School of Pharmacy, Yanbian University, Yanji, 133002, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, China.
AAPS PharmSciTech. 2023 Nov 16;24(8):234. doi: 10.1208/s12249-023-02679-5.
Nimodipine (NMD) is a 1,4-dihydropyridine calcium antagonist that is effective in the prevention and treatment of cerebral arterial vasospasm and cerebral ischemic injury caused by subarachnoid hemorrhage. Since the drug itself is highly insoluble in water and has low oral bioavailability, while injectable formulations may cause pain and inflammation, the blood-brain barrier (BBB) prevents the effective delivery of therapeutic agents to the brain tissue. Therefore, in the present study, NMD liposomes were prepared by ethanol injection and innovatively lyophilised and loaded into temperature-sensitive in situ gels for intranasal administration as sprays to deliver drugs to brain tissues bypassing the blood-brain barrier. The optimal gel formulation was obtained by screening in which liposomes were divided into lecithin, cholesterol, and NMD in the ratio of 40:10: 1; Pluronic P407, Pluronic P188, Tween 80, polyvinyl ketone and ethyl nipagin in the ratio of (180:20:3:1:1); Pluronic P407, Pluronic P188, Tween 80, polyvinyl ketone, and ethyl nipagin in the ratio of (180:20:3:1:1). The prepared flow gel can form a solidified gel after a temperature of 31.07-32.07°C and a time of 58.51-59.89 s. Meanwhile, the NMD liposome gel formulation achieved sustained release over 56 h. The pharmacokinetic results of the developed NMD liposomal temperature-sensitive in situ gel and NMD temperature-sensitive in situ gel showed that liposomal nasal mucosal in situ gel is a more effective brain-targeted drug delivery system for NMD.
尼莫地平（NMD）是一种 1,4-二氢吡啶钙拮抗剂，可有效预防和治疗蛛网膜下腔出血引起的脑动脉血管痉挛和脑缺血损伤。由于药物本身在水中的溶解度低，口服生物利用度低，而注射制剂可能引起疼痛和炎症，血脑屏障（BBB）阻止治疗剂有效递送到脑组织。因此，本研究通过乙醇注入法制备尼莫地平脂质体，并创新性地冻干并载入温度敏感原位凝胶中，制成鼻腔内给药喷雾，通过鼻腔绕过血脑屏障将药物递送到脑组织。通过筛选获得了最佳的凝胶配方，其中脂质体分为卵磷脂、胆固醇和尼莫地平，比例为 40:10:1；泊洛沙姆 P407、泊洛沙姆 P188、吐温 80、聚乙烯酮和乙基尼泊金的比例为（180:20:3:1:1）；泊洛沙姆 P407、泊洛沙姆 P188、吐温 80、聚乙烯酮和乙基尼泊金的比例为（180:20:3:1:1）。所制备的流动凝胶在 31.07-32.07°C 的温度下和 58.51-59.89 s 的时间内形成固态凝胶。同时，尼莫地平脂质体凝胶配方实现了超过 56 小时的持续释放。所开发的尼莫地平脂质体温度敏感原位凝胶和尼莫地平温度敏感原位凝胶的药代动力学结果表明，脂质体鼻黏膜原位凝胶是一种更有效的尼莫地平脑靶向药物传递系统。
