapeutic outcomes for patients with nodular skin lesions.

Original languageEnglish
Pages (from-to)641-647
JournalPhotochemistry and Photobiology
Volume90
Issue number3
Early online date11 Nov 2013
DOIs
Publication statusPublished - 01 May 2014

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry

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