The nasal pathway represents a non-invasive administration route of pharmaceutical agents with local, systemic, and central nervous system action. Intranasal application has a relatively short time to onset of effect and high bioavailability because it avoids hepatic first-pass metabolism. However, sustained delivery is important because drugs can be rapidly eliminated via mucociliary clearance. Protein transduction using arginine-rich cell-penetrating peptides (poly-arginine) shows high delivery efficiency, no cell specificity, and minimal cytotoxicity. We investigated the effect of poly-arginine on protein delivery into the nasal mucosa and brain of mice, and its ability to prolong contact between the delivered molecule and nasal mucosa by preventing mucociliary clearance. Enhanced green fluorescent protein (EGFP) fused to a nine-arginine peptide (EGFP-9R group) or EGFP (EGFP group) was administered once to the bilateral nasal cavities of mice. Histopathological evaluation was conducted for 3–120 h to evaluate side effects, and the number of sneezes was recorded before and after administration. EGFP was detected in cells lining the nasal cavity and their vicinity for 3–96 and 3–24 h in the EGFP-9R and EGFP groups, respectively. EGFP was detected in the brain at 3–96 h in the EGFP-9R group but not in the EGFP group. Nasal symptoms and histopathological assessment revealed no deterioration in either group. These results suggest that protein transduction using poly-arginine can deliver therapeutically relevant molecules for allergic rhinitis, and can be applied for olfactory disturbance and other central nervous system diseases. Further research is necessary to establish therapy protocols using this technique.

中文翻译：

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鼻内药物递送到小鼠鼻粘膜和利用精氨酸丰富的细胞穿透肽介导的蛋白质介导的大脑。

鼻途径代表具有局部，全身和中枢神经系统作用的药剂的非侵入性给药途径。鼻内给药可避免肝首过代谢，因此起效时间相对较短，生物利用度较高。但是，持续给药很重要，因为可以通过粘膜纤毛清除迅速清除药物。使用富含精氨酸的细胞穿透肽（聚精氨酸）进行的蛋白转导显示出高递送效率，无细胞特异性和最小的细胞毒性。我们研究了聚精氨酸对蛋白质向小鼠鼻黏膜和脑中的传递的影响，以及通过防止黏膜纤毛清除而延长了传递分子与鼻黏膜之间接触的能力。将融合至九个精氨酸肽（EGFP-9R组）或EGFP（EGFP组）的增强型绿色荧光蛋白（EGFP）分别施用于小鼠的双侧鼻腔。进行组织病理学评估3–120小时以评估副作用，并记录给药前后的打喷嚏次数。在EGFP-9R和EGFP组中，在鼻腔及其附近的细胞中检测到EGFP的时间分别为3–96和3–24 h。EGFP-9R组在3–96 h在大脑中检测到EGFP，但EGFP组中未检测到。鼻症状和组织病理学评估显示两组均无恶化。这些结果表明，使用聚精氨酸进行蛋白转导可以为过敏性鼻炎提供与治疗相关的分子，可用于嗅觉障碍和其他中枢神经系统疾病。为了使用这种技术建立治疗方案，需要进行进一步的研究。