Doenças fúngicas oculares: uma abordagem de desenvolvimento tecnológico para tratamento in situ

Abstract

Cornea Fungal infections are among the main causes of blindness in the world. The drawbacks displayed by formulations used to treat these diseases are contributing factors for the establishment of this worrisome scenario. Among such biopharmaceutical limitations, one could mention the low absorption and retention of the drug in the target tissue, which results in a poor local bioavailability and, by consequence, therapeutic failure. Therefore, the aim of this work was to develop hydrogels based on poly(vinyl alcohol) (PVA) containing amphotericin B (AmB) to be used as therapeutic contact lenses. For this purpose, a central composite design (CCD) was used, wherein the influence of the sodium hydroxide concentration ([NaOH]), temperature (Cº) and sodium trimethyl phosphate (STMP) concentration were assessed regarding the degree of swelling response (DS %) and loading efficiency (LE%). Additionally, mathematical models were developed in order to predict the behavior of the response variables, as well as to determine the levels of the formulation parameters necessary to obtain a system with desirable characteristics for the ocular pathway. After statistical optimization, the formulations were evaluated for swelling kinetics, the diffusional exponent (n), the diffusion constant (k) and the diffusion coefficient (D). The chosen formulation was characterized of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), Thermogravimetry (TG) and transmittance. Hydrogels with DS % between 125 to 181 and LE% between 39 to 72 were produced. The thickness varied between 0.101 to 0.169 mm. In addition, was observed that only [NaOH] demonstrated a significant effect on the response variables, being possible to elaborate an adequate predictive model for DS %, in which to foresee the concentration of NaOH necessary in the production of the hydrogel to reach the maximum desired swelling degree. In addition, models were developed that made it possible to predict the diffusion rate of the solvent into the hydrogel, the diffusion constant and the mechanism involved in the swelling process of the hydrogel, applying only in the equation the concentration of NaOH. Additionally, the characterization results showed that the crosslinking reaction was effective. This was inferred by the absence of the characteristic peaks of the phosphate ring from the STMP in the FTIR spectra. FTIR and DCS analyses demonstrated that AmB is probably located between the polymeric networks of the hydrogel. DSC and TG data from allowed us to infer that AmB is probably dispersed in amorphous form between the polymeric. Therefore, it is possible to suggest that the developed contact lenses presented some essential properties that make it viable for the ocular route, with prospection to become a new ophthalmic therapeutic alternative.