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Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution
C Khanna1, J C Waldrep, P M Anderson
1Department of Small Animal Clinical Sciences, University of Minnesota, St. Paul, USA.
The Journal of Pharmacy and Pharmacology
|November 19, 1997
Summary
Nebulized liposomes carrying interleukin 2 (IL-2) show stability and even lung deposition in dogs, suggesting a potential new immunotherapy for lung cancer and metastases.
Area of Science:
- Biotechnology
- Immunotherapy
- Drug Delivery Systems
Background:
- Interleukin 2 (IL-2) shows anti-tumour activity but is limited by toxicity.
- Local delivery of IL-2 via liposomal aerosols in the lung is a promising, non-toxic alternative.
- Previous studies in dogs showed regression of pulmonary metastases using this method.
Purpose of the Study:
- To evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes.
- To assess the stability and efficacy of liposomal IL-2 delivered as an aerosol for lung conditions.
Main Methods:
- In vitro analysis of aerosol droplet size distribution (MMAD, GSD) and liposome entrapment efficiency before and after nebulization.
- In vitro biological assessment using the CTLL-2 bioassay to confirm IL-2 activity.
- In vivo studies in dogs to evaluate pulmonary biodistribution and clearance of nebulized technetium (99mTc)-labeled IL-2 liposomes.
Main Results:
- Nebulized IL-2 liposomes exhibited a mass median aerodynamic diameter (MMAD) of 1.98 microns and a geometric standard deviation (GSD) of 2.02.
- High entrapment of IL-2 within liposomes was maintained after nebulization (90 +/- 8.9%).
- In vivo, aerosols were evenly deposited in the lungs, with retention for up to 24 hours and partial uptake by the spleen.
Conclusions:
- Nebulized interleukin 2 liposomes demonstrate physical and biological stability.
- This formulation offers a potentially effective and safe immunotherapeutic strategy for pulmonary metastases and primary lung cancers.