Excipient enhanced aerosol particle formulations and inhaler development for impr
赋形剂增强气雾剂颗粒配方和吸入器开发以提高效果
基本信息
- 批准号:7976385
- 负责人:
- 金额:$ 18.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse effectsAerosolsAffectAlbuterol SulfateAlveolarAlveolar sacAnimalsAreaArtificial nanoparticlesArtsBenchmarkingBenignBlood CirculationBlood capillariesBreathingBudesonideBypassCaliberCharacteristicsChargeControl GroupsCystic FibrosisDepositionDevelopmentDevicesDisadvantagedDoseDrug Delivery SystemsDrug FormulationsEconomicsEffectivenessElectrostaticsEngineeringEnsureEvaluationExcipientsExhalationExhibitsExuberaFutureGene DeliveryGenerationsGeneric DrugsGoalsGrowthGuidelinesHumanHumidityIn VitroInhalation TherapyInhalatorsInsulinJointsLungLung diseasesMalignant neoplasm of lungMedicineMethodsModalityModelingModificationMorphologyOralOral cavityOutcomeParticle SizePeptidesPerformancePharmaceutical PreparationsPharmacologic SubstancePharyngeal structurePhysical condensationPowder dose formProcessPropertyRelative (related person)Research ActivityRespiratory SystemRespiratory tract structureRouteSiteSodium ChlorideSolutionsSurfaceSystemSystemic diseaseSystemic infectionTechniquesTechnologyTestingTracheobronchialUpper respiratory tractVaccinesWaterWeightWettabilityXylitolaerosolizedbasecapillarydesigngene therapyimprovedin vitro testingin vivoinsightiterative designnanoparticlenanosizednew technologynext generationparticleperformance testspublic health relevanceresearch studyrespiratorysimulationsmall moleculesolid statesugarwastingwater vapor
项目摘要
DESCRIPTION (provided by applicant): Pharmaceutical nanoparticles have failed to leverage their unique aerosol drug delivery potential for the treatment of local and systemic diseases due to poor pulmonary deposition efficiency. Because of their submicrometer size, aerosolized nanoparticles can potentially overcome many of the problems associated with traditional inhalation therapy if their lung deposition can be significantly increased. In order to make many next- generation inhaled medications a viable drug delivery alternative, utilizing the full potential of nanoparticles for increased lung delivery and decreased inter- and intra-subject variability are of critical importance. The goal of this project is to address the challenges facing inhaled nanoparticle delivery by developing aerosol formulations that can ensure efficient targeted nanoparticle lung deposition. This concept consists of engineering dry powder nanoparticle aerosols containing a model drug and a hygroscopic excipient. The engineered nanoparticles will be delivered in the size range of 100 - 900 nm in order to minimize mouth- throat deposition and maximize drug payload. After bypassing the upper airways, the natural humidity in the lungs will cause the hygroscopic excipient to accumulate water, increasing the size and weight of the nanoparticles. The increased aerodynamic diameter of the particles will then ensure increased lung deposition rather than exhalation of the aerosol and can potentially be used to target the site of deposition. To achieve this goal, the following specific aims are proposed: Specific Aim 1: Generate and characterize engineered pharmaceutical nanoparticles consisting of drug and a hygroscopic excipient to be used in the excipient enhanced growth (EEG) studies. Specific Aim 2: Evaluate nanoparticle growth in conjunction with upper and lower lung deposition of the engineered aerosol using concurrent CFD modeling and in vitro testing. Specific Aim 3: Evaluate and optimize a dry powder inhaler (DPI) design for nanoparticle dispersion and delivery using a quantitative analysis and design approach. By delivering nanoparticles past the mouth-throat and then increasing their aerosol size through excipient enhanced hygroscopic growth, significant reductions in upper airway deposition are expected. As a result of using this concept, reduced variability in dose can be achieved together with near full lung retention, which are necessary for the effective use of many next-generation pharmaceutical aerosols.
PUBLIC HEALTH RELEVANCE: The inhalation of pharmaceutical nanoparticles may offer many unique advantages compared to conventional delivery methods for the treatment of respiratory diseases, systemic conditions and to unlock the potential use of the lungs to deliver vaccines and gene therapy. However, the current methods used to administer these next-generation nanoparticle pharmaceuticals to the lungs are often inefficient, which can significantly reduce drug effectiveness, increase unwanted side effects, and make dosing difficult to control. The overall goal of this project is to develop a novel technology for the efficient delivery of inhaled nanoparticles that minimizes deposition in the mouth and throat while maximizing deposition in the lungs.
描述(由申请人提供):由于肺沉积效率低,药物纳米颗粒未能利用其独特的气雾剂药物输送潜力来治疗局部和全身疾病。由于其亚微米尺寸,如果能够显著增加肺沉积,雾化纳米颗粒有可能克服与传统吸入疗法相关的许多问题。为了使许多下一代吸入性药物成为可行的给药替代方案,充分利用纳米粒增加肺部给药的潜力并减少受试者间和受试者内的变异性是至关重要的。该项目的目标是通过开发能够确保有效靶向纳米颗粒肺沉积的气雾剂配方来解决吸入性纳米颗粒输送面临的挑战。这一概念包括含有模型药物和吸湿性赋形剂的工程干粉纳米颗粒气雾剂。这种经过改造的纳米颗粒将在100-900纳米的尺寸范围内输送,以最大限度地减少口腔喉咙沉积和最大限度地增加药物有效载荷。在绕过上呼吸道后,肺部的自然湿度会导致吸湿性赋形剂积水,从而增加纳米颗粒的大小和重量。颗粒的空气动力学直径的增加将确保增加肺沉积,而不是气雾剂的呼出,并可能被用于定位沉积的位置。为了实现这一目标,提出了以下具体目标:具体目标1:制备和表征由药物和吸湿性赋形剂组成的工程药物纳米粒,用于赋形剂增强生长(EEG)研究。具体目标2:利用并行的CFD建模和体外测试,评估纳米颗粒的生长与工程气溶胶的上、下肺沉积。具体目标3:使用定量分析和设计方法评估和优化用于纳米颗粒分散和输送的干粉吸入器(DPI)设计。通过将纳米颗粒送入口腔-咽喉,然后通过赋形剂增强吸湿性生长增加其气雾剂尺寸,预计可显著减少上呼吸道沉积。使用这一概念的结果是,可以减少剂量的可变性,同时实现近乎完全的肺滞留,这是许多下一代药物气雾剂有效使用所必需的。
与公共卫生相关:与传统的给药方法相比,吸入药物纳米粒可能提供许多独特的优势,用于治疗呼吸道疾病、全身疾病,并释放肺部提供疫苗和基因治疗的潜在用途。然而,目前用于肺部给药的下一代纳米药物往往效率低下,这可能会显著降低药物有效性,增加不想要的副作用,并使剂量难以控制。该项目的总体目标是开发一种新的技术,以有效地提供吸入的纳米颗粒,最大限度地减少口腔和喉咙中的沉积,同时最大限度地增加肺部的沉积。
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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Michael Hindle其他文献
Michael Hindle的其他文献
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{{ truncateString('Michael Hindle', 18)}}的其他基金
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9889160 - 财政年份:2018
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$ 18.39万 - 项目类别:
High Efficiency Delivery of Surfactant Aerosols to Infants without Intubation
无需插管即可高效向婴儿输送表面活性剂气雾剂
- 批准号:
10089470 - 财政年份:2018
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High Efficiency Inhalation Delivery of Tobramycin for Children with Cystic Fibrosis
妥布霉素高效吸入治疗囊性纤维化儿童
- 批准号:
9236359 - 财政年份:2017
- 资助金额:
$ 18.39万 - 项目类别:
High Efficiency Inhalation Delivery of Tobramycin for Children with Cystic Fibrosis
妥布霉素高效吸入治疗囊性纤维化儿童
- 批准号:
10200865 - 财政年份:2017
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$ 18.39万 - 项目类别:
Effective Delivery of Pharmaceutical Aerosols during Non-Invasive Ventilation
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8080129 - 财政年份:2011
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$ 18.39万 - 项目类别:
Effective Delivery of Pharmaceutical Aerosols during Non-Invasive Ventilation
无创通气期间药物气雾剂的有效输送
- 批准号:
8269658 - 财政年份:2011
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Effective Delivery of Pharmaceutical Aerosols during Non-Invasive Ventilation
无创通气期间药物气雾剂的有效输送
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8445248 - 财政年份:2011
- 资助金额:
$ 18.39万 - 项目类别:
Excipient enhanced aerosol particle formulations and inhaler development for impr
赋形剂增强气雾剂颗粒配方和吸入器开发以提高效果
- 批准号:
8089550 - 财政年份:2010
- 资助金额:
$ 18.39万 - 项目类别:
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