Estudo de filmes de policaprolactona carreados com atorvastatina para potencial aplicação em regeneração tecidual

Abstract

Damage to cartilaginous and bone tissue is caused by several factors such as trauma, inflammation and aging and can lead to tissue loss with functional impairment. Because it is a fabric that has low or even no regenerative capacity, treatment and recovery is difficult. In an attempt to overcome these problems, researchers have developed and perfected different regenerative techniques based on the use of polymeric biomaterials. Along with these, it is of interest to use a drug with beneficial properties to assist the treatment of cartilage areas damaged by the wear and tear caused by inflammation and injury. Atorvastatin (ATV), a cholesterol-lowering statin, has shown interesting secondary actions in several studies, such as bone anabolism due to its prolonged use. However, high doses of this input are necessary for this purpose and the commercialized forms of this drug are tablets for oral use, with little direction for cartilage and bone tissue. Thus, the objective of the work was to develop and evaluate polymeric films for controlled release of atorvastatin. In this context, films composed of polycaprolactone (PCL), a biodegradable synthetic polymer containing ATV, were developed. The films were produced using the solvent casting technique using two different methodologies¸ without and with drug solubilization (methods 1 and 2 respectively) and with different drug / polymer proportions. These were characterized by scanning electron microscopy (SEM), SEM coupled to dispersive energy spectroscopy (EDS), X-ray diffraction (DRX), Fourier transform infrared spectrometry (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry. (DSC). According to the results obtained by these techniques, it was possible to conclude that the films produced by method 2 were considered better because they present greater homogeneity in the dispersion of the drug. The release of the drug present in the best films was evaluated in a phosphate buffer solution (pH 7.4) at 37 ° C and rotation of 75 rpm in a dissolver with fiber optic sensors, recording the release at predefined times for 5 days. Through this test it was demonstrated that it was released in the studied time in a prolonged way, and that both the material morphology and the diffusion process have an influence on the release mechanism, suggesting that the material on the surface is released first and then, the film is eroded, making the drug available. The degradation of the films was observed through the SEM performed after the release, proving the erosion process. Therefore, the developed films have potential application for controlled release of drugs, and may in the future be used as a biomaterial for the regeneration of cartilage tissue