Improved in vitro airway model to evaluate nanoparticle safety and reduce reliance on in vivo models for pre-clinical studies.

This proposal aims to develop an innovative physiologically relevant in vitro test platform which better replicates human lung tissue reduce reliance on in vivo models and streamline the drug development and testing process.

Inhalation of nebulized therapeutics offers promising opportunity for improved delivery and increased efficacy of drugs targeting conditions of the respiratory system. To optimize LNP performance a wide variety of formulations are being designed which need to be rapidly assessed in terms of functionality, performance and safety to allow promising candidate formulations to be selected and prioritised for further development.

This proposal aims to address a major limitation of the current approach identified as a significant bottleneck in the preclinical testing of novel LNP i.e., the status quo use of submerged 2D in vitro cell cultures inappropriate for realistic hazard prediction resulting in an over-reliance in vivo data.

True replacement models should be free of the animal-derived products often included in standard cell and tissue culture systems to support and sustain cell growth. The model underdevelopment in this project will aim to remove animal-derived products such as FBS and collagen and replace with human or synthetic alternatives. This platform will model more realistic clinical drug delivery, bridging gap from bench to clinic when assessing drug delivery platforms and nanomedicines and thereby reducing the reliance on in vivo studies.

Project output will be a novel prototype in vitro system for physiologically evaluation of LNP to streamline the preclinical testing of nebulized drug delivery platforms without the need to rely on in vivo models.