scholarly journals In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters

2020 ◽  
Author(s):  
Sawittree Sahakijpijarn ◽  
Chaeho Moon ◽  
Zachary N. Warnken ◽  
Esther Y. Maier ◽  
Jennie E. DeVore ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Drug Exposure ◽  
Small Animal ◽  
Pulmonary Delivery ◽  
Dosing Regimen ◽  
Small Animal Model ◽  
Dry Powder ◽  
Promising Alternative ◽  
Thin Film Freezing

AbstractRemdesivir dry powder for inhalation was previously developed using thin film freezing (TFF). A single-dose 24-hour pharmacokinetic study in hamsters, a small animal model for SARS-CoV-2, demonstrated that pulmonary delivery of TFF remdesivir can achieve plasma remdesivir and GS-441524 levels higher than the reported EC50s of both remdesivir and GS-441524 (in human epithelial cells) over 20 hours. The half-life of GS-4412524 following dry powder insufflation was about 7 hours, suggesting the dosing regimen would be twice daily administration. Although the remdesivir-Captisol® (80/20 w/w) formulation showed faster and greater absorption of remdesivir and GS-4412524 in the lung, remdesivir-leucine (80/20 w/w) exhibited a greater Cmax with shorter Tmax and lower AUC of GS-441524, indicating lower total drug exposure is required to achieve a high effective concentration against SAR-CoV-2. In conclusion, remdesivir dry powder for inhalation would be a promising alternative dosage form for the treatment of COVID-19 disease.

scholarly journals In Vitro and In Vivo Performance of Dry Powder Inhalation Formulations: Comparison of Particles Prepared by Thin Film Freezing and Micronization

2014 ◽  
Vol 15 (4) ◽  
pp. 981-993 ◽  
Author(s):  
Yi-Bo Wang ◽  
Alan B. Watts ◽  
Jay I. Peters ◽  
Sha Liu ◽  
Ayesha Batra ◽  
...  
Keyword(s):  
Thin Film ◽  
Dry Powder Inhalation ◽  
Dry Powder ◽  
Thin Film Freezing

scholarly journals Development and Characterization of a Guinea Pig-Adapted Sudan Virus

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Small Animal ◽  
Disease Outbreak ◽  
Small Animal Model ◽  
Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

scholarly journals Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 294 ◽  
Author(s):  
Chishti ◽  
Dhamecha ◽  
Jalalpure ◽  
Dehghan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pulmonary Delivery ◽  
Small Cell ◽  
Small Cell Lung ◽  
Dry Powder ◽  
Term Delivery

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around −36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).

scholarly journals Nitroxoline as a promising alternative drug for the treatment of Lyme disease based on an in-vitro study

2021 ◽  
Author(s):  
Hector S. Alvarez-Manzo ◽  
Yumin Zhang ◽  
Wanliang Shi ◽  
Ying Zhang
Keyword(s):  
Lyme Disease ◽  
Stationary Phase ◽  
Drug Exposure ◽  
Drug Combinations ◽  
Stationary Phase Culture ◽  
Promising Alternative ◽  
Alternative Drug ◽  
Tract Infections

AbstractLyme disease (LD) is the most common vector-borne disease in USA and Europe and is caused by Borrelia burgdorferi. Despite proper treatment, approximately one fifth of patients will develop post-treatment LD syndrome (PTLDS), a condition which is poorly understood. One of the possible causes is thought to be due to persister forms of B. burgdorferi that are not effectively killed by the current Lyme antibiotics. In this study, we evaluated nitroxoline, an antibiotic used to treat urinary tract infections, for its activity against a stationary-phase culture enriched with persister forms of B. burgdorferi. Nitroxoline was found to be equivalent in activity against B. burgdorferi to cefuroxime (standard Lyme antibiotic) in different experiments. Moreover, we found that the three-drug combination cefuroxime + nitroxoline + clarithromycin eradicated 98.3% of stationary phase bacteria in the drug-exposure experiment and prevented the regrowth in the subculture study after drug exposure, as well as two-drug combinations cefuroxime + nitroxoline and clarithromycin + nitroxoline. These drug combinations should be further evaluated in a LD mouse model to assess if eradication of persister forms of B. burgdorferi in-vivo is possible and if so, whether nitroxoline could be repurposed as an alternative drug for the treatment of LD.

scholarly journals In vivo performance of an acellular disc-like angle ply structure (DAPS) for total disc replacement in a small animal model

2016 ◽  
Vol 35 (1) ◽  
pp. 23-31 ◽  
Author(s):  
John T. Martin ◽  
Dong Hwa Kim ◽  
Andrew H. Milby ◽  
Christian G. Pfeifer ◽  
Lachlan J. Smith ◽  
...  
Keyword(s):  
Animal Model ◽  
Total Disc Replacement ◽  
Small Animal ◽  
Disc Replacement ◽  
Small Animal Model

scholarly journals In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis

2017 ◽  
Vol 16 ◽  
pp. 153601211771263 ◽  
Author(s):  
Benjamin L. Franc ◽  
Sam Goth ◽  
John MacKenzie ◽  
Xiaojuan Li ◽  
Joseph Blecha ◽  
...  
Keyword(s):  
Animal Model ◽  
Pet Imaging ◽  
Inflammatory Arthritis ◽  
Small Animal ◽  
Small Animal Model
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