Dissolving microneedles containing aminolevulinic acid improves protoporphyrinIXdistribution

One important limitation of topical photodynamic therapy (PDT) is the limited tissue penetration of precursors. Microneedles (MNs) are minimally invasive devices used to promote intradermal drug delivery. Dissolving MNs contain drug-associated to polymer blends, dissolving after insertion into skin, allowing drug release. This study comprises development and characterization of a pyramidal model of dissolving MNs (500 mu m) prepared with 5% wt/wt aminolevulinic acid and 20% wt/wt Gantrez AN-139 in aqueous blend. Protoporphyrin IX formation and distribution were evaluated in tumor mice model by using fluorescence widefield imaging, spectroscopy, and confocal microscopy. MNs demonstrated excellent mechanical resistance penetrating about 250 mu m with minor size alteration in vitro, and fluorescence intensity was 5-times higher at 0.5 mm on average compared to cream in vivo (being 10 +/- 5 a.u. for MNs and 2.4 +/- 0.8 a.u. for cream). Dissolving MNs have overcome topical cream application, being extremely promising especially for thicker skin lesions treatment using PDT.