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盐酸帕罗西汀脂质体和纳米囊的研制及药效学评价。

Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

机构信息

Bioanalysis Laboratory, Health Sciences Institute, Feevale University, Novo Hamburgo, RS, Brazil; Postgraduate Program in Toxicology and Analytical Toxicology, Feevale University, Novo Hamburgo, RS, Brazil.

Bioanalysis Laboratory, Health Sciences Institute, Feevale University, Novo Hamburgo, RS, Brazil.

出版信息

Int J Pharm. 2024 Jul 20;660:124304. doi: 10.1016/j.ijpharm.2024.124304. Epub 2024 Jun 5.

Abstract

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

摘要

抑郁症是最常见的精神障碍之一。纳米技术的出现优化了药物的反应。因此,本工作旨在开发和表征载有盐酸帕罗西汀的脂质体和纳米胶囊,并使用旷场和悬尾试验评估其抗抑郁样作用。脂质体和纳米胶囊分别采用逆向蒸发法和纳米沉淀法制备。制剂的粒径范围为 121.81 至 310.73nm,多分散指数为 0.096 至 0.303,zeta 电位为-11.94 至-34.50mV,pH 值为 5.31 至 7.38,药物含量为 80.82 至 94.36%,结合效率为 98%。与纳米胶囊(95.59%)相比,盐酸帕罗西汀与脂质体结合后(43.82%)在 10 小时内显示出较慢的释放速度。在 Vero 细胞中,纳米结构的体外毒性呈浓度依赖性。两种纳米结构均降低 TST 中不动时间,在 2.5mg/kg 时不影响旷场试验中的穿越次数,提示帕罗西汀具有抗抑郁样作用。此外,纳米胶囊减少了梳理次数,增强了该药物的抗焦虑作用。这些结果表明,即使在低剂量下,纳米结构也能有效保持盐酸帕罗西汀的抗抑郁样作用。

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