Chitosan-modified polymeric nanoparticles for the nose-to-brain drug delivery of paroxetine: an in vitro and in vivo evaluation†

IF 5.8 3区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Nanoscale Pub Date : 2024-12-06 DOI:10.1039/D4NR04250F
Surbhi Sharma, Pammi Gauba, Amit Tyagi and Shweta Dang
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Abstract

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.

Abstract Image

Abstract Image

壳聚糖修饰的聚合物纳米颗粒用于帕罗西汀的鼻到脑药物递送:体外和体内评估
本文主要研究了聚乳酸纳米颗粒的制备及其壳聚糖的表面修饰,以提高其粘接性能和胶态稳定性。制备了壳聚糖包被帕罗西汀负载的PLGA纳米颗粒(PAR-CS-PLGA-NPs),并对其进行了体外和体内评价。得到粒径为181.8 nm, zeta电位为36.3 mV的纳米颗粒。包封效率%为87.5%,载药量%为13.4%。TEM, FTIR和DSC也进行了检查。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。哺乳动物细胞实验显示,即使在最高浓度的PAR-CS-PLGA-NPs下,细胞存活率仍为60%,并且摄取率明显高于PLGA-NPs。经PAR-CS-PLGA-NPs治疗后,鼻上皮组织病理学检查显示未见损伤或炎症。使用瑞士白化病小鼠进行体内研究,以估计经鼻给药PAR-CS-PLGA-NPs后药物的生物分布。小鼠脑内药物浓度显著升高(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,表明行为分析参数得到改善(p <;0.05)。因此,携带帕罗西汀的黏附壳聚糖包被的PLGA纳米颗粒的鼻内递送可能潜在地用于治疗抑郁症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nanoscale
Nanoscale CHEMISTRY, MULTIDISCIPLINARY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
12.10
自引率
3.00%
发文量
1628
审稿时长
1.6 months
期刊介绍: Nanoscale is a high-impact international journal, publishing high-quality research across nanoscience and nanotechnology. Nanoscale publishes a full mix of research articles on experimental and theoretical work, including reviews, communications, and full papers.Highly interdisciplinary, this journal appeals to scientists, researchers and professionals interested in nanoscience and nanotechnology, quantum materials and quantum technology, including the areas of physics, chemistry, biology, medicine, materials, energy/environment, information technology, detection science, healthcare and drug discovery, and electronics.
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