Desenvolvimento de suspensões e granulados nanotecnológicos contendo o antioxidante hidrofílico pirroloquinolina quinona

Abstract

Pyrroloquinoline quinone (PQQ) is a naturally occurring hydrophilic o-quinone which has shown different biological activities, as potent antioxidant activity. In order to improve its pharmacological performance and to exploit its potential, it is possible to associate this active substance to liquid nanostructured systems. In this work, PQQ-loaded polymeric nanoparticle suspensions were developed, using double emulsification-solvent evaporation method, with two different polymers, poly(ε-caprolactone) (PCL) or Eudragit® RS 100, and with two concentrations of active (0,5 or 1,0 mg/mL) optimizing a formulation to evaluate the PQQ release profile and its antioxidant activity in vitro against lipid peroxidation, as well as stability during storage. Later, in order to improve the stability, the optimized nanostructured suspension was converted into granulates by wet granulation technique, which were both physicochemical and technologically characterized and also subjected to the analysis of the kinetics of PQQ release and to stability for 90 days. Considering the results, the suspension developed with the PCL polymer showed particles with micrometric diameter, high polydispersion index (IPd) and reduced encapsulation efficiency (EE%; 6.42%). Conversely, the suspensions prepared with the Eudragit® RS 100 polymer demonstrated adequate physicochemical characteristics, with nanometric particle size (343-384 nm; Zetasizer®) and with acceptable size distribution. The formulation prepared with PQQ in concentration of 0.5 mg/mL was selected to following the study, since it presented EE% (52.17%) significantly higher than the other ones. The atomic force microscopy of this formulation confirmed the presence of spherical colloidal particles with a smooth surface. The nanostructured suspension demonstrated antioxidant activity, in vitro, higher than free PQQ by the TBARS method. In preliminary study, the nanoencapsulation protected PQQ against degradation, when compared to a solution of free PQQ. Considering that the suspension was unstable in only 15 days of storage, it was necessary to developgranulates, which demonstrated adequate both technological (angle of repose, Carr index, Hausner factor) and physicochemical characteristics (average particle diameter, IPd), being packaged in sachets as the final pharmaceutical form. Granulates were stable in all evaluated parameters for 90 days of storage. By scanning electron microscopy, it was also possible to observe the presence of spherical nanometric structures in the granules formed. The optimized colloidal suspension and the granulates containing the nanoencapsulated PQQ demonstrated very similar in vitro release profiles following monoexponential kinetics, with anomalous transport as release mechanism. In view of the obtained results, it is possible to conclude that the use of PQQ in polymeric nanoparticles significantly improve the antioxidant activity of this substance, even with partial encapsulation, as well as its conversion into granulates considerably improved the stability of the system, besides promoting some release control, compared to the free active. Thus, the granules containing the hydrophilic antioxidant PQQ nanoencapsulated are promising systems, mainly, to explore its effects in the prevention and/or treatment of diseases related to oxidative stress.