RESUMO
Topical application of aluminum-chloride phthalocyanine (AlClPc) is a challenge because of the drug's extremely low solubility, which prevents its absorption into deeper skin layers and causes molecule aggregation, reducing the photophysical effect. The goal of this study was to obtain a formulation applied in a certain condition that would allow homogeneous accumulation of AlClPc in cutaneous tissues, meaning a safer and non-invasive topical treatment for skin tumors based on photodynamic therapy. We first prepared and characterized AlClPc complexes with cyclodextrin to increase the photosensitizing agent solubility. The inclusion complex of AlClPc with hydroxypropyl-ß-cyclodextrin (HP-ßCD) amplified its loading dose in aqueous medium and maintained its photosensitizing properties in terms of reactive oxygen species production. Assays to determine the complex's in vitro cytotoxicity against murine melanoma skin cancer cells showed that when irradiated, the complex significantly reduced cell viability, whereas the absence of irradiation did not affect cell viability. Three physical techniques for permeation enhancement (i.e., tape-stripping abrasion, microneedle pretreatment and iontophoresis) were then evaluated. When applied in impaired skin, the complex could not increase drug penetration. The skin penetration of AlClPc, however, increased 2.3-fold following iontophoresis application in a shorter period compared to passive permeation. Therefore, these results suggest the administration of complexed AlClPc mediated by iontophoresis, followed by application of photodynamic therapy, might be an effective and non-invasive alternative for topical treatment of cutaneous tumors.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , Cloreto de Alumínio/administração & dosagem , Indóis/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Compostos Organometálicos/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , 2-Hidroxipropil-beta-Ciclodextrina/química , Administração Cutânea , Cloreto de Alumínio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Indóis/química , Iontoforese , Camundongos , Compostos Organometálicos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/química , Pele/metabolismo , Absorção Cutânea , SuínosRESUMO
Local treatment of vaginal diseases presents advantages over systemic treatments and the interaction of the drug delivery systems with the biological tissue is a key factor for a successful vaginal topical therapy. Conventional protocols for permeation studies have high variability and fail in distinguishing drug penetration from mucoadhesive or colloidal drug delivery systems from conventional formulations, as tissue interaction is normally under estimated. The protocol presented in this paper is a simplified ex vivo vertical model, in which formulations are placed in hung porcine vaginas with the objective of mimicking a condition closer to the biological circumstance, specifically considering the possible leak from the vaginal canal in the vertical position. The results indicate the proposed method was capable of differentiating formulations performances and histological evaluation showed mucosa structures are preserved during this new assay. Therefore, the ex vivo method can be considered reliable for approaching the physiological situation in comparative studies.