Effect of flow lamination device on aerosolized drug delivery characteristics

流动层压装置对雾化给药特性的影响

• 批准号: 10480263
• 负责人: Arevik Mosoian
• 金额: $ 25.96万
• 依托单位: SKINAXIS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480263
• 关键词: 3-Dimensional; Address; Aerosols; Alveolar; Area; Blood Circulation; Cardiac Output; Characteristics; Complex; Custom; Deposition; Destinations; Devices; Distal; Distant; Drug Delivery Systems; Drug Efflux; Drug Receptors; Enzymes; Generations; Geometry; Intercept; Length; Light; Lung; Measures; Modification; Mucous Membrane; Oral cavity; Oral mucous membrane structure; Organ; Oropharyngeal; Outcome; Pathway interactions; Pharmaceutical Preparations; Pharyngeal structure; Phase; Plum; Process; Publications; Pump; Reproducibility; Respiratory System; Role; Route; Structure; Structure of parenchyma of lung; Surface; System; Testing; Thinness; Time; Tissue Model; Tissues; absorption; aerosolized; compare effectiveness; design; fluticasone; foot; improved; prevent; prototype; side effect; square foot; wasting

The respiratory tract is one of the most attractive pathways for delivering aerosolized medications both to the lungs and to systemic circulation. It is the fastest, it's devoid of drug efflux transporters and metabolizing enzymes, it has a huge alveolar surface area (700 square feet) and a very thin mucosal barrier at alveolar level (0.1 mm), and it is perfused by 100% of cardiac output unlike any other organ or system. However there are serious challenges to efficient delivery to the lower lungs and to taking advantage of the large alveolar surface area. Up to 80% of the medication may be deposited in the upper airways, most of it in the oropharyngeal area, causing side effects and waste, and making the delivery to target areas unpredictable, inefficient, and even unreliable. Therefore overcoming the upper airway barriers such as oropharynx is important for more efficient drug delivery to the lower lungs. Among many factors involved in this process, Inertial Impaction, Turbulent Mixing and Interception are especially significant in upper airways. And a single factor that can have an impact on all 3 of them is the turbulence in the outflow of the aerosol delivery device, which has not been studied sufficiently as an independent factor. In our previous study ModiFlow has been shown to reduce turbulence in the incoming flow, and to improve the efficiency of aerosol delivery to distant targets. The objectives of the proposed study are to test the ability of ModiFlow to improve the delivery of aerosolized drugs across a spatial Barrier Imitation of the oropharynx. Objective 1: To test the ability of laminated flow from ModiFlow to improve the delivery of aerosolized Fluticasone to 3D mucosal tissue models placed within a Barrier Imitation. Objective 2: To manipulate the ModiFlow geometry to achieve the best aerosol flow characteristics at the exit of the Barrier Imitation. The Barrier Imitation is designed to mimic two main characteristics of the oropharyngeal barrier in the airways – narrowing and curving. By strategically placing 3D mucosal tissue models at the point of narrowing and at the end of curving, and by measuring the medication deposition on them, we'll be able to draw conclusions about the effects of flow lamination on overcoming these types of barriers. At the same time, detailed characterization of aerosol outflow from the distal end of the Barrier Imitation will pour light on the effects of ModiFlow geometry on it, providing valuable information for improving those effects. The outcomes of the proposed study will help better understand the effects of turbulence in the device outflow on the efficiency of aerosol delivery across upper airway barriers to the lower lungs.

呼吸道是最具吸引力的途径之一，既可以将雾化药物输送到人体，也可以输送到人体