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:8089550
- 负责人:
- 金额:$ 22.43万
- 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 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse effectsAerosolsAffectAlbuterol SulfateAlveolarAlveolar sacAnimalsAreaArtificial nanoparticlesBenchmarkingBenignBlood 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 InfectionsRespiratory 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):由于肺部沉积效率差,药物纳米颗粒未能利用其独特的气雾剂药物递送潜力来治疗局部和全身性疾病。由于它们的亚微米尺寸,如果它们的肺沉积可以显著增加,则雾化纳米颗粒可以潜在地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药物成为可行的药物输送替代方案,充分利用纳米颗粒的潜力来增加肺部输送并减少受试者间和受试者内的变异性至关重要。该项目的目标是通过开发可以确保有效靶向纳米颗粒肺部沉积的气雾剂制剂来解决吸入纳米颗粒递送所面临的挑战。该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。工程纳米颗粒将在100 - 900 nm的尺寸范围内递送,以最小化口腔-咽喉沉积并最大化药物有效载荷。绕过上呼吸道后,肺部的自然湿度将导致吸湿性赋形剂积聚水分,增加纳米颗粒的大小和重量。颗粒的增加的空气动力学直径然后将确保增加的肺沉积而不是气雾剂的呼出,并且可以潜在地用于靶向沉积部位。为了实现这一目标,提出了以下具体目标:具体目标1:生成和表征由药物和吸湿性赋形剂组成的工程药物纳米颗粒,用于赋形剂增强生长(EEG)研究。具体目标二:使用并行CFD建模和体外测试,评估纳米颗粒生长以及工程气溶胶的上肺和下肺沉积。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递送的干粉吸入器(DPI)设计。通过递送纳米颗粒通过口-喉,然后通过赋形剂增强的吸湿性生长增加其气溶胶尺寸,预期上呼吸道沉积显著减少。由于使用了这一概念,可以实现减少剂量的可变性以及几乎完全的肺保留,这是有效使用许多下一代药物气雾剂所必需的。
公共卫生关系:与传统的递送方法相比,药物纳米颗粒的吸入可以提供许多独特的优点,用于治疗呼吸系统疾病、全身性疾病,并释放肺部递送疫苗和基因治疗的潜在用途。然而,目前用于将这些下一代纳米颗粒药物施用于肺部的方法通常效率低下,这会显着降低药物有效性,增加不必要的副作用,并使剂量难以控制。该项目的总体目标是开发一种有效输送吸入纳米颗粒的新型技术,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(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Condensational growth of combination drug-excipient submicrometer particles for targeted high-efficiency pulmonary delivery: evaluation of formulation and delivery device.
- DOI:10.1111/j.2042-7158.2012.01476.x
- 发表时间:2012-09
- 期刊:
- 影响因子:0
- 作者:Hindle M;Longest PW
- 通讯作者:Longest PW
Condensational growth of combination drug-excipient submicrometer particles for targeted high efficiency pulmonary delivery: comparison of CFD predictions with experimental results.
- DOI:10.1007/s11095-011-0596-1
- 发表时间:2012-03
- 期刊:
- 影响因子:3.7
- 作者:Longest PW;Hindle M
- 通讯作者:Hindle M
Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications.
- DOI:10.1007/s11095-013-1165-6
- 发表时间:2014-02
- 期刊:
- 影响因子:3.7
- 作者:Behara, Srinivas R. B.;Farkas, Dale R.;Hindle, Michael;Longest, P. Worth
- 通讯作者:Longest, P. Worth
Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols.
数值模型以表征组合药物和吸湿性纳米粒子气溶胶的大小增加。
- DOI:10.1080/02786826.2011.566592
- 发表时间:2011-01-01
- 期刊:
- 影响因子:0
- 作者:Longest PW;Hindle M
- 通讯作者:Hindle M
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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
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:
9889160 - 财政年份:2018
- 资助金额:
$ 22.43万 - 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
- 资助金额:
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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:
$ 22.43万 - 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
- 资助金额:
$ 22.43万 - 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:
8080129 - 财政年份:2011
- 资助金额:
$ 22.43万 - 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
- 资助金额:
$ 22.43万 - 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:
8445248 - 财政年份:2011
- 资助金额:
$ 22.43万 - 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:
7976385 - 财政年份:2010
- 资助金额:
$ 22.43万 - 项目类别:
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