ALUMINIUM CHLORIDE PHTHALOCYANINE VIA HEXAGONAL LIQUID CRYSTAL NANODISPERSION EFFICIENTLY INHIBITS TUMOUR CELL GROWTH AND INDUCES NUCLEUS DAMAGE AFTER PHOTODYNAMIC THERAPY

Tulio Ruiz Eschiapati, Jessica Bidurin Picolo, Bruna Stangherlin, Gustavo Gonçalves Maciel, Fabiola Garcia Praça, Juliana Rosa Viegas, Ana Vitoria Silvestrini, José Orestes Del Ciampo, Maria Vitoria Lopes Badra Bentley and Wanessa Silva Garcia Medina*

ABSTRACT

Topical photodynamic therapy (PDT) is a two-stage therapy which combines the use of photosensitizing drugs and light energy activating a cascade of phototoxic reactions and consequent tumor death. PDT has been applied to almost every type of cancers including melanoma. Aluminum chloride phthalocyanine (AlClPc) is a lipophilic photosensitizer widely used in preclinical studies of PDT for the treatment of skin cancer.[5] Besides AlClPc has excellent photochemical and photodynamic activity, this is insoluble in water, which limits its bioavailability and its administration in a physiological environment. In this scenario, several strategies have been proposed to improve the skin accumulation of photosensitizers, mainly the use of drug delivery system-based nanotechnology. In this study, we described the preparation and characterization of hexagonal liquid crystalline nanodispersion (LCN) as drug delivery system-based nanotechnology for AlClPc. Also, in vitro phototoxicity effect on A375 cells and cell damage, were evaluated to investigate its efficacy in PDT. AlClPc-loaded LCN was characterized according to their particle size, distribution and zeta potential, morphological aspects by atomic force microscopy, stability and phototoxic action in melanoma cell line (A375). The means of particle size were 198.56 (±1.0) and 179.7 (±2.0) for LCN in absence or AlClPc presence, respectively. Negative zeta potential was approximately 40 and AlClPc-loaded LCN maintained their physical stability from particle size and distribution over 15 days. In addition, AlClPc-loaded LCN also presented biocompatibility in the dark for normal keratinocytes cell (HaCat) from 4 to 1300ng/mL and potent antitumor effect in PDT using 1J/cm2 for melanoma cell (A375) with nuclear cell damage at 300ng/mL. This study demonstrated that AlClPc-loaded LCN is a potent and promising drug delivery system-based nanotechnology for use in PDT.

Keywords: Photodynamic Therapy, Liquid crystal nanodispersion, Chloro-aluminium phthalocyanine, tumor cells, cancer treatment.