This work focuses on the development of PLGA nanoparticles and their surface modification by chitosan to enhance the mucoadhesive properties and colloidal stability for intranasal delivery. Chitosan-coated paroxetine-loaded PLGA nanoparticles (PAR–CS–PLGA-NPs) were developed and characterized along with in vitro and in vivo evaluation. Particle size of 181.8 nm with a zeta potential of 36.3 mV was obtained. Entrapment efficiency % and drug loading % were 87.5% and 13.4%, respectively. TEM, FTIR, and DSC were also performed. In vitro drug release studies were conducted in phosphate buffered saline (pH 7.4) and simulated nasal fluid (pH 5.5), and sustained release was found until 72 h. Cellular assays on mammalian cells depicted the cell viability to be >60% even at the maximum concentration of PAR–CS–PLGA-NPs and showed significantly higher uptake than PLGA-NPs. Histopathological studies on the nasal epithelium showed no damage or inflammation when treated with PAR–CS–PLGA-NPs. In vivo studies were performed using Swiss albino mice to estimate the drug biodistribution after intranasal delivery of PAR–CS–PLGA-NPs. A significantly increased drug concentration was observed in the mouse brains (p < 0.05). Pharmacodynamics studies of the PAR–CS–PLGA-NPs were carried out by forced swimming test and locomotor activity test, demonstrating improved behavioral analysis parameters (p < 0.05). Thus, intranasal delivery of paroxetine-loaded mucoadhesive chitosan-coated PLGA nanoparticles could be potentially used for the treatment of depression.

中文翻译：

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壳聚糖改性聚合物纳米颗粒用于帕罗西汀从鼻子到大脑的药物递送：体外和体内评价


这项工作的重点是 PLGA 纳米颗粒的开发及其壳聚糖表面修饰，以增强鼻内递送的粘膜粘附性能和胶体稳定性。壳聚糖包被的帕罗西汀负载 PLGA 纳米颗粒 （PAR-CS-PLGA-NPs） 被开发和表征，以及体外和体内评估。获得的粒径为 181.8 nm，zeta 电位为 36.3 mV。包埋效率 % 和载药量 % 分别为 87.5% 和 13.4%。还进行了 TEM 、 FTIR 和 DSC 。在磷酸盐缓冲盐水 （pH 7.4） 和模拟鼻液 （pH 5.5） 中进行体外药物释放研究，发现持续释放至 72 小时。哺乳动物细胞的细胞测定显示，即使在 PAR-CS-PLGA-NPs 的最大浓度下，细胞活力也为 >60%，并且显示出显著高于 PLGA-NPs 的摄取。鼻上皮的组织病理学研究表明，用 PAR-CS-PLGA-NPs 治疗时没有损伤或炎症。使用瑞士白化小鼠进行体内研究，以估计 PAR-CS-PLGA-NPs 鼻内递送后的药物生物分布。在小鼠脑中观察到药物浓度显著增加 （p < 0.05）。通过强迫游泳试验和运动活动试验对 PAR-CS-PLGA-NPs 进行药效学研究，证明行为分析参数得到改善 （p < 0.05）。因此，载有帕罗西汀的粘膜粘附壳聚糖涂层 PLGA 纳米颗粒的鼻内递送可能用于治疗抑郁症。