Inhalation Therapy Platform for Coronavirus Infection Treatment
治疗冠状病毒感染的吸入治疗平台
基本信息
- 批准号:10364186
- 负责人:
- 金额:$ 63.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-17 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAlveolar MacrophagesAlveolusAnti-Inflammatory AgentsAntibioticsAntimicrobial ResistanceAntiviral AgentsAzithromycinBiological AvailabilityBiomedical EngineeringBurkholderia pseudomalleiCOVID-19COVID-19 outbreakCOVID-19 pandemicCOVID-19 therapeuticsCaregiversCellsCessation of lifeClinicalCoronavirusCoronavirus InfectionsCrowdingDevelopmentDiffusionDisadvantagedDiseaseDisease modelDoseDoxycyclineDrug CombinationsDrug KineticsDrug TargetingDrug resistanceEffectivenessEnzymesEpithelialEpithelial CellsEvolutionExhibitsFormulationFutureGap JunctionsHistologicHospitalizationHospitalsHumanIndividualInflammatory ResponseInhalationInhalation DeviceInhalation Drug AdministrationInhalation TherapyIntensive CareLeadLeadershipLifeLigandsLungLung infectionsMannoseMediatingMelioidosisMethodsModalityModelingNebulizerOralOrganPatientsPeptidesPharmaceutical PreparationsPolymersPopulationPositioning AttributeProceduresProdrugsPropertyPulmonologyRampResearch PersonnelResistanceResourcesRodent DiseasesRodent ModelSARS-CoV-2 variantSafetyScheduleSolubilitySourceStructureTestingTherapeuticTimeToxic effectTularemiaVaccinationVaccinesVariantViralViral Load resultViral reservoirWorkalveolar epitheliumbacterial resistanceclinical developmentcoronavirus diseasecoronavirus therapeuticsdensitydesigndisadvantaged populationdrug candidateexperienceimprovedliquid chromatography mass spectrometrymacrophagemonomermouse modelnovel vaccinespandemic diseasepathogenpharmacokinetics and pharmacodynamicspolymerizationpreclinical developmentprophylacticpulmonary agentsremdesivirrespiratory pathogenresponseuptakeviral entry inhibitor
项目摘要
PROJECT SUMMARY/ABSTRACT
The newly emerged SARS-CoV-2 coronavirus has demonstrated the deadly threat of pulmonary pathogens in
an exposure-naïve world with no existing vaccines or therapeutics at the ready. The development of effective
vaccines has provided key prophylactic products, but therapeutics remain important due to slow and incomplete
world coverage, along with emergence of resistance variants. There is especially a need for polytherapy
platforms that can be deployed in formats amenable to global settings, and need for platforms that can be rapidly
developed against future pulmonary threats. This project aims to develop a versatile inhalable therapeutic
platform against COVID-19 disease and future coronaviruses. It is designed for nebulizer and distributable
inhalation devices to maximize drug activity in the lung. The polymeric prodrug platform has recently shown
strong potentiating activity against highly lethal and antimicrobial-resistant bacterial lung infections. These
“drugamer” therapeutics improve the activity of pulmonary drugs by targeting them to specific cell reservoirs in
the lung with high and extended dosing profiles. The inhalable platform could be used by infected patients before
hospitalization, to reduce administrations by patients in crowded hospitals, and contribute a key distributable
therapeutic and prophylactic modality that is needed to protect caregivers and disadvantaged populations. The
proposal is structured around 4 specific aims: (1) Develop remdesivir and baracitinib as first drugamer candidates
that exploit the lung macrophage as a reservoir to achieve extended dosing, as well as targeted designs against
lung epithelium viral reservoirs. Remdesivir and baracitinib prodrug monomers will be developed with
corresponding drugamer designs with mannose and peptide targeting ligands for the alveolar macrophage and
epithelial compartments, respectively; (2) Characterize and optimize the drugamer candidates by criteria of how
they load drugs into the lung macrophage and epithelial cells with extended dosing times. This will lead to better
understanding of how to optimize targeting strategies in the lung for future antiviral development. The
mechanisms will be studied by using quantitative LC-MS pharmacokinetics characterization and safety
characterization using lung inflammatory response assessments; (3) Assess and optimize drugamer activity
against SARS-CoV-2 using the hACE2 mouse model. Viral load and survival studies will be used to characterize
and develop optimized drugamer and drugamer combinations that could in the future be carried forward into
preclinical development. Compared to current formulation approaches, the drugamers exhibit higher drug
loading, the ability to co-formulate widely varying drugs for polytherapy, and individually tailorable drug PK
profiles that minimize burst release. The modularity of the platform, together with scaled and rapid manufacturing
response attributes, will allow diverse incorporation of other drugs as combinations. These favorable platform
attributes motivate this project to develop a new repertoire of current and future coronavirus therapeutic products.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Patrick S. Stayton其他文献
Design and development of polymers for gene delivery
用于基因递送的聚合物的设计与开发
- DOI:
10.1038/nrd1775 - 发表时间:
2005-07-01 - 期刊:
- 影响因子:101.800
- 作者:
Daniel W. Pack;Allan S. Hoffman;Suzie Pun;Patrick S. Stayton - 通讯作者:
Patrick S. Stayton
生体温度およびpHに応答するナノゲルの作製と評価
生物温度和pH响应纳米凝胶的制备与评价
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
大村朋幸;荏原充宏;Allan S. Hoffman;Patrick S. Stayton - 通讯作者:
Patrick S. Stayton
Correction to “Mannosylated STING Agonist Drugamers for Dendritic Cell-Mediated Cancer Immunotherapy”
对“用于树突状细胞介导的癌症免疫治疗的甘露糖化 STING 激动剂药物”的更正
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:18.2
- 作者:
Dinh Chuong Nguyen;Kefan Song;Simbarashe Jokonya;Omeed Yazdani;D. Sellers;Yonghui Wang;Abm Zakaria;S. Pun;Patrick S. Stayton - 通讯作者:
Patrick S. Stayton
The effect of the foreign body response on drug elution from subdermal delivery systems
异物反应对皮下给药系统药物洗脱的影响
- DOI:
10.1016/j.biomaterials.2025.123110 - 发表时间:
2025-06-01 - 期刊:
- 影响因子:12.900
- 作者:
Simone Capuani;Nathanael Hernandez;Jocelyn Nikita Campa-Carranza;Nicola Di Trani;Takuma Yoshikawa;Marco Farina;Ashley L. Joubert;Camden A. Caffey;Alessio Simeone;Seo Won Cho;Patrick S. Stayton;Corrine Ying Xuan Chua;Alessandro Grattoni - 通讯作者:
Alessandro Grattoni
188. Internalization of Novel Delivery Vector TAT-Streptavidin into Human Cells
- DOI:
10.1016/j.ymthe.2006.08.212 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Johanna Rinne;Brian Albarran;Juulia Jylhävä;Teemu O. Ihalainen;Pasi Kankaanpää;Vesa P. Hytönen;Patrick S. Stayton;Markku S. Kulomaa;Maija Vihinen-Ranta - 通讯作者:
Maija Vihinen-Ranta
Patrick S. Stayton的其他文献
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{{ truncateString('Patrick S. Stayton', 18)}}的其他基金
Inhalation Therapy Platform for Coronavirus Infection Treatment
治疗冠状病毒感染的吸入治疗平台
- 批准号:
10687201 - 财政年份:2021
- 资助金额:
$ 63.44万 - 项目类别:
Inhalation Therapy Platform for Coronavirus Infection Treatment
治疗冠状病毒感染的吸入治疗平台
- 批准号:
10490888 - 财政年份:2021
- 资助金额:
$ 63.44万 - 项目类别:
Intracellular delivery of proapoptotic peptide drugs for the treatment of cancer
用于治疗癌症的促凋亡肽药物的细胞内递送
- 批准号:
8302741 - 财政年份:2012
- 资助金额:
$ 63.44万 - 项目类别:
Intracellular delivery of proapoptotic peptide drugs for the treatment of cancer
用于治疗癌症的促凋亡肽药物的细胞内递送
- 批准号:
8456142 - 财政年份:2012
- 资助金额:
$ 63.44万 - 项目类别:
Biofunctional Polymers for Intracellular Drug Delivery
用于细胞内药物输送的生物功能聚合物
- 批准号:
7102726 - 财政年份:2003
- 资助金额:
$ 63.44万 - 项目类别:
Biofunctional Polymers for Intracellular Drug Delivery
用于细胞内药物输送的生物功能聚合物
- 批准号:
6932389 - 财政年份:2003
- 资助金额:
$ 63.44万 - 项目类别:
Biofunctional Polymers for Intracellular Drug Delivery
用于细胞内药物输送的生物功能聚合物
- 批准号:
7466737 - 财政年份:2003
- 资助金额:
$ 63.44万 - 项目类别:
Biofunctional Polymers for Intracellular Drug Delivery
用于细胞内药物输送的生物功能聚合物
- 批准号:
7900666 - 财政年份:2003
- 资助金额:
$ 63.44万 - 项目类别:
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