Dissolving microneedles containing aminolevulinic acid improves protoporphyrin IX distribution.

One important limitation of topical photodynamic therapy (PDT) is the limited tissue penetration of precursors. Microneedles (MNs) are minimally invasive devices used to promote intradermal drug delivery. Dissolving MNs contain drug-associated to polymer blends, dissolving after insertion into skin, allowing drug release. This study comprises development and characterization of a pyramidal model of dissolving MNs (500 µm) prepared with 5% wt/wt aminolevulinic acid and 20% wt/wt Gantrez AN-139 in aqueous blend. Protoporphyrin IX formation and distribution were evaluated in tumor mice model by using fluorescence widefield imaging, spectroscopy, and confocal microscopy. MNs demonstrated excellent mechanical resistance penetrating about 250 µm with minor size alteration in vitro, and fluorescence intensity was 5-times higher at 0.5 mm on average compared to cream in vivo (being 10 ± 5 a.u. for MNs and 2.4 ± 0.8 a.u. for cream). Dissolving MNs have overcome topical cream application, being extremely promising especially for thicker skin lesions treatment using PDT.

Theoretical and Experimental Analysis of Protoporphyrin IX Photodegradation Using Multi-Wavelength Light Sources.

Photodynamic procedures have been used in many applications, ranging from cancer treatment to microorganism inactivation. Photodynamic reactions start with the activation of a photosensitizing molecule with light, leading to the production of cytotoxic molecules that promote cell death. However, establishing the correct light and photosensitizer dosimetry for a broadband light source remains challenging. In this study, we proposed a theoretical mathematical model for the photodegradation of protoporphyrin IX (PpIX), when irradiated by multi-wavelength light sources. The theoretical model predicts the experimental photobleaching (temporal change in PpIX concentration) of PpIX for different light sources. We showed that photobleaching occurs independently of the light source wavelengths but instead depends only on the number of absorbed photons. The model presented here can be used as an important mathematical approach to better understand current photodynamic therapy protocols and help achieve optimization of the doses delivered.

Development of a system to treat and online monitor photodynamic therapy of skin cancer using PpIX near-infrared fluorescence.

The limited adoption of photodynamic therapy (PDT) around the medical field may be tied to the unpredicted treatment response that an unmonitored therapy could deliver. Given the high variability in the lesions optical and physiological parameters, it is of fundamental importance to monitor PDT, since different lesions require different therapeutic parameters. We developed a system to treat and online monitor PDT of skin cancer, using protoporphyrin-IX (PpIX) near-infrared fluorescence imaging. The system can be operated up to 150 mW/cm2 at 633 nm, with real-time fluorescence monitoring around 700 nm, using the treatment light itself for fluorescence excitation. This technology allows system portability, simplicity, and low cost. This study describes the system development and its comparison with a 400-450 nm commercial system to detect the PpIX fluorescence during a PDT in murine skin cancer model. The developed device was able to acquire considerably more fluorescence signal from deeper regions when compared to the violet excitation device.