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Published on: November 11, 2020
Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats
Hilliard L Kutscher1, Piyun Chao, Manjeet Deshmukh
1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Abstract:
The relationship between microparticle (MP) size and lung targeting efficiency, intra-lung distribution and retention time was systematically studied after intravenous administration of rigid fluorescent polystyrene MPs of various sizes (2, 3, 6 and 10 microm) to Sprague Dawley rats. Total fluorescence was assessed and it was found that 2 microm and 3 microm MPs readily passed through the lung to the liver and spleen while 10 microm MPs were completely entrapped in the lung for the one-week duration of the study. Approximately 84% of 6 microm MPs that were initially entrapped in the lung were cleared over the next 2 days and 15% were cleared over the remaining 5 days. A Caliper IVIS 100 small animal imaging system confirmed that 3 microm MPs were not retained in the lung but that 6 microm and 10 microm MPs were widely distributed throughout the lung. Moreover, histologic examination showed MP entrapment in capillaries but not arterioles. These studies suggest that for rigid MPs the optimal size range required to achieve transient but highly efficiently targeting to pulmonary capillaries after IV injection is >6 microm but <10 microm in rats and that systemic administration of optimally sized MPs may be an efficient alternative to currently used inhalation-based delivery to the lung.
Insights
For effective lung targeting, rigid microparticles (MPs) between 6 and 10 micrometers are optimal for intravenous delivery. Smaller MPs bypass the lungs, while larger ones cause prolonged retention.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Efficient drug delivery to the lungs is crucial for treating respiratory diseases.
- Current inhalation-based methods have limitations.
- Systemic delivery offers a potential alternative.
Purpose of the Study:
- To investigate the impact of microparticle (MP) size on lung targeting efficiency, distribution, and retention after intravenous administration.
- To determine the optimal MP size range for transient pulmonary capillary targeting.
Main Methods:
- Intravenous administration of rigid fluorescent polystyrene MPs (2, 3, 6, and 10 micrometers) to Sprague Dawley rats.
- Quantification of total fluorescence in lungs, liver, and spleen.
- Small animal imaging (Caliper IVIS 100) for distribution and retention assessment.
- Histological examination of lung tissue.
Main Results:
- 2 and 3 micrometer MPs readily passed through the lungs to other organs.
- 10 micrometer MPs were completely retained in the lungs for one week.
- 6 micrometer MPs showed significant initial lung entrapment (84%), with gradual clearance over 7 days.
- 6 and 10 micrometer MPs were widely distributed in lung capillaries, not arterioles.
Conclusions:
- Rigid MPs between 6 and 10 micrometers are optimal for transient, efficient lung targeting via intravenous injection.
- This size range facilitates entrapment in pulmonary capillaries.
- Systemic administration of optimally sized MPs presents a viable alternative to inhalation delivery for lung targeting.
