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        Neuroprotective effect of ibuprofen by intranasal application of mucoadhesive nanoemulsion in MPTP induced Parkinson model

        Surjyanarayan Mandal,Snigdha Das Mandal,Krishna Chuttani,Krutika K. Sawant,Bharat Bhushan Subudhi 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.1

        This study was to investigate the neuroprotective effect of Ibuprofen by intranasal route against inflammationmediated by dopaminergic neurodegeneration in 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson’s disease (PD). Ibuprofen loaded sodium hyaluronate based mucoadhesive nanoemulsion (MNEI) was developed by using response surface methodology (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 by Ibuprofen for 2 consecutive weeks at 2.86 mg/kg of body weight per day. Optimal MNEI containing 3 % Labrafil M 1944 CS as oil phase, 36 %of Accenon CC and Transcutol P at 3:1 ratio and 0.5 % sodium hyaluronate was stable, non-ciliotoxic with 46.3 ± 2.28 nm as average globule size PdI value and TEM result showed the narrow size distribution of MNEI. The result showed that all three independent variables had a significant effect (p\0.05) on the responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of Ibuprofen through MNEI. MPTP intoxication significantly decreased striatal DA content to 29.92 % which was elevated to 58.21 % after Ibuprofen treatment using MNEI. Significant improvement in motor performance and gross behavioural activity of the mice was observed through the findings of rota-rod and open field test findings. Findings of the investigation revealed that Ibuprofen through developed MNEI was shown to protect neurons against MPTP-induced injury in the striatum and could be a promising approach to treat PD.

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        Brain targeting efficiency of Curcumin loaded mucoadhesive microemulsion through intranasal route

        Snigdha Das Mandal,Surjyanarayan Mandal,Jayvadan Patel 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.2

        This study was aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of curcumin through intranasal route. Suitable oil, surfactant and cosurfactant for the development of microemulsion were selected based on maximum curcumin solubility, drug excipients compatibility through FTIR study and non-toxicity to sheep nasal mucosa. Curcumin loaded mucoadhesive microemulsion (CMME) was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (CME) and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of Curcumin via nasal route was studied by performing biodistribution study in Swiss albino rats. CME was found to be transparent, stable and non ciliotoxic with 57.66 nm ± 3.46, -16.28 mV ± 4.11 and 98.08 % ± 1.01 as average globule size, zeta potential and drug content respectively. PdI and TEM study depicted the narrow size distribution of CME. Following single intranasal administration of CMME and CME at dose of 2.86 mg/kg, Maximum Curcumin uptake in the olfactory bulb was more than 11 fold (51.1 ± 2.8) than that of intravenous injection of Curcumin solution (4.4 ± 1.1). AUC ratio of brain tissues to that in plasma obtained after nasal administration of CMME were significantly higher than those after intravenous administration of Curcumin solution. Findings of the present study revealed that optimal CMME and intranasal route may be considered to be promising and an alternative approach for brain targeting of Curcumin.

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