Restoring the activity of serum-inhibited bovine lung extract surfactant (BLES) using cationic additives.
In this work four cationic additives were used to improve the surface activity of lung surfactants, particularly in the presence of bovine serum that was used as a model surfactant inhibitor. Two of those additives were chitosan in its soluble hydrochloride form with average molecular weights of 113kDa and 213kDa. The other two additives were cationic peptides, polylysine 50kDa and polymyxin B. These additives were added to bovine lipid extract surfactant (BLES) and the optimal additive-surfactant ratio was determined based on the minimum surface tension upon dynamic compression, carried out in a constrained sessile drop (CSD) device in the presence of 50 microl/ml serum. At the optimal ratio all the BLES-additive mixtures were able to achieve desirable minimum surface tensions. The optimal additive-surfactant ratios for the chitosan chlorides are consistent with a previously proposed patch model for the binding of the anionic lipids in BLES to the positive charges in chitosan. For the peptides, the optimal binding ratios were consistent with ratios established previously for the binding of these peptides to monolayers of anionic lipids. The optimal formulation containing these peptides were able to reach low minimum surface tension in systems containing 500 microl/ml of serum, matching the effectiveness of a lung surfactant extract that had not undergone post-separation processes and therefore contained all its proteins and lipids (complete lung surfactant).
Acosta
Edgar J
EJ
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada. edgar.acosta@utoronto.ca
Policova
Zdenka
Z
Lee
Simon
S
Dang
Andrew
A
Hair
Michael L
ML
Neumann
A Wilhelm
AW
D000818:Animals; D002412:Cations; D002417:Cattle; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011112:Polymyxin B / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D044967:Serum / Q000378:metabolism*; D013500:Surface Tension / Q000187:drug effects; D013696:Temperature; D014020:Tissue Extracts / Q000378:metabolism*
D002412:Cations; D011663:Pulmonary Surfactants; D014020:Tissue Extracts; D011107:Polylysine; D048271:Chitosan; D011112:Polymyxin B