Pulmonary surfactant and drug delivery: development of novel carriers for improving distribution, targeting, uptake and cross-talk in the deep lungs

肺表面活性剂和药物递送：开发新型载体以改善肺部深处的分布、靶向、摄取和串扰

• 批准号: 471650084
• 负责人: Dr. Alberto Hidalgo, Ph.D.
• 金额: --
• 依托单位: Institut für Funktionelle Anatomie
• 依托单位国家: 德国
• 项目类别: WBP Position
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/471650084?language=en
• 关键词: Pulmonary; surfactant; drug; delivery; development

Respiratory diseases cause an enormous health burden worldwide and suppose increasing healthcare costs affecting the economies of all countries. A key obstacle limiting the prospects to face on the new therapeutic challenges is the lack of efficient respiratory drug delivery strategies enhancing targeting, pharmacokinetics and pharmacodynamics. The current paradigm in pulmonary drug delivery relies on aerosols that deposit, depending on their aerodynamic properties, directly on the place of action of absorption. However, these strategies are not very efficient to reach the distal airways. In this respect, we propose a new perspective that may change the current respiratory drug delivery paradigm. Pulmonary surfactant (PS), a lipid-protein material essential for the process of breathing, offers novel opportunities for pulmonary drug delivery. After deposition in the upper or conductive airways, PS-based formulations may continue to distal areas by “surfing” over the respiratory air-liquid interface, efficiently reaching and transporting therapeutics to the alveolar region of the lung. Combining biophysical, cellular and pre-clinical in vivo studies, this project aims to address a new drug delivery strategy targeting the lungs from a multidisciplinary and translational perspective: the interfacial delivery. The project is divided into three different Working Packages (WP) that account for designing PS-based therapeutic formulations (WP1), targeting human alveolar cells (WP2), and performing a pre-clinical study on mice (WP3).

呼吸道疾病在全球范围内引起巨大的健康伯恩，并假设影响所有国家经济的医疗保健成本不断增加。限制新治疗挑战前景的关键障碍是缺乏有效的呼吸药输送策略，从而增强了靶向，药代动力学和药效学。肺部药物输送中的当前范式取决于沉积的气溶胶，具体取决于其空气动力学特性，直接取决于抽象的作用地。但是，这些策略并不是到达远端气道的效率。在这方面，我们提出了一种新的观点，该观点可能会改变当前的呼吸道药物递送范例。肺表面活性剂（PS）是一种脂质 - 蛋白质材料，对呼吸过程必不可少，为肺部药物递送提供了新的机会。在上部或导电气道中沉积后，基于PS的公式可以通过在呼吸空气界面上“冲浪”来继续远端区域，从而有效地到达并运输到肺的Alloolar区域。该项目结合了体内研究的生物物理，细胞和临床前研究，旨在解决一种新的药物输送策略，该策略是从多学科和翻译的角度来实现肺部的：界面递送。该项目分为三个不同的工作包（WP），这些工作包（WP）是设计基于PS的治疗配方（WP1），靶向人肺泡细胞（WP2），并对小鼠进行临床前研究（WP3）。