A facile fabrication of dissolving microneedles containing 5-aminolevulinic acid

Photodynamic therapy induced by protoporphyrin IX (PpIX) is widely used to treat precancerous skin lesions. The penetration depth of the prodrug 5-aminolevulinic acid (5-ALA) using topical application is currently limited, which hampers the production of PpIX in deep seated lesions. To enhance 5-ALA delivery in deep skin layers, a soluble microneedles patch (MN-patch) containing 5-ALA has been successfully developed by using a fast solvent casting molding method which could be easily up-scaled. The shape, number and height of the needles have been designed according to the medical application and the mechanical strain necessary for skin insertion. Hyaluronic acid (HA) has been chosen as the needle materials due to its biocompatibility, fast solubility and biodegradation and was mixed with 5-ALA prior to casting. HA-based MN-patch containing 5-ALA have exhibited mechanical properties enabling a good insertion into the skin without significant damages to MN. Interactions between HA and 5-ALA were evaluated by Fourier transform infrared spectroscopy (FTIR) and carbon nuclear magnetic resonance (¹³C NMR), stability of 5-ALA in the MN-patch was monitored by proton nuclear magnetic resonance (¹H NMR) and exhibited a good stability over 5 months after manufacturing. Dissolution rate of the whole patch was completed in 1 hour in ex vivo rat skin without cytotoxicity. Overall, the MN-patch can be a promising technique to enhance 5-ALA penetration and produce PpIX in deeper skin lesions.