Enhancing the Solubility, Stability, and Bioavailability of Retinol Acetate through Mechanochemistry.

This study utilizes mechanochemistry to prepare retinol acetate (RA) solid dispersion (RA-sodium starch octenyl succinate (SSOS)), resulting in improved solubility, stability, and bioavailability compared with raw RA and commercial RA microcapsules. RA, poloxamer 188, SSOS, and milling beads (8 mm) were mixed in a ratio of 2:1:8:220 (w/w) and ball-milled at 100 rpm for 3 h. RA-SSOS exhibited a solubility of 1020.35 µL/mL and a 98.09% retention rate after aging at 30 °C. Rats fed with RA-SSOS showed an ∼30% increase in organ RA content. Characterization analysis attributed the solubility and stabilization of RA-SSOS to hydrogen bonding between RA and SSOS, along with an amorphous state. RA-SSOS offers significant advantages for the pharmaceutical and food industries, leveraging mechanochemistry to enhance solid dispersions for hydrophobic compounds and optimize drug delivery.

Effect of Glycyrrhizic Acid and Arabinogalactan on the Membrane Potential of Rat Thymocytes Studied by Potential-Sensitive Fluorescent Probe.

The effect of the natural saponin glycyrrhizic acid (GA) and polysaccharide arabinogalactan (AG) on the transmembrane potential of rat thymocytes was investigated using the potential-sensitive fluorescent probe 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM). Incubation of cells with GA in micellar form resulted in a decrease of the amplitude of observed fluorescence kinetics that points out to a decrease of the transmembrane potential. The proposed mechanism is an increase of membrane ion permeability (passive ion transport) of the plasma cell membrane due to GA incorporation. The incorporation of GA molecules into the cell membrane is extremely sensitive to the degree of GA dissociation. The neutral form of glycyrrhizic acid enters the lipid bilayer in contrast to the deprotonated anionic form. The incubation of rat thymocytes with anionic form of GA, namely with its disodium salt, has no effect on the fluorescence kinetics. The possible reasons of this phenomenon are discussed in the light of the nuclear magnetic resonance (NMR) and molecular dynamics (MD) data. The treatment of thymocytes with AG affects only the initial rate of the probe incorporation. The proposed mechanism is that AG covers the surface of the cell membrane and forms a barrier for the probe. Additionally, our experiments demonstrated that both polysaccharide AG and GA in the neutral form (but not Na2GA) effectively capture the cationic probe in an aqueous solution and then deliver it to the cell membrane.