Abstract：
The administration of hydrophilic therapeutics has always been a great challenge because of their low bioavailability after administration. For this purpose, W/O/W microemulsion resulted to be a potential successful strategy for the delivery of hydrophilic compounds, interesting for the nasal mucosal therapy. Herein, an optimized biphasic W/O microemulsion was designed, through a preliminary screening, and it was inverted in a triphasic W/O/W microemulsion, intended for the nasal administration. In order to enhance the mucosal retention, surface modification of the biphasic W/O microemulsion was performed adding didodecyldimethylammonium bromide, and then converting the system into a cationic triphasic W/O/W microemulsion. The developed samples were characterized in terms of droplet size, polydispersity, zeta potential, pH and osmolality. The physical long-term stability was analyzed storing samples at accelerated conditions (40 ± 2 °C and 75 ± 5 % RH) for 6 months in a constant climate chamber, following ICH guidelines Q1A (R2). In order to verify the potential retention on the nasal mucosa, the two triphasic systems were analyzed in terms of mucoadhesive properties, measuring the in vitro interaction with mucin over time. Furthermore, fluorescein sodium salt was selected as a model hydrophilic drug to be encapsulated into the inner core of the two triphasic W/O/W microemulsions, and its release was analyzed compared to the free probe solution. The cytocompatibility of the two platforms was assessed on two cell lines, human fibroblasts HFF1 and Calu-3 cell lines, chosen as pre-clinical models for nasal and bronchial/tracheal airway epithelium.
摘要：
亲水性治疗剂的给药一直是一个巨大的挑战,因为它们在给药后的生物利用度很低。为此,W/O/W微乳液是递送亲水性化合物的潜在成功策略，有趣的鼻粘膜治疗。在这里，设计了一种优化的双相W/O微乳液，通过初步筛选,并在三相W/O/W微乳液中倒置，用于鼻腔给药。为了增强粘膜保留，双相W/O微乳液的表面改性是添加二十二烷基二甲基溴化铵，然后将该体系转化为阳离子三相W/O/W微乳液。开发的样品在液滴尺寸方面进行了表征，多分散性，zeta电位,pH和渗透压。在恒定的气候室中在加速条件（40±2°C和75±5％RH）下储存样品6个月，分析了物理长期稳定性。遵循ICH指南Q1A(R2)。为了验证在鼻粘膜上的潜在保留，根据粘膜粘附特性分析了两个三相系统，随着时间的推移，测量与粘蛋白的体外相互作用。此外，选择荧光素钠盐作为模型亲水性药物，将其包封到两种三相W/O/W微乳剂的内核中，并将其释放度与游离探针溶液进行比较分析。在两个细胞系上评估了两个平台的细胞相容性，人成纤维细胞HFF1和Calu-3细胞系，被选为鼻和支气管/气管气道上皮的临床前模型。
