Targeting Gemcitabine hydrochloride to tumor microenvironment through stimuli-responsive Nano-conjugate: Synthesis, characterization, and in vitro assessment

2020 ◽  
Vol 60 ◽  
pp. 101981
Author(s):  
Debarupa Dutta ◽  
Lila Kanta Nath ◽  
Prithviraj Chakraborty ◽  
Debashis Dutta
Keyword(s):  
Tumor Microenvironment ◽  
Stimuli Responsive ◽  
Gemcitabine Hydrochloride ◽  
In Vitro Assessment

In vitro assessment of Labisia pumila and its constituents for interactions with CYPs, P-GP and PXR

Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
VK Manda ◽  
OR Dale ◽  
C Awortwe ◽  
Z Ali ◽  
IA Khan ◽  
...  
Keyword(s):  
In Vitro Assessment ◽  
Labisia Pumila

In Vitro Assessment of Hydroxyapatite Coating on the Surface of Additive Manufactured Ti6Al4V Scaffolds

2016 ◽  
Vol 879 ◽  
pp. 2444-2449 ◽  
Author(s):  
Ekaterina Chudinova ◽  
Maria Surmeneva ◽  
Andrey Koptioug ◽  
Irina V. Savintseva ◽  
Irina Selezneva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Nanocrystalline Structure ◽  
X Ray Diffraction ◽  
Ha Coating ◽  
Magnetron Sputter Deposition ◽  
In Vitro Assessment ◽  
Average Size

Custom orthopedic and dental implants may be fabricated by additive manufacturing (AM), for example using electron beam melting technology. This study is focused on the modification of the surface of Ti6Al4V alloy coin-like scaffolds fabricated via AM technology (EBM®) by radio frequency (RF) magnetron sputter deposition of hydroxyapatite (HA) coating. The scaffolds with HA coating were characterized by Scanning Electron microscopy, X-ray diffraction. HA coating showed a nanocrystalline structure with the crystallites of an average size of 32±9 nm. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells was studied using biological short-term tests in vitro. In according to in vitro assessment, thin HA coating stimulated the attachment and proliferation of cells. Human mesenchymal stem cells cultured on the HA-coated scaffold also formed mineralized nodules.

scholarly journals 695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Tumor Immunity ◽  
Extracellular Vesicle ◽  
The Body ◽  
Checkpoint Inhibition ◽  
Small Intestinal ◽  
The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

Elimination of three doses of gentamicin over three consecutive days using a polyacrylonitrile-derived filter: An in vitro assessment

2021 ◽  
pp. 039139882110322
Author(s):  
Frédéric J Baud ◽  
Vanessa Seif ◽  
Pascal Houzé ◽  
Jean-Herlé Raphalen ◽  
Benoît Pilmis ◽  
...  
Keyword(s):  
Life Span ◽  
Bolus Dose ◽  
Central Compartment ◽  
Daily Session ◽  
Progressive Decrease ◽  
Time Dependency ◽  
Study Results ◽  
In Vitro Assessment ◽  
The Mean

Introduction: Adsorption of gentamicin in a polyacrylonitrile filter was previously evidenced in a session lasting 6 h using the NeckEpur model. We extended the study over three consecutive days to mimic the 72-h life span of a filter. Methods: Prismaflex® monitor and ST150® filter were used in the continuous diafiltration (CDF) mode at a 2.5 L/h flowrate. The daily session started with a 6-h session of CDF. Thereafter, the 5-L central compartment was changed using a bag free of gentamicin to assess gentamicin release over the following 18 h. Experiments were repeated on Day 2 and stopped at the end of the 6-h session of CDF on Day 3. The experiment was performed in duplicate. Results: At a 2.5 L/h diafiltration flowrate, the mean daily clearances of gentamicin were 5.5, 4.0, and 3.3 L/h, respectively. The mean diafiltration and adsorption ratios in the daily elimination of gentamicin were 32/68%, 58/42%, and 88/12%, respectively. During days 1 and 2, the mean amount of gentamicin released from the ST150® filter were 14 and 34 mg, respectively. Conclusion: The pharmacokinetics of gentamicin over 3 days is strongly altered by adsorption in the same filter with a progressive decrease of elimination by adsorption, suggesting saturation of the filter. One limitation of our study results from the mode of administration using a bolus dose instead of an infusion over 30 min. Adsorption adds a clearance to those of diafiltration. The time-dependency of gentamicin clearance precludes using a constant dosage regimen over the filter’s life span.

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