5-Aminolevulinic acid coated microneedles for photodynamic therapy of skin tumors

This study evaluated the potential of coated microneedles for improved dermal delivery of 5-aminolevulinic acid (5-ALA), which naturally gets converted by cells of the tissue in to a photosensitizer called protoporphyrin IX (PPIX). Microneedle patches containing 57 microneedles were coated with 5-ALA using an in-house developed micro-precision dip coater. The coating process was optimized to achieve higher 5-ALA loading on microneedles and a high delivery efficiency into porcine cadaver skin. Using 5 dips with 25% w/v 5-ALA solution, a mass of about 350 μg of 5-ALA was coated per patch, which gave a delivery efficiency of about 90% in porcine cadaver skin. Bright-field and scanning electron microscopy established that coatings of 5-ALA on microneedles of the patch were uniform. In vivo dermal pharmacokinetics showed that delivery of just 350 μg of 5-ALA using coated microneedles led to about 3.2-fold higher PPIX formation after 4 h, as compared to topical application of 20% w/w 5-ALA in a conventional cream formulation (25 mg cream). Furthermore, with use of coated microneedles, PPIX was observed in deeper regions of the skin (~ 480 μm) as compared to topical 5-ALA cream formulation (~ 150 μm). The potential of PPIX for photodynamic therapy was tested in vivo. After light exposure (633 nm; 118 J/cm²), PPIX got photosensitized, and due to higher initial amount of PPIX in the coated microneedle group, about twice the amount of PPIX was photobleached compared to topical cream application. Finally, even with a lower dose of just 1.75 mg 5-ALA, coated microneedles suppressed the growth of subcutaneous tumors by ~ 57%, while a topical cream containing 5 mg of 5-ALA did not suppress the tumor volume and led to tumor growth comparable to the untreated control group. Overall, the strategy of delivering 5-ALA using coated microneedles could be a promising approach for photodynamic therapy of skin tumors.