Localized delivery of Aza-BODIPY photosensitizer using dissolvable microneedle patch to treat oral carcinoma.

The clinical application of photodynamic therapy (PDT) is limited by the phototoxicity of the photosensitizer. Localized application of photosensitizers can reduce the phototoxic effects and improve PDT outcomes. The present study investigates the effectiveness of a microneedle patch administered with modified aza-BODIPY (AZP10) photosensitizer for PDT of oral squamous cell carcinoma. AZP10 showed the total reactive oxygen species (ROS) quantum yield of 0.62 +/- 0.09. The greater ROS production with 670 nm irradiation (100 mW/cm(2)) of AZP10 resulted in 86 +/- 1.9 % and 82 +/- 5.7 % growth inhibition of FaDu and MOC2 cells. Irradiation of FaDu spheroid in the presence of AZP10 significantly (P < 0.05) reduced the spheroid size from 600 +/- 22 to 120 +/- 16 microm in eight days, with 93 +/- 4 % cell growth inhibition. Dissolvable microneedle patch containing AZP10 (AZP10 DMN) showed rapid dissolution within 5 min, resulting in a 9.5-fold increase in flux of AZP10 across the excised porcine buccal mucosa compared with AZP10 solution. In vivo near-infrared fluorescence imaging of AZP10 DMNs application in the dorsal skin of tumor-induced C57BL/6 mice showed localization of AZP10 within the application site for up to 7 days. The application of AZP10 DMNs in MOC2 cell syngenic tumors showed complete remission after three irradiation cycles (670 nm; 100 mW/cm(2)), reducing the average tumor volume from 250 +/- 42 mm(3) to 10.9 +/- 2.7 mm(3), comparable to intratumoral injection of AZP10 solution. In conclusion, AZP10 DMNs can be developed as a potential minimally invasive delivery system for localized PDT of oral carcinoma.