Dissolvable layered microneedle patch containing 5-fluorouracil for localized treatment of oral carcinoma

The matrix-forming microneedle-based drug delivery system has the potential to localize drug dosage to the application site and limit systemic effects. Here, we report the development of sodium carboxymethyl cellulose, sodium alginate, and PEG 400 composite dissolvable microneedle patch for insertion in the buccal mucosa. The patch with pyramidal-shaped microneedles in 20 x 20 array format was fabricated by micromolding technique. The chemotherapeutic agent, 5-fluorouracil (5FU)-loaded microneedle patch, was characterized for physical and mechanical properties using a stereomicroscope, scanning electron microscope, and texture analyzer. Confocal laser scanning microscopy showed that microneedles were able to penetrate up to a depth of 120 µm inside the excised porcine buccal mucosa. The microneedles dissolved within 30s and 20 min after insertion in phosphate buffer and the excised buccal mucosa. 5FU permeation studies in the excised porcine buccal mucosa revealed a 1.8-fold greater flux after applying a microneedle patch compared with the 5FU solution. Applying a microneedle patch in the rat buccal mucosa for 30 min resulted in an accumulation of 330 µg/g of 5FU in the buccal tissue. In contrast, intravenous administration showed 5FU concentration below the detection limit in buccal tissue. In conclusion, a dissolvable microneedle patch can be developed for localized delivery of 5FU to treat oral carcinoma.

Graphical abstract

The pyramidal-shaped dissolvable polymeric microneedle patch loaded with 5-fluorouracil was fabricated through the micromolding technique. The microneedles demonstrated sufficient mechanical strength to penetrate buccal mucosa up to 120 µm. The microneedles dissolved after application into the buccal mucosa releasing 5-fluorouracil for localized drug delivery.