Andrographolide (AG), a compound with low water solubility, possesses various pharmacological activities, particularly anti-inflammatory activity. However, its low oral bioavailability is a major ...obstacle to its potential use. This study developed and optimized an AG-loaded nanoemulsion (AG-NE) formulation to improve AG oral bioavailability and its protective effects against inflammatory bowel disease.
A high-pressure homogenization technique was used to prepare the AG-NE and solubility, viscosity, and droplet size tests were conducted to develop the optimized AG-NE composed of α-tocopherol, ethanol, Cremophor EL, and water. The permeability was assessed using everted rat gut sac method and in vivo absorption and anti-inflammatory effect in rats was also evaluated. The plasma concentration of AG was determined using our validated high performance liquid chromatography method, which was used to generate a linear calibration curve over the concentration range of 0.1-25 μg/mL in rat plasma (
>0.999).
The optimized AG-NE had a droplet size of 122±11 nm confirmed using transmission electron microscopy and a viscosity of 28 centipoise (cps). It was stable at 4 and 25°C for 90 days. An ex vitro intestinal permeability study indicated that the jejunum was the optimal site for AG absorption from the optimized AG-NE, which was 8.21 and 1.40 times higher than that from an AG suspension and AG ethanol solution, respectively. The pharmacokinetic results indicate that the absorption of AG from AG-NE was significantly enhanced in comparison with that from the AG suspension, with a relative bioavailability of 594.3%. Moreover, the ulcer index and histological damage score of mice with indomethacin-induced intestinal lesions were significantly reduced by AG-NE pretreatment.
We conclude that the developed AG-NE not only enhanced the oral bioavailability of AG in this study but may also prove to be an effective formulation of AG for preventing gastrointestinal inflammatory disorders.
This study aimed to design an effective nanoparticle-based carrier for the oral delivery of fisetin (FST) with improved biopharmaceutical properties. FST-loaded nanoparticles were prepared with ...polyvinyl alcohol (PVA) and poly(lactic-co-glycolic acid) (PLGA) by the interfacial deposition method. A central composite design of two independent variables, the concentration of PVA and the amount of PLGA, was applied for the optimization of the preparative parameter. The responses, including average particle size, polydispersity index, encapsulation efficiency, and zeta potential, were assessed. The optimized formulation possessed a mean particle size of 187.9 nm, the polydispersity index of 0.121, encapsulation efficiency of 79.3%, and zeta potential of −29.2 mV. The morphological observation demonstrated a globular shape for particles. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that the encapsulated FST was presented as the amorphous state. The dissolution test indicated a 3.06-fold increase for the accumulating concentrations, and the everted gut sac test showed a 4.9-fold gain for permeability at the duodenum region. In conclusion, the optimized FST-loaded nanoparticle formulation in this work can be developed as an efficient oral delivery system of FST to improve its biopharmaceutic properties.
Glucocorticoids are widely used anti-inflammatory drugs in clinical settings. However, they can induce skeletal muscle atrophy by reducing fiber cross-sectional area and myofibrillar protein content. ...Studies have proven that antioxidants can improve glucocorticoid-induced skeletal muscle atrophy. Quercetin is a potent antioxidant flavonoid widely distributed in fruits and vegetables and has shown protective effects against dexamethasone-induced skeletal muscle atrophy. In this study, we demonstrated that dexamethasone significantly inhibited cell growth and induced cell apoptosis by stimulating hydroxyl free radical production in C2C12 skeletal muscle cells. Our results evidenced that quercetin increased C2C12 skeletal cell viability and exerted antiapoptotic effects on dexamethasone-treated C2C12 cells by regulating mitochondrial membrane potential (ΔΨm) and reducing oxidative species. Quercetin can protect against dexamethasone-induced muscle atrophy by regulating the Bax/Bcl-2 ratio at the protein level and abnormal ΔΨm, which leads to the suppression of apoptosis.
Resveratrol (RES), a natural polyphenolic compound, exerts anti-fatigue activity, but its administration is complicated by its low water solubility. To improve RES bioavailability, this study ...developed a self-nanoemulsifying drug delivery system (SNEDDS) for RES and evaluated its anti-fatigue activity and rat exercise performance by measuring fatigue-related parameters, namely lactate, ammonia, plasma creatinine phosphokinase, and glucose levels and the swimming time to exhaustion. Through solubility and emulsification testing, the optimized SNEDDS composed of Capryol 90, Cremophor EL, and Tween 20 was developed; the average particle size in this formulation, which had favorable self-emulsification ability, was approximately 41.3 ± 4.1 nm. Pharmacokinetic studies revealed that the oral bioavailability of the optimized RES-SNEDDS increased by 3.2-fold compared with that of the unformulated RES-solution. Pretreatment using the RES-SNEDDS before exercise accelerated the recovery of lactate after exercise; compared with the vehicle group, the plasma ammonia level in the RES-SNEDDS group significantly decreased by 65.4%, whereas the glucose level significantly increased by approximately 1.8-fold. Moreover, the swimming time to exhaustion increased by 2.1- and 1.8-fold, respectively, compared with the vehicle and RES-solution pretreatment groups. Therefore, the developed RES-SNEDDS not only enhances the oral bioavailability of RES but may also exert anti-fatigue pharmacological effect.
Sesamin (SSM) is a water-insoluble compound that is easily eliminated by liver metabolism. To improve the solubility and bioavailability of SSM, this study developed and characterized a ...self-nanoemulsifying drug delivery system (SNEDDS) for the oral delivery of SSM and conducted pharmacokinetic assessments. Oil and surfactant materials suitable for SNEDDS preparation were selected on the basis of their saturation solubility at 37 ± 0.5 °C. The mixing ratios of excipients were determined on the basis of their dispersibility, transmittance (%), droplet sizes, and polydispersity index. An SNEDDS (F10) formulation comprising glyceryl trioctanoate, polyoxyethylene castor oil, and Tween 20 at a ratio of 10:10:80 (
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) was the optimal formulation. This formulation maintained over 90% of its contents in different storage environments for 12 weeks. After the self-emulsification of SNEDDS, the SSM dispersed droplet size was 66.4 ± 31.4 nm, intestinal permeability increased by more than three-fold, relative bioavailability increased by approximately 12.9-fold, and absolute bioavailability increased from 0.3% to 4.4%. Accordingly, the developed SNEDDS formulation can preserve SSM's solubility, permeability, and bioavailability. Therefore, this SNEDDS formulation has great potential for the oral administration of SSM, which can enhance its pharmacological application value.
Andrographolide (AG), a major diterpene lactone isolated from
(Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low ...bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (
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) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that
/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.
Hemp nut is commonly incorporated into several food preparations; however, most countries set regulations for hemp products according to their cannabinoid content. In this study, we have developed an ...efficient microwave-assisted extraction (MAE) method for cannabinoids (i.e., Δ9-tetrahydrocannabinol, cannabidiol, and cannabinol) in hemp nut. Optimization of the MAE procedure was conducted through single factor experiments and response surface methodology (RSM). A comparative study was also conducted to determine the differences in the extraction yields and morphology of hemp nut between MAE and reference extraction methods, namely heat reflux extraction (HRE), Soxhlet extraction (SE), supercritical fluid extraction (SFE), and ultrasound-assisted extraction (UAE). Among the independent variables in RSM, the temperature was the most significant parameter. The optimal conditions of MAE were as follows: extraction solvent of methanol, microwave power of 375 W, temperature of 109 °C, and extraction time of 30 min. Compared with reference extraction methods, MAE achieved the highest extraction yields of total cannabinoids in hemp nut (6.09 μg/g for MAE; 4.15 μg/g for HRE; 5.81 μg/g for SE; 3.61 μg/g for SFE; 3.73 μg/g for UAE) with the least solvent consumption and shortest time. Morphological observations showed that substantial cell rupturing occurred in the microstructure of hemp nut after MAE, indicating enhanced dissolution of the target compounds during the extraction process. The MAE method is thus a rapid, economic, and environmentally friendly extraction method that is both effective and practical for industrial applications.
Since 2017, higenamine has been added to the World Anti-Doping Agency (WADA) prohibited list as a β
-agonist prohibited at all times for sportspersons. According to WADA's report, positive cases of ...higenamine misuse have been increasing yearly. However, higenamine occurs naturally in the Chinese herb lotus plumule-the green embryo of lotus (
Gaertn) seeds-commercially available as concentrated powder on the Asian market. This study evaluated the major phytochemical components of lotus plumule products using an appropriate extraction method, followed by a human study in which the products were orally administered in multiple doses to investigate the risk of doping violations. Comparing various extraction methods revealed that optimized microwave-assisted extraction exhibited the highest extraction efficiency (extraction time, 26 min; power, 1046 W; and temperature, 120 °C). Subsequently, the alkaloids in lotus plumule products were quantitatively confirmed and compared. Human study participants (
= 6) consumed 0.8 g of lotus plumule (equivalent to 679.6 μg of higenamine) three times daily for three consecutive days. All participants' urinary higenamine concentrations exceeded the WADA reporting cut-off of 10.0 ng/mL. Accordingly, lotus plumule consumption may engender adverse analytical findings regarding higenamine. Athletes should avoid consuming lotus plumule-containing products during in- and out-of-competition periods.
Chlorphenesin is a legitimate preservative commonly used in cosmetics. It shares one urinary metabolite of 4‐chlorophenoxyacetic acid with meclofenoxate, a prohibited stimulant in sports. Recently, ...there have been cases where athletes using chlorphenesin‐containing products were falsely identified as users of meclofenoxate. This study developed and validated a liquid chromatography method with diode‐array detection to determine the chlorphenesin content in 61 selected personal care products with various functions (e.g., facial care, body cleansing, sun protection, make‐up, hairstyling, perfume, and oral cleaning). The analytical method demonstrated fit‐for‐purpose quantitation and provided good linearity, precision, accuracy, and recovery for analyzing different cosmetic matrices. Among the 27 cosmetics labeled with chlorphenesin, the chlorphenesin concentrations ranged from 0.10 to 2.67 mg/g, with three products showing no detection. None of the products exceeded the maximum limit of 3 mg/g (0.3%) set by regulatory authorities. Among the 34 cosmetics not labeled with chlorphenesin, none of them contained chlorphenesin. This study confirmed the absence of undeclared chlorphenesin in the selected cosmetics, supporting the correctness of chlorphenesin labeling in cosmetics sold in Taiwan. Further investigations studying urinary excretion patterns after different types, doses, frequencies, and sites of cosmetics applications could contribute to strengthen current testing approaches in anti‐doping.
Chlorphenesin, a legitimate preservative in cosmetics, shares the same urinary metabolite with meclofenoxate, a prohibited stimulant in sports. After analyzing the 61 selected personal care products with various functions, we confirmed the absence of undeclared chlorphenesin, and the concentrations of chlorphenesin were all below the 3 mg/g (0.3%) set by regulatory authorities.
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