Desenvolvimento de compostos de inclusão entre ciclodextrinas e metiltestosterona e sua aplicação em aquicultura

Abstract

17α-methyltestosterone (MT) is a synthetic androgen widely employed in the sexual reversion of tilapias. Due to its physico-chemical properties, cyclodextrin (CD) used in the formation of inclusion compounds with MT, represents a new possibility of method for sexual inversion. The hydroxyls, external to the cavity, allow their modification and stabilization in a series of supports, such as silica for example. In this work, the inclusion complexes between MT and γ-cyclodextrin (gCD) were prepared by lyophilization and malaxation, it was made the functionalization of the silica with as α, β and γ CDs, adsorption tests of the MT with the composite obtained with the β-cyclodextrin (bCD)were made and also addressed in the complexation and adsorption systems with dissipative particle dynamics (DPD) models. The complexes were characterized by spectroscopic methods and thermal analyzes. The behavior of the hormone in the presence of gCD was evaluated for the polarity change of the solvation environment. The solubility evaluation was performed by the Higuchi and Connors phase method, whose association with gCD in aqueous medium is quite favorable, with an association constant, Ka, of 26,000 L mol-1 and an increase of seventeen fold in solubility of the hormone. Differential scanning calorimetry evaluated the formation of the solid state complexes, and the included fraction was 83% for the lyophilized formulation. The host-guest interactions were evaluated by 1H NMR and DOSY measurements, JobPlot experiments indicated that the complexation occurs in a molar ratio of 1:1 and the association constant obtained by DOSY was 10,970 L mol-1 (DMSO/D2O, 1:3). ROESY 2D experiments were used to obtain the conformation of the complex, which is totally enclosed in the hydrophobic cavity of the gCD and has the carbonyl group facing the wider face of the oligosaccharide, in agreement with the calculations of molecular mechanics and molecular dynamics. Tests performed in vitro showed a release about 40% slower compared to free MT. The functionalization of CDs on the silica surface was carried out at reflux using xylene as solvent, with an organic anchoring around 60%, determined by thermogravimetric analysis. Citric acid used in the synthesis acted as a linker between the surface hydroxyls of the inorganic matrix and the primary hydroxyl of the oligosaccharides, evidenced by solid-state 13C NMR and infrared spectroscopy. The adsorption of N2 showed a reduction of the surface area of the composites relative to the unmodified silica, in proportion to the size of the CDs. The adsorption experiments of MT in the bCD composite showed better results in acidic pH, and indicated a fast kinetics, in which the interactions involved in the adsorption are of a physical nature, evidenced by the low magnitude in the value of ΔH equal to -3.13 kJ mol-1. The best adsorption correlation with the Sips and Langmuir model indicated a monolayer formation (complexes with functionalized bCDs), with a maximum removal capacity of MT of 13, 12, 11 and 10 mg g-1 of composite, at temperatures of 25, 35, 45 and 55 °C, respectively. The negative ΔG indicated the spontaneity of the adsorption, with a ΔS of 74.3 J mol-1 K-1 characteristic of the coating of the adsorbent surface. The composite was efficient for the removal of the hormone in the column filtration system. Desorption, performed in ethanol, is quick and left the material in perfect reuse condition. DPD modeling did not present conclusive results, possibly due to the incongruences or limitations between the parameters and the model for the MT molecule.