scholarly journals Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

2014 ◽  
Vol 25 (3) ◽  
pp. 379-387.e2 ◽  
Author(s):  
Katrin Fuchs ◽  
Pierre E. Bize ◽  
Olivier Dormond ◽  
Alban Denys ◽  
Eric Doelker ◽  
...  
Keyword(s):  
Animal Model ◽  
Antiangiogenic Agents ◽  
Drug Eluting Beads ◽  
Drug Eluting ◽  
In Vivo Pharmacokinetics

Irinotecan drug eluting beads for use in chemoembolization: In vitro and in vivo evaluation of drug release properties

2007 ◽  
Vol 30 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Rachel R. Taylor ◽  
Yiqing Tang ◽  
M. Victoria Gonzalez ◽  
Peter W. Stratford ◽  
Andrew L. Lewis
Keyword(s):  
Drug Release ◽  
In Vivo Evaluation ◽  
Drug Eluting Beads ◽  
Drug Eluting

Targeted concurrent and sequential delivery of chemotherapeutic and antiangiogenic agents to brain tissue using drug-embedded biodegradable nanofibers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13501-e13501
Author(s):  
Shih-Jung Liu ◽  
Yuan-Yun Tseng
Keyword(s):  
High Performance ◽  
In Vitro Release ◽  
Antiangiogenic Agents ◽  
Electrospinning Technique ◽  
Inflammatory Reactions ◽  
Drug Eluting ◽  
Nanofibrous Membranes ◽  
High Concentrations

e13501 Background: Glioblastoma is the most frequent and devastating primary brain tumor. Surgery followed by radiotherapy with concomitant and adjuvant chemotherapy is the standard of care for patients with glioblastoma. Chemotherapy is ineffective because of the low therapeutic levels of pharmaceuticals in tumor tissues and the well-known tumor cell resistance to chemotherapy. Methods: We developed bilayered poly[(d,l)-lactide- co-glycolide] nanofibrous membranes that enable the sequential and sustained release of carmustine [or bis-chloroethylnitrosourea (BCNU)], irinotecan, cisplatin, and combretastatin by employing an electrospinning technique. An elution method and a high-performance liquid chromatographic assay were employed to characterize the in vitro release behaviors of pharmaceuticals from the nanofibers. Results: The experimental results showed that the drug-eluting nanofibers exhibited a sequential drug release behavior, with the release of high concentrations of BCNU, irinotecan, and cisplatin from day 3, followed by the release of high concentrations of combretastatin from day 21. Biodegradable multidrug-eluting nanofibrous membranes were then placed into the cerebral cavity of rats after operative craniectomy was performed, and the in vivo release characteristics of the pharmaceuticals from the membranes were investigated. The results suggested that the nanofibrous membranes released high concentrations of pharmaceuticals for more than 8 weeks in the cerebral parenchyma of rats. A histological examination revealed the progressive atrophy of brain tissues without inflammatory reactions. Conclusions: Biodegradable drug-eluting nanofibers can be manufactured for the long-term sequential delivery of various chemotherapeutic and antiangiogenic agents in the cerebral cavity, which can potentially enhance the therapeutic efficacy of glioblastoma multiforme treatment and prevent toxic effects resulting from systemic administration.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals A Novel Infection Protocol in Zebrafish Embryo to Assess Pseudomonas aeruginosa Virulence and Validate Efficacy of a Quorum Sensing Inhibitor In Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 401
Author(s):  
Pauline Nogaret ◽  
Fatima El El Garah ◽  
Anne-Béatrice Blanc-Potard
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Animal Model ◽  
Quorum Sensing ◽  
Drug Testing ◽  
Drug Efficacy ◽  
Embryo Viability ◽  
Immersion Method ◽  
Opportunistic Human Pathogen

The opportunistic human pathogen Pseudomonas aeruginosa is responsible for a variety of acute infections and is a major cause of mortality in chronically infected cystic fibrosis patients. Due to increased resistance to antibiotics, new therapeutic strategies against P. aeruginosa are urgently needed. In this context, we aimed to develop a simple vertebrate animal model to rapidly assess in vivo drug efficacy against P. aeruginosa. Zebrafish are increasingly considered for modeling human infections caused by bacterial pathogens, which are commonly microinjected in embryos. In the present study, we established a novel protocol for zebrafish infection by P. aeruginosa based on bath immersion in 96-well plates of tail-injured embryos. The immersion method, followed by a 48-hour survey of embryo viability, was first validated to assess the virulence of P. aeruginosa wild-type PAO1 and a known attenuated mutant. We then validated its relevance for antipseudomonal drug testing by first using a clinically used antibiotic, ciprofloxacin. Secondly, we used a novel quorum sensing (QS) inhibitory molecule, N-(2-pyrimidyl)butanamide (C11), the activity of which had been validated in vitro but not previously tested in any animal model. A significant protective effect of C11 was observed on infected embryos, supporting the ability of C11 to attenuate in vivo P. aeruginosa pathogenicity. In conclusion, we present here a new and reliable method to compare the virulence of P. aeruginosa strains in vivo and to rapidly assess the efficacy of clinically relevant drugs against P. aeruginosa, including new antivirulence compounds.

In vitro AMPK activating effect and in vivo pharmacokinetics of mogroside V, a cucurbitane-type triterpenoid from Siraitia grosvenorii fruits

RSC Advances ◽  
2016 ◽  
Vol 6 (9) ◽  
pp. 7034-7041 ◽  
Author(s):  
Zuliang Luo ◽  
Feng Qiu ◽  
Kailun Zhang ◽  
Xijun Qin ◽  
Yuhua Guo ◽  
...  
Keyword(s):  
Siraitia Grosvenorii ◽  
In Vivo Pharmacokinetics

The aim of this study was to explore the anti-diabetic effects of mogroside V (MV) and its aglycone mogrol (MO), both isolated from the fruits of Siraitia grosvenorii Swingle, and to investigate the pharmacokinetic behaviors of MV and its metabolite MO in rats.

scholarly journals Photopolymerizable Injectable Cartilage Mimetic Hydrogel for the Treatment of Focal Chondral Lesions: A Proof of Concept Study in a Rabbit Animal Model

2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  
Keyword(s):  
Animal Model ◽  
Chondrogenic Differentiation ◽  
Osteochondral Lesions ◽  
Chondral Defect ◽  
Group A ◽  
Group B ◽  
Safranin O

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.

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