[Application of affinity chromatography and its mathematical model in study of active components of traditional Chinese medicine].

Affinity chromatography is characterized by its high specificity,high recovery rate and sensitivity,and it has been widely used in the selection of active ingredients of traditional Chinese medicine,separation and enrichment of low molecular weight sugars and protein peptides,research on mechanism of action and discovery of targets.This paper reviewed the application of affinity chromatography and its adsorption isotherm model,kinetic model and adsorption thermodynamic mechanism in the field of traditional Chinese medicine.This summarizes and provides thinking for comprehensive applications of affinity chromatography theory in the field of active ingredient screening,purification and medicine interaction.

Case report of pulmonary endometriosis and review of the literature.

Pulmonary endometriosis is a rare form of thoracic endometriosis. We herein describe a 29-year-old woman with recurrent hemoptysis associated with her menstrual cycle. The patient had a 4-month history of catamenial hemoptysis without thoracic pain, respiratory embarrassment, cough, fever, night sweating, or loss of appetite. Chest computed tomography revealed exudation shadows in the right lower pulmonary lobe and small fiber lesions in the right middle lobe and left lung. Thoracoscopic wedge resection of the right lower pulmonary lobe was performed, and the pathological result was pulmonary endometriosis. No evidence of hemoptysis during menstruation was found following the operation.

[Study on mechanism and structure-activity relationship of hypolipidemic polysaccharides: a review].

Hypolipidemic polysaccharides have notable activity and safety with a range of diverse sources. In this paper, the classification of hypolipidemic polysaccharides was carried out into polysaccharide sulfate, glycosaminoglycan, homopolysaccharide and heteropolysaccharide. The hypolipidemic activity mechanism and structure-activity relationship hypothesis of those polysaccharides in recent years were briefly reviewed therefore to provide references for the study and product development of polysaccharides.

Granular cell tumor: A report of three cases and review of literature.

OBJECTIVE: In order to improve the understanding of granular cell tumor and avoid missing the best time of treatment, we report three patients with rare granular cell tumors admitted to our hospital in the past 10 years. METHODS: The characteristics, methods of treatment, postoperative pathological results and follow-up results of three cases of granular cell tumor were analyzed; and literatures related to granular cell tumors were reviewed. RESULTS: All patients underwent surgical treatment, and the excised lesions were sent to the laboratory for testing. Postoperative pathological results were as follows: granular cell tumor of the vulva, granular cell tumor within the sheath of the rectus muscle, and granular cell tumor in the left cubit nerve. All three cases were benign, and no recurrence was found during follow-ups after the operation. CONCLUSION: Granular cell tumors are rare tumors derived from the nerve sheath, are mostly benign tumors, and the incidence of malignancy is 2%. The gold standard for diagnosis of granular cell tumor is histopathology. Granular cell tumor is not sensitive to radiotherapy and chemotherapy, and needs to be surgically removed. Since this disease may have no solid lesions and tumor cells can infiltrate local tissues, based on the full excision of the lesion, the extent of resection may be extended to areas without infiltration. This disease has a possibility of recurrence, and patients need to be followed-up.

A novel formulation of [6]-gingerol: Proliposomes with enhanced oral bioavailability and antitumor effect.

[6]-Gingerol, one of the components of the rhizome of Ginger, has a variety of biological activities such as anticoagulant, antioxidative, antitumor, anti-inflammatory, antihypertensive, and so forth. However, as one of the homologous phenolic ketones, [6]-gingerol is insoluble in water which limits its applications. Herein, we prepared [6]-gingerol proliposomes through modified thin-film dispersion method, which was spherical or oval, and physicochemically stable with narrow size distribution. Surprisingly, in vitro release of [6]-gingerol loaded proliposome compared with the free [6]-gingerol was significantly higher and its oral bioavailability increased 5-fold in vivo. Intriguingly, its antitumor effect was enhanced in the liposome formulation. Thus, our prepared [6]-gingerol proliposome proved to be a novel formulation for [6]-gingerol, which significantly improved its antitumor effect.

Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation.

Cardiac glycosides could increase intracellular Ca2+ ion by inhibiting the Na+/K+ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae. The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.

Segetoside I, a plant-derived bisdesmosidic saponin, induces apoptosis in human hepatoma cells in vitro and inhibits tumor growth in vivo.

Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell lines (HepG2, human hepatoma; H22, mouse hepatoma; MCF-7, breast cancer; U251, gliocoma; BGC, HGC & SGC, gastric cancinoma; Lovo-1,colon cancer). MTT bioassay analysis showed that HepG2 cells were the most sensitive to segetoside I compared with other cancer cell lines, with lower toxicity in healthy mouse embryonic fibroblast cells. Segetoside I pretreatment of HepG2 resulted in apoptotic induction, dose-dependent DNA fragmentation, inhibition of cell migration, up-regulation of Bax and down-regulation of Bcl-2, which indicated that an apoptotic signaling event could have been initiated. The segetoside I also suppressed hepato-tumour growth in mice with virtually no cytotoxicity and prolonged animal survival, making it a strong oncology drug agent. These findings showed that segetoside I exhibited its antitumor activity via apoptotic induction and significantly support the possible application of the antitumor agent as a potential chemotherapeutic candidate worthy of further investigations.

Ergosterol-loaded poly(lactide-co-glycolide) nanoparticles with enhanced in vitro antitumor activity and oral bioavailability.

AIM: Ergosterol is a plant sterol with anti-tumor and anti-angiogenic activities, but is poorly soluble. In this study, we attempted to enhance its anti-tumor action and oral bioavailability via poly(lactide-co-glycolide) (PLGA) nanoparticle encapsulation. METHODS: Ergosterol-loaded PLGA nanoparticles (NPs/Erg) were prepared using the emulsion/solvent evaporation technique. Their physicochemical properties were characterized, and their cytotoxicity against human cancer cell lines was evaluated with MTT assay. The pharmacokinetics and tissue distribution of NPs/Erg were investigated in rats and mice, respectively. RESULTS: NPs/Erg were spherical in shape with a particle size of 156.9±4.8 nm and a Zeta potential of -19.27±1.13 mV, and had acceptable encapsulation efficiency and loading capacity. NPs/Erg exerted much stronger cytotoxicity against human cancer cells than the free ergosterol, and showed significantly reduced IC50 values (14.69±0.48 µg/mL in glioma U251 cells; 9.43±0.52 µg/mL in breast cancer MCF-7 cells; 4.70±0.41 µg/mL in hepatoma HepG2 cells). After oral administration of a single dose in rats, NPs/Erg displayed a prolonged plasma circulation with a 4.9-fold increase of oral bioavailability compared with the free ergosterol. After mice received NPs/Erg, the ergosterol in NPs/Erg was rapidly distributed in stomach, kidneys, liver, brain, spleen, and virtually non-existent in heart and lungs. The presence of NPs/Erg in brain was particularly improved compared with the free ergosterol. CONCLUSION: The PLGA nanoparticles serve as a promising carrier for the poorly soluble ergosterol and significantly improve its bioavailability, biodistribution and in vitro anti-tumor activities.

Tumor targeted delivery of octreotide-periplogenin conjugate: Synthesis, in vitro and in vivo evaluation.

Periplogenin (PPG), a cardiac glycoside prepared from Cortex periplocae, with similar structure to bufalin, has been found to induce apoptosis in many tumor cells. However, lots of cardiac glycosides possessing strong antitumor activity in vitro have still not passed phase I clinical trials, mostly due to poor tumor selectivity and systemic toxicity. To overcome this drawback, we designed octreotide-periplogenin (OCT-PPG) conjugate by coupling PPG-succinate to the amino-terminal end of octreotide. In comparison with free PPG, the conjugate exhibited significantly stronger cytotoxicity on HepG2 cells (SSTRs overexpression) but much less toxicity in L-02 cells. After intravenous injection of OCT-PPG conjugate into H22 tumor-bearing mice, its total accumulation in tumor was 2.3 fold higher than that of free PPG, but was 0.71- and 0.84-fold lower in heart and liver, respectively, suggesting somatostatin-mediated target delivery of PPG into the tumor tissue and reduced distribution in heart and liver. In vivo studies using H22 tumor model in mice confirmed the remarkable therapeutic effect of this conjugate. These results suggested that OCT-PPG conjugate could provide a new approach for clinical application of cardiac glycosides and as a targeting agent for cancer therapy.

[Progresses in screening active compounds from herbal medicine by affinity chromatography].

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.

Preparation of Pluronic/Bile salt/Phospholipid Mixed Micelles as Drug Solubility Enhancer and Study the Effect of the PPO Block Size on the Solubility of Pyrene.

Pluronic/bile salt/phospholipid mixed micelles (Pluronic/BS/PS-MM) drug carrier system for solubilization hydrophobic drugs was developed. A typical hydrophobic compound, pyrene, was selected as a representative hydrophobic compound to model the hydrophobic drugs. Five Pluronics, F68, F88, F98, F108, and F127 with different PPO chain length were studied. CMC data and solubilization capacities were obtained from a pyrene solubilization method. A closed association model was used to obtain the thermodynamic parameters: Gibbs free energy (ΔG°), enthalpy, (ΔH°) and entropy (ΔS°) of micellization. The results obtained from these experiments suggest that the mixed micelles was more stable and solubilize more pyrene than single one; and the solubilization of pyrene was strong effected by the PPO block size, thus accentuating synergistic interaction mechanism in Pluronic/BS/PS-MM. The study generated an important dataset so as to compare the effect of different Pluronics on solubility capacity of Pluronic/BS/PS-MM.

Poly(N-isopropylacrylamide-co-N,N'-methylene bisacrylamide) monolithic column embedded with γ-alumina nanoparticles microextraction coupled with high-performance liquid chromatography for the determination of synthetic food dyes in soft drink samples.

The present work proposes a study of the synthesis of poly(N-isopropylacrylamide-co-N,N'-methylene bisacrylamide) monolithic column embedded with γ-alumina nanoparticles and its applications to the extraction of synthetic food dyes in soft drink samples. The monolithic column was synthesized inside fused silica capillaries using thermally initiated free-radical polymerization with N-isopropylacrylamide (NIPAAm) as the monomer, N,N'-methylene bisacrylamide (MBAAm) as the cross-linker, dimethylsulfoxide (DMSO) and dodecanol as the porogen. γ-Alumina nanoparticles were introduced to prevent the swelling of the organic polymer and enhance the loading capacity. In order to obtain optimum experimental conditions, sample pH, sample flow rate, sample volume, eluent flow rate were investigated. Under the optimum conditions, we obtained acceptable linearities, low limits of detection, and good intra-day/inter-day relative standard deviations. When applied to the determination of four synthetic food dyes (Tartrazine, Sunset Yellow, Allura Red, and Azorubine) in soft drink samples, satisfactory recoveries were obtained in the range of 90.4-109.2%.

[Advance in studies on anti-tumor mechanism of matrine].

Matrine is one of the main active components extracted from Sophora flavescens, S. subprostrata and S. alopecuroides. In recent years, its anti-tumor activity has attracted wide attention. According to studies, matrine shows the anti-tumor effect through multiple channels such as inducing apoptosis and autophagy of cancer cells, arresting cell cycle, inhibiting tumor cell migration, angiogenesis and NF-kappaB, as well as the synergistic effect with chemotherapeutics. Along with the further studies on matrine's anti-tumor mechanism, it has a broad prospect for development and application in tumor clinical treatment.

In vitro release and in vitro-in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles.

BACKGROUND: The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles. METHODS: Hollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na(2)CO(3) solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner-Nelson method was used to calculate the in vivo absorption fraction. RESULTS: The results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50-100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m(2)/g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na(2)CO(3) solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro-in vivo correlation revealed that HMSNs in 0.08 M Na(2)CO(3) solution had a correlation coefficient R(2) value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively. CONCLUSION: The findings of in vitro-in vivo correlation indicate that HMSNs together with Na(2)CO(3) solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of water-soluble drugs.

[Advance in hepatic protective formulations of traditional Chinese medicine and their quality control methods].

As many traditional Chinese medicines have been founded to have protective effect on liver damage in recent years, they have also got involved in increasingly wide clinical application. Meanwhile, with the development of new hepatic protective formulations of traditional Chinese medicines, we have set increasingly higher requirements for quality control methods and measures. This essay summarizes the advance in studies on hepatic protective formulations of traditional Chinese medicine and their quality control methods in the combination of relevant domestic and foreign literatures, looking into the future of the development of new hepatic protective formulations of traditional Chinese medicines.

Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo.

AIM: To formulate proliposomes with a polyphase dispersed system composed of soybean phospholipids, cholesterol, isopropyl myristate and sodium cholate to improve the oral bioavailability of dehydrosilymarin, an oxidized form of herbal drug silymarin. METHODS: Dehydrosilymarin was synthesized from air oxidation of silymarin in the presence of pyridine, and proliposomes were prepared by a film dispersion-freeze drying method. Morphological characterization of proliposomes was observed using a transmission electron microscope. Particle size and encapsulation efficiency of proliposomes were measured. The in vitro release of dehydrosilymarin from suspension and proliposomes was evaluated. The oral bioavailability of dehydrosilymarin suspension and proliposomes was investigated in rabbits. RESULTS: The proliposomes prepared under the optimum conditions were spherical and smooth with a mean particle size in the range of 7 to 50 nm. Encapsulation efficiency was 81.59%±0.24%. The in vitro accumulative release percent of dehydrosilymarinloaded proliposomes was stable, which was slow in pH 1.2, and increased continuously in pH 6.8, and finally reached 86.41% at 12 h. After oral administration in rabbits, the relative bioavailability of proliposomes versus suspension in rabbits was 228.85%. CONCLUSION: Proliposomes may be a useful vehicle for oral delivery of dehydrosilymarin, a drug poorly soluble in water.

Formulation and pharmacokinetic evaluation of tetracycline-loaded solid lipid nanoparticles for subcutaneous injection in mice.

The aim of this work was to prepare tetracycline-loaded solid lipid nanoparticles (Tet-SLN), and to evaluate the potential of these colloidal carriers for subcutaneous injection. Tet-SLN was prepared by microemulsion method and the preparation conditions were optimized by ternary phase diagram. At optimized process conditions, lyophilized Tet-SLN showed spherical particles with a mean diameter of 87.2±46.9 nm and a negative zeta potential of -6.69 mV, up to 1.7% tetracycline drug content was achieved after loading. In vitro release test showed a biphasic release profile for Tet-SLN and more than 80% of the drug was liberated from Tet-SLN in 48 h. After subcutaneous injection of Tet-SLN to mice, a considerable sustained release was observed; tetracycline in blood could be detected lasting 36 h, and lower concentrations of tetracycline in all tissues tested compared to the free tetracycline solution were observed. In conclusion, Tet-SLN can be prepared well by microemulsion method and subcutaneous injection of SLN provide a new perspective for drug sustained release.

Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles.

AIM: To evaluate a mixed micellar drug delivery system composed of sodium cholate and phospholipid for oral administration of silybin, a promising hepatoprotectants. METHODS: The optimum formulation of sodium cholate/phospholipid-mixed micelles containing silybin was obtained based on the study of pseudo-ternary phase diagram. The dissolution of silybin-mixed micelles was investigated. The pharmacokinetic characteristics and bioavailability after oral administration of silybin-mixed micelles and silybin-N-methylglucamine were compared in dogs. RESULTS: The mean particle size of prepared mixed micelles was 75.9+/-4.2 nm. The largest solubility of silybin was found to be 10.0+/-1.1 mg/mL in the optimum formulation of mixed micelles. The silybin-sodium cholate/phospholipid-mixed micelles showed a very slow release of silybin 17.5% (w/w) within 72 h in phosphate buffer (pH 7.4) and 15.6% (w/w) in HCl solution (pH 1.2). After oral administration to dogs, the relative bioavailability of mixed micelles versus silybin-N-methylglucamine in dogs was 252.0%. CONCLUSION: Sodium cholate/phospholipid-mixed micelles are promising carriers in orally delivery of silybin, considering their capability of enhancing bioavailability and large-scale production.