Abstract
CHF5633 is a novel synthetic clinical pulmonary surfactant preparation composed by two phospholipid species, dipalmitoyl phosphatidylcholine (DPPC) and palmitoyloleoyl phosphatidylglycerol (POPG), and synthetic analogues of the hydrophobic surfactant proteins SP-B and SP-C. In this study, the interfacial properties of CHF5633 in the absence and in the presence of inhibitory serum proteins have been assessed in comparison with a native surfactant purified from porcine lungs and with poractant alpha, a widely used clinical surfactant preparation. The study of the spreading properties of CHF5633 in a Wilhelmy balance, its ability to adsorb and accumulate at air-liquid interfaces as revealed by a multiwell fluorescence assay, and its dynamic behavior under breathing-like compression-expansion cycling in a Captive Bubble Surfactometer (CBS), all revealed that CHF5633 exhibits a good behavior to reduce and sustain surface tensions to values below 5 mN/m. CHF5633 shows somehow slower initial interfacial adsorption than native surfactant or poractant alpha, but a better resistance to inhibition by serum proteins than the animal-derived clinical surfactant, comparable to that of the full native surfactant complex. Interfacial CHF5633 films formed in a Langmuir-Blodgett balance coupled with epifluorescence microscopy revealed similar propensity to segregate condensed lipid domains under compression than films made by native porcine surfactant or poractant alpha. This ability of CHF5633 to segregate condensed lipid phases can be related with a marked thermotropic transition from ordered to disordered membrane phases as exhibited by differential scanning calorimetry (DSC) of CHF5633 suspensions, occurring at similar temperatures but with higher associated enthalpy than that shown by poractant alpha. The good interfacial behavior of CHF5633 tested under physiologically meaningful conditions in vitro and its higher resistance to inactivation by serum proteins, together with its standardized and well-defined composition, makes it a particularly useful therapeutic preparation to be applied in situations associated with lung inflammation and edema, alone or in combined strategies to exploit surfactant-facilitated drug delivery.
Highlights
Www.nature.com/scientificreports of exogenous materials to these patients, has been so far prevented
Formation and performance of surface films under more physiological conditions were assessed in the Captive Bubble Surfactometer (CBS)
We have investigated on both the functional and structural features of a new synthetic clinical pulmonary surfactant, CHF
Summary
Www.nature.com/scientificreports of exogenous materials to these patients, has been so far prevented In this line, enough amounts of clinical surfactants with well-defined composition and resistance to inactivation are required to treat adult injured lungs. CHF5633 (CHF) is a synthetic surfactant, which has completed a phase I clinical trial[8] and is currently under phase II It is a simple mixture which contains 98.3% lipids by mass in a 1:1 ratio of dipalmitoyl phosphatidylcholine (DPPC):palmitoyloleoyl phosphatidylglycerol (POPG), and 1.7% by mass of analogues for both hydrophobic pulmonary surfactant proteins, 0.2% of an analogue of SP-B and 1.5% of an analogue of SP-C9,10. Previous efforts have been done to obtain a synthetic surfactant as simple as possible but with a proper biophysical performance to treat patients (revised in[7]). Particular attention has been paid to the biophysical behaviour of the surfactants in the presence of serum or albumin, well-established inhibitors of surfactant performance[13]
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