Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

Summary

During development of drugs for pulmonary delivery, it is necessary to evaluate pharmacokinetics and efficacy in an animal model. We present a method to build a disposable aerosol dispersion system from of-the-shelf components that can be used to administer intrapulmonary dry powder aerosol to rodents.

Abstract

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered. This precludes conducting early feasibility studies as insufficient drug is available at the research or early development stage to support the dose delivery requirements for conventional aerosol delivery systems. When designing an aerosol drug product, aerodynamic performance can relate directly to delivery efficiency and efficacy. Dispersion of powder into an aerosol requires energy input sufficient to overcome interparticulate forces, and particle engineering approaches can substantially improve aerosol performance. We have developed a dispersion system (dosator) which can aerosolize engineered dry powder aerosols efficiently for the purpose of direct pulmonary insufflation, dispersion into an exposure system or generation for analytical purposes.

Introduction

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically ¹. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered ².

This precludes conducting early feasibility studies as insufficient drug is ava....

Protocol

1. Preparation of Components of the Dosators

1. Perforate the bottom of a 0.5 mL polypropylene microcentrifuge tube by drilling or by simply grinding or cutting off the bottom with a grinding wheel or a sharp pair of scissors. Ensure that the hole is in the center and is no more than 2 mm in diameter and no less than 1 mm in diameter (Figure 1).
2. Perforate the top of the microcentrifuge tube. Using a #22 drill bit (approximately 4 mm in diameter), drill a hole in the center of the cap. This results in a hole that will fit a slip-tip syringe (Figure 1).
3. Prepare the fine screens to be inserted into the microc....

Results

For easily dispersible powders such as those spray-dried with the intent for pulmonary delivery ^5,8,9, the dosators deliver a bolus dose out of the device. There are many applications for the dosators, including in vitro particle characterization, direct intrapulmonary administration in live animals, and aerosol generation for passive inhalation systems.

Discussion

The dispersion from the dosators was suitable for animals to receive a therapeutic dose via passive nose-only respiration, indicating a large proportion of aerosol dispersed to primary particle size. These dosators can be used for endotracheal administration, in vitro evaluation of powder performance, and general purpose dry powder aerosol dispersion for analytical or efficacious experiments. If used for intrapulmonary delivery, it is important to use an appropriate volume of air for the species chosen, as over-.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
0.5 mL microcentrifuge tube	VWR	89000-026
High-Volume Particle-Filtering Stainless Steel Wire Cloth, Woven, 304 Stainless Steel, 60 x 60 Mesh, .0045" Wire Diameter	McMaster Carr	9230T44
Stainless Steel Dispensing Needle, Straight, 18 Gauge, 1" Long	McMaster Carr	75165A676	Any luer-fit needle will suffice
Cotton balls	McMaster Carr	54845T16
Parafilm M® Laboratory Film	VWR	100229-550
Black-Oxide High-Speed Steel Jobbers' Drill Bit, Wire Gauge 22, 3-1/8" Overall Length, 1.8" Drill Depth, 135Deg Point	McMaster Carr	2901A195