Nanokristalle & beladene poröse Silika für erhöhte orale Bioverfügbarkeit

1\. CapsMorph® technology for oral drug delivery Hesperidin CapsMorph® was produced by loading drug in mesoporous silica material, AEROPERL® 300 Pharma, through wetness impregnation method. First hesperidin was dissolved in DMSO or a mixture of DMSO and Tween 80, then the solution was added to AEROPERL® 300 Pharma. Hesperidin was encapsulated in mesopores in amorphous state after the elimination of DMSO due to the spatial-constraint effect of tiny mesopores and the H-bonds generated between drug and carrier. It was proven that the addition of Tween 80 decreased the kinetic saturation solubility of hesperidin in CapsMorph® compared with the formulation without Tween 80. Compared to the raw material and nanocrystals, hesperidin CapsMorph® showed significantly improved kinetic saturation solubility and increased dissolution rate. 2\. Controlled release of poorly water soluble drug by different loadings in AEROPERL® 300 Pharma The wetness impregnation method was applied to monitor the loading capacity of AEROPERL® 300 Pharma in terms of hesperidin. When more than 57.5% of hesperidin was loaded in AEROPERL® 300 Pharma crystalline characteristics of hesperidin were detected via XRD and DSC, implying the over-load of the system. Hesperidin CapsMorph® with different drug loadings were obtained by applying different times of drug loading processes. It turned out that with the increase of drug loading, the dissolution rate was decreased. Via adjusting the drug loading, the drug in-vitro release rate can be controlled. CapsMorph® with 28.6 wt.% of drug loading showed a complete dissolution behavior within a short period. This may be due to that the low drug loading causes a large drug exposed surface area. When the loaded drug in the mesopores was increased, the exposed drug surface area was decreased because of the overlay of drug molecules. 3\. Tablet performance of amorphous rutin in AEROPERL® 300 Pharma Rutin CapsMorph® powder was produced by loading rutin in AEROPERL® 300 Pharma. The kinetic saturation solubility of rutin CapsMorph® powder in water was measured as 4.93 ± 0.15 mg/ml, approx. 133-fold of rutin raw material. Rutin CapsMorph® tablet and raw material tablet were prepared by adding Explotab® as a disintegrate and compared with rutin market tablet. Rutin CapsMorph® tablet showed lower hardness compared with the rutin market tablet. Due to the large exposed surface area of amorphous drug the rutin CapsMorph® tablet displayed the fastest dissolution rate, almost 95.6 ± 6.9% of drug was released in water within 5 minutes. However, for the rutin market tablet only 42.7 ± 0.8% of drug release was observed in water after 3 hours. 4\. Application of DoE on the solidification of nanosuspension via spray drying method Wet bead milling was performed to produce hesperidin nanosuspension and poloxamer 188 was used as a stabilizer. The solidification of hesperidin nanosuspension through spray drying was investigated systematically by the principle of design of experiment (DoE). PVP K25 was added in nanosuspension as a protectant before spray drying. MODDE 9 was applied to design the experiment. After the screening modeling and the response surface modeling, the inlet temperature of spray drying and the concentration of PVP K25 were considered as the most important factors affecting the re-dispersion of nanocrystals. Well re-dispersed nanocrystals were obtained when 5.5% of PVP K25 was added in hesperidin nanosuspension and the spray drying was performed under 100 oC of inlet temperature. Spray drying was demonstrated to be an ideal method to realize the solidification of nanosuspension.1 CapsMorph®-Technologie für die orale Wirkstoffapplikation Hesperidin CapsMorph® wurde mit der Imprägniermethode durch Beladung von mesoporösem Silica, AEROPERL® 300, hergestellt. Zunächst wurde Hesperdin in DMSO oder einer Mischung von DMSO und Tween 80 gelöst, im nächsten Schritt dann diese Hesperidin-Lösung zu AEROPERL® 300 gegeben. Nach Evaporation des DMSO präzipitierte Hesperidin in den Mesoporen und wurde darin im amorphen Zustand verkapselt aufgrund der räumlichen Einschränkung in den kleinen Mesoporen (2-50 nm) und den H-Bindungen zwischen Wirkstoff und Porenoberfläche des Trägers. Es konnte gezeigt werden, daß der Zusatz von Tween 80 die kinetische Sättigungslöslichkeit im Vergleich zur Formulierung ohne Tween 80 erniedrigte. Im Vergleich zum Rohmaterial (Pulver) und Nanokristallen zeigte Hesperidin CapsMorph® eine signifikant erhöhte kinetische Sättigungslöslichkeit und erhöhte Lösungsgeschwindigkeit. 2 Kontrollierte Freisetzung von schwer wasserlöslichen Wirkstoffen aus AEROPERL® 300 Pharma durch Variation des Beladungsgrades Unter Verwendung der Imprägniermethode wurde die Beladungskapazität von AEROPERL® 300 Pharma für die Beladung mit Hesperidin untersucht. Wenn eine Beladung von mehr als 57,5% mit Hesperidin erfolgte, konnten kristalline Eigenschaften mit Röntgenstrukturanalyse (X-ray) und DSC detektiert werden, was die Überladung des Systems anzeigte. Hesperidin CapsMorph® mit unterschiedlichen Beladungen wurde kontrolliert erzeugt durch die Anwendung unterschiedlicher Beladungsprozeduren. Es zeigte sich, daß mit ansteigender Beladung die Lösungsgeschwindigkeit abnahm. Dadurch kann durch Variation des Beladungsgrades die in-vitro Freisetzungsgeschwindigkeit von Arzneistoffen kontrolliert werden. CapsMorph® mit 28,6% Beladung zeigte eine komplette Freisetzung innerhalb sehr kurzer Zeit. Dies kann möglicherweise darauf zurückgeführt werden, dass bei niedriger Beladung eine relative große Wirkstoffoberfläche in den Poren in Kontakt mit dem Lösungsmittel steht (keine geschlossenen Poren). Mit ansteigender Beladung nimmt die Oberfläche in den Poren durch zusätzliche Einlagerung von Wirkstoff ab. 3 Tablettierung von amorphem Rutin in AEROPERL® 300 Pharma Rutin CapsMorph® Pulver wurde hergestellt durch beladen von AEROPERL® 300 Pharma. Die kinetische Sättigungslöslichkeit von Rutin CapsMorph® Pulver in Wasser betrug 4,93 ± 0,15 mg/ml, rund 133-fach höher als die von Rutinpulver. Rutin CapsMorph® Tabletten, und zum Vergleich Tabletten mit Rutinpulver, wurden durch Zugabe von Explotab® als Zerfallshilfsmittel hergestellt, und anschließend mit einem Rutin Marktprodukt verglichen. Die Rutin CapsMorph® Tablette zeigte eine geringere Härte als die Tablette im Markt. Aufgrund der großen Oberfläche des amorphen Rutin und seiner verbesserten Löseeigenschaften zeigte die Rutin CapsMorph® Tablette die höchste Auflösungsgeschwindigkeit, fast 95,6 ± 6,9% des Wirkstoffes wurde innerhalb von 5 Minuten freigesetzt. Im Gegensatz dazu setzte die Tablette vom Markt nur 42,7 ± 0,8% über einen Zeitraum von 3 Stunden frei. 4 Anwendung von DOE zur Optimierung der Sprühtrocknung von Nanosuspensionen Nanosuspensionen von Hesperidin wurden mit der Rührwerkskugelmühle hergestellt, wobei Poloxamer 188 als Stabilisator benutzt wurde. Sprühtrocknung wurde eingesetzt zur Überführung der wässrigen Nanosuspension in ein Pulver. Die Parameter der Sprühtrocknung wurden mittels “design of experiment” (DOE) optimiert. PVP K25 wurde den Nanosupensionen als “Protectant” zur Minimierung der Kristallaggregation zugesetzt. MODDE 9 wurde zur Plaung der Experimemte verwendet. Nach erfolgtem “screening modeling” und “response surface modeling” wurden die Einlasstemperatur beim Sprühtrocknen und die Konzentration an PVP K25 als die bestimmenden Parameter für die anschließende Redispergierbarkeit der Nanokristalle identifiziert. Gut redispergierbare Nanokristalle wurden erhalten nach Zugabe von 5,5% an PVP K25 zur Nanosuspension und anschließendem Sprühtrocknen mit 100 °C Einlasstemperatur. Sprühtrocknung ist eine ideale Methode zur Trocknung

The Efficacy of Brucea javanica Oil Emulsion Injection as Adjunctive Therapy for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

Purpose. To evaluate the efficacy of Brucea javanica oil emulsion injection (BJOEI) in patients with advanced non-small-cell lung cancer (NSCLC) during chemotherapy. Method. Electronic database of EMBASE and PubMed and the conference proceeding of ASCO, CNKI, CBMdisc, VIP, and Wanfang database were searched to select RCTs comparing BJOEI plus chemotherapy with chemotherapy alone in the treatment of advanced NSCLC, until June 1, 2016. Two reviewers independently performed the analysis according to the inclusion and exclusion criteria. Review Manager 5.3 and STATA 12.0 were employed for data analysis. Result. Twenty-one studies including 2234 cases were included. The pooled result indicated that there were significant differences in ORR (RR=1.25; 95% CI: 1.14–1.36; P<0.00001), improvement of QOL (RR=1.87; 95% CI: 1.63–2.15; P<0.00001), nausea and vomiting (RR=0.67; 95% CI: 0.46–0.98; P=0.04), leukopenia (RR=0.63; 95% CI: 0.52–0.75; P<0.00001), but there was no difference in thrombocytopenia (RR=0.78; 95% CI: 0.49–1.23; P=0.29). Begg’s funnel plot and Egger’s test indicated that no publication bias was found. The sensitivity analysis suggested the stability of the pooled result. Conclusion. The addition of BJOEI can enhance efficacy, improve QOL, and decrease incidence of nausea and vomiting and leukopenia for advanced NSCLC patients. However, higher quality RCTs are needed to further confirm this finding

CASB: a concanavalin A‐based sample barcoding strategy for single‐cell sequencing

Abstract Sample multiplexing facilitates single‐cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost‐effective strategies are rather limited. Here, we reported a concanavalin A‐based sample barcoding strategy (CASB), which could be followed by both single‐cell mRNA and ATAC (assay for transposase‐accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, and high sensitivity in detecting doublets by three applications: 1) CASB followed by scRNA‐seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound‐specific heterogeneous response; 2) CASB together with both snATAC‐seq and scRNA‐seq to illustrate the IFN‐γ‐mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN‐γ response; and 3) combinatorial indexing by CASB, which demonstrated its high scalability

Influence of aromatic heterocycle of conjugated side chains on photovoltaic performance of benzodithiophene-based wide-bandgap polymers

Extensive efforts have been focused on the study of wide-band gap (WBG) polymers due to their important applications in multiple junction and ternary blend organic solar cells. Herein, three WBG copolymers named PBDT(X)-T1 (X = O, S, Se) were synthesized based on the benzodithiophene (BDT) donor unit and 1,3-bis(5-bromothiophen-2-yl)-5,7-bis(2-ethylhexyl)-4H,8H-benzo[1,2-c:4,5-c???]dithiophene-4,8-dione (T1) acceptor unit. Different aromatic heterocycle groups (furan, thiophene and selenophene) were introduced to modify the BDT unit to investigate the influence of conjugated side chains on the photovoltaic properties of conjugated polymers. Photophysical properties, electrochemistry, charge transport and crystalline properties of the polymers were studied to discuss the role of chalcogen atoms on the performance of conjugated polymers. Solar cells based on these three WBG copolymers were fabricated. Among them, the PBDT(Se)-T1-based solar cell shows the best photovoltaic performance with the highest power conversion efficiency (PCE) of 8.52%, an open-circuit voltage (Voc) of 0.91 V, and a high fill factor (FF) of 72%. The high crystallinity and preferential face-on orientation in the blend film partially explain the superior photovoltaic performance achieved in PBDT(Se)-T1-based solar cells. The results indicate the important role of chalcogen atoms in conjugated side chains and that high photovoltaic performance can be realized through side chain engineering of BDT-based WBG conjugated polymers.clos

Additional file 1: of Enhanced Photocatalytic Activity of the Carbon Quantum Dot-Modified BiOI Microsphere

Supplementary data associated with this article. (DOCX 17472 kb