Synthesis and controlled drug delivery studies of a novel Ubiquinol-Polyethylene glycol-Vitamin E adduct
Synthesis and controlled drug delivery studies of a novel Ubiquinol-Polyethylene glycol-Vitamin E adduct
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DOI：
10.1016/j.bioorg.2020.104329
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发表时间：
2020-12-01
影响因子：
5.1
通讯作者：
Procida, Giuseppe
中科院分区：
文献类型：
--
作者：
Cateni, Francesca;Zacchigna, Marina;Procida, Giuseppe
辅酶Q10和维生素E用于医药领域，但它们都是亲脂性分子，在水介质中的溶解性差，导致给药效率低，生物利用度低，并具有潜在的毒性。为了提高辅酶Q10和维生素E的生物利用度，合成了一种泛喹酚-聚乙二醇-维生素E混合结合物，并对其进行了表征。合成的混合结合物用核磁共振氢谱和MALDI光谱进行了表征。测定了结合物在不同pH条件下和人血浆中的体外释放度，并进行了游离辅酶Q10和维生素E的测定。结果表明，在pH为7.4时，聚乙二醇偶联物在24 h内释放出较多的辅酶Q10和维生素E，并通过DPPH法对其抗氧化活性进行评价。结果表明，两种药物泛喹酚和维生素E经聚乙二醇酯化后的化学修饰对其抗氧化能力无明显影响。
CoQ10 and Vitamin E are used in medicinal applications, but they are both lipophilic molecules and the poor solubility in aqueous media results in an inefficient administration, poor bioavailability and potential toxicity. A mixed conjugate Ubiquinol-Polyethylene glycol-Vitamin E was synthesized and characterized to improve the bioavailability of CoQ10 and Vitamin E. The synthesized mixed PEG conjugate was characterized by H-1 NMR spectroscopy and MALDI spectrometry. The in vitro release of the conjugate was measured at various pH conditions and in human plasma and the evaluation of free CoQ10 and Vitamin E were also conducted. The obtained results demonstrated that more CoQ10 and Vitamin E were released from PEG conjugate at pH 7.4 and in plasma within the 24 h. The antioxidant activity evaluation was carried out by DPPH assay. Our results indicated that the chemical modification after esterification with PEG of the two drugs Ubiquinol and Vitamin E doesn't significantly affected their antioxidant potential.