Genistein Co-Amorphous Systems with Amino Acids: An Investigation into Enhanced Solubility and Biological Activity

Abstract

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.

Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions

“…Consequently, the Tg of PTR was ascertained through the melting and cooling method within a DSC oven, and this value was employed in the G-T and C-K equations (XRPD analysis confirmed the amorphous state of melted PTR). The same approach was used by Löbmann et al for carbamazepine [ 77 ], Rosiak et al for hesperidin and kaempferol [ 52 , 60 ], Wdowiak et al for curcumin, hesperetin, and piperine [ 50 , 70 ], and Garbiec et al for genistein [ 78 ].…”

“…Based on a previous report [ 50 ], in vitro gastrointestinal (GIT) and blood–brain barrier (BBB) permeability were studied using the Parallel Artificial Membrane Permeability Assay (PAMPA) models. The HPLC method was employed for the examination of PTR concentrations, and the subsequent formulas were utilized for the computation of the apparent permeability coefficient (P app ) [ 78 ]: where V D —donor volume, V A —acceptor volume, C equilibrium —equilibrium concentration , C D —donor concentration, C A —acceptor concentration, S—membrane area, and t—incubation time (in seconds).…”

“…According to the literature [ 78 , 120 ], substances categorized as having low permeability typically exhibit a Papp value below 0.1 × 10 −6 cm·s −1 . Compounds designated as moderately permeable fall within the range of 0.1 × 10 −6 cm·s −1 ≤ Papp < 1 × 10 −6 cm·s −1 , while those with a Papp value ≥ 1 × 10 −6 cm·s −1 are classified as highly permeable.…”

Myricetin Amorphous Solid Dispersions—Antineurodegenerative Potential

“…Additionally, researchers show that a single glass transition seen in an amorphous dispersion’s thermogram indicates complete miscibility [ 50 , 66 , 67 ]. For instance, based on thermal analysis, the full miscibility of curcumin-piperine-PVP VA64 [ 55 ], genistein-amino acids [ 68 ], hesperidin-Soluplus ® and hesperidin-HPMC [ 46 ], hesperetin-piperine-PVPVA64 [ 48 ], kaempferol-Eudragit ® [ 46 ], pterostilbene-Soluplus ® [ 50 ], and tannic acid-poly(ε-caprolactone) [ 69 ] were confirmed.…”

“…ABTS, DPPH, CUPRAC, and FRAP were used to determine the antioxidant activity of the water solution of MYR, MYR-PVP 1:8 w / w , and MYR-PVP 1:9 w / w samples. All procedures were described previously [ 46 , 50 , 68 ]. All tests were done in Multiskan GO UV reader (Thermo-Scientific, Waltham, MA, USA).…”