Bromocriptine Mesylate (BRM) acts as a dopamine receptor agonist along with antioxidant effect and is utilized in the treatment of Parkinson’s disease (PD). Glutathione (GSH) is a thiol- reducing agent having antioxidant properties in the brain. Replenishment of GSH inside the brain can play a major role in the management of PD. Both BRM and GSH suffer from low oral bioavailability and poor absorption. The objective of the present study was to develop BRM and GSH loaded nanoemulsion for the combined and synergistic effect delivered through the intranasal route for the better and effective management of PD. After extensive screening experiments, Capmul PG-8 NF was selected as oil, polyethylene glycol (PEG) 400 as a surfactant and propylene glycol as co-surfactant. Ultrasonication technique was employed for the fabrication of nanoemulsion. Central composite rotatable design (CCRD) was used to obtain the best formulation by optimization. Oil (%), S_mix (%), and sonication time (second) were chosen as independent variables for the optimization. Particle size, PDI, zeta potential, % transmittance, pH, refractive index, viscosity and conductivity of the optimized nanoemulsion were found to be 80.71 ± 2.75 nm, 0.217 ± 0.009, −12.60 ± 0.10 mV, 96.00 ± 3.05 %, 6.48 ± 0.28, 1.36 ± 0.03, 30.12 ± 0.10 mPas and 214.28 ± 2.79 μS/cm respectively. Surface morphology demonstrated that nanoemulsion possessed spherical and globular nature of the particle which showed 3.4 times and 1.5 times enhancement in drug permeation in the case of BRM and GSH respectively as compared to suspension. MTT assay done on neuro-2a cell lines revealed that nanoemulsion was safe for intranasal delivery. Behavioural studies were carried out to prove the efficacy of optimized nanoemulsion in PD using forced swimming test, locomotor activity test, catalepsy test, rota-rod test, and akinesia test in Wistar rats. The outcomes of the behavioural studies revealed that BRM and GSH loaded nanoemulsion treatment showed significant improvement in behavioural activities of PD (haloperidol-induced) rats after intranasal administration. This study concluded that BRM and GSH loaded nanoemulsion could be promising for the combined and synergistic anti-parkinson effect for the effective management of PD.

Bromocriptine Mesylate (BRM) 作为一种多巴胺受体激动剂，具有抗氧化作用，用于治疗帕金森病 (PD)。谷胱甘肽 (GSH) 是一种硫醇还原剂，在大脑中具有抗氧化特性。大脑内 GSH 的补充可以在 PD 的管理中发挥重要作用。BRM 和 GSH 都具有口服生物利用度低和吸收差的问题。本研究的目的是开发 BRM 和 GSH 负载纳米乳剂，通过鼻内途径提供联合和协同作用，以更好和有效地管理 PD。经过大量筛选实验，选择 Capmul PG-8 NF 作为油、聚乙二醇 (PEG) 400 作为表面活性剂和丙二醇作为辅助表面活性剂。采用超声波技术制备纳米乳剂。中心复合可旋转设计（CCRD）用于通过优化获得最佳配方。油 (%), S_混合(%) 和超声处理时间 (秒) 被选为优化的自变量。发现优化的纳米乳液的粒径、PDI、zeta 电位、透光率百分比、pH、折射率、粘度和电导率为 80.71 ± 2.75 nm、0.217 ± 0.009、-12.60 ± 0.10 mV、96.00 ± 3.05 %、0.288 ± 6.28 , 1.36 ± 0.03, 30.12 ± 0.10 mPas 和 214.28 ± 2.79 μS/cm。表面形态表明纳米乳剂具有颗粒的球形和球状性质，与悬浮液相比，在 BRM 和 GSH 的情况下，其药物渗透率分别提高了 3.4 倍和 1.5 倍。对神经 2a 细胞系进行的 MTT 测定表明，纳米乳剂对于鼻内递送是安全的。进行了行为研究以证明优化的纳米乳液在 PD 中使用强迫游泳试验的功效，Wistar 大鼠的运动活动试验、僵住症试验、旋转棒试验和运动不能试验。行为研究的结果表明，BRM 和 GSH 负载纳米乳剂治疗显示鼻内给药后 PD（氟哌啶醇诱导）大鼠的行为活动显着改善。该研究得出结论，负载 BRM 和 GSH 的纳米乳剂有望通过联合和协同的抗帕金森效应有效管理 PD。