Respiratory Tract Deposition and Distribution Pattern of Microparticles in Mice Using Different Pulmonary Delivery Techniques.

Nitesh Kunda,Dominique Price,Pavan Muttil

doi:10.3390/vaccines6030041

Abstract

Pulmonary delivery of drugs and vaccines is an established route of administration, with particulate-based carriers becoming an attractive strategy to enhance the benefits of pulmonary therapeutic delivery. Despite the increasing number of publications using the pulmonary route of delivery, the lack of effective and uniform administration techniques in preclinical models generally results in poor translational success. In this study, we used the IVIS Spectrum small-animal in vivo imaging system to compare the respiratory tract deposition and distribution pattern of a microsphere suspension (5 µm) in mice after 1, 4, and 24 h when delivered by oropharyngeal aspiration, the Microsprayer® Aerosolizer, and the BioLite Intubation System, three-widely reported preclinical inhalation techniques. We saw no significant differences in microsphere deposition in whole body images and excised lungs (at 1, 4, and 24 h); however, the three-dimensional (3D) images showed more localized deposition in the lungs with the MicroSprayer® and BioLite delivery techniques. Further, oropharyngeal aspiration (at 1 h) showed microsphere deposition in the oral cavity, in contrast to the MicroSprayer® and BioLite systems. The studies shown here will allow researchers to choose the appropriate pulmonary delivery method in animal models based on their study requirements.

Highlights

Inhalational delivery of therapeutics has been utilized for many centuries around the world
We evaluated three widely reported preclinical inhalation techniques: the MicroSprayer® Aerosolizer (Penn-Century, Wyndmoor, PA, USA; recently discontinued), the BioLite Intubation System (Braintree Scientific, Braintree, MA, USA), and oropharyngeal aspiration
The lung has been used as a target organ to deliver vaccines and immunotherapeutics because it is the primary port of entry for many infectious pathogens [1]

Summary

Introduction

Pulmonary delivery is a non-invasive route of administration with many benefits, such as a large lung surface area for absorption (100 m2 ), elevated blood flow, rapid absorption, and avoidance of hepatic first-pass metabolism [1,2]. These benefits of pulmonary drug and vaccine delivery outweigh the challenges which include, most notably, mucociliary clearance, physiological barriers limiting deep lung deposition, formulation difficulties, and variability in inhaler use [2]. One promising strategy to further improve pulmonary therapeutics is to formulate drugs and vaccines in particulate carriers such as micro- and nano-particles to offer benefits such as higher therapeutic efficacy with lower doses, enhanced immune responses due to particle uptake by antigen presenting cells (APCs), improved drug and antigen loading, and adjuvant properties of particulate

Methods

Results

Conclusion