Garbiec Ewa, Rosiak Natalia, Zalewski Przemysław, Tajber Lidia, Cielecka-Piontek Judyta
Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, 3 Rokietnicka St., 60-806 Poznan, Poland.
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, University of Dublin, D02 PN40 Dublin, Ireland.
Pharmaceutics. 2023 Nov 21;15(12):2653. doi: 10.3390/pharmaceutics15122653.
Genistein, an isoflavone known for its antioxidant and antidiabetic effects, suffers from the drawback of low solubility. To overcome this limitation, co-amorphous systems were synthesized by incorporating amino acids that were chosen through computational methods. The confirmation of the amorphous state of lysine and arginine-containing systems was ascertained by X-ray powder diffraction. Subsequently, the characterization of these systems was extended by employing thermo-gravimetry, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The investigation also included an assessment of the physical stability of the samples during storage. The apparent solubility of the systems was studied in an aqueous medium. To evaluate the in vitro permeability through the gastrointestinal tract, the parallel artificial membrane permeability assay was employed. The biological properties of the systems were assessed with regard to their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl and cupric ion-reducing antioxidant capacity assays, as well as their ability to inhibit α-glucosidase. The systems' glass transition temperatures were determined, and their homogeneity confirmed via differential scanning calorimetry analysis, while Fourier-transform infrared spectroscopy analysis provided data on molecular interactions. Stability was maintained for the entire 6-month storage duration. The co-amorphous system containing lysine displayed the most pronounced apparent solubility improvement, as well as a significant enhancement in antioxidant activity. Notably, both systems demonstrated superior α-glucosidase inhibition relative to acarbose, a standard drug for managing type 2 diabetes. The results indicate that co-amorphous systems with lysine and arginine have the potential to significantly enhance the solubility and biological activity of genistein.
染料木黄酮是一种以其抗氧化和抗糖尿病作用而闻名的异黄酮，但存在溶解度低的缺点。为了克服这一限制，通过纳入经计算方法选择的氨基酸合成了共无定形体系。含赖氨酸和精氨酸体系的无定形状态通过X射线粉末衍射得以确认。随后，通过热重分析、差示扫描量热法、傅里叶变换红外光谱和扫描电子显微镜对这些体系进行了表征扩展。该研究还包括对样品在储存期间物理稳定性的评估。在水介质中研究了这些体系的表观溶解度。为了评估其在胃肠道的体外渗透性，采用了平行人工膜渗透性测定法。使用2,2-二苯基-1-苦基肼自由基和铜离子还原抗氧化能力测定法评估了这些体系的抗氧化活性等生物学特性，以及它们抑制α-葡萄糖苷酶的能力。测定了这些体系的玻璃化转变温度，并通过差示扫描量热分析确认了其均匀性，而傅里叶变换红外光谱分析提供了分子相互作用的数据。在整个6个月的储存期内稳定性得以保持。含赖氨酸的共无定形体系表现出最显著的表观溶解度提高，以及抗氧化活性的显著增强。值得注意的是，相对于用于治疗2型糖尿病的标准药物阿卡波糖，这两种体系均表现出优异的α-葡萄糖苷酶抑制作用。结果表明，含赖氨酸和精氨酸的共无定形体系有可能显著提高染料木黄酮的溶解度和生物活性。
