scholarly journals A new ex vivo model for optimizing distribution of therapeutic aerosols: the (inverted) bovine urinary bladder

2017 ◽  
Vol 2 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Daniel Schnelle ◽  
Frank-Jürgen Weinreich ◽  
Janek Kibat ◽  
Marc A. Reymond
Keyword(s):  
Urinary Bladder ◽  
Bladder Neck ◽  
Quality By Design ◽  
Ex Vivo ◽  
Abdominal Cavity ◽  
Cost Effective ◽  
Preclinical Models ◽  
Ex Vivo Model ◽  
Oval Shape ◽  
Bacteriological Contamination

AbstractBackgroundDevelopment of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) requires adequate preclinical models.MethodsThe model should be easy to use, reproducible and cost-effective. It should have a volume similar to the human abdominal cavity, and an oval shape. The inner surface should be lined with serosa. The model should allow pharmacological and biological analysis, including histology. No living animals should be used.ResultsThe fresh urinary bladder is explanted from an adult bovine in the slaughterhouse. A 4-cm incision is performed into the bladder neck. The bladder can be inverted through the incision, which allows exposition of the serosa on its inner side. A balloon trocar is inserted through the incision and a ligature placed, ensuring full tightness. The therapeutic capnoperitoneum is installed. The bovine bladder has a volume somewhat smaller (2–3 L) than the human abdominal cavity (3–5 L). Costs are minimal. There is no significant bacteriological contamination. Manipulation is simple.ConclusionsThe (inverted) bovine urinary bladder is an innovative and versatile ex vivo model for optimizing drug delivery with therapeutic aerosols both onto the mucosa or the serosa. This model can be used for pharmaceutical Quality-by-Design approaches and will replace a large number of experiments in the animal.

scholarly journals Molecular characterization of a precision-cut rat lung slice model for the evaluation of antifibrotic drugs

2019 ◽  
Vol 316 (2) ◽  
pp. L348-L357 ◽  
Author(s):  
Xinqiang Huang ◽  
Li Li ◽  
Ron Ammar ◽  
Yan Zhang ◽  
Yihe Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Attrition Rate ◽  
Molecular Signature ◽  
Matrix Remodeling ◽  
Preclinical Models ◽  
Ex Vivo Model ◽  
Mesenchymal Transition

The translation of novel pulmonary fibrosis therapies from preclinical models into the clinic represents a major challenge demonstrated by the high attrition rate of compounds that showed efficacy in preclinical models but demonstrated no significant beneficial effects in clinical trials. A precision-cut lung tissue slice (PCLS) contains all major cell types of the lung and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study pulmonary fibrosis. In this study, using RNA sequencing, we demonstrated that transforming growth factor-β1 (TGFβ1) induced robust fibrotic responses in the rat PCLS model, as it changed the expression of genes functionally related to extracellular matrix remodeling, cell adhesion, epithelial-to-mesenchymal transition, and various immune responses. Nintedanib, pirfenidone, and sorafenib each reversed a subset of genes modulated by TGFβ1, and of those genes we identified 229 whose expression was reversed by all three drugs. These genes define a molecular signature characterizing many aspects of pulmonary fibrosis pathology and its attenuation in the rat PCLS fibrosis model. A panel of 12 genes and three secreted biomarkers, including procollagen I, hyaluronic acid, and WNT1-inducible signaling pathway protein 1 were validated as efficacy end points for the evaluation of antifibrotic activity of experimental compounds. Finally, we showed that blockade of αV-integrins suppressed TGFβ1-induced fibrotic responses in the rat PCLS fibrosis model. Overall, our results suggest that the TGFβ1-induced rat PCLS fibrosis model may represent a valuable system for target validation and to determine the efficacy of experimental compounds.

scholarly journals Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melica Nourmoussavi Brodeur ◽  
Kayla Simeone ◽  
Kim Leclerc-Deslauniers ◽  
Hubert Fleury ◽  
Euridice Carmona ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Therapeutic Response ◽  
Ex Vivo ◽  
Model Systems ◽  
Preclinical Models ◽  
Ex Vivo Model ◽  
In Vivo Models ◽  
3D Spheroids

AbstractEpithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level. Previous work has highlighted the discrepancies in therapeutic response between current in vitro and in vivo models. To address this, we conducted a comparison study to differentiate the carboplatin chemotherapy response across four different model systems including 2D monolayers, 3D spheroids, 3D ex vivo tumors and mouse xenograft models. We used six previously characterized EOC cell lines of varying chemosensitivity and performed viability assays for each model. In vivo results from the mouse model correlated with 2D response in 3/6 cell lines while they correlated with 3D spheroids and the ex vivo model in 4/6 and 5/5 cell lines, respectively. Our results emphasize the variability in therapeutic response across models and demonstrate that the carboplatin response in EOC cell lines cultured in a 3D ex vivo model correlates best with the in vivo response. These results highlight a more feasible, reliable, and cost-effective preclinical model with the highest translational potential for drug screening and prediction studies in EOC.

Introduction of a variable electrostatic field for targeted drug application following intraperitoneal aerosol chemotherapy (PIPAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14211-e14211
Author(s):  
Veria Khosrawipour ◽  
Haris Chaudhry ◽  
Agata Mikolajczyk ◽  
Justyna Schubert ◽  
Alessio Pigazzi ◽  
...  
Keyword(s):  
Electric Field ◽  
Aerosol Particle ◽  
Electrostatic Field ◽  
Ex Vivo ◽  
Abdominal Cavity ◽  
Drug Application ◽  
Drug Distribution ◽  
Basic Knowledge ◽  
Particle Collision ◽  
Ex Vivo Model

e14211 Background: In the treatment of Peritoneal Metastasis, the delivery of pressurized chemo-aerosols into the capnoperitoneum has been reported to show superior qualities to the application of conventional liquid chemotherapy. However, there is little basic knowledge on how aerosol particle motion within the abdominal cavity may be influenced and directed by means of an electrostatic field. This study aims to investigate aerosol motion within the abdominal cavity using an ex-vivo model. Material and Methods: All experiments were performed in an ex-vivo box as well as on postmortem swine abdomen, both established ex-vivo PIPAC models previously introduced by our research team. Extra-abdominally created, unipolar charged aerosols are introduced to the abdominal cavity. A modulated electrostatic field within the abdominal cavity is established to examine aerosol particle collision via fluorescence microscopy and photography. Results: Aerosol particle collision was observed on the peritoneum in the varying electric field. Preliminary data suggests that tissue penetration rates change with a varying electric field (p < 0.05). Drug distribution pattern showed a significant improvement with a varying electric field vs. without (p < 0.05). Conclusions: Our data suggest that extra-abdominally created, highly drug concentrated aerosol particles have the capacity to achieve high drug penetration rates in the peritoneum. The addition of a varying electric field enhances particle collision as well as significantly improves drug distribution patterns. Further studies are required to investigate the in-vivo safety and efficacy of a varying electric field and the significance of extra-abdominally created chemo-aerosols with regards to possible clinical applications.

1849: Systematic Evaluation of 21μm Thulium Laser Device for Treatment of Benign Prostatic Enlargement in an Ex-VIVO Model

2007 ◽  
Vol 177 (4S) ◽  
pp. 614-614 ◽  
Author(s):  
Gunnar Wendt-Nordahl ◽  
Stefanie Huckele ◽  
Patrick Honeck ◽  
Peter Aiken ◽  
Thomas Knoll ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Systematic Evaluation ◽  
Thulium Laser ◽  
Laser Device ◽  
Benign Prostatic Enlargement ◽  
Ex Vivo Model ◽  
Prostatic Enlargement

Porcine small intestine, a good ex vivo model to investigate absorption and metabolism of natural products

2017 ◽  
Author(s):  
J Houriet ◽  
YE Arnold ◽  
C Petit ◽  
YN Kalia ◽  
JL Wolfender
Keyword(s):  
Natural Products ◽  
Small Intestine ◽  
Ex Vivo ◽  
Ex Vivo Model

Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
In Vitro Study ◽  
Ex Vivo Model ◽  
Suitable Candidate ◽  
Significant Prolongation ◽  
High Doses ◽  
Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

EMR+: Vorstellung einer neuen endoskopischen Resektionsmethode im ex-vivo Model

2019 ◽  
Author(s):  
RF Knoop ◽  
E Wedi ◽  
V Ellenrieder ◽  
A Neesse ◽  
S Kunsch
Keyword(s):  
Ex Vivo ◽  
Ex Vivo Model

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

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