Preparation of luteolin loaded nanostructured lipid carrier based gel and effect on psoriasis of mice.

This study investigated a nanostructured lipid carrier (NLC)-gel system containing luteolin (LUT), a potential drug delivery system for the treatment of psoriasis. LUT-NLC was prepared by solvent emulsification ultrasonication method. The particle size was 199.9 ± 2.6 nm, with the encapsulation efficiency of 99.81% and drug loading of 4.06%. X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the LUT-NLC. The NLC was dispersed in Carbomer 940 to form the NLC based gel. The rheological characteristics of LUT-NLC-gel showed an excellent shear-thinning behavior (non-Newtonian properties) and coincided with the Herschel-Bulkley model. LUT-NLC-gel (78.89 µg/cm2) exhibited better permeation properties and released over 36 hours than LUT gel (32.17 µg/cm2). The dye-labeled LUT-NLC presented intense fluorescence in the epidermis and dermis by the visualization of fluorescence and confocal microscopy, and it could accumulate in the hair follicles. The effect of LUT-NLC-gel on imiquimod-induced psoriasis mice was evaluated by psoriasis area severity index scoring, spleen index assay, histopathology, and inflammatory cytokines. These results confirmed that LUT-NLC-gel with high dose (80 mg/kg/day) remarkably reduced the level of inflammatory and proliferation factors such as TNF-α, IL-6, IL-17, and IL-23 in both skin lesions and blood. LUT-NLC-gel improved the macroscopic features. Therefore, the LUT-NLC-gel had great potential as an effective delivery system for skin diseases.

1D Chiral Enantiomer Lead-Free Perovskites Induced Chiralopical Activity and Photoelectric Response.

Chirality is a fascinating geometrical concept with widespread applications in biology, chemistry, and materials. Incorporating chirality into hybrid perovskite materials can induce novel physical properties (chiral optical activity, nonlinear optics, etc.). Hybrid lead-free or lead-substituted perovskite materials, as representatives of perovskites, have been widely used in fields such as photovoltaics, sensors, catalysis, and detectors. However, the successful introduction of chirality into hybrid lead-free perovskites, which can enable their potential applications in areas such as circularly polarized light photodetectors, memories, and spin transistors, remains a challenging research topic. Here, we synthesized two new chiral lead-free perovskites, [(R)-2-methylpiperazine][BiI5] and [(S)-2-methylpiperazine][BiI5]. The material possesses a perovskite structure with a one-dimensional (1D) arrangement, denoted as ABX5. This structure is composed of chiral cations, specifically methylpiperazine, and endless chains of [BiI3] along the a-axis. These chains are assembled from distorted coplanar [BiI5]2- octahedra. The testing results revealed that (R)-1 and (S)-1 have narrow band gaps (Eg-R = 2.016 eV, Eg-S = 1.964 eV), high photoelectric response, and long carrier lifetime [R = 4.94 µs (τ), S = 7.85 µs (τ)]. It is worth noting that 1D chiral lead-free perovskites (R)-1 and (S)-1, which are synthesized in this study with narrow band gaps, high photoelectric response, and long carrier lifetime, have the potential to serve as alternative materials for the perovskite layer in future iterations of lead-free perovskite solar cells. Moreover, this research will inspire the preparation of multifunctional, lead-free perovskites.

A host-guest compound formed by Cu3[P2W18O62] and HKUST-1 with capacitance and H2O2 sensing properties.

Polyoxometalate-based metal-organic frameworks (POMOFs) have received wide attention in supercapacitors and H2O2 detection due to their possession of the rich redox active sites of polyoxometalates (POMs) and the ordered structure of metal-organic frameworks (MOFs). In this study, we successfully synthesized a host-guest Cu3[P2W18O62]@HKUST-1 (HRBNU-7) compound by a grinding method. Cu3[P2W18O62] successfully entered the HKUST-1 pores as confirmed by the results of infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The specific capacitance of HRBNU-7 is 318.6 F g-1 at 1 A g-1 in a three-electrode system using nickel foam as the collector. The specific capacity retention is 92.36% after 5000 cycles. The assembled symmetrical supercapacitor (SSC) achieved a high energy density of 10.58 W h kg-1 at a power density of 500.00 W kg-1. In addition, HRBNU-7 exhibits excellent electrochemical detection of H2O2, including a wide linear range of 0.5 µM-0.3 mM, a low detection limit of 0.17 µM, and excellent selectivity and stability, and it can be effectively utilized for the analysis of H2O2 content in actual serum samples. These excellent properties are attributed to the unique redox activity of Cu3[P2W18O62] and the high specific surface area of HKUST-1. This work offers a strategy for exploring POMOFs as electrode materials in supercapacitors and electrochemical sensors.

Correction: Uncovering the effect of Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea on sensory properties, volatile profiles and anti-obesity activity.

Correction for 'Uncovering the effect of Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea on sensory properties, volatile profiles and anti-obesity activity' by Xin Li et al., Food Funct., 2023, 14, 2404-2415, https://doi.org/10.1039/D2FO03531F.

Uncovering the effect of Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea on sensory properties, volatile profiles and anti-obesity activity.

As a nutritious plant with valuable potential, the Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea (FBT) for co-fermentation is an industrial innovation and a new route to make full use of Moringa oleifera Lam. leaves. However, the sensory properties, volatile profiles and anti-obesity activity of Fuzhuan Brick (Moringa oleifera Lam.) tea (MFBT) are still unknown. The results demonstrated that MFBT has richer and more complex smell and taste, better color and higher overall acceptance scores. In total, 57 volatile flavor compounds, consisting of 3 acids, 16 hydrocarbons, 5 esters, 8 ketones, 13 aldehydes, 6 alcohols and others, were identified using HS-SPME-GC-MS. The characteristic odor components in MFBT were 3-buten-2-one, 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)- and 1-cyclohexene-1-carboxaldehyde, 2,6,6-trimethyl-, which gave it a floral, woody, sweet, herbal and fruity aroma. 2-Octenal, (E) contributed significantly to the aroma of FBT, which could impart fresh, fatty and green aromas. In addition, MFBT could better regulate lipid accumulation, glucose tolerance, insulin tolerance and inflammation response more effectively than FBT. The mechanism is that MFBT could better regulate the dysbiosis of gut microbiota induced by HFFD, mainly increasing the abundance of beneficial bacteria such as SCFA-producing bacteria (Bacteroidetes, Lactobacillaceae, Bacteroidales_S24-7_group and Clostridiaceae_1) and decreasing the abundance of harmful bacteria such as pro-inflammatory/obesity and metabolic syndrome-related bacteria (Proteobacteria, Deferribacteres, Desulfovibrio, Catenibacterium and Helicobacter), which in turn increased feces short-chain fatty acids and lowered circulating lipopolysaccharides. These results suggested that co-fermentation with Moringa oleifera Lam. leaf could significantly improve the quality and enhance the anti-obesity effect of FBT.

An inorganic-organic hybrid nanomaterial with a core-shell structure constructed by using Mn-BTC and Ag5[BW12O40] for supercapacitors and photocatalytic dye degradation.

Creating inorganic-organic hybrids with polyoxometalates (POMs) and metal-organic frameworks (MOFs) as energy storage and dye-degradation materials remains challenging. Here, a new hybrid nanomaterial Mn-BTC@Ag5[BW12O40] is synthesized by using Ag5[BW12O40] and Mn3(BTC)2(H2O)6 (Mn-BTC, BTC = 1,3,5-benzenetricarboxylic acid) through a plain grinding method. The structure and morphology characterization by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and transmission electron microscopy (TEM) shows that the synthetic products have core-shell construction. Due to its unique structure wherein the core is Mn-BTC and the shell is Ag5[BW12O40], it exhibits excellent capacitance performance. In a three-electrode system where nickel foam is a collector, at a current density of 1 A g-1, its specific capacitance is 198.09 F g-1; after 5000 cycles, the capacitance retention rate is 94.4%. When the power density is 503.1 W kg-1, the symmetrical supercapacitor reveals a high energy density which is 10.9 W h kg-1. At the same time, the capacitance retention is 92.9% after 5000 cycles which showed good cycle stability. The photocatalytic degradation efficiencies of rhodamine B (RhB), methyl orange (MO) and methylene blue (MB) dyes exceed 90% after 140 min, and the degradation results remained unchanged after five photocatalytic cycles. The photocatalytic degradation mechanism shows that ˙OH has a major effect. The results show that this research provides a fresh idea for the development of energy storage and dye photocatalytic degradation materials.

Interaction of Companilactobacillus crustorum MN047-derived bacteriocins with gut microbiota.

Companilactobacillus crustorum MN047-derived bacteriocins (CCDB) have inhibitory effects on the growth of pathogens. In this study, a pectin/zein beads delivery system was used to investigate the effects of CCDB on the dextran sulfate sodium-induced colitis in mice. The focus was given on aspects linked with the gut microbiota, intestinal epithelial barrier, oxidative stress, and inflammation. Results suggested that CCDB alleviated the pathological symptoms of colitis, including increased disease activity index and shortened colon length. CCDB strengthened the gut barrier by increasing goblet cells and promoting the expressions of MUC2 and tight junctions-related proteins. CCDB decreased oxidative mediators and increased antioxidant mediators in serum or colon tissue. Furthermore, CCDB reduced harmful bacteria and enriched beneficial bacteria, which further decreased serum LPS and increased fecal butyric acid. In addition, CCDB inhibited the overexpressions of proinflammatory cytokines, chemokines, and pathogens/LPS-activated TLR4/NF-κB pathway. Therefore, CCDB is a potential dietary supplement to relieve colitis.

A review on the potential use of natural products in overweight and obesity.

With the increase in unhealthy lifestyles, obesity is increasingly common, which could cause many metabolic diseases. In recent research, natural product extracts have shown tremendous potential antiobesity effects via different mechanisms. In this review, we focused on widely adopted extraction methods, bioactive ingredients types, and antiobesity mechanisms of natural product extracts in the recent reports. The extraction methods include solid-liquid extraction, microwave-assisted extractions, and supercritical fluid extraction. Moreover, the bioactive ingredients identified in natural product extracts are phenolic compounds, oligosaccharides, polysaccharides, and terpenoids. These exert antiobesity effects through multiple mechanisms, including suppressing the appetite, increasing energy expenditure, inhibiting enzyme activity, modulating lipid homeostasis and adipocyte lifecycle, reducing oxidative and inflammation, and improving intestinal bacteria. However, the antiobesity effects of natural products require further evaluation. Furthermore, the improvement of the bioavailability and effective and safe human dose of these bioactive ingredients should be the focus of future work.

Challenges of layer-structured cathodes for sodium-ion batteries.

As the most promising alternative to lithium-ion batteries (LIBs), sodium-ion batteries (SIBs) still face many issues that hinder their large-scale commercialization. Layered transition metal oxide cathodes have attracted widespread attention owing to their large specific capacity, high ionic conductivity, and feasible preparation conditions. However, their electrochemical properties are usually limited by the irreversible phase transition and harsh storage conditions caused by humidity sensitivity. Recently, tremendous efforts have been devoted to solving these issues toward advanced high-performance layered oxide cathodes. Herein, we summarize these remaining challenges of layered oxide cathodes and the corresponding modification strategies such as the variations in chemical compositions, the architecture of (nano)micro-structures, surface engineering, and the regulation of phase compositions. We hope that the understanding presented in this review can provide useful guidance to developing high-performance layer-structured cathode materials for advanced SIBs.

Protective Effects of Companilactobacillus crustorum MN047 against Dextran Sulfate Sodium-Induced Ulcerative Colitis: A Fecal Microbiota Transplantation Study.

Gut microbiota dysbiosis could aggravate the development of ulcerative colitis (UC). Companilactobacillus crustorum MN047 (CCMN) is a potential gut microbiota-regulating probiotic that could produce multiple novel bacteriocins. In this study, fecal microbiota transplantation (FMT) was used to verify whether CCMN could alleviate dextran sulfate sodium-induced UC by regulating gut microbiota. Results showed that both CCMN and FMT ameliorated the symptoms of UC, including attenuating the increased disease activity index, shortened colon length, gut barrier damage, and inflammation. Briefly, CCMN and FMT upregulated the expressions of MUCs and tight junctions, downregulated the expressions of proinflammatory cytokines and chemokines, increased fecal short-chain fatty acids, and lowered serum lipopolysaccharides, which were associated with the regulation of gut microbiota (e.g., increased Akkermansia, Blautia, and Ruminococcus levels). These results demonstrated that CCMN could ameliorate UC by modulating gut microbiota and inhibiting the TLR4/NF-κB pathway. Therefore, CCMN could be considered as a potential probiotic supplement for ameliorating UC.

Screening and follow-up results of fatty acid oxidative metabolism disorders in 608 818 newborns in Jining, Shandong province.

To investigate the incidence and gene mutation characteristics of fatty acid oxidative metabolism disorders in Jining area of Shandong province , and to evaluate the therapeutic effect. Blood samples of newborns were collected in Jining of Shandong province between July 14, 2014 and December 31, 2019. Tandem mass spectrometry was used to determine the levels of carnitine and acylcarnitine in the blood to screen for fatty acid oxidative metabolism disorder. For newborns with positive screening result, blood DNA was analyzed by MassARRAY and high-throughput sequencing, then verified by Sanger sequencing. The diagnosed children were given early intervention and treatment, and followed up. Forty-two children with fatty acid oxidative metabolism disorders were screened out of 608 818 newborns, with an incidence rate of 1/14 496. Primary carnitine deficiency (16 cases, 38.10%) and short-chain acyl-CoA dehydrogenase deficiency (16 cases, 38.10%) were the most common, followed by very long-chain acyl-CoA dehydrogenase deficiency (6 cases, 14.29%), medium-chain acyl-CoA dehydrogenase deficiency (4 cases, 9.53%). In children with primary carnitine deficiency, c.1400C>G (p.S467C) and c.51C>G were the most common in mutations; and c.278C>T (p.S93L), c.1049T >C (p.L350P), c.572A>G (p.K191R), c.431T>C (p.L144P) were newly discovered mutations. Ten children with carnitine replacement therapy showed normal development during the follow-up. In 6 children without carnitine replacement treatment, hypoglycemia developed during the neonatal period in 1 case, in whom the creatine kinase was increased, and the intellectual and language development delayed in the later period; the other 5 children developed normally during the follow-up period. The gene mutations c.1031A>G (p.E344G) and c.164C>T (p.P55L) were common in children with short-chain acyl-CoA dehydrogenase deficiency, and the children developed normally during the follow-up. In children with very long-chain acyl-CoA dehydrogenase deficiency, the c.1349G>A was common in gene mutations; and c.488T>A , c.1228G>T (p.D410Y), c.1276G>A (p.A426T), c.1522C>T (p.Q508*), c.1226C>T (p.T409M) were newly discovered mutations. Three children treated with milk powder rich in medium-chain fatty acids had normal development during the follow-up. The other 3 cases with combined carnitine reduction were treated with levocarnitine and milk powder enriched of medium-chain fatty acids, 1 case developed normally during the follow-up, 1 case died of acute illness at the age of and 1 case had acute illness and recovered after treatment, and developed normally during the follow-up. c.449_452del (p.T150Rfs*4) was the most common gene mutation in children with medium-chain acyl-CoA dehydrogenase deficiency, and c. 718A>G (p.M240V) was a newly discovered mutation. All children received low-fat diet, and hunger and fatigue were avoided; 1 child was supplemented with L-carnitine, and the other 3 children were not treated with drugs, and all of them developed normal during the follow-up. Primary carnitine deficiency and short-chain acyl-CoA dehydrogenase deficiency are the most common fatty acid oxidative metabolism disorders in Jining area. There are gene hotspot mutations and new discovered gene mutations in patients. Patients with early diagnosis and treatment through neonatal screening have a good prognosis.

Development and evaluation of lutein-loaded alginate microspheres with improved stability and antioxidant.

BACKGROUND: Lutein has been of great interest to the food processing and pharmaconutrient industries owing to its beneficial effects on human health. However, lutein is very sensitive to heat, light, pH and oxidative conditions, which limits its application in food systems. The present study aimed to prepare lutein-alginate microspheres by a calcium chloride gelation method with the purpose of improving the stability and antioxidant abilities of lutein. RESULTS: The loading capacity of lutein in the microspheres was approximately 5.3% (w/w) and the entrapment efficiency was about 63%. The loaded microspheres were nearly spherical with an average size of 150 µm. They exhibited a crimped surface by scanning electron microscopy. The lutein was in amorphous state by X-ray powder diffraction. Analysis by Fourier transform infrared spectroscopy and molecular docking revealed an intermolecular hydrogen bond interaction between lutein and sodium alginate. In vitro release experiments showed that the microspheres presented slower release at acidic conditions than at neutral intestinal conditions. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of the microencapsulated lutein was higher than that of free lutein. The stability of lutein in the microspheres was improved significantly when compared with that of free lutein at various temperatures. CONCLUSION: The present work successfully developed well-protected lutein-alginate microspheres. This indicates that it is feasible to use microspheres loaded with lutein as antioxidant functional ingredients in food products. © 2019 Society of Chemical Industry.

Nanosheet-Filled Polymer Film from Flow-Induced Coassembly: Multiscale Structure Visualization and Application.

The nanoplatelet-filled polymer composite (NFPC) materials have received increasing attention because of their high strength-to-weight ratio and toughness. However, high-performance NFPC materials still face many challenges: (1) how to transfer the intrinsic extraordinary performance of individual nanoplatelets into highly ordered macroscale bulk materials; (2) how to obtain a strong interface bonding between polymer and nanoplatelet filler; and (3) how to truly reflect the structure of NFPC film. Here, to address these problems, the flow-induced assembly method is employed to fabricate the large-size continuous, flexible, highly oriented, and transparent NFPC film. During flow-induced orientation, nanoplatelet and polymer can be coassembling together to form a highly ordered layered structure with dozens of layers. On the other hand, the layered double hydroxide (LDH) nanosheet filler with single layer and abundant hydroxyl sites is prepared to strengthen interface by forming hydrogen bonds with polymers. To explore the effect of multiscale structure on property, carbon dots (CDs) are introduced to light up the inorganic nanoplatelet. By fixing and confining CDs in a rigid environment, the CD-LDH-based composite film shows excellent dual emission characteristics, which can be used to evaluate gas barrier, humidity, and temperature with direct visualization, high sensitivity, and easy to operation.

Development and evaluation of orally disintegrating tablets containing the mosapride resin complex.

The purpose of this study was to prepare a mosapride citrate-resin (Amberlite® IRP 88) complex and orally fast-disintegrating tablets of the resin complex. The resinate complex of mosapride-Amberlite® IRP 88, mass ratio 2:1, was prepared in an ethanol-water solution. The effects of alcohol concentration, temperature, and pH of the solution on complex formation were evaluated. The complex physicochemical properties were characterized by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Orally disintegrating tablets were prepared by direct compression and were optimized using the response surface method. Optimized orally fast-disintegrating tablets disintegrated within 18 s. The pH dependence of mosapride release from the tablet decreased drug dissolution in simulated saliva, whereas it promptly released in the pH 1.0 solution. The data reported herein clearly demonstrate that tablets containing the mosapride-Amberlite® IRP 88 complex for oral disintegration could be particularly useful for patients with swallowing difficulties.

Interfacial molecular interactions based on the conformation recognition between the insoluble antitumor drug AD-1 and DSPC.

In this study, molecular interactions between the anti-cancer agent 20(R)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (AD-1) and phospholipid 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) were investigated using the Langmuir film balance technique. The characteristics of binary Langmuir monolayers consisting of DSPC and AD-1 were conducted on the basis of the surface pressure-area per molecule (π-A) isotherms. It was found that the drug was able to become efficiently inserted into preformed DSPC monolayers, indicating a preferential interaction between AD-1 and DSPC. For the examined lateral pressure at 20mN/m, the largest negative values of ΔGex were found for the AD-1/DSPC monolayer, which should be the most stable. Based on the calculated values of ΔGex, we found that the AD-1/DSPC systems exhibited the best mixed characteristics when the molar fraction of the AD-1 was 0.8; at that relative concentration, the AD-1 molecules can mix better and interact with the phospholipid molecules. In addition, the drug-DSPC binary supramolecular structure was also deposited on the mica plates as shown by atomic force microscopy (AFM). Finally, molecular docking calculations explained satisfactorily that, based on the conformations interactions (conformation recognition), even at an AD-1/DSPC molar ratio as high as 8:2, the interfacial stabilization of the AD-1/DSPC system was fairly strong due to hydrophobic interactions. A higher loading capacity of DSPC might be possible, as it is associated with a more flexible geometrical environment, which allows these supramolecular structures to accept larger increases in drug loading upon steric binding.

Direct Observation of Early-Stage High-Dose Radiotherapy-Induced Vascular Injury via Basement Membrane-Targeting Nanoparticles.

Collagen IV-targeting peptide-conjugated basement membrane-targeting nanoparticles are successfully engineered to identify early-stage blood vessel injury induced by high-dose radiotherapy.

UPLC-MS/MS-ESI assay for simultaneous determination of magnolol and honokiol in rat plasma: application to pharmacokinetic study after administration emulsion of the isomer.

ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis is one of the commonly used in traditional Chinese medicine for the treatment of fever, chronic bronchitis and stomach ailments. Magnolol and honokiol are isomers with hydroxylated biphenol compound in the extract of Magnolia officinalis. This study aims to determine the isomers in rat plasma and evaluate their pharmacokinetic pattern after administration emulsion. MATERIALS AND METHODS: Sprague Dawley male rats received either an intravenous (i.v.25, mg/kg) or oral (50mg/kg) dose of the emulsion of the isomer. A sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the investigation of the pharmacokinetics of magnolol and honokiol in rats. Kaempferol was employed as an internal standard. RESULTS: The plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Acetonitrile and 5 mmol/L ammonium acetate buffer solution (65: 35, v/v) was used as the mobile phase at a flow rate of 0.2 mL/min. Following oral administration of emulsion to rats, magnolol attained mean peak plasma concentrations of 426.4 ± 273.8 ng/mL at 1.20 h, whereas honokiol reached peak plasma concentrations of 40.3 ± 30.8 ng/mL at 0.45 h. The absolute bioavailability of magnolol and honokiol is 17.5 ± 9.7% and 5.3 ± 11.7%. By comparison, the AUC0-∞ of magnolol was 5.4 times higher than that of honokiol after intravenous administration, but AUC0-∞ of magnolol was about 18-fold higher than honokiol after oral administration.

In vitro metabolism of 20(R)-25-methoxyl-dammarane-3, 12, 20-triol from Panax notoginseng in human, monkey, dog, rat, and mouse liver microsomes.

The present study characterized in vitro metabolites of 20(R)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (20(R)-25-OCH3-PPD) in mouse, rat, dog, monkey and human liver microsomes. 20(R)-25-OCH3-PPD was incubated with liver microsomes in the presence of NADPH. The reaction mixtures and the metabolites were identified on the basis of their mass profiles using LC-Q/TOF and were quantified using triple quadrupole instrument by multiple reaction monitoring. A total of 7 metabolites (M1-M7) of the phase I metabolites were detected in all species. 25(R)-OCH3-PPD was metabolized by hydroxylation, dehydrogenation, and O-demethylation. Enzyme kinetic of 20(R)-25-OCH3-PPD metabolism was evaluated in rat and human hepatic microsomes. Incubations studies with selective chemical inhibitors demonstrated that the metabolism of 20(R)-25-OCH3-PPD was primarily mediated by CYP3A4. We conclude that 20(R)-25-OCH3-PPD was metabolized extensively in mammalian species of mouse, rat, dog, monkey, and human. CYP3A4-catalyzed oxygenation metabolism played an important role in the disposition of 25(R)-OCH3-PPD, especially at the C-20 hydroxyl group.

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol: preparation and evaluation.

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3ß;12ß;20-triol (25-OCH3-PPD). Optimized SMEDDS formulations for 25-OCH3-PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH3-PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH3-PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

Simultaneous determination by LC-MS/MS of 25-methoxydammarane-3ß,12ß,20-triol epimers and active metabolites in rat plasma after intravenous administration.

1. The pharmacokinetics of the 25-OCH3-PPD epimers and active metabolites in rat plasma after a single intravenous (i.v.) administration were studied by a rapid, selective and sensitive UPLC-MS/MS method. 2. Chromatographic separation was performed on an Acquity UPLC with Agela C18 column, and the solvents of 5 mM ammonium acetate (pH 7.8) - acetonitrile (65: 35, v/v) were used as mobile phase for elution. The quantification was performed with the transitions of m/z 493.5 → 475.5 for 20(R,S)-25-OCH3-PPD, m/z 479.5 → 461.5 for 20(R,S)-25-OH-PPD. The Lower Limit Of Quantitation (LLOQ) was 20.0 ng mL(-1) for 20(R,S)-25-OCH3-PPD, 2.0 ng mL(-1) for 20(R,S)-25-OH-PPD in the plasma samples assay. 3. The pharmacokinetic parameters of AUC, t1/2 and MRT had no difference between 20(R)- and (S)-25-OCH3-PPD, but S-epimer has a lower plasma clearance compared to the R-isomer. The active metabolite 20(S)-25-OH-PPD showed significantly higher AUC, MRT and a longer half-life than that of 20(R)-25-OH-PPD. These assay results are necessary for the evaluation of the pharmacokinetic behavior of 25-methoxydammarane-3ß,12ß,20-triol in vivo.