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

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.

Differential Biodistribution of Adenoviral-Vectored Vaccine Following Intranasal and Endotracheal Deliveries Leads to Different Immune Outcomes

“…Unfortunately, to date there has been a paucity in experimental studies to compare intranasal delivery with intratracheal/endotracheal deepairway delivery in vaccine biodistribution, vaccine-specific mucosal immune responses, and protective efficacy. Although there are experimental studies that suggest intratracheal delivery of non-vaccine biologic agents including LPS and microbes to lead to deeper/wider biodistribution and/or manifestation of tissue inflammation, over the intranasal delivery method (12)(13)(14), other studies report the opposite observations (15,16). To our knowledge, there are only two experimental studies where intranasal and intratracheal vaccine delivery methods were compared but these studies did not assess vaccine biodistribution and/or both mucosal T cell immunity and protective efficacy (17,18).…”

Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice

“…In the evaluation of lung damage, our negative pressure method caused no bleeding, and only minimal damage to the alveoli ( Figure 2). Drug administration with positive pressure was used and evaluated, too [14][15][16]. However, total lung volume and the volume of alveolar air in a mouse are about 0.9 to 1.9 cm 3 and 0.5 to 1.0 cm 3 , respectively [17].…”

Carbon Nanotubes as Carriers in Drug Delivery for Non-Small Cell Lung Cancer, Mechanistic Analysis of Their Carcinogenic Potential, Safety Profiling and Identification of Biomarkers

“…However, the drug would be deposited in the respiratory tract (trachea and lungs), whereas pharyngeal aspiration leads to a likely deposition of the drug in the oral cavity. 117 Among these two routes, pharyngeal aspiration seems to be more suitable for further trials at the clinical level as it reduces the perioperative and experiment-associated deaths in animal models. 118 Since pulmonary toxicity is a key issue associated with CNTs, the usage of these materials must be closely monitored with respect to their size, functionalization, dose and route of administration for studies in animal models and for use in clinical therapeutic approaches for lung cancer.…”