Evaluating the Controlled Release Properties of Inhaled Nanoparticles Using Isolated, Perfused, and Ventilated Lung Models

Abstract

Polymeric nanoparticles meet the increasing interest for inhalation therapy and hold great promise to improve controlled drug delivery to the lung. The synthesis of tailored polymeric materials and the improvement of nanoparticle preparation techniques facilitate new perspectives for the treatment of severe pulmonary diseases. The physicochemical properties of such drug delivery systems can be investigated using conventional analytical procedures. However, the assessment of the controlled drug release properties of polymeric nanoparticles in the lung remains a considerable challenge. In this context, the isolated lung technique is a promising tool to evaluate the drug release characteristics of nanoparticles intended for pulmonary application. It allows measurements of lung-specific effects on the drug-release properties of pulmonary delivery systems.Ex vivomodels are thought to overcome the common obstacles ofin vitrotests and offer more reliable drug release and distribution data that are closer to thein vivosituation.

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…In such a setup, aerosolized drug delivery during controlled ventilation of the lung allows investigation of the effect of different ADD patterns on pharmacokinetics and biological endpoints. (98) On the next lower level of biological complexity, slices of the lung may closely mimic the 3D microenvironment of the lung and capture organ-specific mechanisms of disease for days to weeks. A unique feature of organ slices is the combination of biomimetic tissue characteristics and direct tissue access for four-dimensional confocal live tissue imaging techniques allowing for simple assessment of molecular and functional characteristics of the sample.…”

Characterization of lung-delivered in-situ forming controlled release formulations

“…The drug absorption characteristics from the in‐situ forming controlled release formulations were evaluated in an IPL model as previously described [6,17–19]. Experiments were performed in accordance with the German Law on the Use and Protection of Laboratory Animals ( TierSchG ).…”

Inhaled sildenafil nanocomposites: lung accumulation and pulmonary pharmacokinetics

“…However, certain drugs of conventional inhalation therapy results in a short duration of drug action at the target site. So, recent strategy is the development of pulmonary controlled release formulations with the aim of improving patient compliance 9,10 .…”

“…At this point, nanotechnology by applying biodegradable polymers, opens new perspectives in the design of novel drug delivery systems intended for local treatment of respiratory diseases 9 . Polymeric nanoparticles can be delivered to the lung by dry powder aerosolization and can affect duration and intensity of pharmacological effect.…”

“…Polymeric nanoparticles can be delivered to the lung by dry powder aerosolization and can affect duration and intensity of pharmacological effect. Also, very small size of nanoparticles facilitates penetration into the airway mucosa 9,11,12 .…”