Department of Pharmacy, Maliba Pharmacy College, Bardoli Mahuva Road, Dist. Surat, Gujarat, India.
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Ministry of Defence, Brig. S.K. Mazumdar Marg, New Delhi, India.
Curr Drug Deliv. 2021;18(6):805-824. doi: 10.2174/1567201817666200708115627.
Intranasal administration of biodegradable nanoparticles has been extensively studied for targeting the drug directly to CNS through the olfactory or trigeminal route bypassing the blood brain barrier.
The objective of the present study was to optimize Clonazepam loaded PLGA nanoparticles (CLO-PNPs) by investigating the effect of process variables on the responses using 3 full factorial design.
Effect of two independent factors-amount of PLGA and concentration of Poloxamer 188, were studied at low, medium, and high levels on three dependent responses-%Entrapment efficiency, Particle size (nm), and % cumulative drug release at 24hr.
%EE, Particle size, and %CDR at 24hr of the optimized batch was 63.7%, 165.1 nm, and 86.96%, respectively. Nanoparticles were radiolabeled with Tc and biodistribution was investigated in BALB/c mice after intranasal and intravenous administrations. Significantly higher brain/blood uptake ratios and AUC values in the brain following intranasal administration of CLO-PNPs indicated more effective brain targeting of CLO. Higher brain uptake of intranasal CLO-PNPs was confirmed by rabbit brain scintigraphy imaging. A histopathological study performed on goat nasal mucosa revealed no adverse response of nanoparticles. TEM image exhibited spherical shaped particles in the nano range. DSC and XRD studies suggested Clonazepam encapsulation within the PLGA matrix. The onset of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as compared to intranasal and intravenous CLO-SOL.
This investigation exhibits rapid rate and higher extent of CLO transport in the brain with intranasal CLO-PNPs suggesting a better option as compared to oral and parenteral route in the management of acute status epilepticus.
经鼻腔给予可生物降解的纳米粒子已被广泛研究，通过嗅觉或三叉神经途径将药物直接靶向 CNS，绕过血脑屏障。
本研究的目的是通过 3 因素完全设计考察工艺变量对响应的影响来优化载氯硝西泮 PLGA 纳米粒（CLO-PNPs）。
研究了两个独立因素- PLGA 的量和泊洛沙姆 188 的浓度，在低、中、高 3 个水平上对 3 个依赖响应-包封效率、粒径（nm）和 24 小时时的累积药物释放率（%）的影响。
优化批的 %EE、粒径和 24 小时时的 %CDR 分别为 63.7%、165.1nm 和 86.96%。纳米粒用 Tc 放射性标记，并在 BALB/c 小鼠经鼻内和静脉给予后进行了体内分布研究。与经鼻内给予 CLO-SOL 相比，经鼻内给予 CLO-PNPs 后脑中脑/血摄取比和 AUC 值显著升高，表明 CLO 更有效地靶向大脑。兔脑闪烁成像证实了经鼻 CLO-PNPs 的更高脑摄取。对山羊鼻黏膜进行的组织病理学研究显示纳米粒无不良反应。TEM 图像显示纳米范围内的球形粒子。DSC 和 XRD 研究表明氯硝西泮包封在 PLGA 基质内。与经鼻内和静脉给予 CLO-SOL 相比，经鼻内给予纳米粒显著延迟了 PTZ 诱导的癫痫发作的发生。
与口服和静脉途径相比，经鼻内给予 CLO-PNPs 可使 CLO 在脑中更快地转运，且程度更高，提示在治疗急性癫痫持续状态方面是更好的选择。
