Surfactant as a carrier: influence of immunosuppressive agents on surfactant activity.
BACKGROUND
It has been proposed that exogenous pulmonary surfactant can be used as a drug delivery system for immunosuppressive agents to the alveolar compartment of the lung while reducing the risk of systemic toxicity. Before using this combination, however, alterations in activity of both substances should be examined. Therefore, this study investigated whether the activity of a natural derived surfactant preparation is changed after it is mixed with cyclosporine A (CsA) or rapamycin (RPM).


METHODS
A surfactant suspension was mixed with CsA or RPM and minimal surface tension of these mixtures was measured in vitro. Surfactant activity was evaluated in vivo by its capacity to restore gas exchange in an established model of surfactant deficiency in rats. CsA-surfactant, RPM-surfactant or surfactant alone was instilled intratracheally and blood gases were measured under standardized ventilatory conditions.


RESULTS
Minimal surface tension of surfactant-CsA was comparable with that of surfactant alone, whereas minimal surface tension of the surfactant-RPM mixture was increased. In vivo partial arterial oxygen pressure levels increased immediately to prelavage values after instillation of CsA-surfactant, RPM-surfactant and surfactant only and were comparable during the entire study period.


CONCLUSIONS
The activity of a naturally derived surfactant was affected when mixed with RPM but not when mixed with CsA at the used concentrations.
Gommers
D
D
Department of Anaesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands. d.gommers@erasmusmc.nl
Haitsma
J J
JJ
Lachmann
B
B
D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000032:analysis; D010313:Partial Pressure; D004364:Pharmaceutical Preparations; D011175:Positive-Pressure Respiration; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000503:physiopathology; D020123:Sirolimus / Q000494:pharmacology*; D013500:Surface Tension / Q000187:drug effects
D007166:Immunosuppressive Agents; D004364:Pharmaceutical Preparations; D011663:Pulmonary Surfactants; D016572:Cyclosporine; D010100:Oxygen; D020123:Sirolimus