New Method to Produce Liposome-Incorporated Interferon to Deliver as Aerosol

TATYANA KOTOVA (1), Anastasiya Pevneva (2)

Research Institute of Highly Pure Biopreparations, Saint-Petersburg, Russia

     Abstract Number: 809
     Last modified: May 25, 2010

Abstract
Delivery of aerosolized interferon (IFN) in a form of dry powder is a convenient therapeutic method for therapy of respiratory viral diseases. Inhalation therapy allows a rapid targeted delivery of a fewer drug dose onto the respiratory surfaces. Liposome-encapsulated IFN for oral and nasal delivery is a promising candidate for aerosol inhalation therapy. A novel method to prepare liposomal dry-powder IFN compositions for aerosolizing has been developed. Dry powder IFN aerosol delivery through oral or nasal routes provided formation of liposome-entrapped IFN on mucus membranes.
Materials and Methods
Powder mixtures containing phopholipids, glycine and recombinant IFN-alpha2b were milled with a jet mill to produce finest dry compositions of bioactive IFN. The produced particles were of 0.5 micrometers in size and of 3.5 micrometers mass-median diameter. The fine-dispersed particles deposited on mucus-secreting membranes of the respiratory tract form micronized lamellar liposome vehicles ranging from 0.5 to 15 micrometers. Particle size distribution in in the liposomes formed was characterized by light microscopy.
By data of high-pressure exclusion chromatography, the liposome entrapment efficacy was 47%. Pharmacokinetics and anti-inflammatory efficacy of the drug was studied in mice. Dry powder IFN aerosol was administered either orally or nasally by means of a dry powder inhaler (PENN CENTURY).
Results
The maximum IFN concentration was registered in mouse blood 15 minutes after administration of 1 microgram/mouse of liposomal IFN. Administration the liposome-entrapped IFN resulted in a longer-lasted blood IFN titers (6 hours) compared to 2 hours after intraperitoneal injections of IFN at the same dose. Liposome-entrapped IFN administered nasally at a dose of 1 microgram/mouse stopped the acute pulmonary inflammation in mice.