Berberine is a plant-origin quaternary isoquinoline alkaloid with a vast array of biological activities, including antioxidant and blood-glucose- and blood-lipid-lowering effects. However, its therapeutic potential is largely limited by its poor oral bioavailability. The aim of this study was to investigate the in vitro solubility and Caco-2 cell permeability followed by pharmacokinetic profiling in healthy volunteers of a new food-grade berberine delivery system (i.e., Berberine LipoMicel^®). X-ray diffractometry (XRD), in vitro solubility, and Caco-2 cell permeability indicated higher bioavailability of LipoMicel Berberine (LMB) compared to the standard formulation. Increased aqueous solubility (up to 1.4-fold), as well as improved Caco-2 cell permeability of LMB (7.18 × 10⁻⁵ ± 7.89 × 10⁻⁶ cm/s), were observed when compared to standard/unformulated berberine (4.93 × 10⁻⁶ ± 4.28 × 10⁻⁷ cm/s). Demonstrating better uptake, LMB achieved significant increases in AUC_0–24 and C_max compared to the standard formulation (AUC: 78.2 ± 14.4 ng h/mL vs. 13.4 ± 1.97 ng h/mL, respectively; p < 0.05; C_max: 15.8 ± 2.6 ng/mL vs. 1.67 ± 0.41 ng/mL) in a pilot study of healthy volunteers (n = 10). No adverse reactions were reported during the study period. In conclusion, LMB presents a highly bioavailable formula with superior absorption (up to six-fold) compared to standard berberine formulation and may, therefore, have the potential to improve the therapeutic efficacy of berberine. The study has been registered on ClinicalTrials.gov with Identifier NCT05370261.

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters—including maximum concentration (C_max), time to reach C_max (T_max), and area under the curve (AUC)—were calculated. Results: Mean AUC_0–24, C_max, T_max, and T_½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC_0–24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed T_max (6–8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS’ pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results.

Background: Silymarin, a flavonoid complex, and the main bioactive component of milk thistle (Silybum marianum), is known for its hepatoprotective properties but suffers from poor bioavailability due to its low solubility and extensive first-pass metabolism. Method: This study aimed to evaluate the pharmacokinetics and tolerability of a novel micellar milk thistle formulation designed to enhance silymarin absorption, compared to an unformulated/standard milk thistle product, in a small-scale human bioavailability trial. In a randomized, double-blinded, crossover study, 16 healthy participants received a single dose of either the micellar formulation (LipoMicel Milk Thistle; LMM) or the standard formulation (STD) at a total daily dose of 130 mg silymarin. Blood concentrations were measured over 24 h, and key pharmacokinetic parameters—maximum plasma concentration (C_max), time to reach maximum concentration (T_max), and area under the curve (AUC)—were calculated. Tolerability and safety were assessed through adverse event monitoring during the study period. Results: Results demonstrated a significant increase in bioavailability with the micellar formulation, with 18.9-fold higher C_max (95% CI: 1.9–30.7 ng/mL vs. 74.4–288.3 ng/mL; p = 0.007) and 11.4-fold higher AUC_0–24 (95% CI: 7.40–113.5 ng·h/mL vs. 178–612.5 ng·h/mL; p = 0.015). T_max was 0.5 (95% CI: 0.5–4.0) hours for the micellar formulation versus 2.5 (95% CI: 0.5–8.0) hours for the standard product (p = 0.015) indicating faster absorption of LMM. The standard formulation exhibited a significantly longer mean residence time compared to the LMM formulation (95% CI: 4.4–7.5 h vs. 2.8–4.2 h; p = 0.015). Conclusions: No adverse events or significant safety concerns were observed in either group. Compared to the standard, the micellar formulation showed superior pharmacokinetic outcomes, suggesting it may enhance silymarin’s clinical efficacy in liver health.

This study evaluated the differences in the metabolite profile of three n-3 FA fish oil formulations in 12 healthy participants: (1) standard softgels (STD) providing 600 mg n-3 FA; (2) enteric-coated softgels (ENT) providing 600 mg n-3 FA; (3) a new micellar formulation (LMF) providing 374 mg n-3 FA. The pharmacokinetics (PKs), such as the area under the plot of plasma concentration (AUC), and the peak blood concentration (C_max) of the different FA metabolites including HDHAs, HETEs, HEPEs, RvD1, RvD5, RvE1, and RvE2, were determined over a total period of 24 h. Blood concentrations of EPA (26,920.0 ± 10,021.0 ng/mL·h) were significantly higher with respect to AUC_0-24 following LMF treatment vs STD and ENT; when measured incrementally, blood concentrations of total n-3 FAs (EPA/DHA/DPA3) up to 11 times higher were observed for LMF vs STD (iAUC _0-24: 16,150.0 ± 5454.0 vs 1498.9 ± 443.0; p ≤ 0.0001). Significant differences in n-3 metabolites including oxylipins were found between STD and LMF with respect to 12-HEPE, 9-HEPE, 12-HETE, and RvD1; 9-HEPE levels were significantly higher following the STD vs. ENT treatment. Furthermore, within the scope of this study, changes in blood lipid levels (i.e., cholesterol, triglycerides, LDL, and HDL) were monitored in participants for up to 120 h post-treatment; a significant decrease in serum triglycerides was detected in participants (~20%) following the LMF treatment; no significant deviations from the baseline were detected for all the other lipid biomarkers in any of the treatment groups. Despite a lower administered dose, LMF provided higher blood concentrations of n-3 FAs and certain anti-inflammatory n-3 metabolites in human participants—potentially leading to better health outcomes.

Background/Objectives: Berberine is a naturally occurring compound found in several plants and has been traditionally used for its various health benefits. However, its poor bioavailability limits its therapeutic potential. Berberine LipoMicel^® is a novel micellar formulation of berberine, microencapsulated within an emulsified matrix, designed to enhance bioavailability and bioactivity. This study aims to evaluate its safety, ensuring that improved bioavailability does not introduce new safety concerns. Methods: To assess its safety, a randomized, double-blind, placebo-controlled crossover study with a minimum 4-week washout period was conducted in 19 healthy participants over 30 days. The participants received 1000 mg of the treatment daily (i.e., 2 capsules/d), and their capillary blood was analyzed every week to monitor for changes in established safety markers related to liver and kidney function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), creatinine, fasting glucose (GLU), HbA1c, and various electrolytes. Additionally, potential side effects were recorded through the collection of weekly health questionnaires to determine treatment tolerability. Results: Compared to placebo, no statistically significant changes in any of the safety markers related to liver or kidney health were detected. Within-group analysis revealed a significant reduction of total cholesterol (TC) in females after 30 days of Berberine LipoMicel^® treatment. Although not significant, both male and female participants showed a noticeable improvement in the mean AST, potentially signaling a hepatoprotective effect. As for tolerability, no adverse events were reported by any of the participants. Conclusions: Based on these findings, despite higher bioavailability of berberine in a newly formulated delivery system (LipoMicel^®), the treatment was found to be safe and well tolerated by human participants, with no significant deviations in blood chemistry that would indicate safety concerns over a period of 30 days.

Chrysin is a dietary flavonoid with antioxidant and anti-inflammatory activity, but its clinical potential is limited by poor oral bioavailability. This randomized double-blind three period crossover trial evaluated the pharmacokinetics of a novel micellar chrysin formulation co-encapsulated with quercetin and rutin (LMC) compared with a non-micellar chrysin formulation (NMC) and unformulated chrysin (UFC). Secondary objectives included in vitro permeability (Caco-2) and a 30-day safety assessment of daily LMC supplementation. Sixteen healthy adults received a single oral dose of each formulation in randomized order separated by a 7-day washout. Plasma chrysin was quantified over 24 h to determine pharmacokinetic parameters. In vitro Caco-2 assays evaluated permeability, and clinical biochemistry of 15 participants were assessed weekly during 30 days of daily LMC use. LMC achieved >2-fold higher systemic exposure than unformulated chrysin (AUC_0–24 = 914.8 ± 697.5 ng·h/mL; C_max = 87.3 ± 59.4 ng/mL; both p < 0.05) and >2.6-fold higher than NMC, supported by >10-fold higher in vitro permeability. Daily LMC supplementation was well tolerated, with only mild, reversible adverse events and no clinically relevant safety changes, despite higher systemic exposure. Small, but significant, reductions in fasting glucose were observed in both sexes. The novel micellar chrysin–quercetin–rutin formulation substantially improved bioavailability and was well tolerated during 30 days of daily use, supporting its potential as an advanced delivery strategy for flavonoids with poor oral absorption and identifying glucose regulation as a physiological effect of interest.