Lung surfactant as a drug delivery system.
Lung surfactant is a complex mixture of mainly phospholipids and proteins. The composition leads to a unique spreading effect of the surfactant as well as spontaneous vesicle formation, which may be favourable characteristics of a drug delivery system for pulmonary delivery. The aim of study was to investigate the potential use of the surfactant extract, HL10 (LeoPharma, DK) as a drug delivery system. Studies involved incorporation of hydrophilic- and amphipathic model drugs (sucrose and acylated peptides) into HL10 and elucidation of the influence of surfactant proteins on the HL10 behaviour. Results showed that HL10 vesicles did not retain sucrose indicating formation of leaky vesicles. Studying the influence of surfactant proteins on release from DPPC-liposomes showed tendencies toward a protein-induced release. Hence, the surfactant proteins may influence the membrane lipid packing and characteristics resulting in leakiness of the membranes. Incorporation of acylated peptides into HL10 depended on the chain length rendering a successful incorporation of the peptide acylated with C14-acyl chains. This study suggests that HL10 may be a promising drug delivery system for the pulmonary delivery of amphipathic drug substances, e.g. therapeutically active acylated peptides (e.g. acylated insulin).
Vermehren
C
C
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Frokjaer
S
S
Aurstad
T
T
Hansen
J
J
D000215:Acylation; D000280:Administration, Inhalation; D005452:Fluoresceins / Q000737:chemistry; D008081:Liposomes; D010455:Peptides / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013395:Sucrose / Q000737:chemistry
D005452:Fluoresceins; D008081:Liposomes; D010455:Peptides; D011663:Pulmonary Surfactants; D013395:Sucrose; C007740:fluorexon