Box-Behnken design optimized silibinin loaded glycerylmonooleate nanoliquid crystal for brain targeting

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2022-05-01 DOI:10.1016/j.chemphyslip.2022.105193

Ajit Singh, Ajay Vaish, Rahul Shukla

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引用次数: 6

Abstract

Silibinin (SIL) is a neuroprotective and amyloid aggregate inhibitor that showed therapeutic applications in preclinical studies of Alzheimer’s disease (AD). Due to poor aqueous solubility free SIL is unable to reach the brain after oral administration. Therefore SIL was encapsulated in nano-liquid crystals (NLCs) to increase payload in brain using glyceryl monooleate (GMO). The NLCs were prepared through the emulsification and probe sonication method. The optimization of SIL-NLCs was done using Box-Behnken design (BBD). BBD investigated the effect of independent variable such as GMO weight, pluronics-127 (PF-127) concentration, and sonication time on critical quality attributes such as particle size and percentage drug loading (%DL) for enhancement of drug availability at targeted site. The particle size of SIL-NLCs optimized by BBD was found to be 113.2 ± 3.3 nm particle size and 8.02 ± 0.4% DL. The FTIR and DSC characterization of SIL-NLCs showed SIL is dispersed in the GMO matrix in the amorphous form. TEM analysis confirmed the cubical and crystal-like shape of the NLCs having particle size less than 150 nm. After single oral gavage of a 30 mg/kg dosage of SIL in Wistar rats, the pharmacokinetic investigations revealed that the amount of SIL available in plasma of animals administered with NLCs showed AUC_0-∞ = 19.61 µg mL⁻¹ h compared to free SIL group having AUC_0-∞ = 6.72 µg mL⁻¹ h (P > 0.005). Brain uptake studies showed SIL-NLCs treated groups have 2.25 µg/g availability of SIL compared to 10.02 µg/g for the free SIL group. The outcomes of this investigation are promising in terms of potential use of SIL-NLCs in further studies as well as using SIL for the treatment of AD.

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Box-Behnken设计优化了装载水飞蓟宾的单油酸甘油纳米液晶的脑靶向性

水飞蓟宾(SIL)是一种神经保护和淀粉样蛋白聚集抑制剂，在阿尔茨海默病(AD)的临床前研究中显示出治疗应用。由于水溶性差，游离SIL在口服后不能到达大脑。因此，使用单油酸甘油(GMO)将SIL包封在纳米液晶(NLCs)中以增加脑内负载。采用乳化法和探针超声法制备NLCs。采用Box-Behnken设计(BBD)对SIL-NLCs进行优化。BBD研究了转基因生物重量、pluronics-127 (PF-127)浓度和超声时间等自变量对关键质量属性(如粒径和载药量百分比(%DL))的影响，以增强靶向部位的药物可用性。经BBD优化的SIL-NLCs粒径为113.2±3.3 nm, DL为8.02±0.4%。对SIL- nlcs的FTIR和DSC表征表明，SIL以非晶形式分散在GMO基体中。TEM分析证实了nlc的立方体和晶体状，粒径小于150 nm。Wistar大鼠单次灌胃30 mg/kg剂量的SIL后，药代动力学研究显示，NLCs给药动物血浆中SIL的可用量AUC0-∞= 19.61 μ g mL - 1 h，而游离SIL组的AUC0-∞= 6.72 μ g mL - 1 h (P >0.005)。脑摄取研究表明，SIL- nlcs处理组SIL的可用性为2.25 μ g/g，而游离SIL组为10.02 μ g/g。这项研究的结果很有希望在进一步的研究中使用SIL- nlcs，以及使用SIL治疗AD。

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

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.