23 research outputs found
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
Solidification of hesperidin nanosuspension by spray drying optimized by design of experiment (DoE)
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