Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR has been hampered due to its low bioavailability resulting from gastrointestinal degradation, inefficient permeability, and low aqueous solubility. The objective of the present research was to formulate and characterize naringenin-loaded chitosan nanoparticles (NAR NPs) for nose-to-brain delivery. The cellular uptake, cytotoxicity, and neuroprotective effects of NAR NPs were determined using the SH-SY5Y cell line in vitro. NAR NPs were prepared using the ionic gelation method and characterized by zetasizer, transmission electron microscopy (TEM), and field emission microscopy (FESEM). The average particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h in vitro release profile were 87.6 ± 8.47 nm, 0.31 ± 0.04, 15.36 ± 2.05 mV, 91.12 ± 2.99%, and 54.80 ± 4.22%, respectively. The percentage NAR permeation through nasal mucosa from NPs was found to be 67.90 ± 0.72%. Cellular uptake of prepared NPs was confirmed by fluorescence microscopy. Neuroprotective activity of NAR NPs was evaluated through viability assays and by estimating reactive oxygen species (ROS) levels. NAR NPs showed enhanced neuroprotective ability and antioxidant effect against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. However, animal studies are necessary to establish the potential of NAR NPs to be an effective carrier for the treatment of PD for nose-to-brain delivery.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder that results in a decreased nigrostriatal availability of dopamine [1]
As we know from the previous literature [29,30], dopamine agonists induce antioxidant activities via increasing the activities of radical-scavenging enzymes or by direct scavenging of free radicals. These results show an improvement in antioxidant activity of naringenin-loaded chitosan nanoparticles (NAR NPs) in SH-SY5Y cells as compared to NAR itself; this is probably due to the small size of the NAR NPs and their better cellular uptake [29,30]
The NAR NPs were optimized on the basis of various process variables such as CS concentration, TPP
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder that results in a decreased nigrostriatal availability of dopamine [1]. In the context of the pathogenesis of PD, oxidative stress is generated because of dysfunction of mitochondria and oxidative metabolism of dopamine [2]. Free radicals generated due to mitochondrial dysfunction could be responsible for the oxidative damage which further generates reactive oxygen species (ROS) resulting in a vicious cycle. The increase metabolism of dopamine, lipid peroxidation, and nitric oxide and reduced level of endogenous antioxidant enzymes such as glutathione (GSH) and superoxide dismutase in the brain could be responsible for neuronal death [3]. Antioxidants have been shown to be highly effective in experimental PD [4,5,6], controlled clinical trials have shown no therapeutic effect [7]. There is an ongoing quest to identify antioxidant-based therapeutics
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