Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

HPLC-ELSD fingerprints of oligosaccharide sites from mycelia of Hericium erinaceum solid cultures and Weilening Tablets / 中成药

AIM To establish the HPLC-ELSD fingerprints of oligosaccharide sites from mycelia of Hericium erinaceum solid cultures and Weilening Tablets.METHODS The analysis of aqueous extract from samples was performed on a 80 ℃ thermostatic Waters XBridge TM Amide column (4.6 mm × 150 mm,3.5 μm),with the mobile phase comprising of acetonitrile-0.2％ ammonium acetate flowing at 1 mL/min in a gradient elution manner.RESULTS There were eight and nine common peaks in two HPLC-ELSD fingerprints with the similarties of 0.994-0.966 and 0.990-0.997,respectively.Three of them were mannitol,lactose and trehalose,which showed good linear relationships within their own ranges (r ≥ 0.999 0),the average recoveries were 95.08％-104.82％ with the RSDs of 1.12％-2.90％.CONCLUSION This simple and accurate method can be used for the rapid quality control of mycelia of Hericium erinaceum solid cultures and Weilening Tablets.

Simultaneous determination of four saikosaponins in Xiaozheng Pellets by QAMS / 中成药

AIM To establish a quantitative analysis of multi-components by single-marker (QAMS) method for the simultaneous content determination of four saikosaponins in Xiaozheng Pellets (Bupleuri Radix,Cyperi Rhi-zoma,Rhei Radix et Rhizoma,etc.).METHODS The analysis of 5％ ammonia-methanol extract of this drug was performed on a Waters Xbridge C18column (250 mm ×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-water flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 210 nm and 254 nm.With saikosaponin a as a internal standard,the relative correction factors of saikosaponins b1,b2 and c were calculated,followed by the determination of their contents.RESULTS Four saikosaponins showed good linear relationships within their own ranges (r ≥ 0.999 5),whose average recoveries were 98.08％-102.94％ with the RSDs of 0.85％-1.82％.The results obtained by QAMS approximated those obtained by external standard method.CONCLUSION This simple,precise and feasible method can be used for the quality control of Xiaozheng Pellets.

Pharmacokinetics of ginsenoside Rb1 in lincomycin-induced gut microbiota dysbiosis rats / 中国药科大学学报

@#Gut microbiota-mediated deglycosylationplays an important role in the metabolism of ginsenoside Rb1. Thus, a lincomycin-induced gut microbiota dysbiosis rat model was selected to explored the pharmacokinetics and deglycosylation metabolism of ginsenoside Rb1. An UPLC-MS/MS analytical method was developed to detect ginsenoside Rb1 and its deglycosylated metabolite, Rd in rat plasma. The triple quadruple mass spectrometer was set in negative electrospray ionization mode by multiple reaction monitoring. The method was validated to meet the requirements of biological applications, by evaluating specificity, linearity, lower limits of quantification(LLOQ), precision, accuracy, matrix effect, recovery and stability. Gut microbiota dysbiosis rats were induced by oral administration of lincomycin(5 000 mg/kg)for 7 continuous days. The in vitro and in vivo results reveal that the reduced β-D-glucosidase activity significantly decreases the Rd formation rate in lincomycin-induced gut microbiota dysbiosis rats, leading to the pharmacokinetic alteration of ginsenoside Rb1 and Rd in gut microbiota dysbiosis rats.

Study on Fingerprint of Chuanxiong Rhizoma by HPLC / 中国中医药信息杂志

Objective To establish analysis methods for fingerprint of Chuanxiong Rhizoma by HPLC. Methods Thermo C18 chromatographic column (4.6 mm×250 mm, 5 μm) was used with methanol-0.1% Formic acid in gradient elution. The flow rate was 1 mL/min, the detection wavelength was set at 323 nm, and the temperature was 25 ℃. The similarities of the 18 batches of samples were compared by similarity evaluation, cluster analysis and principal component analysis. Results Based on the fingerprints of 18 batches of Chuanxiong Rhizoma, 11 common peaks were identified, the similarities were almost greater than 0.9 among all batches. The samples were clustered into 3 categories. Conclusion The method is simple, steady and repeatable. It provides a basis for the quality control and evaluation of Chuanxiong Rhizoma.

Plasma metabonomics study of ischemic cerebral apoplexy rats treated with Tongsaimai pellets / 中国中药杂志

<p><b>OBJECTIVE</b>To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.</p><p><b>METHOD</b>Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.</p><p><b>RESULT</b>Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.</p><p><b>CONCLUSION</b>Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.</p>

Study on in situ intestinal absorption of active ingredients in Shuanghuanglian oral liquid in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the intestinal absorption kinetics characteristic of the main four active ingredients in Shuanghuanglian oral liquid (SHL) and to investigate the influence of herbal compatibility in SHL on absorption of main effective ingredients.</p><p><b>METHOD</b>The in situ rat circulation model was used to investigate the concentration change differences of the four active components in SHL during perfusion.</p><p><b>RESULT</b>The absorption quantity of different concentrations of baicalin, chlorogenic acid, phillyrin and forsythoside A ranging from 40-160, 6-24, 3-12, 2.6-10.4 mg x L(-1) respectively was linear with concentration and showed no saturation at high concentration. The absorption rate constant K(a) and the hourly absorption percentages A were essentially unchanged. The pH changing from 5.0-7.43 had little influence on the absorption of phillyrin except baicalin, chlorogenic acid and forsythoside A. The calculated K(a) and A of the four active ingredients had no significant differences from that obtained after perfusing via duodenum, jejunum, ileum and colon; The calculated K(a) and A of baicalin in Scutellariae Radix (SR), chlorogenic acid in Lonicerae Japonicae Flos (LJF) and phillyrin in Forsythiae Fructus (FF) had no significant differences compared with that in SHL, but the calculated K(a) and A of forsythoside A in FF were obviously superior to that in SHL.</p><p><b>CONCLUSION</b>The intestinal absorption of the four active ingredients in SHL was mainly passive diffusion and had no difference in different segments of rat intestine; the compatibility of SHL compounds changed the absorption of forsythoside A in FF obviously.</p>

Effects of glycyrrhiza extract on pharmacokinetics property of daphnetin in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To research the influence of glycyrrhiza extract on the pharmacokinetics characteristic parameters of daphnetin, which was aimed to explore the rationality of concert application of drugs.</p><p><b>METHOD</b>The rats received intragastric administration of daphnetin and glycyrrhiza extract containing the same daphnetin respectively. The blood concentration of daphnetin was assayed by LC-MS. The data was processed by program DAS2.1.1.</p><p><b>RESULT</b>Glycyrrhiza extract can reduce the t(1/2), tmax and Ke of daphnetin, while increased the Ka and AUC(0-infinity).</p><p><b>CONCLUSION</b>Glycyrrhiza extract promoted the oral absorption of daphnetin, slowed down the elimination and increased the biological availability.</p>

Effects of different excipients on properties of Tongsaimai mixture and pellet molding / 中国中药杂志

<p><b>OBJECTIVE</b>To study preliminarily on the relationship between properties of the mixture composed of Tongsaimai extract and different excipients and pellet molding.</p><p><b>METHOD</b>The multivariate regression analysis was used to investigate the correlation of different mixture and pellet molding by measuring the cohesion, liquid-plastic limit of mixture, and the powder properties of pellets. The weighted coefficients of the powder properties were determined by analytic hierarchy process combined with criteria importance through intercriteria correlation.</p><p><b>RESULT</b>The results showed that liquid-plastic limit seemed to be a major factor, which had positive correlation with pellet molding, while cohesion had negative correlation with pellet molding in the measured range.</p><p><b>CONCLUSION</b>The physical properties of the mixture has marked influence on pellet molding.</p>

Advances in studies on absorption and metabolism of natural coumarins / 中国中药杂志

Natural coumarins have strong pharmacological activities. In this paper, the absorption and metabolism of natural coumarins were introduced by analyzing and summarizing the related literature in recent years. The research of absorption and metabolism will be propitious to further understand their pharmacological mechanism and provide basis for developing new drugs of coumarins.

Analysis of metabolites of daphnetin in the intestinal wall of rats by liquid chromatography and quatrupole-time of flight mass spectrometry / 药学学报

In this study, daphnetin and its major metabolites in the intestinal wall of rats were identified by liquid chromatography and quatrupole-time of flight mass spectrometry. Perfusion fluid of duodenum, jejunum, ileum and colon were collected separately for 2 hours from the rat intestine following perfusion with daphnetin. The metabolites of daphnetin in the perfusion fluid of different intestine segments were analyzed by the liquid chromatography and quatrupole-time of flight mass spectrometry. It is shown that the parent drug daphnetin and four metabolites were found in the perfusion fluid of duodenum, jejunum and ileum. However, no metabolites were found in the colon. Among the four metabolites, two daphnetin sulfates (m/z 257) were first discovered as the phase II metabolites of daphnetin in rats, which revealed a new way of daphnetin metabolism in rats.

Simultaneous determination of chlorogenic acid, cryptochlorogenic acid, caffeic acid, naringin, hesperidin and linarin in xiao'erjinning oral liquid by an HPLC method / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a HPLC method for the simultaneous determination of chlorogenic acid, cryptochlorogenic acid, caffeic acid, naringin, hesperidin and linarin in xiao' erjinning oral liquid.</p><p><b>METHOD</b>The chromatographic separation was achieved on a Lichrospher C18 (4.6 mm x 250 mm, 5 microm) column with a mobile phase which was composed of acetonitrile(A) and 0.4% phosphoric acid(B) for gradient elution (10:90-18:82-27:73). The flow rate was (0.8-1.1-0.8) mL x min(-1), the column temperature was 30 degrees C and the detection wavelength was set at 300 nm.</p><p><b>RESULT</b>The results showed that 6 effective components were separated well and showed good linearity. The average recoveries were between 95%-105%.</p><p><b>CONCLUSION</b>The method is proved to be rapid, accurate, credible and repeatable. It can be used for the quality control of Xiao'erjinning oral liquid.</p>

Important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of active ingredients of Chinese materia medica / 中国中药杂志

Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.

Intestinal absorption of the effective components of Schisandra chinensis Baill by rats single-pass perfusion in situ / 药学学报

The aim of the study is to investigate rat intestinal absorption behavior of three main active components, schisandrol A, schisandrin A and schisandrin B in Schisandra chinensis Baill extracts in intestine of rats. With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and the concentrations of three main active components in perfusion solution of different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC in combination with diode array detection. The results showed that the absorption rate constant (Ka) and effective permeability values (Peff) of three main active components in Schisandra chinensis Baill extracts had significant difference (P 0.05). The absorption of the three active components displayed significant difference (P schisandrin B > schisandrol A in other intestinal segments, and there is significant difference (P < 0.05) between them.

Intestinal absorption of forsythoside A by rat circulation in situ / 药学学报

This study is to investigate the effects of concentration, intestinal section, pH, paracellular route, substrate/inhibitor of enzyme (CYP3A) and proteins (P-gp, MRP2, SGL1) on the absorption of forsythoside A. The absorption of three concentrations (2.6, 5.2, and 10.4 microg x mL(-1)) of forsythoside A in different intestinal segments was studied with phenol red as the marker by rat circulation in situ. The results showed that the residue of forsythoside A with different concentrations had little significant difference from that obtained after perfusing via duodenum, jejunum, ileum and colon, which indicated that the absorption of forsythoside A was passive diffusion and had no difference in different segments of rat intestine. The residue of forsythoside A increased to 466.160 and 463.429 microg respectively when cyclosporine (4 microg x mL(-1)) or midazolam (50 micromol x L(-1)) was added to the circulation fluid, which showed significant difference compared to the control group (P < 0.05). Moreover, the residue of forsythoside A showed a tendency of increase with the increase of cyclosporine or midazolam. When digoxin (50 micromol x L(-1)) or EDTA (10 microg x mL(-1)) was added to the circulation fluid, the residue of forsythoside A decreased to 325.110 and 369.888 microg respectively, which showed significant difference as compared to the control group (P < 0.05). Besides, the residue of forsythoside A showed a tendency of reduction with the increase of digoxin or EDTA. However, there is no significant change in the absorption of forsythoside A when the different concentrations of mannitol were added to the circulation fluid. The results above indicated that the absorption of forsythoside A was mainly passive diffusion and involved paracellular route at the same time. In addition, the substrates of P-gp or CYP3A had dose-dependent effect on the absorption of forsythoside A.

Intestinal absorption properties of three components in salvianolic acid extract and the effect of borneol on their absorption in rats / 药学学报

This study aimed to investigate the effects of concentration, intestinal section and borneol on the intestinal absorption of salvianolic acids. The experiment not only studied the intestinal absorption properties of three concentrations of rosmarinic acid, salvianolic acid B and salvianolic acid A at duodenum, jejunum and ileum, but also of salvianolic acids compatible with borneol at different concentrations using single-pass intestinal perfusion model in rat with phenol red as the marker. The results showed that salvianolic acids was stable under weak-acid condition and affected by metabolism enzyme; The Peff and Ka significantly different among three concentrations of rosmarinic acid and salvianolic acid B, whose intestinal absorption were saturated in high concentration, suggesting that the transport mechanisms of rosmarinic acid and salvianolic acid B were similar to active transport or facilitated diffusion; However, there was inconspicuousness in the Peff and Ka of salvianolic acid A at different concentrations, whose absorption was not saturated in high concentration, indicating that the transport mechanisms of salvianolic acid A was passive diffusion; The Peff and Ka in the ileum obviously higher than those in the duodenum and jejunum, namely the ileum was the best absorption section; When concentration of borneol increased, the enhancing effect of intestinal absorption of salvianolic acids increased, but significantly decreased when borneol increased to some degree. The enhancing effect of medium borneol concentration was the optimum. This implied that borneol can enhance the intestinal absorption of salvianolic acids, and the capacity of enhancing effect was influenced by the concentration of borneol.

Investigation of research method of fingerprint pharmacodynamics of traditional Chinese medicines / 中国中药杂志

Fingerprinting techniques play a increasingly important role in the quality control standards of traditional Chinese medicines (TCM), research and establish the fingerprint about spectral-efficiency could improve the quality control of TCM. The necessity of the fingerprint pharmacodynamics research and the analysis and evaluation of the research methods in the existing literature at home and abroad were reviewed in this article, Combined with the author's laboratory research, we proposed the research methods of fingerprint pharmacodynamics of TCM and provided the basis for effectively promoting the the establishment and development of fingerprint pharmacodynamics of Chinese medicine compound preparations.

Studies relationship between powder characteristic of kinds of granules and their hygroscopicity / 中国中药杂志

<p><b>OBJECTIVE</b>To choose the granuling way for preparing granules that had low moisture-absorption characteristics.</p><p><b>METHOD</b>Granules were prepared by five ways, for studying the relationship between characteristics of powder and hygroscopicity were determined.</p><p><b>RESULT</b>The prepared ways of granuling that had low hygroscopicity were dry granuling and secondary swinging granuling.</p><p><b>CONCLUSION</b>The hygroscopicity of granules can be explained by characteristics of powder, which are made in different granuling ways. The prepared ways of granuling that have low hygroscopicity are dry granuling and secondary swinging granuling.</p>

Determination of Chlorogenic Acid and Hyperoside in Leaves of Acanthopanax Senticosus Produced in Different Areas by HPLC / 中国中医药信息杂志

Objective To establish a HPLC method for the content determination of Chlorogenic acid and Hyperoside in the leaves of acanthopanax senticosus from different areas.Methods The samples were separated on Hedera? ODS-2 C18 column,using acetonitrile-0.4% phosphoric acid(17∶83) as mobile phase,the detection wavelength was 360 nm.Result Chlorogenic acid and Hyperoside showed good linear relationship over the ranges of 10.2～306 ?g/mL(r =0.999 5) and 10.4～312 ?g/mL(r =0.999 8),respectively.The average recoveries were 97.14% and 98.21% with RSD at 1.65% and 1.09%,respectively.The contents of Chlorogenic acid and Hyperoside were different obviously in samples from different areas.Conclusion This method is simple,rapid and sensitive,and it can be used for the further development and the quality control of the leaves of acanthopanax senticosus.

Preparation Technology of Volatile Oils Obtained from Asarum and Lily magnolia Complexed with ?-cyclodextrin and Hydroxypropyl-?-cyclodextrin and Its Impacts of Transdermal Absorption / 中国中医药信息杂志

Objective To study the preparation of volatile oils obtained from asarum and lily magnolia complexed with ?-cyclodextrin and hydroxypropyl-?-cyclodextrin in Xuetie Dingchuan plaster,and to study its impacts of transdermal absorption.Methods The volatile oil was complexed with ?-cyclodextrin and hydroxypropyl-?-cyclodextrin.GC method was used in the determination of volatile oils complexed with ?-cyclodextrin and hydroxypropyl-?-cyclodextrin to investigate the impacts of transdermal absorption.Results The accumulation transmission of the volatile oils complexed with ?-cyclodextrin was superior to that with hydroxypropyl-?-cyclodextrin.Conclusion The inclusion of volatile oils with ?-cyclodextrin can enhance drug penetration via skin.