Mandal Surjyanarayan, Mandal Snigdha Das, Chuttani Krishna, Sawant Krutika K, Subudhi Bharat Bhushan
a School of Pharmaceutical Sciences , Siksha 'O' Anusandhan University , Khandagiri Square , Bhubaneswar , Orissa , India ;
b Department of Pharmacology , Parul Institute of Pharmacy and Research , Vadodara , Gujarat , India ;
Drug Dev Ind Pharm. 2016 Aug;42(8):1340-50. doi: 10.3109/03639045.2015.1135936. Epub 2016 Jan 24.
The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD).
Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed.
Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p < 0.05) on the responses. Rota-rod and open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups.
Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.
本研究旨在探讨通过鼻内给予黏膜黏附微乳剂（MMEI）的布洛芬对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）帕金森病（PD）模型中多巴胺能神经变性介导的炎症的神经保护作用。
采用响应面法（RSM）制备了负载布洛芬的聚卡波非基MMEI。以2.86 mg/kg/天的剂量对雄性C57BL/6小鼠进行连续两周的鼻内给药，这些小鼠预先每隔2小时腹腔注射4次MPTP（20 mg/kg体重）。进行免疫组织化学分析。
最佳MMEI稳定且无纤毛毒性，平均球粒大小为66.29±4.15 nm，ζ电位为-20.9±3.98 mV。PDI值和透射电子显微镜结果显示MMEI的球粒大小分布狭窄。结果表明，所有三个自变量对响应均有显著影响（p<0.05）。转棒试验和旷场试验结果显示，小鼠的运动性能和总体行为活动有显著改善。体内研究和免疫组织化学结果表明，鼻内给予布洛芬可显著减少MPTP介导的多巴胺耗竭。此外，发现布洛芬治疗组黑质中TH神经元计数和纹状体多巴胺能神经末梢密度显著更高。
研究结果表明，通过开发的MMEI给予的布洛芬可保护神经元免受MPTP诱导的黑质致密部（SNpc）和纹状体损伤，因此，通过鼻内途径将布洛芬靶向脑内治疗PD可能是一种有前景的方法。
