The MYB transcription factor Seed Shattering 11 controls seed shattering by repressing lignin synthesis in African rice.

African cultivated rice (Oryza glaberrima Steud.) was domesticated from its wild progenitor species (Oryza barthii) about 3000 years ago. Seed shattering is one of the main constraints on grain production in African cultivated rice, which causes severe grain losses during harvest. By contrast, Asian cultivated rice (Oryza sativa) displays greater resistance to seed shattering, allowing higher grain production. A better understanding in regulation of seed shattering would help to improve harvesting efficiency in African cultivated rice. Here, we report the map-based cloning and characterization of OgSH11, a MYB transcription factor controlling seed shattering in O. glaberrima. OgSH11 represses the expression of lignin biosynthesis genes and lignin deposition by binding to the promoter of GH2. We successfully developed a new O. glaberrima material showing significantly reduced seed shattering by knockout of SH11 in O. glaberrima using CRISPR-Cas9 mediated approach. Identification of SH11 not only supplies a new target for seed shattering improvement in African cultivated rice, but also provides new insights into the molecular mechanism of abscission layer development.

Synthetic relaxometry combined with MUSE DWI and 3D-pCASL improves detection of hippocampal sclerosis.

PURPOSE: To investigate the diagnostic value of synthetic MRI combined MUSE DWI and 3D-pCASL in hippocampal sclerosis (HS). METHOD: A total of 30 HS patients participated in the study. At the same time, 51 healthy volunteers were collected as the control group. All patients and healthy volunteers underwent epilepsy MR scanning protocol (including oblique coronal MAGiC, MUSE DWI, and axial 3D-pCASL) at 3.0 T MR scanner.The independent samples T test and Mann-Whitney U test were used to compare the differences of the apparent dispersion coefficient(ADC), cerebral blood flow(CBF) and quantitative parameters, including T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) values, in the hippocampus of the affected side of HS and the contralateral and control groups, respectively. The diagnostic performance was evaluated using binary logistic regression analysis and area under the receiver operating characteristic (ROC) curves (AUC). RESULTS: Significant statistical differences in T1, T2, CBF, and ADC values were observed between the affected hippocampus of HS patients and contralateral and control hippocampus (all P < 0.005). The T2 has higher discrimination abilities compared with other univariable parameters, with the AUC of 0.899. The combined T2, ADC and CBF model had the best diagnostic performance of HS in MTLE patients with AUC, sensitivity and specificity of 0.946, 86.67 %, 93.33 %, respectively. CONCLUSIONS: Relaxometry parameters derived from synthetic MRI contributed to diagnosis of HS. The proposed approach combining T2, ADC and CBF showed a strong diagnostic capability.

Improving Image Quality and Reducing Scan Time for Synthetic MRI of Breast by Using Deep Learning Reconstruction.

Objectives: To investigate a deep learning reconstruction algorithm to reduce the time of synthetic MRI (SynMRI) scanning on the breast and improve the image quality. Materials and Methods: A total of 192 healthy female volunteers (mean age: 48.1 years) underwent the breast MR examination at 3.0 T from September 2020 to June 2021. Standard SynMRI and fast SynMRI scans were collected simultaneously on the same volunteer. Deep learning technology with a generative adversarial network (GAN) was used to generate high-quality fast SynMRI images by end-to-end training. Peak signal-to-noise ratio (PSNR), mean squared error (MSE), and structural similarity index measure (SSIM) were used to compare the image quality of generated images from fast SynMRI by deep learning algorithms. Results: Fast SynMRI acquisition time is half of the standard SynMRI scan, and the generated images of the GAN model show that PSNR and SSIM are improved and MSE is reduced. Conclusion: The application of deep learning algorithms with GAN model in breast MAGiC MRI improves the image quality and reduces the scanning time.

Prediction of VEGF and EGFR Expression in Peripheral Lung Cancer Based on the Radiomics Model of Spectral CT Enhanced Images.

Background: Energy spectrum CT is an effective method to evaluate the biological behavior of lung cancer. Radiomics is a non-invasive technology to obtain histological information related to lung cancer. Purpose: To investigate the value of the radiomics models on the bases of enhanced spectral CT images of peripheral lung cancer to predict the expression of the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Material and Methods: This study retrospectively analyzed 73 patients with peripheral lung cancer confirmed by postoperative pathology. All patients underwent dual-phase enhanced spectral CT scans before surgery. Regions of interest (ROI) were delineated in the arterial phase and venous phase. Key radiomics features were extracted and models were established to predict the expression of VEGF and EGFR, respectively. All models were established based on the expression levels of VEGF and EGFR in tissues detected by immunohistochemical staining as reference standards. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of each model, and decision curve analysis (DCA) was used to evaluate the clinical utility of the models. Results: In predicting the expression level of VEGF, the combined (COMB) model composed of one spectral feature and two radiomics features achieved the best performance with area under ROC (AUC) 0.867 (95% CI: 0.767-0.966), accuracy of 0.812, sensitivity of 0.879, and specificity of 0.667. According to the expression level of EGFR, three importance radiomics features were retained in the arterial and venous phases to establish the multiphase phase model which has the best performance with AUC of 0.950 (95% confidence interval: 0.89-1.00), accuracy of 0.896, sensitivity of 0.868, and specificity of 1. Conclusion: The radiomics model of enhanced spectral CT images of peripheral lung cancer can predict the expression of EGFR and VEGF.

A New Calcium(II)-Based Substitute for Enrofloxacin with Improved Medicinal Potential.

Enrofloxacin (EFX) reacting with Ca(II) afforded a new complex, [Ca(EFX)2(H2O)4] (EFX-Ca), which was structurally characterized both in solid and solution chemistry. E. coli and S. typhi were tested to be the most sensitive strains for EFX-Ca. The LD50 value of EFX-Ca in mice was 7736 mg/kg, implying the coordination of EFX to Ca(II) effectively reduced its acute toxicity. EFX-Ca also decreased the plasma-binding rate and enhanced the drug distribution in rats along with longer elimination half-life. EFX-Ca also showed similar low in vivo acute toxicity and higher anti-inflammation induced by H2O2 or CuSO4 in zebrafish, with reactive oxygen species (ROS)-related elimination. The therapeutic effects of EFX-Ca on two types (AA and 817) of E. coli-infected broilers were also better than those of EFX, with cure rates of 78% and 88%, respectively. EFX-Ca showed promise as a bio-safe metal-based veterinary drug with good efficacy and lower toxicity.

Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne.

The main objective of the study was to prepare the microemulsions containing adapalene (MEs-Ap) to enhance epidermal penetration, dermal retention, and local bioavailability compared with the commercial preparation. The optimal formulations were selected by solubility experiments, pseudo-ternary phase diagram, and percutaneous permeation experiments and the physiochemical properties were also investigated. Then, the study of permeability, retention, safety, pharmacodynamics, and pharmacokinetics in the skin for MEs-Ap compared with the commercial preparation were researched. The optimized formulation was developed as follows: the ratio of AP, isopropyl myristate, polyoxyethylene hydrogenated castor oil, ethanol, and water was 0.01:1:1.25:3.75:4 (w/w). The globule size and average viscosity of the optimized MEs-Ap were 99.34 nm and 1.7 mPa·s, respectively, which was oil-in-water microemulsion without serious irritation or allergy for skin. The Js, Qn, and Qretention of MEs-Ap (0.81 ± 0.19 µg/cm2/h, 24.73 ± 4.24 µg/cm2, 2.08 ± 0.18 µg/cm2) were apparently higher than Differin® (0.022 ± 0.009 µg/cm2/h, 0.536 ± 0.103 µg/cm2, and 0.523 ± 0.130 µg/cm2) respectively. The local bioavailability study showed that the AUC0 → 36h of the MEs-Ap in the dermal (19.6 ± 1.22 µg/cm2) was significantly improved comparing to Differin® (13.9 ± 1.73 µg/cm2) (p < 0.01). The pharmacodynamics study showed that the therapeutic effect of MEs-Ap was better than that of Differin® in the acne model of rabbit auricle. These results suggested that the MEs-Ap could be considered as a having higher epidermal penetrability, dermal retention, local bioavailability, efficacy, and safety topical preparations for acne. Graphical abstract.

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro.

Multidrug resistance (MDR) is a main clinical hurdle for chemotherapy of cancer, and overexpression of P-glycoprotein (P-gp) is a key factor. In the present study, a new co-delivery system for reversing MDR was designed and developed. The system was composed of curcumin (Cur) and piperine (Pip) encapsulated in solid lipid nanoparticles (SLNs) with tocopheryl polyethylene glycol succinate (TPGS) and Brij 78 [(Cur+Pip)-SLNs]. TPGS and Brij 78 could sensitize MDR tumors by inhibiting the P-gp drug efflux system. The combination of Cur and Pip, when administered in SLNs formulations, resulted in a significant enhancement in cytotoxicity and allowed efficient intracellular delivery of the drugs in drug-resistant A2780/Taxol cells. This dual inhibitory strategy may have significant potential in the clinical management of MDR in cancer.

Nanoemulsion enhances α-tocopherol succinate bioavailability in rats.

The vitamin E analogue, α-tocopherol succinate (α-TOS), has a broad anti-tumor effect. α-TOS can induce cancer cells apoptosis and suppress tumor growth by targeting mitochondria. Low bioavailability of α-TOS is the major problem encountered with formulation development. In our study, α-TOS nanoemulsion (α-TOS-NE) was demonstrated as a new drug delivery system of α-TOS to increase the bioavailability. MTT-based cytotoxicity assay and mitochondrial membrane potential (ΔY) were performed on human breast cancer cell lines MCF-7 and human oral epithelial cancer cell lines KB to evaluate in vitro anticancer efficacy of α-TOS-NE. In comparison with free α-TOS, α-TOS-NE exhibited a stronger cytotoxicity and decreased ΔΨ. Pharmacokinetic profiles of I.V. α-TOS-NE group, I.P. α-TOS-NE group, and I.P. free α-TOS group (7% DMSO/93% PEG) were drawn. First of all, nanoemultion (NE) enables the I.V. injection of α-TOS, make it possible to be an I.V. preparation. Second, compare to the I.P. free α-TOS group, I.P. α-TOS-NE group had a higher bioavailability. Thus, NE improved the strong anti-cancer efficacy of α-TOS while increasing its in vivo bioavailability in rats. In conclusion, our laboratory-made NE was a safe drug delivery system for clinical trials and could be a promising formulation for α-TOS by I.V administration.

A novel eye drop of alpha tocopherol to prevent ocular oxidant damage: improve the stability and ocular efficacy.

The aim of this study was to design novel mixed micelles as an ophthalmic delivery system for alpha-tocopherol (TOC) to prevent its degradation and improve ocular efficacy. The nonionic polymers, Polyoxyl 15 Hydroxystearate (Solutol® HS15) and Pluronic® F127, were discovered to be the most effective agents for retaining the activity and solubilization of TOC, respectively. Prepared by a thin-film hydration method, HS15/Pluronic® F127 yielded good encapsulation percentages of TOC, with a 27.7% drug loading efficiency. Incorporation of cetalkonium chloride (CKC) into HS15/Pluronic® F127 mixed micelles made the zeta potential of the micelles +17 mV, potentially prolonging the residence time of formulations on ocular surfaces. The optimized micelle preparation remained stable when diluted in a synthetic tear solution. It is known that the antioxidant ability of TOC in typical formulations reduces to around 85% of its initial value after 1 month when stored at 4 or 25 °C under an air atmosphere, which limits ophthalmic applications to less than 1 month. However, encapsulated TOC in investigated micelles remained stable for at least 6 months when sealed with N2. Finally, the cationic micelles were well tolerated after multiple administrations in rabbits, and they improved ocular accumulation of TOC. Taken together, these data suggest that the optimized micelle preparations described in this study may be suitable drug carriers for the treatment of ocular oxidant damage.

Vitamin E derivative-based multifunctional nanoemulsions for overcoming multidrug resistance in cancer.

The multidrug resistance (MDR), including intrinsic and acquired multidrug resistance, is a major problem in tumor chemotherapy. Here, we proposed a strategy for modulating intrinsic and/or acquired multidrug resistance by altering the levels of Bax and Bcl-2 expression and inhibiting the transport function of P-gp, increasing the intracellular concentration of its substrate anticancer drugs. Vitamin E derivative-based nanoemulsions containing paclitaxel (MNEs-PTX) were fabricated in this study, and in vitro anticancer efficacy of the nanoemulsion system was evaluated in the paclitaxel-resistant human ovarian carcinoma cell line A2780/Taxol. The MNEs-PTX exhibited a remarkably enhanced antiproliferation effect on A2780/Taxol cells than free paclitaxel (PTX) (p < 0.01). Compared with that in the Taxol group, MNEs-PTX further decreased mitochondrial potential. Vitamin E derivative-based multifunctional nanoemulsion (MNEs) obviously increased intracellular accumulation of rhodamine 123 (P-gp substrate). Overexpression of Bcl-2 is generally associated with tumor drug resistance, we found that MNEs could reduce Bcl-2 protein level and increase Bax protein level. Taken together, our findings suggest that anticancer drugs associated with MNEs could play a role in the development of MDR in cancers.

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

PURPOSE: The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. METHODS: The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. RESULTS: The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution. CONCLUSION: Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

Ephedra water decoction and cough tablets containing ephedra and liquorice induce CYP1A2 but not CYP2E1 hepatic enzymes in rats.

1. Ephedra water decoction (EWD) and cough tablets containing ephedra and liquorice (maxing cough tablets, MXCT) have been widely used in the treatment of asthma. In the clinic, EWD and MXCT may be prescribed with theophylline, one of the most popular antiasthmatic drugs. CYP1A2 and CYP2E1 are mainly involved in the oxidative metabolism of theophylline in human liver. Drug interactions involving the cytochrome P450 (CYP) isoforms generally are of two types: enzyme induction or enzyme inhibition. Enzyme inhibition reduces metabolism, whereas induction can increase it. 2. To evaluate the pretreatment effect of EWD and MXCT on CYP1A2 and CYP2E1, CYP1A2 and CYP2E1 activity, the protein expression and mRNA expression levels were determined. After pretreatment with EWD or MXCT, the enzyme activity, mRNA expression and protein expression of CYP1A2 were increased significantly (p < 0.05), but enzyme activity of CYP2E1 did not change compared with the control. 3. It was demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2, therefore, in patients taking EWD or MXCT, possible CYP-induced drug interaction should be noted to decrease the risk of therapeutic failure or adverse effects resulting from the use of additional therapeutic agents.

Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea.

PURPOSE: Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route. METHODS: A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic(®) F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously. RESULTS: Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. CONCLUSION: Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants.

Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: in vitro, in vivo and in situ intestinal permeability studies.

The main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed Cmax1, Cmax2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2- and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p < 0.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.

Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats.

Ephedra water decoction (EWD) and cough tablets containing ephedra and liquorice (maxing cough tablets, MXCT) have been used widely in the treatment of asthma. In the clinic, EWD and MXCT may be prescribed with theophylline, one of the most popular antiasthmatic drugs and a typical substrate of cytochrome P450 (CYP) 1A2. So in the present study the potential effects of EWD and MXCT on CYP1A2 activity and the pharmacokinetics of theophylline in rats were evaluated. In the in vivo CYP1A2 activity research, the rats were given oral caffeine (10 mg/kg) after a 14 day pretreatment with EWD (18 g/kg) and MXCT (0.1, 0.2 or 0.4 g/kg). Then the CYP 1A2 activity was expressed by using the caffeine metabolic ratio (CMR). The results showed that the CMR increased markedly compared with the control groups. In the pharmacokinetics experiment, the rats were given oral theophylline (10 mg/kg) after a 14 day pretreatment with EWD (18 g/kg) and MXCT (0.2 g/kg). The results showed that the AUC(0-24 h) and C(max) of theophylline were reduced markedly compared with the control groups. These results demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2 activity, therefore, speeding up the metabolism of theophylline. The concomitant use of EWD or MXCT may decrease the effect of theophylline in rats.

Eudragit nanoparticles containing genistein: formulation, development, and bioavailability assessment.

BACKGROUND: Genistein, one of the major isoflavones, has received great attention as a phytoestrogen and potential cancer chemoprevention agent. However, the dissolution and bioavailability of genistein from solid oral preparations is low due to its poor water solubility. METHODS: In order to improve the oral bioavailability of genistein, genistein nanoparticles were prepared by the nanoprecipitation technique using Eudragit(®) E100 as carriers and an optimized formulation of mass ratio (genistein:Eudragit E100, 1:10). The mean particle size of genistein nanoparticles was approximately 120 nm when diluted 100 times with distilled water. The drug-loaded nanoparticles were spherical on observation by transmission electric microscopy. RESULTS: Encapsulation efficiency and drug loading of the genistein nanoparticles were approximately 50.61% and 5.02%, respectively. Release of drug from the genistein nanoparticles was two times greater than that from the conventional capsules. After administration of genistein suspension or genistein nanoparticles at a single dose of 100 mg/kg to fasted rats, the relative bioavailability of genistein from the nanoparticles compared with the reference suspension was 241.8%. CONCLUSION: These results suggested that a nanoparticle system is a potentially promising formulation for the efficient delivery of poorly water-soluble drugs by oral administration.

Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice.

This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) model of mice. The study employed female C57BL/6 mice (n = 50), and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol-phosphate buffered solution. The mice were divided into five groups (n = 10): vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg(-1)) daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO), interleukin (IL)-12, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ). The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg(-1). When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation.

Enhanced oral bioavailability of Wurenchun (Fructus Schisandrae Chinensis extracts) by self-emulsifying drug delivery systems.

BACKGROUND: Wurenchun is the alcohol extract from Fructus Schisandrae Chinensis, which has good efficiency in lowering abnormal serum glutamic pyruvic transaminase (SGPT) level of patients suffering from acute or chronic hepatitis. The main purpose of this work is to prepare self-emulsifying drug delivery systems (SEDDS) for enhancing the solubility, dissolution rate, and oral bioavailability of poorly water-soluble traditional Chinese medicines, Wurenchun. METHODS: Pseudoternary phase diagrams were used to evaluate the efficient self-emulsification domains, and particle size distributions of resultant emulsions were determined. The dissolution test was performed according to the second method of Chinese Pharmacopoeia dissolution procedure. The pharmacokinetic study in rats for the optimized formulation was performed and compared to commercial capsules. RESULTS: The optimized formulation for bioavailability assessment consisted of 20% oleic acid, 65% Tween 20, and 15% Transcutol P. The mean droplet size distribution of the optimized SEDDS was approximately 240 nm when diluted with 1000-fold volume of the distilled water. The in vitro dissolution rates of the active components of Wurenchun SEDDS were significantly higher than those of the commercial capsules. SEDDS have significantly increased the C(max) and area under the curve) (AUC) of Wurenchun compared to reference capsules (P < 0.05). And the relative bioavailability of SEDDS for schisandrin and schisandrin B was 292.2% and 205.8% compared to the commercial capsules, respectively. CONCLUSION: The results suggest the potential use of SEDDS to improve oral absorption of the sparingly soluble drugs or traditional Chinese medicine, such as Wurenchun.

Pharmacokinetics and biodistribution of itraconazole in rats and mice following intravenous administration in a novel liposome formulation.

Novel itraconazole (ITZ)-loaded liposomes (ITZ-LPs) were prepared and their pharmacokinetics and biodistribution were assessed in comparison with commercial formulations (ITZ-CD). The ITZ-LPs were prepared by thin-film hydration method and the physicochemical characterizations of the ITZ-LPs were evaluated. The pharmacokinetics and biodistribution were studied in the rats and mice, and compared with commercially available formulations (Sporanox((R))) after administration by the tail vein at a dose of 10 mg/kg. The concentration of ITZ in plasma and tissues was determined by means of HPLC-MS/MS. The size distribution of the liposomes was 264.5 nm and the entrapment efficiency of ITZ-LPs was 73.82 +/- 0.73%. In pharmacokinetics study, the two formulations demonstrated pronounced differences following i.v. administration to rats. The AUC(0-->24 h) for ITZ-CD was 87.12 mg/L.h and that for ITZ-LPs was 155.47 mg/L.h (p < 0.05). The MRT(0-->24 h) value was 1.70 h for ITZ-CD and 3.68 h for ITZ-LPs. In tissue distribution study, there were no differences of distributions in the lung between two formulations. Nevertheless, in the liver and spleen, itraconazole levels for the group treated with ITZ-LPs were significantly higher than those for the group treated with ITZ-CD. Meanwhile, the low distribution of ITZ-LPs in heart and kidney was of great advantage to reduce the toxicity for heart and kidney. These results indicated that the ITZ-LPs can be a potential intravenous formulation of itraconazole.

Highly sensitive determination of Schisandrin and Schisandrin B in plasma of rats after administration of Wurenchun (Fructus Schisandrae Chinensis Extracts) preparations by LC-ESI-MS/MS.

A sensitive and specific method based on liquid chromatography-tandem mass spectrometry using electrospray ionization (LC-ESI-MS/MS) has been developed for the determination of Schisandrin and Schisandrin B in rat plasma. A 100 microL plasma sample was extracted by methyl tert-butyl ether after spiking the samples with nimodipine (internal standard) and performed on an XTerra(R)MS-C(18) column (150 mm x 2.1 mm, 3.5 mum) with the mobile phase of acetonitrile-water-formic acid (80:20:0.2, v/v) at a flow rate of 0.2 mL/min in a run time of 8.5 min. The lower limit of quantification of the method was 40 ng/mL for Schisandrin and 20 ng/mL for Schisandrin B. The method showed reproducibility with intra-day and inter-day precision of less than 13.8% RSD, as well as accuracy, with inter- and intra-assay accuracies between 93.5 and 107.2%. Finally, the LC-ESI-MS/MS method was successfully applied to study the pharmacokinetics of Schisandrin and Schisandrin B in rats after administration of Wurenchun commercial formulations to rats.