Development of an Intratracheal Device to Automate Airway Drug Delivery in Animal Models

Microtek, Inc., San Diego CA

Investigators

Abstract

Project Summary / Abstract The rate of FDA approval for respiratory drugs is only 3%, much lower than drugs developed for other key therapeutic areas. The lower success rate for respiratory drugs can be attributed to the lack of innovation for developing inhaled therapeutics, especially tools needed for early drug development phases. The early assessment of a drug?s metabolism, pharmacokinetics, and toxicology (DMPK/tox) are extremely critical. Preclinical animal studies reduce the time and costs expended with the development of new drugs, thus increasing the overall success of bringing new therapies to market. However, for animal models of lung diseases, current methods for airway dosing have major limitations that greatly affect the data quality, reliability and feasibility of DMPK/tox studies. To address these limitations, our proposed project will develop a new tool for use during the preclinical stages of drug development of inhaled therapeutics. We will design and assemble a working prototype of a miniaturized intratracheal device that will produce aerosolized drug particles < 1 µm in size, which is the optimum particle size to allow even drug distribution to the distal lungs. We will then optimize the surgical procedure for implantation of the intratracheal device in the trachea of the rat model, quantify particle deposition in the lung in single and multiple dose studies, and evaluate biocompatibility of the device. Implantable catheters are commonly used for DMPK/tox testing of oral and intravenous drugs, but a technology for an implantable system for inhaled dosing is not yet available. Upon completion of Phase I, we will have a working prototype and surgical implantation methods for an intratracheal device that demonstrates efficient particle distribution in the lungs when administered via airway using single or multiple dosing strategies. This will provide the foundation for Phase II studies, in which we will evaluate costs, conduct comparative DMPK/tox studies with existing inhalation dosing methods, and demonstrate utility in disease models in order to define specific viable market sectors. The integration of a new tool for preclinical development of respiratory drugs will greatly improve the early stage drug development process for respiratory drugs and help advance therapeutics towards FDA approval.