Glycyrrhiza uralensis polysaccharides (GUPS) are widely applied in biomedicine and functional food due to their multiple pharmacological activities and low toxicity. Despite their widespread use, the in vivo metabolic profile of GUPS remains poorly understood. To address this gap, we developed a quantitative analysis method that involves labeling GUPS with visible fluorescein (5-DTAF) and near-infrared (NIR) fluorescein (Cy7), resulting in stable conjugates with substitution degrees of 0.81% for 5-DTAF and 0.39% for Cy7. The pharmacokinetic studies showed a biphasic elimination pattern in the blood concentration-time curve following both intravenous and oral administration, consistent with a two-compartment model. Using fluorescence quantification and NIR imaging, we observed that GUPS was distributed to various tissues, exhibiting higher concentrations particularly in liver, kidney and lung. Excretion studies indicated that feces were the major excretion pathway of GUPS after oral administration (60.98%), whereas urine was the main pathway after intravenous administration (31.16%). Notably, GUPS could be absorbed rapidly by gut (Tmax 1 ± 0.61 h) and showed a biological half-time t1/2 26.4 ± 7.72 h after oral administration. Furthermore, the Caco-2 cells uptake studies illustrated that macropinocytosis and clathrin-mediated endocytosis were participated in the transport of GUPS in intestine epithelium. This comprehensive analysis of the in vivo pharmacokinetics of GUPS not only enhances our understanding of its metabolic pathways but also establishes a foundational basis for its clinical application, optimizing its therapeutic potential and safety profile.

Folate is an essential component of many metabolic processes, and folate deficiency is known to cause various disorders. Folate and folic acid, a synthetic and chemically stable form of folate, enriched diet are typically used to overcome this deficiency. Folic acid and folate however, are susceptible to harsh environment and folates enrichment using nanoparticles is an intensively studied strategy in food industry. This review highlights the current methods and types of matrices utilized to develop folic acid/folate carrying nanoparticles. The folic acid/folate loaded nanoparticles prevent cargo degradation during gut absorption and under harsh food processing conditions including, high temperatures, UV light, and autoclaving. The data demonstrates that nanofortifcation of folates using proteins and biopolymers effectively enhances the bioavailability of the cargo. The encapsulation of folic acid in biopolymers by emulsion, spray drying and ionic gelation represent simplistic methods that can be easily scaled up with applications in food industry.

UNASSIGNED: Zeaxanthin is a yellow‑coloured dietary carotenoid widely recognized as an essential component of the macula. It exerts blue light filtering and antioxidant activities, offering eye health and vision benefits.
UNASSIGNED: This study explores the oral absorption and systemic disposition of zeaxanthin from biopharmaceutical and pharmacokinetic perspectives.
UNASSIGNED: In vivo intravenous (5 and 10 mg/kg) and intraportal (5 mg/kg) pharmacokinetic studies were performed to determine intrinsic tissue‑blood partition coefficient, elimination pathway, and hepatic clearance, of zeaxanthin in rats. Moreover, in vitro physicochemical property test, in situ closed loop study, in vivo oral pharmacokinetic study (20 and 100 mg/kg), and in vivo lymphatic absorption study (100 mg/kg) were conducted to investigate the gut absorption properties of zeaxanthin and assess the effects of several lipids on the lymphatic absorption of zeaxanthin in rats.
UNASSIGNED: Zeaxanthin exhibited poor solubility (≤144 ng/mL) and stability (6.0-76.9% of the initial amount remained at 24 h) in simulated gut luminal fluids. Gut absorption of zeaxanthin occurred primarily in the duodenum, but the major fraction (≥84.7%) of the dose remained unabsorbed across the entire gut tract. Considerable fractions of intravenous zeaxanthin accumulated in the liver, lung, and spleen (21.3, 11.7, and 2.0%, respectively). It was found that the liver is the major eliminating organ of zeaxanthin, accounting for 53.5-90.1% of the total clearance process (hepatic extraction ratio of 0.623).
UNASSIGNED: To our knowledge, this is the first systematic study to report factors that determine the oral bioavailability and systemic clearance of zeaxanthin.

Velpatasvir is a novel inhibitor of hepatitis C virus nonstructural protein 5A that received US Food and Drug Administration approval for the treatment of patients with chronic hepatitis C virus genotypes 1-6. In the present study, a sensitive bioanalytical method for velpatasvir was developed using high-performance liquid chromatography coupled with a fluorescence detector system, which was applied to elucidate the factors determining the oral bioavailability and disposition of velpatasvir. This method offered sufficient sensitivity, with a lower limit of quantification of 0.5 ng/mL, which is comparable to previously reported methods using liquid chromatography coupled with tandem mass spectrometry. Velpatasvir exhibited low oral bioavailability, moderate intestinal permeability, and significant biliary excretion in rats. It was also found to be significantly metabolized in the liver, with a low-to-moderate extraction ratio; however, its intestinal metabolism and enterohepatic circulation did not occur. Thus, our present results demonstrate that the oral bioavailability of velpatasvir is primarily dependent on gut absorption and hepatic first-pass metabolism. The fractions of velpatasvir dose unabsorbed from the gut and eliminated by the liver before reaching the systemic circulation following oral administration were estimated to be 32.8%-58.6% and 4.74%-30.54% of the oral dose, respectively. To our knowledge, this is the first systematic study to investigate the contributory roles of biopharmaceutical and pharmacokinetic factors on the oral bioavailability of velpatasvir, together with a new bioanalytical method for velpatasvir.

BACKGROUND: Alterations of intestinal permeability (IP) may contribute to the pathophysiology of immune-mediated diseases.
OBJECTIVE: We investigated the possible association between IP changes and multiple sclerosis (MS).
METHODS: We studied 22 patients with relapsing-remitting multiple sclerosis (RRMS) and 18 age- and sex-matched healthy donors (HDs), including five twin pairs (one concordant, and four discordant for disease). Measurement of lactulose (L) and mannitol (M; two non-metabolized sugars) levels in urine samples, after an oral load, allowed to quantify gut dysfunction.
RESULTS: The proportion of participants with increased IP was significantly higher in patients than in HDs (16/22 (73%) versus 5/18 (28%); p = 0.001). Accordingly, the L/M urinary ratio showed significantly higher values in patients than in controls ( p = 0.0284). Urinary mannitol concentration was significantly lower in patients than in controls ( p = 0.022), suggesting a deficit of absorption from intestinal lumen. Such changes did not appear related to patients\' clinical-radiological features.
CONCLUSIONS: The relatively high proportion of IP changes in RR-MS patients seems to confirm our work hypothesis and warrants more work to confirm the result on a larger sample, and to understand the implications for related immunological disturbances and intestinal microbiota alterations. Our finding may also have relevance for oral treatments, recently introduced in clinical practice.