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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.

SUBMITTER: Kunda NK

PROVIDER: S-EPMC6161314 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Kunda Nitesh K NK Price Dominique N DN Muttil Pavan P

Vaccines 20180710 3

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 ...[more]

PMID: 29996506

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Project description:BackgroundTargeted delivery of gene therapy vectors to the mouse respiratory tract is often performed via intranasal or intratracheal administration; however, there can be a great deal of variability between these methods, which could potentially influence experimental results. Improving the accuracy and precision of lung delivery will not only reduce the number of animals required to detect statistically significant differences, but may reduce the variability of studies from different laboratories.ResultsHere we evaluated three different methods of adeno-associated virus (AAV) vector administration to the respiratory tract in mice (intranasal, intubation, and intratracheal injection) and discuss the advantages, challenges, and shortcomings of each. We also present a modified-intranasal delivery technique that is superior to passive administration of vector into the nares of anesthetized supine animals. Transgene expression was consistently visible in the nasal cavity, trachea, and proximal to middle aspect of all lung lobes for all four methods, whereas transgene expression was consistently observed in the most distal aspect of lung lobes only with the intubation and intratracheal injection techniques. AAV vector genome copy numbers in the lung were approximately four-fold lower in mice that received vector via intranasal administration in comparison to the other three methods of vector delivery. The modified intranasal, intubation and intratracheal injection methods of vector administration did not yield statistical differences in AAV vector genome copy numbers in the lung. With regard to reproducibility of vector distribution within and between animals, the modified-intranasal technique was superior.ConclusionOur results show that mode of AAV vector administration to the murine respiratory tract should be selected based on desired target site and skill of the researcher, and that appropriate technique selection may greatly influence experimental outcomes.

Project description:BACKGROUND:Although nanoparticles and their hazardous effects on human health are well elucidated meanwhile, inhalation and distribution of these materials in the human respiratory tract still represent partly enigmatic phenomena. Main objective of the present study was the detailed description of a mathematical method, with the help of which spatial distributions of nanoparticles deposited in the tracheobronchial tree may be visualized appropriately. METHODS:The technique is founded on a stochastic model of the bronchial network, within which inhaled particles follow individual, randomly selected trajectories. The lengths of these random paths depend on the airway-specific deposition probabilities calculated for the particles and the duration of the breath cycle. Positions of the deposited material were determined by computation of the exact lengths of individual particle trajectories and the orientation of single path segments within a Cartesian coordinate system, where the z-direction corresponds with the trachea. For a better quantification of the particle distribution and its eventual comparison with experimental data particle coordinates were fitted into a voxel grid [1 voxel = (0.467 cm)(3)]. Particle deposition is chiefly controlled by diffusive processes, whereas deposition mechanisms associated with inertia or gravity play a subordinate role. RESULTS:Deposition patterns were visualized for particles with sizes of 1, 10, and 100 nm. As clearly demonstrated by the results obtained from the modeling procedure, under normal breathing conditions 1-nm particles tend to deposit in the upper airways, whilst 10- and 100-nm particles are preferably accumulated in the airways of the central and peripheral lung. The particle dose deposited in the extrathoracic and thoracic airways within one breath cycle significantly declines with increasing particle size. CONCLUSIONS:Based on the predictions presented in this study possible consequences of nanoparticle inhalation to the health of subjects increasingly exposed to these airborne materials were discussed.

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

Publications

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

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