Zhuang Ding

This study selected three approved folate sources—folic acid (FA), L-5-methyltetrahydrofolate (MTFA), and calcium 5-methyltetrahydrofolate (CMTFA)—to explore their interaction mechanisms with soy protein isolate (SPI) through spectrofluorometric analysis and molecular docking simulations. We investigated how these interactions influence the structural and physicochemical stability of folates and SPI. Three folates spontaneously bound to SPI, forming complexes, resulting in a decrease of approximately 30 kJ·mol⁻¹ in Gibbs free energy and an association constant (K_a) of 10⁵ L·mol⁻¹. The thermodynamic parameters and molecular docking study revealed the unique binding mechanisms of FA and MTFA with SPI. FA’s planar pteridine ring and conjugated double bonds facilitate hydrophobic interactions, whereas MTFA’s reduced ring structure and additional polar groups strengthen hydrogen bonding. Although the formation of SPI–folate complexes did not result in substantial alterations to the SPI structure, their binding has the potential to enhance both the physical and thermal stability of the protein by stabilizing its conformation. Notably, compared with free FA, the FA-SPI complexes significantly enhanced FA’s stability, exhibiting 71.1 ± 1.2% stability under light conditions after 9 days and 63.2 ± 2.6% stability in the dark after 60 days. In contrast, no similar effect was observed for MTFA. This discrepancy can be ascribed to the distinct degradation pathways of the Fa and MTFA molecules. This study offers both theoretical and experimental insights into the development of folate-loaded delivery systems utilizing SPI as a matrix.

Phase separation is quite common in formulations for hydrophobic active pharmaceutical ingredients (APIs) due to their thermodynamic instability in a supersaturated state during in vitro dissolution or in vivo absorption. Phase separation possibly accompanies the formation of a disordered drug-rich phase, but this is still not thoroughly understood. In this study, the phase separation of supersaturated axitinib (Axi) in media with or without polymers was evaluated via multiple analytical methods, including UV–vis and fluorescence spectroscopy, dynamic light scattering, and microscopy. The phase separation of Axi occurred at an Axi concentration of 25–30 µg/mL in the media, while the addition of quantitative hypromellose acetate succinate (HPMCAS) MG and povidone (PVP) K30 did not alter its phase separation concentration. The second scattering dispersion phase of the system exhibited superior stability and reversibility as the formative filamentous crystalline condensates could disintegrate upon dilution. These disparate analyses consistently detected the phase separation of Axi. This manuscript could provide a better understanding of the supersaturation state of hydrophobic APIs upon pharmaceutical application.

Folates, a crucial B-group vitamin, serve as a significant functional food supplement. Nevertheless, considerable obstacles persist in improving folates stability in liquid products. In this study, folic acid (FA) and 5-methyltetrahydrofolate (MTFA), two approved sources of folates, were encapsulated with sodium caseinate (NaCas) to enhance their stability. The protective effect of NaCas on folate molecules was investigated using experimental and computational methods. Meanwhile, the influence of divalent calcium ion (Ca²⁺) on the properties of the NaCas-MTFA complex was examined to evaluate the potential application of calcium 5-methyltetrahydrofolate (CaMTFA). Fluorescence tests showed both folates had static quenching behavior and bound to NaCas with a binding constant of 10⁴–10⁵ M⁻¹. Hydrophobic interactions were crucial in NaCas-FA complex formation, while hydrogen bonding drove NaCas-MTFA binding. The encapsulation of caseinate notably slowed down the degradation of folates under both light and dark conditions. Moreover, the addition of a low concentration of Ca²⁺ did not adversely impact the binding mechanism of the NaCas-MTFA complex or the degradation curve of MTFA. The results of this study could serve as a valuable resource for the utilization of caseinates in incorporating folates, specifically MTFA, in the creation of natural liquid dietary supplements.

Carotenoids, which are inherent pigments occurring in plants and microorganisms, manifest a diverse array of vivid hues. Owing to their multifarious health advantages, carotenoids have engendered substantial interest among scholars and consumers alike. Presently, carotenoids are extensively employed in the realms of food, nutrition and health commodities, pharmaceuticals, and cosmetics, rendering them an indispensable constituent of our quotidian existence. Therefore, the objective of this review is to present a succinct and methodical examination of the sources, constituents, and factors influencing formation of carotenoids. Particular attention will be given to encapsulation strategies that maintain intrinsic characteristics, as the growing desire for carotenoids is propelled by individuals’ escalating standards of living. Moreover, the applications of natural carotenoids in multiple fields, including pharmaceutical, food and feed, as well as cosmetics, are discussed in detail. Finally, this article explores the main challenges hindering the future advancement of carotenoids, aiming at facilitating their effective integration into the circular economy.

Paxlovid^®, a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we developed a liquid formulation containing NRV and RTV by adopting strategies that used co-solvents and surfactants to enhance the solubility and inhibit possible recrystallization. The in vitro release results showed that NRV and RTV could be maintained at high concentrations in solution for a certain period in the investigated media. In vivo studies in rats showed that the oral bioavailability of NRV/RTV solution was significantly enhanced. Compared to Paxlovid^® tablets, the AUC_(0–t) of NRV and RTV increased by 6.1 and 3.8 times, respectively, while the C_max increased by 5.5 times for both. Furthermore, the promoting effect of the absorption of RTV on the bioavailability of NRV was confirmed. Experiments with a beagle showed a similar trend. Stability studies were also conducted at 4 °C, 25 °C, and 40 °C for 90 days, indicating that the oral liquid formulation was physically and chemically stable. This study can be used as a valuable resource for developing and applying oral liquid NRV/RTV formulations in a clinical context.