Comparison of Three Lipid Formulations for Synthetic Surfactant With a Surfactant Protein B Analog

Abstract

Surfactant protein B (SP-B) is an essential component of pulmonary surfactant. Synthetic dimeric SP-B(1-25) (SP-B(1-25)), a peptide based on the N-terminal domain of human SP-B, efficiently mimics the functional properties of SP-B. The authors investigated the optimum lipid composition for SP-B(1-25) by comparing the effects of natural lung lavage lipids (NLL), a synthetic equivalent of NLL (synthetic lavage lipids SLL), and a standard lipid mixture (TL) on the activities of SP-B(1-25). Surfactant preparations were formulated by mixing 2 mol% SP-B(1-25) in NNL, SLL, and TL. Calfactant, a calf lung lavage extract with SP-B and SP-C, was a positive control and lipids without peptide were negative controls. Minimum surface tension measured on a captive bubble surfactometer was similar for the three SP-B(1-25) surfactant preparations and calfactant. The effects on lung function were compared in ventilated, lavaged, surfactant-deficient rats. Oxygenation and lung volumes were consistently higher in rats treated with calfactant and SP-B(1-25) in NLL or SLL than in rats treated with SP-B(1-25) in TL. Fourier transform infrared spectra observed abnormal secondary conformations for SP-B(1-25) in TL as a possible cause for the reduced lung function. Lipid composition plays a crucial role in the in vitro and in vivo functions of SP-B(1-25) in surfactant preparations.

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

“…All surfactant preparations were formulated at a concentration of 35 mg phospholipids/ml. The composition of the synthetic phospholipid mixture was based on the lipid composition of native lung surfactant (Notter, 2000; Walther et al, 2005). Infasurf, which contains 35 mg/ml of phospholipids with 1.5% proteins, of which 0.8% is SP-B, was used as positive control and synthetic lipids alone as negative control.…”

“…Specifically, the 33-residue SP-C33 (primary sequence, NH 2 -IPSSPVHLKRLKLLLLLLLLILLLILGALLMGL-COOH) was adapted from the native porcine sequence (see above), in which the vicinal palmitoylcysteines were replaced by serines, ten valine residues were swapped with leucines and a cationic amino acid was moved from the N-terminus closer to the other positively charged residues (Johansson et al, 2003; Almlén et al, 2010). Surface activity is not only dependent on the quantity and quality of surfactant peptides in lipid mixtures, but also on the lipid constituents themselves, their interaction with surfactant peptides, and the viscosity of peptide/lipid mixtures (Tanaka et al, 1986; Walther et al, 2005; Seurynck-Servoss et al, 2007). Recent research has led us to formulate advanced SP-B and SP-C peptides in a lipid mixture that mimics the composition of native lung surfactant (Notter, 2000; Walther et al, 2005).…”

“…Surface activity is not only dependent on the quantity and quality of surfactant peptides in lipid mixtures, but also on the lipid constituents themselves, their interaction with surfactant peptides, and the viscosity of peptide/lipid mixtures (Tanaka et al, 1986; Walther et al, 2005; Seurynck-Servoss et al, 2007). Recent research has led us to formulate advanced SP-B and SP-C peptides in a lipid mixture that mimics the composition of native lung surfactant (Notter, 2000; Walther et al, 2005). …”

Surfactants: past, present and future

“…35,36 Another synthetic surfactant with SP-B fragments such as Mini-B has been tested in animal models but not yet studied in humans. 41 At least four different peptides have been shown to have clear effects both in vivo and in vitro but it is believed that a commercially produced surfactant is some time away. 42 To date it has not been possible to synthesize SP-B as it has a complex structure and although KL4 has been described as an SP-B mimic it seems to form a transmembrane a-helix making it more likely to function as an SP-C mimic.…”

New Synthetic Surfactant – How and When?

“…The physiological effects of synthetic surfactant preparations have been assessed in both premature animals with surfactant defi ciency [14,15,[19][20][21][22][23][24] and in animals with acute respiratory distress syndrome (ARDS) [11,13,[25][26][27] . Various animal models have been used but in contrast to natural surfactant preparations, synthetic surfactants seem to need positive end-expiratory pressure (PEEP) for surfactant response [15] .…”