Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, 201307, India.
Nuclear Medicine Division, INMAS, Defense Research and Development Organization, New Delhi, 110061, India.
Drug Deliv Transl Res. 2020 Dec;10(6):1862-1875. doi: 10.1007/s13346-020-00754-z.
Alzheimer disease (AD) is very common among the older people. There are few medications available as oral and suspension dosage forms for the management of AD. Due to the rising cases of AD and the associated risks of the existing line of treatment, oil in water (o/w) nanoemulsion (NE) loaded with donepezil was prepared to explore intranasal route of administration. The NE was prepared using labrasol (10%), cetyl pyridinium chloride (1% in 80% water), and glycerol (10%), with a drug concentration of 1 mg/ml. The developed NE was characterized for particle size, polydispersity index (PDI), and zeta potential. In vitro release studies were conducted to observe the release of drug. Further in vivo studies of developed NE were done on Sprague Dawley rats using technetium pertechnetate (Tc) labeled formulations to investigate the nose to brain drug delivery pathway. The nanoemulsion showed particle size of 65.36 nm with a PDI of 0.084 and zeta potential of -10.7 mV. In vitro release studies showed maximum release of 99.22% in 4 h in phosphate-buffered saline, 98% in 2 h in artificial cerebrospinal fluid, and 96% in 2 h in simulated nasal fluid. The cytotoxicity and antioxidant activity of the NE showed dose-dependent cytotoxicity and % radical scavenging activity (%RSA). The images of giemsa staining also confirmed that the developed formulation has no impact on the morphology of cells. Scintigrams showed maximum uptake of NE in the brain. The findings suggested that the developed NE loaded with donepezil hydrochloride could serve as a new approach for the treatment of Alzheimer via nose to brain drug delivery. Graphical abstract.
阿尔茨海默病（AD）在老年人中非常常见。目前，可用于治疗 AD 的口服和混悬剂剂型的药物很少。由于 AD 病例不断增加，以及现有治疗方法存在相关风险，因此制备了载有多奈哌齐的油包水（o/w）纳米乳（NE）以探索经鼻给药途径。该 NE 采用 Labrasol（10%）、十六烷基吡啶氯（80%水中的 1%）和甘油（10%）制备，药物浓度为 1mg/ml。对所开发的 NE 进行了粒径、多分散指数（PDI）和zeta 电位的表征。进行了体外释放研究以观察药物的释放。进一步对 Sprague Dawley 大鼠进行了开发的 NE 的体内研究，使用锝标记制剂研究鼻内脑递药途径。纳米乳的粒径为 65.36nm，PDI 为 0.084，zeta 电位为-10.7mV。体外释放研究表明，在磷酸盐缓冲液中 4 小时内最大释放 99.22%，在人工脑脊液中 2 小时内最大释放 98%，在模拟鼻液中 2 小时内最大释放 96%。NE 的细胞毒性和抗氧化活性表现出剂量依赖性细胞毒性和自由基清除活性（%RSA）。吉姆萨染色图像也证实了所开发的制剂对细胞形态没有影响。闪烁图显示 NE 在大脑中的最大摄取量。研究结果表明，载有盐酸多奈哌齐的开发型 NE 可作为通过鼻内脑递药治疗阿尔茨海默病的新方法。
