Desenvolvimento de nanocápsulas peguiladas de risperidona em diferentes óleos: avaliação in vitro e in vivo

Abstract

This study aims to develop PEGylated nanocapsules containing Risperidone (RIS) in different oils and evaluate its performance in vivo and in vitro. The oils utilized for the results comparison were sesame (Ge), linseed (Li), safflower (Ca), cod liver (Ba) and Caprylic/Capric Triglyceride (Tc). Nanocapsules containing RIS were elaborated by the interfacial deposition of performed polymer method, based on the 2³ factorial design, being the polymer, the drug and the oil the dependent variables. The validated method for RIS quantification, independent of the utilized oil showed itself specific, linear, accurate and robust; and it can be used for quantitative determination and predicative stability studies. The drug showed affinity in all tested oils and did not cause any degradation in the chosen polymer (PCL). PEG-4000 was the one chosen for the nanocapsules covering, due to the fact that it did not interfere in the basic parameters of characterization in these systems, and also because it is described in the literature as efficient in surpassing the blood-brain barrier. All the studied oils showed the capacity of abducing DPPH radical, but Tc. PEGylated nanocapsules of Risperidone in different oils, in a general manner, presented adequate characteristics of pH, mean diameter, PDI, zeta potential, content and rate of association and the oils rich in omega 3 and omega 6 showed themselves promising for the development of these systems, being paramount in several aspects to Caprylic/Capric Triglyceride (Tc). The factorial design showed itself adequate for the development of nanocapsules of Risperidone with different oils, proving the high prognostic capacity of the technique used in the optimization of laboratorial studies. The formulations NcTcF7, NcBaF8, NcGeF4, NcCaF4 e NcLiF4 were selected because they presented a good rate of association, diameter and zeta potential adequate, low PDI and a predicative value coherent with the practical. The studies of liberation of nanocapsules of Risperidone were conducted in a pH 1,2 buffer, since it was the local in which the drug presented better solubility and release profile. The release drug presented a monoexponential model of releasing and all the biexponential nanocapsules, presenting an initial burst effect, followed by a sustained releasing. The formulations NcCa-F4 e NcGe-F4 presented a differentiated profile, showing that they can extend the releasing of the active of the formulation. Based on the carried out studies, it was chosen the NcGe-F4 formulation because it liberated RIS from the system adequately and also because it presented a more consistent antioxidant capacity in all the evaluated concentrations. NcGe-F4 e NcTC-F7 did not present cytotoxic and genotoxic effects in the tested cells, demonstrating to be safe of the in vivo application. The in vivo study, which induced the pseudo psychosis, was carried out with the selected formulation and comparatively, with NcTC-F7. The results showed a significant difference among the formulations and the released drug, evidencing a superiority of NcGe-F4 in the releasing of RIS, over time. The in vitro studies were very similar to the in vivo studies, showing a good correlation among them. Besides, it was studied the possibility of raising the encapsulation efficiency of RIS in the linseed oil, controlling the pH in the aqueous phase of the formulation. Promising results were obtained when it was altered for the pH 7,0, obtaining a rise of 10,15% in the encapsulation efficiency.