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A microfluidic hepatic coculture platform for cell-based drug metabolism studies.
TLDR
The results show that the flow-based coculture system is capable of clearing, with improved resolution and predictive value, compounds with high, medium, and low clearance values, and when coculture is coupled with flow, higher metabolite production rates are obtained than in static systems. Expand
Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance
TLDR
A microenvironment in which primary human and rat hepatocytes maintain a high level of metabolic competence without a long adaptation period is presented and oxygenated co-cultures demonstrate a remarkable ability to predict in vivo drug clearance rates of both rapid and slow clearing drugs with an R2 of 0.92. Expand
Evaluation of a microfluidic based cell culture platform with primary human hepatocytes for the prediction of hepatic clearance in human.
TLDR
The functionality of the liver-relevant chamber in the HmuREL device is demonstrated, and the feasibility of utilizing the system for predicting hepatic clearance is demonstrated. Expand
Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats.
TLDR
It is suggested that for rigid MPs the optimal size range required to achieve transient but highly efficiently targeting to pulmonary capillaries after IV injection is >6 microm but <10 microm in rats and that systemic administration of optimally sized MPs may be an efficient alternative to currently used inhalation-based delivery to the lung. Expand
Use of intrinsic clearance for prediction of human hepatic clearance
TLDR
Novel models incorporating flow and protein binding in the system may be the most complete models for prediction of human in vivo metabolism. Expand
Pharmacokinetic and pharmacodynamic evaluation of a novel in situ forming poly(ethylene glycol)-based hydrogel for the controlled delivery of the camptothecins.
TLDR
A 2-phase drug depot consisting of TPT-loaded liposomes entrapped in a poly(ethylene glycol) hydrogel was designed and displayed a rapid release rate and its potential value for enhancing safety and efficacy in chemotherapy. Expand
A series of alpha-amino acid ester prodrugs of camptothecin: in vitro hydrolysis and A549 human lung carcinoma cell cytotoxicity.
TLDR
Results suggest that 2d is the best candidate for a passively targeted sustained release lung delivery system, indicating a higher cell death rate at lower concentrations than CPT and the other prodrugs tested. Expand
Design and application of microfluidic systems for in vitro pharmacokinetic evaluation of drug candidates.
TLDR
Recent advancements in human hepatocyte microscale culture are highlighted, and the next generation of integrated devices, whose potential allows for the high throughput assessment of drug metabolism, distribution and pharmacokinetics are described. Expand
Metabolic Activation of the Anti-Hepatitis C Virus Nucleotide Prodrug PSI-352938
TLDR
The CYP3A4-dependent metabolism of PSI-352938 makes it an effective liver-targeted prodrug, in part accounting for the potent antiviral activity observed clinically. Expand
Pulmonary targeting microparticulate camptothecin delivery system: anticancer evaluation in a rat orthotopic lung cancer model
TLDR
CPT–Nva-MPs were able to achieve effective local lung and low systemic CPT concentrations at a dose that was 10 times lower than systemically administered CPT resulting in a significant improvement in anticancer efficacy in an orthotopic rat model of lung cancer. Expand
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