Dissolving microneedles with aminolevulinic acid for PDT

Abstract

Photodynamic Therapy (PDT) is a therapeutic modality that has been applied mainly to skin cancer treatment. For topical PDT, the photosensitizer (PS) precursors are usually applied in a cream form. Aminolevulinic Acid (ALA) and its derivatives are the most common photosensitizer’s precursors used, allowing the Protoporphyrin IX (PpIX) accumulation. One of the challenges in topical PDT for skin cancer is to increase the cream permeation to improve the success rate and treat deeper lesions. Microneedles (MNs) are minimally invasive systems already used for intradermal vaccination, delivery of systemic drugs such as antibiotics or hormones. In this study, we prepared dissolving MNs using 5% ALA concentration and 20% of Gantrez AN-139 polymer. The patch has 361 pyramidal microneedles with 500 μm high. The tests of mechanic strength, dissolution, and stability of MNs were encouraging to perform this study. Three healthy volunteers received the MNs patches on the forearm, and optical coherence tomography (OCT) images were collected showing the induced microholes in the skin after the MN removal. We compared the superficial PpIX formation of the dissolving MNs and the standard cream at 20% concentration by a fluorescence spectroscopy system. The study showed that even in lower concentration, the MNs were able to produce a similar amount of PpIX compared to the cream in the same incubation time. The results were encouraging to perform an animal tumor model to support the understanding of the PDT.