A bioanalytical assay for estimation of thymoquinone in rats cerebrospinal fluid and brain tissues of nasally administrated thymoquinone loaded lipo-polymeric nanoshells and its pharmacokinetic profiling

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Sagar Trivedi, Rishabh Agade, Veena Belgamwar
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引用次数: 0

Abstract

Thymoquinone (TH) has been one of the major phytochemical used in the treatment of cancers since long time, especially in the management of glioblastoma multiforme (GBM). The formulation of lipo-polymeric nanoshells (LPNs) and their nasal delivery are fascinating approaches for overcoming the drawbacks of low solubility and poor bioavailability of TH. Hence targeting LPNs to the brain requires a validated bioanalytical method for the assessment of TH concentration in Cerebrospinal fluid (CSF) and brain tissue homogenates (BTH). Therefore, the current work focuses on the development and validation of high-performance liquid chromatography (HPLC) method in CSF by employing nasal simulated fluid (NSF) as one of the major components of the mobile phase. The developed method was checked for linearity in the range of 0.05 to 1.6 μg/mL, having an r2 value of 0.999 with mean % recovery >95% and % RSD values below <2.0%. The developed method gave a clear separation of TH at 6.021 ± 0.17 min with an internal standard at 4.102 ± 0.09 min and a CSF spike at 2.170 ± 0.12 min. The developed method assisted in determining the in-vitro and in-vivo drug release study of LPNs, pharmacokinetic profiling, qualitative in-vivo brain uptake study, in-vitro cellular uptake, and generating stability data of formulated LPNs proposed for intranasal administration in rats.

鼻腔给药脂质聚合物纳米壳大鼠脑脊液和脑组织中胸腺醌含量的生物分析法及其药代动力学特征描述
长期以来,胸腺醌(Thymoquinone,TH)一直是治疗癌症的主要植物化学物质之一,尤其是在治疗多形性胶质母细胞瘤(GBM)方面。脂质聚合物纳米壳(LPNs)的配方及其鼻腔给药是克服 TH 溶解度低和生物利用度差等缺点的有效方法。因此,将 LPNs 用于大脑需要一种有效的生物分析方法来评估脑脊液(CSF)和脑组织匀浆(BTH)中的 TH 浓度。因此,本研究以鼻腔模拟液(NSF)作为流动相的主要成分之一,重点开发并验证了CSF中的高效液相色谱(HPLC)方法。所建立的方法在0.05-1.6 μg/mL范围内线性关系良好,r2值为0.999,平均回收率为95%,RSD值低于2.0%。所开发的方法可在 6.021 ± 0.17 分钟与 4.102 ± 0.09 分钟的内标和 2.170 ± 0.12 分钟的 CSF 加标时间内明确分离出 TH。所开发的方法有助于确定 LPNs 的体外和体内药物释放研究、药代动力学分析、体内脑摄取定性研究、体外细胞摄取研究以及生成拟用于大鼠鼻内给药的配制 LPNs 的稳定性数据。
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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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