An in vitro model for screening penetration of ocular drug products
An in vitro model for screening penetration of ocular drug products
批准号:
10546892
负责人:
Carrie German
金额:
$30.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-09-01 至 2024-01-31
关键词:
AcetatesAnatomyAnimal ModelAnteriorAqueous HumorArchitectureBiological AssayBiological MarkersCell Culture TechniquesCell DensityCell modelCellsCollagenCorneaDataDevelopmentDevicesDexamethasoneDimensionsDrainage procedureDrug Delivery SystemsDrug TargetingEndothelial CellsEndotheliumEpithelialEpithelial CellsEvaluationExclusionExposure toExtracellular MatrixEyeEyedropsFibroblastsFilmFluoresceinFluorescein-5-isothiocyanateFluorescent DyesFormulationGoalsHealth SciencesHigh Pressure Liquid ChromatographyHumanIn VitroIndividualInjectionsLiquid substanceLiteratureMedicalMicrofabricationMicrofluidic MicrochipsMicrofluidicsModelingMolecularMolecular WeightMorphologyOcular PhysiologyOrganPenetrationPermeabilityPharmaceutical PreparationsPharmacologic SubstancePhasePhenotypePhysiologicalPhysiologyPositioning AttributePrecision therapeuticsPropertyProtocols documentationRapid screeningResearchResearch PersonnelRhodamine BStromal CellsTestingTexasTherapeuticThickTight JunctionsTimeTissuesTopical applicationUniversitiesValidationVisualizationaqueous humor flowbaseclinically relevantcommercializationconjunctivacorneal epitheliumdensitydrug discoveryexperiencefluorescein isothiocyanate dextranhydrophilicityimprovedin vitro Modelin vivoinnovationlipophilicitymultidisciplinarymultiplex assayneglectnovelophthalmic drugorgan on a chipphase 1 studyprednisoloneprototyperesponsescreeningsuccesstargeted treatment
中文摘要
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英文摘要
Project Summary/Abstract:
The overall objective of this study is to develop a novel, predictive in vitro platform for studying physiological
responses of the cellular layers of the anterior eye for therapeutics. Current in vitro models mostly rely on a single
cellular architecture of the corneal epithelium and do not mimic the in vivo physiological relevance of cell-cell
and cell-ECM interactions. In addition, they lack the capability for real-time visualization and quantitation of
cellular interactions. Animal models do not accurately represent the anatomy and physiology of the human eye.
We propose to develop and demonstrate a microfluidic-based multicellular architecture of the human cornea
based on in vivo morphological and structural parameters. Phase I will culminate with a clear demonstration on
the ability of the model to match drug penetration profiles with detailed functional characterization of the cellular
interactions and matrix development. During Phase II, we will expand the platform to incorporate additional tissue
layers such as the conjunctiva and integration with well plates for a multiplexed assay followed by further
validation against in vivo studies. A multi-disciplinary, partnership with expertise in microfluidic cell-based
assays, eye physiology and therapeutic screening with clinical relevance has been assembled to successfully
meet the research objectives. The end-product will be commercialized to pharmaceutical firms, drug research
labs and universities/non-profit centers engaged in precision therapeutics, drug discovery, and drug delivery in
the ophthalmic space.
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海外基金