Abstract
This study was to investigate the neuroprotective effect of curcumin against inflammation-mediated dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease (PD). Curcumin loaded sodium hyaluronate based mucoadhesive microemulsion (CMME) was developed by using Box Behnken design of Response surface method (RSM) and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals followed CMME intranasal administration for 14 days at 2.86 mg of curcumin/kg of body weight per once a day. Optimal CMME containing 3% Capmul MCM as oil phase, 37 % of Accenon CC and Transcutol HP at 2.5:1 ratio and 0.5% sodium hyaluronate was stable, non-ciliotoxic with 57.66 nm±3.46 as average globule size. PdI value (0.190 ± 0.19) and TEM result depicted the narrow size distribution of CMME.All three independent variables had a significant effect (p<0.05) on the responses and the designed model was significant for all taken responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of CMME. MPTP intoxication significantly decreased striatal DA content to 21.29 % which was then elevated to 55.37% after intranasal curcumin treatment. Significant improvement in motor performance as well as gross behavioural activity of mice was observed from rota-rod and open field test findings. Findings of the investigation revealed the symptomatic neuroprotection of curcumin against MPTP-induced neurodegradation in the striatum and hence could be considered as a promising approach to treat PD.
Highlights
Neuroinflammation may contribute to the progressive dopaminergic neuronal loss in substantia nigra pars compacta (SNPS) of brain that has been observed in some experimental models of Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra (Lindvall et al, 2003; Hirsch, Hunot, 2009)
MPTP is enzymatically converted into its toxic metabolite MPP+ (1-methyl-4-phenylpyridinium) by the enzyme monoamine oxidase-B (MAO-B), primarily in astrocytes of brain and is known to damage dopaminergic neurons in the substantia nigra pars compacta (SNpc) (Reznichenko et al, 2010)
Group IV- Animals were first treated with MPTP (4×20 mg/kg/day) in the same above method followed by intranasal applied plain drug solution (CPG) at 2.86 mg of curcumin/kg of body weight for 14 consecutive days
Summary
Neuroinflammation may contribute to the progressive dopaminergic neuronal loss in substantia nigra pars compacta (SNPS) of brain that has been observed in some experimental models of Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra (Lindvall et al, 2003; Hirsch, Hunot, 2009). The nasal route may provide a better alternative to oral or intravenous administration for the brain delivery of Curcumin. Microemulsions are thermodynamically stable and isotropic systems of oil, water, surfactant and cosurfactant mixture with a droplet size usually in the range of 10-100 nm These systems, by virtue of their low globule size and ability of improving aqueous solubility of poor water soluble drug like Curcumin, are widely explored as nasal drug delivery system to enhance CNS uptake (Patel, Mandal, Rajesh, 2012). The objective of this investigation is to explore the unique nose to brain connection through the optimal CMME and to perform the comparative neuroprotective effect of curcumin in MPTP induced mice model of Parkinson’s disease
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