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载唑来曲普坦壳聚糖纳米粒在大鼠体内的药代动力学研究及脑组织分析。

Pharmacokinetic study and brain tissue analysis of Zolmitriptan loaded chitosan nanoparticles in rats by LC-MS method.

机构信息

Department of Pharmaceutics, Nargund College of Pharmacy, II Main, Dattatreya Nagar, Banashankari III Stage, Bangalore, Karnataka, India.

Department of Pharmaceutics, Nargund College of Pharmacy, II Main, Dattatreya Nagar, Banashankari III Stage, Bangalore, Karnataka, India.

出版信息

Int J Biol Macromol. 2020 Jan 1;142:52-62. doi: 10.1016/j.ijbiomac.2019.08.236. Epub 2019 Oct 5.

Abstract

INTRODUCTION

Migraine has recently become a major interest to the neuroscientists. Zolmitriptan is an effective medicine used in the treatment of migraine. The nasal spray was prepared from Zolmitriptan loaded chitosan nanoparticles and evaluated for pharmacokinetic properties.

METHODS

In this study male Wistar albino rats weighing between 200 and 250 g were taken and divided into 4 groups with 6 rats in each group. Nasal spray containing Zolmitriptan loaded Chitosan nanoparticles were administered nasally (using specific inhalation mask) at a dose of 0.5 mg/kg as a test formulation and compared with the control groups which received either water for injection or marketed standard drug (Zolmist) or standard drug solution at a same dose. The pharmacokinetic parameters such as C, T, and brain tissue analyses for accumulation of drug were performed for Zolmitriptan by LC-MS method.

RESULTS

Amount of drug in the plasma from the test formulation, standard marketed drug (Zolmist) and standard drug solution was found to be 41.37 ± 2.31, 34.76 ± 4.22 and 23.74 ± 2.42 ng/ml at 10 min respectively, which indicated significantly (p < 0.05) greater amount of drug being delivered from the test formulation compared to the both standard groups. The amount of the drug (Zolmitriptan) present in brain tissue (Olfactory lobe) was found to be 15 ± 0.08, 13 ± 0.14 and 8 ± 0.13 ng/g at 60 min for test formulation, marketed standard and standard drug solution respectively which indicates significantly (p < 0.05) higher amount of drug absorption in brain tissue from the test formulation compared to both the standard groups.

CONCLUSION

Pharmacokinetics studies of nasal spray containing Zolmitriptan loaded chitosan nanoparticles proved rapid onset of action in animals and is promising in treatment of migraine.

摘要

简介

偏头痛最近引起了神经科学家的极大兴趣。佐米曲普坦是一种用于治疗偏头痛的有效药物。本研究制备了载佐米曲普坦壳聚糖纳米粒的鼻用喷雾剂,并对其进行了药代动力学研究。

方法

本研究采用雄性 Wistar 白化大鼠,体重 200-250g,随机分为 4 组,每组 6 只。以 0.5mg/kg 剂量经鼻给予载佐米曲普坦壳聚糖纳米粒的鼻喷雾剂(使用专用吸入面罩)作为试验制剂,并与对照组(分别给予注射用水、市售标准药物(Zolmist)或标准药物溶液)进行比较。采用 LC-MS 法测定佐米曲普坦的药代动力学参数,如 C、T 和脑组织中药物的积累。

结果

试验制剂、市售标准药物(Zolmist)和标准药物溶液的血浆中药物含量分别在 10min 时达到 41.37±2.31、34.76±4.22 和 23.74±2.42ng/ml,表明试验制剂较标准组药物含量显著增加(p<0.05)。试验制剂、市售标准药物和标准药物溶液在 60min 时脑(嗅球)组织中药物(佐米曲普坦)的含量分别为 15±0.08、13±0.14 和 8±0.13ng/g,表明试验制剂较标准组药物在脑内的吸收量显著增加(p<0.05)。

结论

载佐米曲普坦壳聚糖纳米粒鼻用喷雾剂的药代动力学研究表明,该制剂在动物体内具有快速起效的特点,有望用于偏头痛的治疗。

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