Intranasal (IN) drug delivery is recognized to be an innovative strategy to deliver drugs to the Central Nervous System. One of the main limitations of IN dosing is the low volume of drug that can be administered. Accordingly, two requirements are necessary: the drug should be active at a low dosage, and the drug solubility in water must be high enough to accommodate the required dose. Drug nanocrystals may overcome these limitations; thus, curcumin was selected as a model drug to prepare nanocrystals for potential IN administration. With this aim, we designed curcumin nanocrystals (NCs) by using Box Behnken design. A total of 51 formulations were prepared by the sonoprecipitation method. Once we assessed the influence of the independent variables on nanocrystals’ mean diameter, the formulation was optimized based on the desirability function. The optimized formulation was characterized from a physico-chemical point of view to evaluate the mean size, zeta potential, polidispersity index, pH, osmolarity, morphology, thermotropic behavior and the degree of crystallinity. Finally, the cellular uptake of curcumin and curcumin NCs was evaluated on Olfactory Ensheathing Cells (OECs). Our results showed that the OECs efficiently took up the NCs compared to the free curcumin, showing that NCs can ameliorate drug permeability.

中文翻译：

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姜黄素纳米晶体的优化作为从鼻到脑的应用的有前途的策略。

鼻内（IN）药物输送被认为是一种将药物输送到中枢神经系统的创新策略。IN给药的主要限制之一是可给药的药物量少。因此，有两个要求是必要的：药物应在低剂量下具有活性，药物在水中的溶解度必须足够高以适应所需剂量。药物纳米晶体可以克服这些限制。因此，姜黄素被选作模型药物以制备潜在的IN给药的纳米晶体。为此，我们使用Box Behnken设计设计了姜黄素纳米晶体（NC）。通过超声沉淀法总共制备了51种制剂。一旦我们评估了独立变量对纳米晶体平均直径的影响，便根据所需函数对配方进行了优化。从理化角度对优化配方进行了表征，以评估平均粒径，ζ电位，多分散指数，pH，渗透压，形态，热致行为和结晶度。最后，在嗅鞘细胞（OEC）上评估姜黄素和姜黄素NCs的细胞摄取。我们的结果表明，与游离姜黄素相比，OECs有效吸收了NCs，这表明NCs可以改善药物渗透性。