Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration
Fabiola Silva Garcia Praca,
Wanessa Silva Garcia Medina,
Maria Vitoria Lopes Badra Bentley.
Topical photodynamic therapy (PDT) has been applied to almost all types of nonmelanoma skin cancer and numerous superficial
benign skin disorders. Strategies to improve the accumulation of photosensitizer in the skin have been studied in recent years. Although
the hydrophilic phthalocyanine zinc compound, zinc phthalocyanine tetrasulfonate (ZnPcSO4) has shown high photodynamic efficiency
and reduced phototoxic side effects in the treatment of brain tumors and eye conditions, its use in topical skin treatment is currently
limited by its poor skin penetration. In this study, nanodispersions of monoolein (MO)-based liquid crystalline phases were studied
for their ability to increase ZnPcSO4 uptake by the skin. Lamellar, hexagonal and cubic crystalline phases were prepared and identified by
polarizing light microscopy, and the nanodispersions were analyzed by dynamic light scattering. In vitro skin penetration studies were
performed using a Franz's cell apparatus, and the skin uptake was evaluated in vivo in hairless mice. Aqueous dispersions of cubic and
hexagonal phases showed particles of nanometer size, approximately 224 ±10 nm and 188 ± 10 nm, respectively. In vitro skin retention
experiments revealed higher fluorescence from the ZnPcSO4 in deeper skin layers when this photosensitizer was loaded in the hexagonal
nanodispersion system when compared to both the cubic phase nanoparticles and the bulk crystalline phases (lamellar, cubic and hexagonal).
The hexagonal nanodispersion showed a similar penetration behavior in animal tests. These results are important findings, suggesting
the development of MO liquid crystal nanodispersions as potential delivery systems to enhance the efficacy of topical PDT.
Keywords: Liquid crystalline phases, nanodispersion, skin cancer, skin penetration, photodynamic therapy, zinc phthalocyanine
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