Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

Abstract

Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson's disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml(-1) of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

“…Liver index was significantly higher than the steatosis group only in the RSV group (Table 1). Such protective effect of RSV on steatohepatitis may be attributed to its antioxidant and antiinflammatoty potentials (Al Maruf & O'Brien, 2014;Bujanda et al, 2008;Pangeni et al, 2014), promoting regeneration of old damaged hepatocytes.…”

“…It acts as a strong antioxidant, reported to inhibit low-density lipoprotein oxidation and to ameliorate oxidative stress induced in vivo and in vitro (Al Maruf & O'Brien, 2014;Pangeni et al, 2014;Suwalsky et al, 2015). RSV acts also by lowering hepatic fat content, reducing cholesterol levels and inhibiting platelet aggregation (Prasad, 2012).…”

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

“…34,152,162 Resveratrol has multiple health benefits, including antiaging, anticancer, cardioprotective, and PD protective effects. 66,68,145 Resveratrol exists in cis and trans forms, in which trans-resveratrol is more stable than cis-resveratrol which is pharmacologically less active. 66 Trans-resveratrol is readily converted to cis-resveratrol when exposed to sunlight for 1 hour; therefore, protecting these compounds is biologically more important for a sustained effect.…”

“…144 Similarly, a vitamin E-loaded resveratrol nanoemulsion with 102 nm particles was produced using the spontaneous emulsification technique and reduced brain-induced oxidative stress to treat PD. 145 A pomegranate seed oil nanoemulsion with 135 nm particles was produced using the sonication technique and reduced lipid peroxidation and neuronal loss with strong protective effects. 146 Several other plant bioactive compounds have been studied using nanoemulsion delivery methods, such as a betlunic acid nanoemulsion with 200 nm particles produced by sonication and enhanced bioavailability.…”

“…9,11,60,66,[149][150][151] Nanosizing of phytobioactive compounds along with suitable protective agents enhances the bioavailability of the compound to the brain. 24,72,95,145,152 A few of the bioactive nanosize compounds with enhanced bioactivity and less toxicity are discussed in this section. Some of these nanobioactive compounds are listed in Table 1.…”