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Methods in Experimental Pathology of Pulmonary Vasculature
Published in Joan Gil, Models of Lung Disease, 2020
Paul Davies, Daphne deMello, Lynne M. Reid
In the technique of Reid et al., a solution of gelatin at 60°C containing a suspension of barium sulfate is injected into the vasculature at a pressure of 100 cm H2O generated by an air pump. This is sufficiently high to fill patent beds from the most hypertensive subjects and, by distending vessels to maximal or near maximal levels, counteracts the effects of tone. The composition of the mixture prevents it from passing through the capillary bed. It is thus an excellent marker for the arterial or venous sides of the circulation, pulmonary or bronchial, depending on the vessel into which it was introduced. After the vascular bed is injected, the lung is fixed by intratracheal instillation at a transpulmonary pressure sufficient to inflate it to maximal volume (e.g., 25 cm H2O). The gelatin quickly polymerizes. One major advantage is that the barium sulfate contained in the mixture allows the injected bed to be radiographed and the angiograms are useful in analyzing the degree of filling and showing the branching pattern and the sites of blockage.
Genosomes for Gene Delivery and Transfection
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
Genosomes can be administered by the same routes as liposomal formulations. These include systemic, local (intramuscular, intratumor, subcutaneous, intracerebral, intra-articular, etc.), and intraperitoneal injection, as well as topical (skin and inhalation of an aerosol, intratracheal instillation) application. Regular and double-balloon catheters can be used as well for direct delivery to arterial walls. The portal artery can be used for the delivery of complexes to the liver. Currently, studies concentrate on a tail vein injection in mice and rats, intratracheal administration, direct injection into muscle and tumors, as well as inhalation of a genosome aerosol. Especially for aerosol administration and genetic vaccination larger animals were also used, from rabbits, dogs, monkeys, primates, and sheep to cows and horses. When performing such studies, researchers must be aware that not only geometry of the airways but also various cell proportions and their physiology can cause significant changes between species and, for instance, high expression in the sheep lung cannot be generalized to other animal species.
Respiratory System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Tom P. McKevitt, David J. Lewis
Intratracheal instillation and oropharyngeal aspiration are used, particularly in the early stages of compound development. Intratracheal instillation involves the insertion of a dosing catheter to the distal trachea under anesthesia and delivery of a bolus dose (typically 200 μl) that is aspirated into the lungs. Oropharyngeal aspiration involves the placement of a bolus dose at the base of the extended tongue in an anesthetized animal. The dose is then aspirated into the lungs. Both techniques are an efficient use of test material, and intratracheal instillation bypasses the difficulties of estimating deposited lung dose encountered upon standard inhalation delivery. Distribution of the test article in the lungs following intratracheal dosing may, however, not be uniform, with the potential for hot spots of compound deposition and associated pathology.
Dual antitubercular drug loaded liposomes for macrophage targeting: development, characterisation, ex vivo and in vivo assessment
Published in Journal of Microencapsulation, 2021
Priya Shrivastava, Laxmikant Gautam, Rajeev Sharma, Devyani Dube, Sonal Vyas, Suresh P. Vyas
The relative antitubercular activity of the formulations was assessed in MtbH37Ra infected Balb/c mice. The animals were divided into various groups and equivalent drug(s) in various formulations were administered. Intratracheal instillation protocol was followed as reported previously with a slight modification i.e. in place of nebulisation, intratracheal instillation was used (Pandey et al. 2003, Wijagkanalan et al. 2008). Accordingly, the free drug(s) solution equivalent to the dose of RIF (12 mg/kg body weight) and INH (10 mg/kg body weight) was instilled daily for 30 days, whereas, equivalent dose contained in liposomes (non mannosylated and mannosylated) was instilled every 10th day up to 30th day (i.e. 3 doses) and relative therapeutic efficacy was measured as residual bacterial count assessed microbiologically and CFU were counted.
The early onset and persistent worsening pulmonary alveolar proteinosis in rats by indium oxide nanoparticles
Published in Nanotoxicology, 2020
Sung-Hyun Kim, Soyeon Jeon, Dong-Keun Lee, Seonghan Lee, Jiyoung Jeong, Jong Sung Kim, Wan-Seob Cho
Six-week-old specific-pathogen-free female Wistar rats were purchased from Samtako (Gyeonggi-do, Korea) and acclimatized for 7 days before experimentation. All animal experiments were performed according to guidelines approved by the Institutional Animal Care and Use Committee at Dong-A University (DIACUC-2017-16-26). The rats were housed in the micro-ventilation cage system (Three-shine, Daejeon, Korea) with controlled conditions (22 ± 1 °C, 50 ± 10% humidity, and 12-h dark/light cycle). Food and water were supplied ad libitum. The intratracheal instillation was performed according to the previously described method (Jeong et al. 2015). Briefly, rats were deeply anesthetized with isoflurane (Piramal Critical Care, Bethlehem, PA) using a rodent anesthesia system (VetEquip, Pleasanton, CA). A 16-gauge plastic catheter (BD Biosciences, San Diego, CA) was intubated into the trachea and the suspension of NPs was instilled at a volume of 500 μL.
Innovative preclinical models for pulmonary drug delivery research
Published in Expert Opinion on Drug Delivery, 2020
Stephan Ehrmann, Otmar Schmid, Chantal Darquenne, Barbara Rothen-Rutishauser, Josue Sznitman, Lin Yang, Hana Barosova, Laurent Vecellio, Jolyon Mitchell, Nathalie Heuze-Vourc’h
Bulk liquid application without aerosolization is the most widely used experimental method mainly due to ease-of-use, delivery efficiency, and dose control. Liquid may be delivered through intranasal or oropharyngeal aspiration as well as through intratracheal instillation. For intranasal aspiration a drop of liquid is pipetted onto the nostril of an animal [98]; with the next breath, the liquid is sucked into the nasal cavity where it turns into a spray which is transported via the airflow into the lungs [98]. Similarly, for oropharyngeal aspiration, a drop of liquid is pipetted into the back of the pharynx or the glottis from where it is sucked into the trachea. For intratracheal instillation, animals are orotracheally intubated, a liquid-containing syringe is connected to the intubation cannula and the bulk liquid is squirted directly into the trachea.