[Dexamethasone acetate microemulsions: formulation and effect on skin permeability].

The present project was designed to optimize the microemulsion (ME) formulation of oil in water (O/W) for dexamethasone acetate (DA), and examine its impact on DA percutaneous permeation. The saturated solubility of DA in different oils, surfactants and co-surfactants was tested. The ratio of surfactant to co-surfactant was selected by constructing pseudo three phase diagrams to investigate the maximal microemulsion area. In vitro permeation studies of DA from microemulsion and suspension were performed to optimize the formulation further. Differential scanning calorimetry(DSC) and attenuated total reflection flourier transformed infrared spectroscopy (ATR-FTIR) were performed to investigate the mechanism of microemulsion action on skin. The optimized formulation was composed of oleic acid/Labrasol/propylene glycol/water with 8/45/15/32 (w/w), and the DA loading was 0.75% (w/w). The permeation enhancement of microemusion was 6.00-fold as that of suspension, and the DA from microemulsion retained in the skin was 4.79-fold as that of suspension. DSC and ATR-FTIR results suggested that microemulsion could affect the intercellular lipid lamellae and keratin of the stratum corneum. The barrier function of stratum corneum was disordered by the microemulsion so that the dermal drug delivery was enhanced. Therefore, the optimized microemulsion enhanced DA percutaneous permeation significantly through the interaction of microemulsion with skin, microemulsion is a promising approach for DA percutaneous delivery.

[In vitro targeting effect of lactoferrin modified PEGylated liposomes for hepatoma cells].

A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma.

Association study identifying a new susceptibility gene (AUTS2) for schizophrenia.

Schizophrenia (SCZ) is a severe and debilitating mental disorder, and the specific genetic factors that underlie the risk for SCZ remain elusive. The autism susceptibility candidate 2 (AUTS2) gene has been reported to be associated with autism, suicide, alcohol consumption, and heroin dependence. We hypothesized that AUTS2 might be associated with SCZ. In the present study, three polymorphisms (rs6943555, rs7459368, and rs9886351) in the AUTS2 gene were genotyped in 410 patients with SCZ and 435 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and forced PCR-RFLP methods. We detected an association between SCZ and the rs6943555 genotype distribution (odds ratio (OR)=1.363, 95% confidence interval (CI): 0.848-2.191, p=0.001). The association remained significant after adjusting for gender, and a significant effect (p=0.001) was observed among the females. In the present study, rs6943555 was determined to be associated with female SCZ. Our results confirm previous reports which have suggested that rs6943555 might elucidate the pathogenesis of schizophrenia and play an important role in its etiology.

[In vivo imaging in tumor-bearing animals and pharmacokinetics of PEGylated liposomes modified with RGD cyclopeptide].

The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.

In vitro study of transdermal penetration and iontophoresis of hepatitis B vaccines through rat skin.

In vitro percutaneous delivery of hepatitis B vaccines was investigated in order to assess the penetration of vaccine under passive diffusion and iontophoresis conditions. The study was carried out using Franz vertical diffusion cell through the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the cumulative amount of permeation and the retention amount of drug in skin. Passive diffusion alone resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1 +/- 0.1) ng x cm(-2) and (2.3 +/- 0.1) ng x cm(-2) after 24 h when the initial concentration of vaccine in the donor compartment was 23 microg x mL(-1) and 46 microg x mL(-1), respectively. After removing the stratum corneum, the permeation and retention amount of hepatitis B vaccines increased to (383.7 +/- 86.2) ng x cm(-2) and (16.8 +/- 4.6) ng x cm(-2), respectively, 171.6-folds and 2.1-folds more than that from its intact skin with the drug loaded at 46 microg x mL(-1). Iontophoresis induced a significant increase of cumulative and retention amount of hepatitis B vaccines through the skin (P < 0.05). Application of iontophoresis significantly enhanced the permeation of hepatitis B vaccines (P < 0.05) by 2.7-folds and 6.6-folds for the intact skin, and by 1.6-folds and 1.8-folds for the tape-stripped skin with initial drug loading of 23 microg x mL(-1) and 46 microg x mL(-1), respectively. Iontophoresis also significantly increased the amount of drug retained in the skin. After applying iontophoresis for 6 h, the amount of skin retention was nearly the same as passive diffusion for 24 h both from intact skin [(16.8 +/- 4.6) ng x cm(-2) vs (13.3 +/- 5.4) ng x cm(-2)] (P > 0.05) and tape-stripped skin [(36.7 +/- 14.1) ng x cm(-2) vs (26.8 +/- 11.2) ng x cm(-2)] (P > 0.05). Overall, these findings revealed that the transportation efficiency of bioactive substance like hepatitis B vaccines may be improved by iontophoresis, which can be potentially used in the field of transcutaneous immunization.

Effect of composite salvia injection on platelet parameters in children with anaphylactoid purpura.

OBJECTIVE: To explore the effect of composite salvia injection (CSI) on platelet parameters in children with anaphylactoid purpura (AP) and its clinical significance. METHODS: One hundred and fifty children with AP were assigned to two groups, 80 in Group A and 70 in Group B. They were treated, respectively, with conventional therapy only or conventional therapy combined with CSI. Their platelet parameters, including blood platelet count (BPC), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) were determined at the acute stage and convalescent stage, respectively. RESULTS: At the acute stage, the BPC in AP children of both groups was in the normal range, but significant abnormality was shown in the levels of MPV, PDW and PCT. As for comparisons of these parameters at the convalescent stage, significant difference between the two groups was also shown in terms of MPV, PDW and PCT (P<0.05 or P<0.01). CONCLUSION: Although platelet shows no quantitative change in the pathogenic process of AP, important functional changes are surely existent. CSI could promote the normalization of platelet function.

[Effect of atractylodes rhizome oil and other volatile oils on percutaneous absorption of baicalin].

OBJECTIVE: To study the effects of atractylodes rhizome oil, patchouli oil, angelica volatile oil on the transdermal delivery of baicalin. METHODS: The modified Valia-Chien diffusion cells was used. With saline isotonic solution as receptor fluid and different concentration of atractylodes rhizome oil, patchouli oil, angelica volatile oil as enhancers, the cumulative amount of baicalin penatrating through the skin was determined in vitro. RESULTS: All the three volatile oils improved the skin penetration of baicalin, and the effect of atractylodes rhizome oil was the best. CONCLUSION: Atractylodes rhizome oil is an effective enhancer for percutaneous penetration of baicalin.

[Optimization of ligustrazine phosphate thermosensitive gel formulation by central composite design-response surface methodology].

OBJECTIVE: To optimize the formulation of ligustrazine phosphate thermosensitive gel by the central composite design-response surface methodology (RSM plus CCD). METHODS: In the formulation design using RSM plus CCD, independent variables were the amounts of poloxamer 407 and poloxamer 188, and gel temperature was dependent variable. Multilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables, select the optimal formulations and validate. RESULTS: The quantitative relationships between two factors and evaluation index were characterized, quadratic model had better prediction capability than multilinear model. CONCLUSION: Quadratic model is performed in the optimization of formulation due to the statistical confidence. The optimization of ligustrazine phosphate thermosensitive gel formulation can be achieved by the central composite design and response surface methodology.

[Effect of micronization on the quality of Salvia miltiorrhiza Bge].

OBJECTIVE: The powder characteristic, water extraction amount and active ingredients cryptotanshinone (CTS), tanshinone II A (TS) and protocaechuic aldehyde (PA) were comparatively studies between crude powder and micronized powder to study the application of micronization technology to Salvia miltiorrhiza Bge. METHODS: Salvia miltiorrhiza Bge powedr was characterized by laser diffraction analyzer and scanning electron microscopy. The angle of repose and bulk density was measured. The water extraction was quantified by heated extraction method. The active ingredinents CTS, TS and PA were detected by RP-HPLC after it released from Salvia miltiorrhiza Bge. RESULTS: The differences of particle characteristic and surface modality between crude powder and superfine were significant. Water extraction amount of micronized powder was 1.23 times as that of crude powder. The CTS, TS and PA extraction amount of micronized powder were 1.54, 1.48 and 1.90 times as those of crude powder. CONCLUSION: The extraction content of lipo-solubility and water-solubility active ingredients of Salvia miltiorrhiza Bge. are improved by micronization. Micronization can economize the resource of Salviae miltiorrhiza Bge. The bioavability of Salviae miltiorrhiza Bge. will be improved with the new techonology.

[Solubilization on cryptotanshinone by hydroxypropyl-beta-cyclodextrin and preparation of their inclusion compound].

OBJECTIVE: To prepare cryptotanshinone (CT)-cyclodextrin inclusion compound and improve dissolution of CT. METHOD: Inclusion ratio was determined by plotting the phase solubility curve of CT versus hydroxypropyl-beta-cyclodextrin (HPCD). CT-cyclodextrin inclusion compound was made by wet grinding method. Properties of the inclusion compound was investigated by in vitro dissolution test, DTA and IR spectrum. RESULT: Inclusion ratio of CT versus HPCD was 1:1. Dissolution of CT-HPCD inclusion compound at 45 min was 21.6 times of material drug. CONCLUSION: Dissolution of CT was improved remarkably in CT-HPCD inclusion compound. The complexation force of the inclusion compound was hydrogen bond formed by carbonyl group of CT and hydroxyl group of HPCD.

[Diagnostic Value of (18)F-FDG-PET/CT for Multiple Myeloma].

OBJECTIVE: To study the diagnostic value of (18)F-FDG-PET/CT in multiple myeloma (MM). METHODS: A total of 66 patients, who were highly suspected of MM in our hospital from July 2012 to December 2014, were chosen as study objects. All patients were diagnosed or excluded by pathological examination. All patients were detected by (18)F-FDG-PET/CT, and its diagnostic value was analyzed. The number of focuses were counted. RESULTS: Out of 66 patients 59 patients (89.39%) were diagnosed with multiple myeloma. The sensitivity of PET was 98.31%, the specificity of PET was 85.71%, the Youden index was 0.8402; the sensitivity of CT was 96.61%, the specificity of CT was 85.71%, the Youden index was 0.8232; the sensitivity of PET/CT was 100.00%, the specificity of PET/CT was 83.33%, the Youden index was 0.8333. In 59 MM patients, 635 focuses were detected, out of them 572 focuses (90.08%) were detected by CT, 593 focuses (93.39%) were detected by PET, 530 focuses (83.46%) were coincided on PET/CT. CONCLUSION: (18)F-FDG-PET/CT has diagnostic value for multiple myeloma, and it can be used in locating and counting focuses, as well as in evaluating the treatment efficacy and guiding the clinical work.

[Review and analysis of present status of the micronization of Chinese traditional medicine].

Micronization is one of the methods to improve the solubility and bioavailability of drug, the micronization of TCM is a new techonology of TCM mordenization. status in quo of TCM micronization was reviewed and analyzed. Effects of micronization on the dissolution of active ingredients and pharmacological action were widely studied, however some fundmental aspects, such as engineering factors of superfine powder preparation, stability of them and the optimal particle size, are urgently to be studied.

Plasma pharmacokinetics and lung distribution of tetrahydropalmatine after topical application of cold asthma recipe extract: Feishu (BL 13) versus Non-Feishu acupoint.

ETHNOPHARMACOLOGICAL RELEVANCE: Acupoint application of cold asthma recipe (CAR) was a traditional Chinese medicine (TCM) method, widely used as an alternative medicine for clinical prevention of the common winter diseases of asthma and bronchitis. Tetrahydropalmatine (THP) was a main active ingredient of CAR extract. The aim of this study is to compare plasma pharmacokinetics and lung distribution of THP between Feishu (FS) acupoint (BL 13) and Non-Feishu (NFS) acupoint application of CAR extract by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). MATERIALS AND METHODS: The extract of CAR was topically administrated in FS and NFS acupoint of rats for plasma pharmacokinetics, and topically administrated in FS and NFS acupoint of mice for lung distribution. The plasma and lung homogenates were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column with a mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The detection was accomplished by multiple-reaction monitoring (MRM) scanning in the positive electrospray ionization (ESI(+)) mode. All pharmacokinetic parameters were estimated by non-compartmental analysis. RESULTS: A sensitive, accurate and precise UPLC-MS/MS method was successfully established for determination of THP in 100 µL plasma and lung homogenate. The lower limit of quantification (LLOQ) of THP was 0.05 ng/mL and 0.072 ng/mL, respectively. The pharmacokinetic results manifested that THP was absorbed and eliminated slowly in plasma. Additionally, it was found that there was significantly higher amount of THP absorbed into blood and lung after FS acupoint application compared to NFS acupoint application. CONCLUSIONS: Both of the rat plasma pharmacokinetics and mice lung distribution of THP could support that FS acupoint application of CAR extract has greater advantages of absorption into the blood circulation and distribution in target tissue over NFS acupoint application. The results might be helpful in providing a rational explanation for why the TCM chose the acupoint application and elucidating the underlying mechanism of this treatment.

Antidiarrheal properties of different extracts of Chinese herbal medicine formula Bao-Xie-Ning.

OBJECTIVE: Bao-Xie-Ning (BXN), a traditional Chinese herbal medicine (CHM) formula composed of Fructus Evodiae, Flos Caryophylli and Cortex Cinnamomi, and used for the treatment of infant diarrheal illness, was subject to systematic assessment for its putative multiple pharmacodynamic effects and pharmacological antidiarrheal mechanisms. METHODS: High-performance liquid chromatography-diode array detector-electrospray ionization-mass spectrometric/mass spectrometry was developed and validated for identification and quantification of the main constituents in different extracts of BXN. Male Kunming mice weighing 20 to 25 g were used for detecting the antidiarrheal activity of the extracts. Ethanolic extract (EE), volatile oil extract (VOE), and aqueous extract (AE) of BXN were respectively subjected to pharmacodynamic and pharmacological comparison in assessing antidiarrheal effects with senna-induced diarrhea, castor oil-induced diarrhea, acetic acid-induced writhing assay, and isolated duodenum test. RESULTS: The highest yields of three detected components of BXN, rutaecarpine, eugenol and cinnamaldehyde were observed in EE. EE showed the most remarkable antidiarrheal activity in dose-dependent and time-dependent manners in both senna- and castor oil-induced diarrhea models, and presented dose-dependent analgesic activity in acetic acid-induced algesthesia model. In addition, EE extract of BXN also exhibited strong antimobility action on the intestine and strongest depression on spontaneous contraction of isolated duodenum. CONCLUSION: Ethanol extraction is an efficient method to extract the active constituents of BXN. BXN extract demonstrated multiple pharmacological activities affecting the main mechanisms of diarrhea, which validated BXN's usage in the comprehensive clinical treatment of diarrhea.

[Preparation of docetaxel liposomes and their pharmacokinetics in rabbits].

BACKGROUND & OBJECTIVE: Docetaxel is used to treat non-small cell lung cancer, breast cancer and ovarian cancer. It is indissolvable and the solvent containing polysorbate-80 and 13% solution of ethanol is used for injections. Its clinical application is limited because of frequent severe hypersensitive responses. This study was to prepare docetaxel (DOC) liposomes and investigate their pharmacokinetics in rabbits after intravenous administration. METHODS: DOC liposomes, with or without modification of polyethylene glycol (PEG), were prepared by thin-film ultrasonic dispersion method. The entrapment efficiency and mean diameter of the liposomes were measured. After intravenous administration in rabbits, plasma DOC concentration was detected by solid phase extraction high-performance liquid chromatography (SPE-HPLC). The pharmacokinetic parameters were calculated and analyzed by 3p87 pharmacokinetic program. RESULTS: The entrapment efficiency of DOC liposomes was above 75%. The mean diameter was about 150 nm. The half-life of distribution (T(1/2alpha)) were (0.17+/-0.04) h for market docetaxel injection (M-DOC), (0.31+/-0.11) h for common DOC liposome (L-DOC), and (0.32+/-0.06) h for PEG-2000-modified DOC long circulating liposome (PEG-DOC-LCL); the half-life of clearance (T(1/2beta)) were (8.54+/-1.05), (11.18+/-1.33), and (10.51+/-1.13) h, respectively; the apparent volume of distribution (V(d)) were (13.66+/-3.62), (8.65+/-1.11), and (6.31+/-0.55) L, respectively; the area under the concentration-time curve from 0 to 24 h (AUC(0-->24)) were (13.45+/-2.44), (22.83+/-3.57), and (29.31+/-5.96) mg x (h x L)(-1), respectively; the area under the concentration-time curve from 0 to infinity h (AUC(0-->infinity)) were (15.07+/-2.76), (28.70+/-4.95), and (36.95+/-9.13) mg x (h x L)(-1), respectively; the clearance (CL) were (1.10+/-0.18), (0.54+/-0.08), and (0.42+/-0.07) L/h, respectively. CONCLUSION: The thin-film prepared DOC liposomes have high entrapment efficiency and small particle size. Both liposomes, especially PEG-DOC-LCL, can raise AUC and prolong the resident time of drugs in the blood circulating system.