Estudo da presença de colesterol na atividade fotodinâmica de ftalocianinas lipossomais

Abstract

The treatment of diseases in modern civilization using new models instead classical interventions has been considered an important research line for infection and tumors treatment. In this context, the photodynamic inactivation appears as an alternative way to inviabilize cells in cancer treatment and pernicious infections. The combination of light in appropriate wavelength, a photosensitizer, like phtalocyanines, and molecular oxygen is capable to generate oxydizing species as singlet oxygen causing damages in cells. A drug delivery system is capable to increase the delivery effectiveness of drugs into cells and tissues. Liposomes are lipid formed vesicles containing phospholipids and cholesterol derivatives in several proportions and was used in this work to deliver zinc phtalocyanines to sheep red blood cells. Liposomal parameters like encapsulation rates, hemolysis caused by photoinactivation, effects of different proportions of cholesterol/phospholipids, nanoparticle diameters, superficial charge and stability on storage, were performed. We also performed computational simulations of lipid membranes added or not with cholesterol and zinc phthalocyanine, to obtain membrane density values, zinc phthalocyanine side diffusion, system and drug atomic mobility and density maps of the system. Liposomes with suitable ratio between free cholesterol and esterified cholesterol and phospholipids showed encapsulation rates of approximately 80%. The combination of an appropriated luminous intensity is capable to activate the photosensitizer generating reactive oxygen species that promotes the photoinactivation of red blood cells. The interation between photosensitizer and cholesterol or esterified cholesterol may change the spacial disposition of these species in vesicle affecting directly photoinactivation effectiveness. The liposomal formulations proposed in this work showed good stability in 45 days periods.