Ma Lin, Zhao Yang, Li Tianyang, Piao Jingshu, Piao Mingguan
School of Pharmacy, Yanbian University, Yanji, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China.
Pak J Pharm Sci. 2022 Sep;35(5):1423-1436.
Pramipexole hydrochloride (PPX) is a dopamine receptor agonist for the treatment of Parkinson's disease. It does not penetrate easily into the brain due to the presence of the blood-brain barrier (BBB), which hinders the treatment of the disease. The nasal mucosal drug delivery system is an effective method to deliver drugs to the brain bypassing the blood-brain barrier and the concentration of drugs targeted to the brain by intranasal administration is quite low due to the limitation of the permeability of the nasal mucosa and the nasal environment. Therefore, this study innovatively encapsulates prepared PPX microcapsules in a temperature-sensitive in situ gel for intranasal drug delivery to increase the target concentration of the drug in the brain and prolong the duration of treatment. The gel formulation containing 24% poloxamer 407 and 6% poloxamer 188 and 0.3% ice chips as absorption enhancers formed a hard gel at 30.44-31.36C and allowed a slow release within 12 hours. A pharmacokinetic comparison of the developed PPX microencapsulated temperature-sensitive in situ gel (PPX-MTISG) with PPX temperature-sensitive in situ gel (PPX-TISG) revealed that the microencapsulated nasal mucosal in situ gel was a more effective PPX brain-targeted drug delivery system.
盐酸普拉克索（PPX）是一种用于治疗帕金森病的多巴胺受体激动剂。由于存在血脑屏障（BBB），它不易穿透进入大脑，这阻碍了该疾病的治疗。鼻黏膜给药系统是一种绕过血脑屏障将药物递送至大脑的有效方法，但由于鼻黏膜通透性和鼻腔环境的限制，经鼻给药靶向大脑的药物浓度相当低。因此，本研究创新性地将制备的PPX微胶囊包封于温度敏感型原位凝胶中用于鼻内给药，以提高药物在大脑中的靶向浓度并延长治疗持续时间。含有24%泊洛沙姆407、6%泊洛沙姆188和0.3%冰片作为吸收促进剂的凝胶制剂在30.44 - 31.36℃形成硬凝胶，并在12小时内实现缓慢释放。对所研制的PPX微囊化温度敏感型原位凝胶（PPX - MTISG）与PPX温度敏感型原位凝胶（PPX - TISG）进行的药代动力学比较表明，微囊化鼻黏膜原位凝胶是一种更有效的PPX脑靶向给药系统。
