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Jake' Project Page - RISE Summer 2007 |
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Intern: Jake Vestal, Chemical Engineering, North Carolina State University
Mentor: Patrick Stenger
Faculty Supervisor: Joseph Zasadzinski
Department: Chemical Engineering |
A SYNTHETIC LUNG SURFACTANT FOR TREATMENT OF RESPIRATORY DISTRESS SYNDROME
Lung surfactant (LS) is a complex mixture of lipids and proteins (SP-A, B, C
and D) that lowers surface tension in the alveoli, thereby insuring a negligible
work of breathing and preventing alveolar collapse upon exhalation. LS is
functionally inhibited during Acute Respiratory Distress Syndrome (ARDS) which
afflicts 150,000 individuals per year with a 40% mortality rate. ARDS is
characterized by elevated levels of serum proteins in the alveoli which
interfere with the formation of a LS monolayer at the alveolar air-liquid
interface. In a related disorder, Neonatal Respiratory Distress Syndrome (NRDS), premature infants which lack functional LS are successfully treated with animal derived replacement LS. Our objective is to develop a synthetic LS that resists inhibition as seen in ARDS and could also be used to treat NRDS at lower cost and avoiding possible contamination issues.
A Langmuir trough was used to study the surface properties of different LS
mixtures, their response to serum protein inhibition, and subsequent inhibition
reversal. Studies on Survanta, an animal derived replacement LS which contains
SP-B and SP-C, showed that inhibition could be reversed by treatment with
chitosan, CaCl2, and polyethylene glycol. To determine the minimum recipe that
would yield a synthetic LS resistant to inhibition, mixtures containing only
“Survanta-like” lipids and lipids with SP-B/SP-C peptide analogues were
evaluated. Addition of peptide analogs showed improved the surface performance
of lipids on a clean subphase. However, results showed that no combination of
synthetic lipids and/or peptides resists serum protein as well as Survanta.
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