Tailoring Deep Eutectic Solvents to Provoke Solubility and Bioavailability of Naringin: Implications of a Computational Approach

Abstract

Recently, the applications of deep eutectic solvents (DESs) as green and sustainable solvents for the solubilization of functional foods and phytophenols have dramatically risen concerning global issues on the utilization of organic solvents. Nevertheless, developing a suitable DES system for phytocomponents to enhance its solubility and bioavailability is complex and requires a sound experimental setup. Herein, we have attempted to develop DES encompassing the choline chloride (ChCl) along with oxalic acid (OA), l-glutamine (l-Glu), urea (U), and glycerol (Gro) at different ratios to elicit the solubility and bioavailability of naringin (NAR). Several DES systems were designed and tested for solubility, kinematic viscosity, and pH. Among these, DES-NAR encompassing ChCl/Gro in a 1:3 ratio exhibited the maximum solubility of NAR (232.56 ± 7.1 mg/mL) and neutral characteristic and thus considered suitable for NAR. Further, the conductor-like screening model for real solvents (COSMO-RS) has been employed to estimate the molecular and electrostatic interactions. DES-NAR was evaluated by polarized optical microscopy, Fourier-transform infrared (FTIR), differential scanning calorimetry (DSC), and 1H NMR to investigate the molecular transition and interaction. Further, diffusion and permeability studies were performed, which suggest significant improvements in DES-NAR. Likewise, the pharmacokinetic studies revealed a two times increase in the oral bioavailability of NAR in a designed DES system. Thus, the work represents a systematic and efficient development of the DES system for a potential phytocomponent considering the biosafety impact, which may widen the interest in pharmaceutical and food sciences.

Biological Activities and Solubilization Methodologies of Naringin

“…Then, after oral administration of NG for 8 h, the concentration of naringenin obtained from naringin in the body reaches a maximum of approximately 2600 ng/mL [ 15 ]. After oral administration of 50 mg/kg NG for 6 h, the plasma concentration of NG in rats reaches the maximum of only 500 ng/mL [ 16 ]. This limitation has been attributed to NG’s low solubility and permeability, which curtails its applicability in the pharmaceutical and food industries.…”

Effect of Deep Eutectic System (DES) on Oral Bioavailability of Celecoxib: In Silico, In Vitro, and In Vivo Study

“…A study by Chen et al [ 12 ] suggested that oral administration of a salvianolic acid–DES formulation with a choline chloride–glycerol (1:2) DES resulted in enhanced Cmax and reduced Tmax compared to the corresponding aqueous suspension. Recently, Dangre et al [ 13 ] showed that two-fold enhancement of the relative oral bioavailability of naringenin was achieved with a narigenin–DES formulation with choline chloride–glycerol (1:3) compared to aqueous suspension. However, more investigations are needed to completely understand the oral absorption-enabling potential of DES and the underlying mechanisms.…”