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In this work we evaluated the photophysical and in vitro properties of Foscan®, a second-generation photosensitizer drug (PS) widely used in systemic clinical protocols for cancer therapy based on Photodynamic Therapy (PDT). We employed biodegradable nanoemulsions (NE) as a colloidal vehicle of the oil/water (o/w) type focusing in topical administration of Foscan® and other photosensitizer drugs. This formulation was obtained and stabilized by the methodology described by Tabosa do Egito et al., based on the mixture of two phases: an aqueous solution and an organic medium consisting of nonionic surfactants and oil. The photodynamic potential of the drug incorporated into the NE was studied by steady-state and time-resolved spectroscopic techniques. We also analyzed the in vitro biological behavior carried out in mimetic biological environment protocols based on the animal model. After topical application in a skin animal model, we evaluated the Foscan®/NE diffusion flux into the skin layers (stratum corneum and epidermis + dermis) by classical procedures using Franz Diffusion cells. Our results showed that the photophysical properties of PS were maintained after its incorporation into the NE when compared with homogeneous organic medium. The in vitro assays enabled the determination of an adequate profile for the interaction of this system in the different skin layers, with an ideal time lag of 6 h after topical administration in the skin model. The Foscan® diffusion flux (J) was increased when this PS was incorporated into the NE, if compared with its flux in physiological medium. These parameters demonstrated that the NE can be potentially applied as a drug delivery system (DDS) for Foscan® in both in vitro and in vivo assays, as well as in future clinical applications involving topical skin cancer PDT.

publicado na web em 07/06/2018 Natural naphthoquinones such as lapachol (Lp) have demonstrated promising biological activities. However, these quinones present low systemic biodisponibility due to its poor aqueous solubility. To overcome this problem, nanoemulsions (NE) formed by oily core are able to incorporate hydrophobic molecules thus enabling them to be dispersed into an aqueous phase. The present study reports the development, characterization, and physical stability of NE containing lapachol. NE formulations (F1, F2, F3, F4, and F2-Lp) were prepared using emulsion phase inversion (EPI) method and characterized in relation to droplet size, size distribution (PDI), zeta potential, and physical stability. The formulation chosen to incorporate lapachol (F2-Lp) showed droplet size in nanometric scale with homogeneous size distribution (PDI < 0.2) and negative zeta potential (about −30 mV). In addition, good physical stability of F2 and F2-Lp was demonstrated using analytical centrifugation with photometric detection where the light transmission profiles did not change throughout the dispersions. Nanoemulsion containing lapachol presented a strong reddish aspect; however, the incorporation of this naphthoquinone did not alter the main physicochemical parameters of NE formulation. The in vitro release study demonstrated a sustained release profile from NE with about 60% of lapachol released within 54 h.

The labels with Mitotracker and NAO demonstrated mitochondrial migration to the perinuclear region, confirmed through electron microscopy, suggesting that intact mitochondria were solicited for possible DNA fragmentation.