DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO EX VIVO EM ERITRÓCITOS DE NANOCÁPSULAS POLIMÉRICAS CONTENDO FERULATO DE HEXADECILA

Abstract

Many neurological disorder treatments are unsuccessful because they can not effectively reach the central nervous system (CNS). The presence of the blood-brain barrier (BBB) hinders this access and a lot of substances are unable to pass through it when used without any chemical or physical-chemical modification. The ferulic acid, a polyphenol found abundantly in nature and well known for its antioxidant, anti-inflammatory and anti-cancer activity, is widely studied and their neuroprotective activity has been described. One of the main problem, which limits its clinical use, is its low bioavailability when administered orally, it can be circumvented by changes in their structure and/or for preparing lipid-based formulations. In this way, the aim of this study was to synthesize a lipophilic derivative of AF, the hexadecyl ferulate (HF), and then get polymeric nanocapsules as vectoring system for its potential action in the CNS. The HF was obtained by esterification reaction and their structural characterization was performed by spectroscopy in the Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance. The structural modification did not annul the scavenger activity against the DPPH•, ABTS•+ and HOCl. The polymeric nanocapsules in concentration from 0 to 2.0 mg.mL-1 were developed by interfacial deposition method of the polymer using poly (-caprolactone) (PCL), and blends with polyethylene glycol (PEG). All prepared formulations presented spherical and smooth surface, as observed by scanning electron microscopy (SEM) with field emission, pH between 5.75 and 6.04, proper sizes below 234 nm, polydispersity index below 0.26, ensuring homogeneity, and zeta potential with negative values between -28 and -38 mV, suggesting stability of the suspensions of polymeric nanocapsules. The nanoencapsulation process promoted the FH amorphization. This was verified by X-ray diffraction analysis, differential scanning calorimetry (DSC) and SEM. It also promoted the increasing thermal stability of the FH which was verified by thermogravimetry and DSC, and FTIR analysis demonstrated there was no interaction between HF and the used polymers.Toxicity studies in erythrocytes showed that HF , in free or nanocapsule formulations of PCL- PEG, showed no hemolytic action, even with variations in dose tested and function of time. Additionally, introduced protective effect on hemolysis promoted by AAPH. The possible action of the developed formulations of CNS, considering that they have appropriate characteristics for your vectorization, should be investigated in the future.