Effect of PEGylation on the Stability of Liposomes During Nebulisation and in Lung Surfactant

Abstract

Oral inhalation of anticancer drugs or drug delivery system is a novel therapeutic approach in the treatment of lung cancer and requires formulations which are sufficiently stabile during nebulisation and subsequent interaction with the surfactant lining of the lungs. In this study, we assessed the stability of plain and PEGylated transferrin-conjugated liposomes after nebulisation using two different nebulisers (i.e., air-jet and ultrasonic type). Furthermore, the integrity of the liposomal membranes was assessed after incubation in commercial lung surfactant solutions (Alveofact<snm>®</snm>). All liposomal formulations showed no significant changes in their size after nebulisation, independent of the type of nebuliser or the liposomal formulation, respectively. However, PEGylation was of advantage when it came to interactions between liposomes and the surfactant lining of the lungs. PEGylated liposomes were significantly more stable and retained >80% of their drug load over 48 h, which is more than sufficient time for the drug carriers to be taken up by transferrin receptor over-expressing cancer cells in the lung. In conclusion, PEGylated and plain Tf-conjugated liposomes are stable enough to undergo nebulisation in the course of an inhalational therapy, but PEG-stabilisation results in a higher degree of membrane integrity in lung surfactant.