Fluorocarbon-hybrid pulmonary surfactants for replacement therapy--a Langmuir monolayer study.
Effective additives to pulmonary surfactant (PS) preparations for therapy of respiratory distress syndrome (RDS) are being intensively sought. We report here the investigation of the effects of partially fluorinated amphiphiles (PFA) on the surface behavior of a model PS formulation. When small amounts of a partially fluorinated alcohol C(8)F(17)C(m)H(2m)OH (F8HmOH, m = 5 and 11) are added to the PS model preparation (a dipalmitoylphosphatidylcholine (DPPC)/Hel 13-5 peptide mixture) considered here, the effectiveness of the latter in in vitro pulmonary functions is enhanced. The mechanism for the improved efficacy depends on the hydrophobic chain length of the added PFA molecules. The shorter PFA, F8H5OH, when incorporated in the monolayer of the PS model preparation, promotes a disordered liquid-expanded (LE) phase upon lateral compression (fluidization). In contrast, the addition of the longer PFA, F8H11OH, reduces the disordered LE/ordered liquid-condensed (LC) phase transition pressure and promotes the growth of ordered domains (solidification). Furthermore, compression-expansion cycles suggest that F8H5OH, when incorporated in the PS model preparation, undergoes an irreversible elimination into the subphase, whereas F8H11OH enhances the squeeze-out phenomenon of the SP-B mimicking peptide, which is important in pulmonary functions and is related to the formation of a solid-like monolayer at the surface and of a surface reservoir just below the surface. F8H11OH particularly reinforces the effectiveness of DPPC in terms of minimum reachable surface tension, and of preservation of the integrated hysteresis area between compression and expansion isotherms, the two latter parameters being generally accepted indices for assessing PS efficacy. We suggest that PFA amphiphiles may be useful potential additives for synthetic PS preparations destined for treatment of RDS in premature infants and in adults.
Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
Hiromichi
H
Nakahara
Sannamu
S
Lee
Marie Pierre
MP
Krafft
Osamu
O
Shibata
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000328:Adult; D001672:Biocompatible Materials / Q000737:chemistry; D001703:Biophysics; D015195:Drug Design; D005466:Fluorocarbons / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D008422:Materials Testing; D018625:Microscopy, Atomic Force / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D010455:Peptides / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D013499:Surface Properties
D001672:Biocompatible Materials; D005466:Fluorocarbons; D010455:Peptides; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine