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Poly-(D,L-lactic acid) microspheres incorporating histological dyes for intra-pulmonary histopathological
D J Armstrong1, P N Elliott, J L Ford
1Drug Delivery and Pharmaceutical Technology Research Group, School of Pharmacy, Liverpool John Moores University, UK.
Abstract:
Polylactic acid (PLA) microspheres incorporating fluorescein as a histological marker have been prepared and used as a model for the testing of inhaled PLA microspheres (2-5 microns) in the lung. PLA microspheres (20 mg) were delivered to rabbits in the form of a saline nebulization. The distribution pattern within the pulmonary system showed that the fluorescein-labelled microspheres were distributed about the four lobes in discrete groups. The comparative numbers of these groups showed a trend towards a reduced concentration in the lower lobes. Subsequent histological examination revealed that the microsphere-treated lungs had been significantly damaged after 24 h. Histological damage was assessed in terms of pulmonary haemorrhage, eosinophilia and neutrophil infiltration.
Insights
Inhaled polylactic acid (PLA) microspheres caused significant lung damage in rabbits, with reduced concentrations in lower lobes. Histological analysis revealed pulmonary hemorrhage, eosinophilia, and neutrophil infiltration 24 hours post-administration.
Area of Science:
- Biomaterials Science
- Pulmonary Toxicology
- Drug Delivery Systems
Background:
- Polylactic acid (PLA) microspheres are utilized in various biomedical applications.
- Assessing the pulmonary effects of inhaled PLA microspheres is crucial for safety evaluations.
- Fluorescein serves as a reliable histological marker for tracking microsphere distribution.
Purpose of the Study:
- To evaluate the distribution and pulmonary effects of inhaled polylactic acid (PLA) microspheres in a rabbit model.
- To investigate the histological damage induced by PLA microspheres in lung tissue.
Main Methods:
- Preparation of fluorescein-labeled PLA microspheres (2-5 microns).
- Administration of PLA microspheres (20 mg) via saline nebulization to rabbits.
- Analysis of microsphere distribution across lung lobes and subsequent histological examination of lung tissue.
Main Results:
- Fluorescein-labeled PLA microspheres distributed in discrete groups across the four lung lobes.
- A trend of reduced microsphere concentration was observed in the lower lung lobes.
- Significant histological damage, including pulmonary hemorrhage, eosinophilia, and neutrophil infiltration, was evident 24 hours post-inhalation.
Conclusions:
- Inhaled PLA microspheres can cause substantial acute histological damage to lung tissue.
- The distribution pattern suggests potential regional variations in pulmonary response to inhaled microspheres.
- Further research is warranted to understand the long-term implications and safety profiles of inhaled PLA microspheres.