Cyclodextrin Derivatives as Promising Solubilizers to Enhance the Biological Activity of Rosmarinic Acid

Abstract

Rosmarinic acid (RA) is a natural antioxidant with neuroprotective properties; however, its preventive and therapeutic use is limited due to its slight solubility and poor permeability. This study aimed to improve RA physicochemical properties by systems formation with cyclodextrins (CDs): hydroxypropyl-α-CD (HP-α-CD), HP-β-CD, and HP-γ-CD, which were prepared by the solvent evaporation (s.e.) method. The interactions between components were determined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier Transform infrared spectroscopy (FTIR). The sites of interaction between RA and CDs were suggested as a result of in silico studies focused on assessing the interaction between molecules. The impact of amorphous systems formation on water solubility, dissolution rate, gastrointestinal (GIT) permeability, and biological activity was studied. RA solubility was increased from 5.869 mg/mL to 113.027 mg/mL, 179.840 mg/mL, and 194.354 mg/mL by systems formation with HP-α-CD, HP-β-CD, and HP-γ-CD, respectively. During apparent solubility studies, the systems provided an acceleration of RA dissolution. Poor RA GIT permeability at pH 4.5 and 5.8, determined by parallel artificial membrane permeability assay (PAMPA system), was increased; RA–HP-γ-CD s.e. indicated the greatest improvement (at pH 4.5 from Papp 6.901 × 10−7 cm/s to 1.085 × 10−6 cm/s and at pH 5.8 from 5.019 × 10−7 cm/s to 9.680 × 10−7 cm/s). Antioxidant activity, which was determined by DPPH, ABTS, CUPRAC, and FRAP methods, was ameliorated by systems; the greatest results were obtained for RA–HP-γ-CD s.e. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was increased from 36.876% for AChE and 13.68% for BChE to a maximum inhibition of the enzyme (plateau), and enabled reaching IC50 values for both enzymes by all systems. CDs are efficient excipients for improving RA physicochemical and biological properties. HP-γ-CD was the greatest one with potential for future food or dietary supplement applications.

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

“…However, with respect to our systems, this effect seems to be of negligible importance—in the CUPRAC assay, the concentration of LYS needed to reach an IC 0.5 value was nearly 23 times greater than the concentration of LYS present in the system being studied; whereas when it comes to the DPPH assay, LYS failed to achieve the IC 50 value, which is in line with a report from the literature [ 56 ] (maximum radical inhibitory activity in our study was equal to 38.8% for the LYS concentration more than twice of the concentration in the studied system). Taking into account these considerations and the reports from the literature indicating that an increase in the solubility of the compound may translate into antioxidant activity improvement [ 45 , 57 ], we correlated an increase in SA properties in the DPPH and CUPRAC assays mainly with the solubility improvement.…”

Amorphous Pterostilbene Delivery Systems Preparation—Innovative Approach to Preparation Optimization

“…In another study, Garbiec et al [65] confirmed that the ASD showing the best solubility improvement had the smallest particle size through SEM analysis. Lee et al [74] confirmed that the It was inferred that the improved apparent solubility might positively affect the antioxidant properties of the compound [34,55,77]. The improvement of PTR solubility after its introduction into amorphous dispersions translated into a change in its biological properties, such as the antioxidant potential.…”

Co-Dispersion Delivery Systems with Solubilizing Carriers Improving the Solubility and Permeability of Cannabinoids (Cannabidiol, Cannabidiolic Acid, and Cannabichromene) from Cannabis sativa (Henola Variety) Inflorescences

“…During the assay, the green ABTS radical can be converted into a colorless neutral form in the presence of an antioxidant. In this assay, 200.0 µL of ABTS •+ solution and 10.0 µL of the system/trolox solution were pipetted into 96-well plates and incubated for 10 min in the dark at room temperature while shaking [62]. After incubation, the absorbance values were measured at λ = 734 nm using a plate reader (Multiskan GO, Thermo Fisher Scientific, Waltham, MA, USA).…”

“…In this assay, the antioxidants' phenolic groups undergo oxidation to form quinones, while the bluish neocuproine and copper (II) ion complex is reduced to the yellow neocuproine and copper (I) ion complex. To perform this study, a mixture of 50.0 µL of the system/trolox solution and 150.0 µL of the CUPRAC reagent was added to the plate and then incubated for 30 min at room temperature while shaking in the dark [62]. The control and systems' own absorbance were also measured simultaneously.…”

“…The FRAP technique was also used to determine the reducing properties of the systems, which involves reducing colorless Fe 3+ ion to Fe 2+ to form a dark blue complex with 2,4,6-tris(2-pyridyl)-1,3,5-triazine (TPTZ) [62]. In this method, 25.0 µL of the system/trolox solution and 175.0 µL of the FRAP mixture (consisting of 25 mL acetate buffer, 2.5 mL TPTZ solution, and 2.5 mL of FeCl 3 •6H 2 O solution) were applied to the plate and incubated in dark conditions at 37 • C for 30 min.…”