Abstract The purpose of this research was to develop cubosomal mucoadhesive in situ nasal gel to enhance the donepezil HCl delivery to the brain. Glycerol mono-oleate (GMO) and surfactant poloxamer 407 were used to prepare cubosomes. The developed formulations were characterized for particle size (PS), poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), transmission electron microscopy (TEM), in vitro drug release and in vivo bio-distribution study in blood and brain tissue. Central composite design was used for the optimization purpose and the selected formulation (containing GMO 2 g and poloxamer 1.5%) was prepared in presence of gellan gum and konjac gum as gelling agent and mucoadhesive agent respectively. The optimal cubosomal dispersion and optimal cubosomal mucoadhesive in situ nasal gel were subjected to in vivo bio-distribution studies in rat model. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the drug solution. Thus, the formulated cubosomal mucoadhesive in situ gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.

中文翻译：

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原位鼻凝胶系统中的纳米结构立方体：一种将盐酸多奈哌齐控制递送至大脑的替代方法

摘要 本研究的目的是开发立方体黏膜黏附原位鼻凝胶，以增强盐酸多奈哌齐向大脑的输送。甘油单油酸酯 (GMO) 和表面活性剂泊洛沙姆 407 用于制备立方体。对开发的制剂的粒度 (PS)、多分散指数 (PDI)、zeta 电位 (ZP)、包封率 (EE)、透射电子显微镜 (TEM)、体外药物释放和体内生物分布研究进行表征血液和脑组织。中心复合设计用于优化目的，所选配方（含 GMO 2 g 和泊洛沙姆 1.5%）分别在结冷胶和魔芋胶作为胶凝剂和粘膜粘附剂存在下制备。在大鼠模型中对最佳立方体分散和最佳立方体粘膜粘附原位鼻凝胶进行了体内生物分布研究。与药物溶液相比，它显示出显着更高的经鼻渗透和更好的大脑分布。因此，配制的立方体粘膜粘附原位凝胶可被认为是通过经鼻途径靶向中枢神经系统作用药物的大脑的有前途的载体。