Estudo e avaliação de pontos quânticos bifuncionais para aplicação como marcadores ópticos e transportadores de fármaco para o segmento posterior do olho.

Abstract

The eye is a highly specialized organ, endowed with a specific conformation of its structures that is fundamental for the visual function. Disorders that affect the interior of the eye bulb tend to be highly harmful, since they compromise the homeostasis of this organ. The eye also has anatomical barriers that prevent the entry of substances, including drugs, in addition to a clearance mechanism that quickly removes substances from its interior. Thus, diseases that affect the retina are among those that present greater difficulty in treatment. In many cases, there is an abnormal proliferation of blood vessels (neovascularization) from the layers below the retina, with physiological and anatomical damage to its structure, causing rapid and irreversible vision loss. Therefore, this work aimed to develop and characterize nanosuspensions of quantum dots conjugated to bevacizumab, a biodrug used in the treatment of ocular neovascularization, in order to optimize its therapy. Quantum dots with CdS and AgInS2 cores coated with ZnS were produced by aqueous route, stabilized with chitosan and conjugated to bevacizumab. These systems were characterized for their absorption in the ultraviolet-visible region, photoluminescence, quantum yield, infrared absorption spectrum, zeta potential, hydrodynamic diameter, morphology by TEM and chemical composition by EDX spectroscopy. The data indicated that the samples showed high absorptivity between 190 and 550 nm, consistent with the type of material used in its composition, and photoluminescence between about 400 and 700 nm. The evaluation of infrared absorption and hydrodynamic diameter confirmed the conjugation of the antibody to chitosan. The evaluation of biosafety in animals, after its intravitreal administration, was performed by means of electroretinography, intraocular pressure measurement, histological, morphometric and immunohistochemical evaluation. No significant alterations that suggested damage to the retinal function by the samples were detected by means of electroretinography. Also, no significant changes in intraocular pressure were detected. Histological sections showed no signs of acute inflammation, however, there was evidence of late damage and accumulation of particles in the retina. The antiangiogenic activity was evaluated in a CAM model, whose results indicated conservation of the activity of bevacizumab. The results suggest that quantum dots have potential as a theranostic tool for the treatment of ocular neovascularization.