P1‐006: Incorporation of resveratrol into lipid‐core nanocapsules improves its cerebral bioavailability and reduces the Aβ‐induced toxicity

Abstract

Several studies have considered the resveratrol one promising molecule in protecting against Alzheimer's disease; however, its use is limited because it is easily oxidized and presents a very low bioavailability. Considering that nanoparticles have become an important component of therapeutic researches, the aims of this study were: 1) develop a polymeric lipid-core nanocapsules system containing resveratrol; 2) evaluate the bioavailability of resveratrol carried by these nanocapsules in healthy rat tissues; and 3) evaluate the effects of treatment with nanocapsules against Aß1-42-induced damage in rats. Nanocapsules containing resveratrol (1 mg/ml - RSV-NC) were prepared by interfacial deposition of the polymer. The mean diameters, polydispersity and zeta potentials were measured. Health rats were treated with free resveratrol or RSV-NC (5 mg/Kg) for 14 days using intraperitoneal (i.p.) and gavage routes. The amount of resveratrol in the brain, the liver and the kidney was analyzed by high-performance liquid chromatography (HPLC). Aß1-42 peptide (2 nmol) was stereotaxically injected bilaterally into lateral ventricles of Wistar rats. Behavioral analysis was performed 14 days after Aß1-42 intracerebroventricle injection. The treatment with free resveratrol or RSV-NC (5 mg/Kg i.p. every 12h) started 24h after Aß1-42 injection and was maintained for 14 days. >RSV-NC had a mean diameter of 241 nm, a polydispersity index of 0.2, a zeta potential of -15 mV as well as a high entrapment of resveratrol. Healthy animals treated with RSV-NC presented 2.5-, 6.6-, and 3.4-fold higher resveratrol concentration in the brain, liver and kidney, respectively than those treated with free resveratrol. The intracerebral infusion of Aß1-42 in rats, 2 weeks later, induced memory impairment. This impairment was significantly reduced only by the treatment with RSV-NC. Moreover, the lipid-core nanocapsules were able to successfully carry, at least 3-fold, more resveratrol into the brain when compared to free resveratrol treatment. Taken together, lipid-core nanocapsules exhibited great resveratrol encapsulation efficiency and increased the concentration of this polyphenol in the brain tissue. The present observations that resveratrol-loaded lipid-core nanocapsules reduce the memory impairment induced by Aß1-42 provide interesting perspectives on the use of this formulation for future therapeutic strategies for Alzheimer's disease.