A simple and sensitive LC-MS/MS method for the determination of loganic acid in rat plasma and its pharmacokinetic analysis.

Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C18 column (2.1 × 50 mm, 1.7 µm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2 mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).

Curcumin-loaded scaffolds in bone regeneration.

In recent years, there has been a notable surge in the development of engineered bone scaffolds intended for the repair of bone defects. While autografts and allografts have traditionally served as the primary methods in bone tissue engineering, their inherent limitations have spurred the exploration of novel avenues in biomedical implant development. The emergence of bone scaffolds not only facilitates bone reconstruction but also offers a platform for the targeted delivery of therapeutic agents. There exists a pervasive interest in leveraging various drugs, proteins, growth factors, and biomolecules with osteogenic properties to augment bone formation, as the enduring side effects associated with current clinical modalities necessitate the pursuit of safer alternatives. Curcumin, the principal bioactive compound found in turmeric, has demonstrated notable efficacy in regulating the proliferation and differentiation of bone cells while promoting bone formation. Nevertheless, its utility is hindered by restricted water solubility and poor bioavailability. Strategies aimed at enhancing the solubility, stability, and bioavailability of curcumin, including formulation techniques such as liposomes and nanoparticles or its complexation with metals, have been explored. This investigation is dedicated to exploring the impact of curcumin on the proliferation, differentiation, and migration of osteocytes, osteoblasts, and osteoclasts.

Absorption enhancement of peach kernel oil on hydroxysafflor yellow A in safflower extracts and its mechanisms.

Carthamus tinctorius L. (Safflower) is extensively used as a functional food and herbal medicine, with its application closely associated with hydroxysafflor yellow A (HSYA). However, the low oral bioavailability of HSYA in safflower extract (SFE) limits its health benefits and application. Our study found that co-administration of 250, 330, and 400 mg/kg peach kernel oil (PKO) increased the oral bioavailability of HSYA in SFE by 1.99-, 2.11-, and 2.49-fold, respectively. The enhanced bioavailability is attributed to improved lipid solubility and intestinal permeability of HSYA in SFE due to PKO. PKO is believed to modify membrane fluidity and tight junctions, increase paracellular penetration, and inhibit the expression and function of P-glycoprotein, enhancing the transcellular transport of substrates. These mechanisms suggest that PKO is an effective absorption enhancer. Our findings provide valuable insights for developing functional foods with improved bioavailability.

Flaking of millets and its impact on bioactivity, pasting, digestibility, structural and thermal properties.

Five different millets (foxtail, little, barnyard, kodo and browntop) with and without sprouting were subjected to flaking. Phytic acid and phenolic content tends to decrease significantly, whereas antioxidant activity increased up to 77.32% on flaking of millets. A significant decrease in peak and final viscosity was observed in millet flakes. A-type diffraction pattern was predominant for unsprouted millets whereas the flaked millets showed V-type crystallinity. The protein digestibility significantly increased up to 37.77% in flakes made from sprouted millets. The mineral bioavailability upon flaking of millets increased, especially Ca (88.22% for little), Fe (43.04% for barnyard) and Zn (61.77% for kodo), which is attributed to the reduction in phytic acid. Flaking, however, led to an increase in rapidly and slowly digestible starch with a corresponding decrease in resistant starch. Among the unsprouted and sprouted millet flakes, foxtail received the highest sensory scores for overall acceptability.

Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Polysaccharide-polyphenol interactions: a comprehensive review from food processing to digestion and metabolism.

Most studies on the beneficial effects of polyphenols on human health have focused on polyphenols extracted using aqueous organic solvents, ignoring the fact that a portion of polyphenols form complexes with polysaccharides. Polysaccharides and polyphenols are interrelated, and their interactions affect the physicochemical property, quality, and nutritional value of foods. In this review, the distribution of bound polyphenols in major food sources is summarized. The effect of food processing on the interaction between polyphenols and cell wall polysaccharides (CWP) is discussed in detail. We also focus on the digestion, absorption, and metabolic behavior of polysaccharide-polyphenol complexes. Different food processing techniques affect the interaction between CWP and polyphenols by altering their structure, solubility, and strength of interactions. The interaction influences the free concentration and extractability of polyphenols in food and modulates their bioaccessibility in the gastrointestinal tract, leading to their major release in the colon. Metabolism of polyphenols by gut microbes significantly enhances the bioavailability of polyphenols. The metabolic pathway and product formation rate of polyphenols and the fermentation characteristics of polysaccharides are affected by the interaction. Furthermore, the interaction exhibits synergistic or antagonistic effects on the stability, solubility, antioxidant and functional activities of polyphenols. In summary, understanding the interactions between polysaccharides and polyphenols and their changes in food processing is of great significance for a comprehensive understanding of the health benefits of polyphenols and the optimization of food processing technology.

Design, synthesis and evaluation of carbamate-bridged amino acid prodrugs of cycloicaritin with improved antitumor activity, aqueous solubility and phase II metabolic stability.

Cycloicaritin (CICT), a bioactive flavonoid derived from the genus Epimedium, exhibits a variety of beneficial biological activities, including promising anticancer effects. However, its poor oral bioavailability is attributed to its extremely low aqueous solubility and rapid elimination via phase II conjugative metabolism. To overcome these limitations, we designed and synthesized a series of carbamate-bridged prodrugs, protecting the hydroxyl group at the 3-position of cycloicaritin by binding with the N-terminus of a natural amino acid. The optimal prodrug 4b demonstrated a significant increase in aqueous solubility as compared to CICT, as well as improved stability in phase II metabolism, while allowing for a rapid release of CICT in the blood upon gastrointestinal absorption. The prodrug 4b also facilitated oral absorption through organic anion-transporting polypeptide 2B1-mediated transport and exhibited moderate cytotoxicity. Importantly, the prodrug enhanced the oral bioavailability of CICT and displayed dose-dependent antitumor activity with superior safety. In summary, the prodrug 4b is a novel potential antitumor drug candidate, and the carbamate-bridged amino acid prodrug approach is a promising strategy for the oral delivery of CICT.

Preparation, characterization, oral bioavailability, and pharmacodynamic study of eugenol-porous silica solidified powder.

Eugenol possesses anti-inflammatory and antioxidant properties, and may serve as a potential therapeutic agent for hepatic fibrosis. However, the development of solid eugenol formulations is challenging due to its volatility. To address this issue, this study employed porous silica to adsorb solidified eugenol. The solidified powder was characterized using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In addition, the differences in in vitro release and oral bioavailability between eugenol and solidified eugenol powder were investigated. The effectiveness of eugenol and eugenol powder in treating liver fibrosis was investigated using enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and histopathological observations. Our results indicate that porous silica can effectively solidify eugenol into powder at a lower dosage. Furthermore, we observed that porous silica accelerates eugenol release in vitro and in vivo. The pharmacodynamic results indicated that eugenol has a positive therapeutic effect against hepatic fibrosis and that porous silica does not affect its efficacy. In conclusion, porous silica was able to solidify eugenol, which may facilitate the preparation and storage of solid formulations.

Phosphate limitation enhances malic acid production on nitrogen-rich molasses with Ustilago trichophora.

BACKGROUND: An important step in replacing petrochemical products with sustainable, cost-effective alternatives is the use of feedstocks other than, e.g., pure glucose in the fermentative production of platform chemicals. Ustilaginaceae offer the advantages of a wide substrate spectrum and naturally produce a versatile range of value-added compounds under nitrogen limitation. A promising candidate is the dicarboxylic acid malic acid, which may be applied as an acidulant in the food industry, a chelating agent in pharmaceuticals, or in biobased polymer production. However, fermentable residue streams from the food and agricultural industry with high nitrogen content, e.g., sugar beet molasses, are unsuited for processes with Ustilaginaceae, as they result in low product yields due to high biomass and low product formation. RESULTS: This study uncovers challenges in evaluating complex feedstock applicability for microbial production processes, highlighting the role of secondary substrate limitations, internal storage molecules, and incomplete assimilation of these substrates. A microliter-scale screening method with online monitoring of microbial respiration was developed using malic acid production with Ustilago trichophora on molasses as an application example. Investigation into nitrogen, phosphate, sulphate, and magnesium limitations on a defined minimal medium demonstrated successful malic acid production under nitrogen and phosphate limitation. Furthermore, a reduction of nitrogen and phosphate in the elemental composition of U. trichophora was revealed under the respective secondary substrate limitation. These adaptive changes in combination with the intricate metabolic response hinder mathematical prediction of product formation and make the presented screening methodology for complex feedstocks imperative. In the next step, the screening was transferred to a molasses-based complex medium. It was determined that the organism assimilated only 25% and 50% of the elemental nitrogen and phosphorus present in molasses, respectively. Due to the overall low content of bioavailable phosphorus in molasses, the replacement of the state-of-the-art nitrogen limitation was shown to increase malic acid production by 65%. CONCLUSION: The identification of phosphate as a superior secondary substrate limitation for enhanced malic acid production opens up new opportunities for the effective utilization of molasses as a more sustainable and cost-effective substrate than, e.g., pure glucose for biobased platform chemical production.

Pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid in rainbow trout (Oncorhynchus mykiss).

BACKGROUND: Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties. OBJECTIVES: The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C. METHODS: The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis. RESULTS: The elimination half-life (t1/2ʎz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent. CONCLUSIONS: While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.

Validation of the analytical methodology used in obtaining the oral bioavailability of organic target pollutants in atmospheric particulate matter (PM10) applying an in-vitro method.

In recent years, scientists have started evaluating the portion of PM-bound pollutants that may be liberated (bioaccessible fraction) in human fluids and spread through the digestive system ultimately entering systemic circulation (known as the bioavailable fraction). In the current research, an analytical procedure was validated and applied to characterize the oral bioavailable fraction of PM10 samples. The approach encompassed the determination of 49 organic contaminants. The proposed method aims to biomimetic complete mouth-gastric-intestinal system basing on an adaptation of the unified bioaccessibility method (UBM) modified by the inclusion of a dialysis membrane to mimic intestinal absorption and obtain the orally bioavailable fractions. It was followed by a vortex-assisted liquid-liquid extraction (VALLE) step, using gas chromatography-tandem mass spectrometry (GC-MS/MS). Analytical procedure was effectively validated by employing selected reaction monitoring (SRM) mode in MS/MS, matrix-matched calibration, and deuterium-labelled surrogate standards. This approach ensured heightened sensitivity, minimized matrix effects, and compensated for any losses during the process. The validation process covered various aspects, including studying linearity, determining detection and quantification limits, assessing analytical recoveries at three concentration levels, and evaluating precision both within a single day and across multiple days. The validated method was applied to PM10 samples, revealing that polycyclic aromatic hydrocarbons (PAHs) were the most frequently detected, with significant seasonal variations in their concentrations. Organophosphorus flame retardants (OPFRs) like TCPP were also detected in bioavailable fractions, highlighting their potential health impact. Bisphenols, SMCs, and PAEs were not detected, suggesting low levels in the studied urban area. Further research is needed to understand the bioavailability of PM-bound pollutants in different environments.

The Recent Development of Luteolin-loaded Nanocarrier in Targeting Cancer.

INTRODUCTION: Luteolin (LUT), a naturally occurring flavonoid found in vegetables, fruits, and herbal medicines, has been extensively studied for its pharmacological activities, including anti-proliferative and anticancer effects on various cancer lines. It also exhibits potent antioxidant properties and pro-apoptotic activities against human cancers. However, its therapeutic potential is hindered by its poor solubility in water (5 µg/ml at 45°C) and low bioavailability. This research on the development of luteolin-loaded nanocarrier aims to overcome these limitations, thereby opening up new possibilities in cancer treatment. METHODS: This paper covers several nanoformulations studied to increase the solubility and bioavailability of LUT. The physicochemical characteristics of the nanoformulation that influence luteolin's solubility and bioavailability have been the subject of more in-depth investigation. Furthermore, it examines how LUT's anti-inflammatory and antioxidant properties aid in lessening the side effects of chemotherapy. RESULTS: Most nanoformulations, including phytosomes, lipid nanoparticles, liposomes, protein nanoparticles, polymer micelles, nanoemulsions, and metal nanoparticles, have shown promising results in improving the solubility and bioavailability of LUT. This is a significant step forward in enhancing the therapeutic potential of LUT in cancer treatment. Furthermore, the study found that LUT's ability to scavenge free radicals can significantly reduce the side effects of cancer treatment, further highlighting its potential to improve patient outcomes. CONCLUSION: Nanoformulations, because of their unique surface and physiochemical properties, improve the solubility and bioavailability of LUT. However, poor in-vitro and in-vivo correlation and scalability of nanoformulations need to be addressed to achieve good clinical performance of LUT in oncology.

Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Drug targeting for brain malignancies is restricted due to the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which act as barriers between the blood and brain parenchyma. Certainly, the limited therapeutic options for brain malignancies have made notable progress with enhanced biological understanding and innovative approaches, such as targeted therapies and immunotherapies. These advancements significantly contribute to improving patient prognoses and represent a promising shift in the landscape of brain malignancy treatments. A more comprehensive understanding of the histology and pathogenesis of brain malignancies is urgently needed. Continued research focused on unraveling the intricacies of brain malignancy biology holds the key to developing innovative and tailored therapies that can improve patient outcomes. Lipid nanocarriers are highly effective drug delivery systems that significantly improve their solubility, bioavailability, and stability while also minimizing unwanted side effects. Surface-modified lipid nanocarriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lipid nanocapsules, lipid-polymer hybrid nanocarriers, lipoproteins, and lipoplexes) are employed to improve BBB penetration and uptake through various mechanisms. This systematic review illuminates and covers various topics related to brain malignancies. It explores the different methods of drug delivery used in treating brain malignancies and delves into the benefits, limitations, and types of brain-targeted lipid-based nanocarriers. Additionally, this review discusses ongoing clinical trials and patents related to brain malignancy therapies and provides a glance into future perspectives for treating this condition.

Polystyrene sulfonate resin as an ophthalmic carrier for enhanced bioavailability of ligustrazine phosphate controlled release system.

Topical ocular sustained-release drug delivery systems represent an effective strategy for the treatment of ocular diseases, for which a suitable carrier has yet to be sufficiently developed. Herein, an eye-compatible sodium polystyrene sulfonate resin (SPSR) was synthesized with a uniform particle size of about 3 µm. Ligustrazine phosphate (LP) was adsorbed to SPSR by cation exchange to form LP@SPSR. LP@SPSR suspension eye drops were further developed using the combination of Carbopol 934P and xanthan gum as suspending agents. The LP@SPSR suspension showed a sustained release in vitro, which was consistent with the observed porcine corneal penetration ex vivo. Pharmacokinetics in tear fluid of rabits indicated that LP@SPSR suspension led to prolonged ocular retention of LP and a 2-fold improved the area under the drug concentration-time curve (AUC0-t). Pharmacokinetics in the aqueous humor of rabbits showed 2.8-fold enhancement in the AUC0-t compared to LP solution. The LP@SPSR suspension exhibited no cytotoxicity to human corneal epithelial cells, nor irritation was observed in rabbit eyes. Thus, the LP@SPSR suspension has been validated as a safe and sustained release system leading to enhanced ophthalmic bioavailability for treating ocular diseases.

Plastics and plastic-bound toxic metals in municipal solid waste compost from Sri Lanka.

This study examined plastics and toxic metals in municipal solid waste compost from various regions in Sri Lanka. Plastics were extracted using density separation, digested using wet peroxidation, and identified using Fourier Transform Infra-Red Spectroscopy in Attenuated Total Reflection mode. Compost and plastics were acid-digested to quantify total Cd, Cu, Co, Cr, Pb, and Zn concentrations and analyzed for the bioavailable fraction using 0.01 M CaCl2. Notably, plastics were highly abundant in most compost samples. The main plastic types detected were polyethylene, polypropylene, and cellophane. However, the average Cd, Cu, Co, Cr, Pb, and Zn levels were 0.727, 60.78, 3.670, 25.44, 18.95, and 130.7 mg/kg, respectively, which are well below the recommended levels. Zn was the most bioavailable (2.476 mg/kg), and Cd was the least bioavailable (0.053 mg/kg) metal associated with compost. The Contamination factor data show that there is considerable enhancement of Cd and Cu, however, Cr, Cu, Co, and Pb are at low contamination levels. Mean geo accumulation index values were 1.39, 1.07, - 1.06, - 0.84, - 0.32, and 0.08 for Cd, Cu, Co, Cr, Pb, and Zn. Therefore, the contamination level of compost samples with Cd and Cu ranges from uncontaminated to contaminated levels, whereas Co, Cr, Pb, and Zn are at uncontaminated levels. Despite no direct metal-plastic correlation, plastics in compost could harm plants, animals, and humans due to ingestion. Hence, reducing plastic and metal contamination in compost is crucial.

Reduction of the exchangeable cadmium content in soil by appropriately increasing the maturity degree of organic fertilizers.

To enhance the remediation effect of heavy metal pollution, organic fertilizers with different maturity levels were added to cadmium-contaminated soil. The remediation effect was determined by evaluating the form transformation and bioavailability of cadmium in heavy metal-contaminated soil. -Results showed that when the maturity was 50%, although the soil humus (HS) content increased, it didn't contribute to reducing the bioavailability of soil Cd. Appropriately increasing the maturity (GI ≥ 80%), the HS increased by 113.95%∼157.96%, and reduced significantly the bioavailability of soil Cd, among the exchangeable Cd decreased by 16.04%∼33.51% (P < 0.01). The structural equation modeling (SEM) revealed that HS content is a critical factor influencing the transformation of Cd forms and the reduction of exchangeable Cd accumulation; the HS and residual Cd content were positively correlated with the maturity (P < 0.01), while exchangeable Cd content was negatively correlated with maturity (P < 0.01), and the correlation increased with increasing maturity. In summary, appropriately increasing the maturity (GI ≥ 80%) can increase significantly HS, promote the transformation of exchangeable Cd into residual Cd, and ultimately enhance the effectiveness of organic fertilizers in the remediation of soil Cd pollution. These results provide a new insight into the remediation of Cd-contaminated soil through organic fertilizer as soil amendment in Cd-contaminated soil.

In vivo determination of the bioavailability of folic acid through the utilization of the PBPK model in conjunction with UPLC.

This paper employed a physiologically based pharmacokinetic model (PBPK) to investigate the transformations of folic acid and its metabolites in vivo. Additionally, an ultra-performance liquid chromatography (UPLC) method was developed to accurately measure the body's retention rate and conversion rate of folic acid, tetrahydrofolate, and 5-methyltetrahydrofolate. Furthermore, the bioavailability of folic acid in the body was assessed by combining this method with an evaluation technique for animal models. The study found that the gastric metabolism time was 2 h, while the small intestinal metabolism duration was 4 h. The maximum conversion rate was observed in plasma and liver after 6 h, and in the brain after 8 h. This serves as a framework for creating a model to assess the bioavailability of folic acid in living organisms, to enhance the safety and efficacy of folic acid intake.

Metabolic activity of gut microbial enrichment cultures from different marine species and their transformation abilities to plastic additives.

The role of the gut microbiota in host physiology has been previously elucidated for some marine organisms, but little information is available on their metabolic activity involved in transformation of environmental pollutants. This study assessed the metabolic profiles of the gut microbial cultures from grouper (Epinephelus coioides), green mussel (Perna viridis) and giant tiger prawn (Penaeus monodon) and investigated their transformation mechanisms to typical plastic additives. Community-level physiological profiling analysis confirmed the utilization profiles of the microbial cultures including carbon sources of carbohydrates, amines, carboxylic acids, phenolic compounds, polymers and amino acids, and the plastic additives of organophosphate flame retardants, tetrabromobisphenol A derivates and bisphenols. Using in vitro incubation, triphenyl phosphate (TPHP) was found to be rapidly metabolized into diphenyl phosphate by the gut microbiota as a representative ester-containing plastic additive, whereas the transformation of BPA (a representative phenol) was relatively slower. Interestingly, all three kinds of microbial cultures efficiently transformed the hepatic metabolite of BPA (BPA-G) back to BPA, thereby increasing its bioavailability in the body. The specific enzyme analysis confirmed the ability of the gut microbiota to perform the metabolic reactions. The results of 16S rRNA sequencing and network analysis revealed that the genera Escherichia-Shigella, Citrobacter, and Anaerospora were functional microbes, and their collaboration with fermentative microbes played pivotal roles in the transformation of the plastic additives. The structure-specific transformations by the gut microbiota and their distinct bioavailability deserve more attention in the future.

Development of optimized resveratrol/piperine-loaded phytosomal nanocomplex for isoproterenol-induced myocardial infarction treatment.

Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (-33.33 ± 1.5 and -48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant (p < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.