Dolinina Ekaterina S, Parfenyuk Elena V
Laboratory "Chemistry of Hybrid Nanomaterials and Supramolecular Systems", G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 153045 Ivanovo, Russia.
Materials (Basel). 2021 Feb 18;14(4):963. doi: 10.3390/ma14040963.
Powerful antioxidant α-lipoic acid (LA) exhibits limited therapeutic efficiency due to its pharmacokinetic properties. Therefore, the purpose of this work was to evaluate the ability of silica-based composites of LA as well as its amide (lipoamide, LM), as new oral drug formulations, to control their release and maintain their therapeutic concentration and antioxidant activity in the body over a long time. The composites synthesized at different sol-gel synthesis pH and based on silica matrixes with various surface chemistry were investigated. The release behavior of the composites in media mimicking pH of digestive fluids (pH 1.6, 6.8, and 7.4) was revealed. The effects of chemical structure of the antioxidants, synthesis pH, surface chemistry of the silica matrixes in the composites as well as the pH of release medium on kinetic parameters of the drug release and mechanisms of the process were discussed. The comparative analysis of the obtained data allowed the determination of the most promising composites. Using these composites, modeling of the release process of the antioxidants in accordance with transit conditions of the drugs in stomach, proximal, and distal parts of small intestine and colon was carried out. The composites exhibited the release close to the zero order kinetics and maintained the therapeutic concentration of the drugs and antioxidant effect in all parts of the intestine for up to 24 h. The obtained results showed that encapsulation of LA and LM in the silica matrixes is a promising way to improve their bioavailability and antioxidant activity.
强大的抗氧化剂α-硫辛酸（LA）由于其药代动力学特性，治疗效率有限。因此，本研究的目的是评估基于二氧化硅的LA复合材料及其酰胺（硫辛酰胺，LM）作为新型口服药物制剂，在长时间内控制其释放并维持其在体内的治疗浓度和抗氧化活性的能力。研究了在不同溶胶-凝胶合成pH值下合成的、基于具有不同表面化学性质的二氧化硅基质的复合材料。揭示了复合材料在模拟消化液pH值（pH 1.6、6.8和7.4）的介质中的释放行为。讨论了抗氧化剂的化学结构、合成pH值、复合材料中二氧化硅基质的表面化学性质以及释放介质的pH值对药物释放动力学参数和过程机制的影响。通过对所得数据的比较分析，确定了最有前景的复合材料。使用这些复合材料，根据药物在胃、小肠近端和远端以及结肠中的转运条件，对抗氧化剂的释放过程进行了建模。复合材料表现出接近零级动力学的释放，并在肠道所有部位维持药物的治疗浓度和抗氧化作用长达24小时。所得结果表明，将LA和LM包裹在二氧化硅基质中是提高其生物利用度和抗氧化活性的一种有前景的方法。
