Name of Excellence: Recovery of Activity of Albumin Inhibited Exogenous Surfactant Preparations by Hydrophilic Polymers
Author: Prof. Zdravko Lalchev, DSc, Corresponding member of BAS, Department of Biochemistry
Research domain: Biophysics
| Prof. Zdravko Lalchev, DSc, Corresponding member of BAS is a lecturer at the Faculty of Biology, Department of Biochemistry. He graduated from the Faculty of Chemistry of Sofia University (1972). PhD in 1984; Associate Professor in 1988; DSc in 2004; Professor of Biophysics (2005); Corresponding member of the Bulgarian Academy of Sciences (2012). Guest-professor at the Technical University of Denmark; Tokai University; University of New Jersey; Institute of Food Research, Norwich; and University of East Anglia, UK. Founder and Head of Laboratory of Model Membranes at the Faculty of Biology (since 1988). He received the fi rst award of the Union of Scientists in Bulgaria for scientific achievements (2011) and the Grand Award for Science and Research of Sofia University for 2012. | |
| Prof. Zdravko Lalchev, DSc |
Research team: Prof. Zdravko Lalchev, DSc, Corresponding member of BAS; Prof. Christian Vassilieff, DSc; Associate Prof. Georgi Georgiev, PhD; Associate Prof. Albena Jordanova, PhD; PhD students of Medical Faculty of Sofia University, etc.
In Acute Respiratory Distress Syndrome (ARDS) the concentration of albumin in the alveolar fl uid reaches 25–100 mg ml−1. Therapy of ARDS in clinical practice includes lifesaving exogenous surfactant preparations (ESP) which effects in vivo are inhibited by albumin.
The objective of the project is to study in vitro the effect of hydrophilic polymers on the surface properties of albumin inactivated ESP by two complementary models, which mimic the air/water interface of the alveoli: Langmuir monolayers and foam films.
Two commercially available ESP for ARDS treatment (Curosurf and Survanta), and four hydrophilic polymers (PEG, dextran, PVP, hyaluronic acid-HA) were systematically studied in presence and absence of albumin. Successive compression–expansion cycles of monolayers revealed that minimal surface tension ≤10 mN m−1 for Survanta is achieved with PEG, PVP, and HA, while for Curosurf - with dextran, PVP, and HA (Fig. 1).
Fig. 1. Values of minimal surface tension from ten successive compression/expansion cycles of adsorption monolayers formed by Survanta: pure, in the presence of BSA (2 mg/ml) or included in the triple mixtures ESP/BSA/polymer. Experiments are performed at the threshold surfactant concentration for black foam fi lm formation, electrolytes: 0.15 M NaCl plus 2.5 mM CaCl2, pH 6.87.0, 25єC. The polymer concentrations are equal to the clinically used ones reported in the literature. Inhibited Survanta is repaired by PEG and PVP (but not by dextran) while inhibited Curosurf is repaired by dextran and PVP (but not by PEG)
Foam film experiments with Curosurf and Survanta revealed the ability of the polymers to decrease the effect of albumin inhibition in restoring the formation of stable and homogeneous black films - by Survanta with PEG, PVP and HA, while by Curosurf - with dextran, PVP and HA (Figs. 2, 3).
Fig.2. Inhibition of Survanta by BSA in foam films, and the impact of hydrophilic polymers on the recovery of surfactant surface properties in foam films by the triple mixture surfactant/BSA/ hydrophilic polymer. PEG and PVP are efficient (but not dextran)
Fig. 3. IInhibition of Curosurf by BSA in foam films, and the impact of hydrophilic polymers on the recovery of surfactant surface properties in foam films by the triple mixture surfactant/BSA/ hydrophilic polymer. Dextran and PVP are efficient (but not PEG)
Kinetic data of spontaneous foam fi lm thinning of thick films (h > 500 nm) were interpreted to obtain values of the disjoining pressure. An interesting change from repulsion to attraction of the two foam film monolayers in presence of the polymers was observed at a film thickness of appr. 100 nm (Fig. 4).
Fig. 4. Disjoining pressure in foam films of Curosurf and Curosurf/BSA/Polymers from film thinning data by the dynamic method of Scheludko-Exerowa. The theoretical (red/green/blue) dependences of Пvdw (attraction) on film thickness are calculated with different values of the Hamaker constant or function. The experimentally determined additional attraction at h≤100 nm can be attributed to “depletion” osmotic pressure
The obtained original results were explained by depletion attraction (quantitatively estimated by us) overcoming the steric repulsion of monolayers in presence of polymers.
The main conclusion of the study that the inactivation of ESP is prevented by specific hydrophilic polymers could be used for improving the quality of lifesaving ESP.
This study was supported by a research project (No DO02-107/2008) of the Ministry of Education and Science.