Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model

Abstract

Purpose. The present study is an attempt to develop a vitamin E loaded naringenin (NRG) Nanoemulsion (NE) for direct nose-to-brain delivery for better management of Parkinson's disease (PD). Methods. The optimized NE was evaluated for efficacy in PD using multiple behavioral studies (including narrow beam test, muscular coordination test, grip strength test, forced swimming test, and akinesia test) in a rat model. Optimized formulation was evaluated for droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential, and viscosity. Results. Optimized NE had a droplet size of 38.70 ± 3.11nm, PDI of 0.14 ± 0.0024, refractive index of 1.43 ± 0.01, transmittance of 98.12 ± 0.07 %, zeta potential of − 27.4 ± 0.14 mV, and viscosity of 19.67 ± 0.25 Pa s. Behavioral studies showed that 6-OHDA induced PD in rats were successfully reversed when administered with NRG NE intranasally along with the levodopa. While the levels of GSH and SOD were significantly higher, levels of MDA were significantly lower in the group treated with NRG NE via intranasal route along with levodopa. Conclusion. Encouraging results from current study provide evidence for possible efficacy of a novel noninvasive intranasal delivery system of NRG for management of PD related symptoms.

Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells

“…Nanoemulsions are thermodynamically stable systems, thus showing good physical stability and would be expected to pass all thermodynamic stability tests [ 23 , 25 ]. Indeed, the selected naringenin-loaded nanoemulsion successfully passed all the thermodynamic stability tests, with no phase separation, creaming, or cracking.…”

“…Nanoemulsions provide a potential drug carrier for treatment of cancer and are suitable for various administration routes, such as oral, parenteral, and topical [ 21 ]. Nanoemulsions are produced by the dispersion of two immiscible phases of nanometric sizes ranging between 20 and 200 nm [ 23 ]. The kinetic stability of nanoemulsions results from using a surfactant, or mixture of surfactant with a co-surfactant, allowing immiscible liquids to become miscible in a single phase by lowering the interfacial tension between them [ 23 , 24 ].…”

“…Nanoemulsions are produced by the dispersion of two immiscible phases of nanometric sizes ranging between 20 and 200 nm [ 23 ]. The kinetic stability of nanoemulsions results from using a surfactant, or mixture of surfactant with a co-surfactant, allowing immiscible liquids to become miscible in a single phase by lowering the interfacial tension between them [ 23 , 24 ]. Naringenin nanoemulsions have been developed for the treatment of experimental Parkinson’s [ 23 ] and Alzheimer’s [ 25 ] diseases, but there have been few attempts to develop such nanoemulsions for the treatment of cancer.…”

“…The kinetic stability of nanoemulsions results from using a surfactant, or mixture of surfactant with a co-surfactant, allowing immiscible liquids to become miscible in a single phase by lowering the interfacial tension between them [ 23 , 24 ]. Naringenin nanoemulsions have been developed for the treatment of experimental Parkinson’s [ 23 ] and Alzheimer’s [ 25 ] diseases, but there have been few attempts to develop such nanoemulsions for the treatment of cancer. Sandhu et al [ 26 ] developed a self-emulsifying nanosystem for the co-delivery of naringenin and tamoxifen, demonstrating its effectiveness on MCF-7 breast cancer cells, as well as its in vivo effectiveness in a rat breast cancer model [ 26 ].…”

Control of Reactive Oxygen Species for the Prevention of Parkinson’s Disease: The Possible Application of Flavonoids

“…Consequently, flavonoids can control the secondary oxidative stress through the induction of antioxidant enzymes and reduction of inflammation and cytotoxicity-induced ROS ( Figure 2 ) [ 34 , 43 , 147 ]. Several studies evaluating the potential usage of flavonoids as preventive or therapeutic agents against PD by reducing the loss of dopaminergic neurons, vulnerable to oxidative stress, are organized in Table 3 [ 31 , 34 , 134 , 144 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 ].…”