Hydrogel‐Forming and Dissolving Microneedles for Enhanced Delivery of Photosensitizers and Precursors |
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| Authors: | 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 |
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| Institution: | 1. School of Pharmacy, Queen's University Belfast, Medical Biology Centre, , Belfast, UK;2. School of Pharmacy, Zarqa University, , Zarqa, Jordan;3. Tyndall National Institute, University College Cork, , Cork, Ireland;4. School of Pharmacy and Pharmaceutical Sciences, University of Ulster, , Coleraine, UK |
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| 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. |
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