Behavior of thin liquid films from aqueous solutions of a pulmonary surfactant in presence of corticosteroids

Todorov, R.; Exerowa, D.; Alexandrova, L.; Platikanov, Dimo; Terziyski, Ivan; Nedyalkov, M.; Pelizzi, Nicola; Salomone, Fabrizio

doi:10.1016/j.colsurfa.2016.09.024

Cited by 6 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We presume that corticosteroid molecules, somehow similar to cholesterol, a natural component of pulmonary surfactant in most species, likely integrate into phospholipid surfactant membranes simulating the way how cholesterol distributes between liquid-disordered and liquid-ordered regions. , Pulmonary surfactant composition and structures are prepared to accept a certain proportion of steroids, at least up to ca. 15–20% (by weight with respect to phospholipids), without any impairment in surfactant function, as it has been demonstrated in the past. − Our drug incorporation experiments determined that both natural surfactant and clinical surfactants like Poractant alfa or CHF5633 can readily incorporate up to 10% by weight of corticosteroids, constituting a very efficient potential vehicle to convert the drugs into a deliverable formulation. Porcine natural surfactant already contains around 5–8% of cholesterol, while Poractant alfa and CHF5633 are produced in the absence of cholesterol.…”

Section: Discussionsupporting

confidence: 55%

Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pulmonary surfactant is a crucial system to stabilize the respiratory air-liquid interface. Furthermore, pulmonary surfactant has been proposed as an effective method for targeting drugs to the lungs. However, few studies have examined in detail the mechanisms of incorporation of drugs into surfactant, the impact of the presence of drugs on pulmonary surfactant performance at the interface under physiologically meaningful conditions, or the ability of pulmonary surfactant to use the air-liquid interface to vehiculise drugs to long distances. This study focuses on the ability of pulmonary surfactant to interfacially vehiculize corticosteroids such as beclomethasone dipropionate (BDP) or Budesonide (BUD) as model drugs. The main objectives have been to (a) characterize the incorporation of corticosteroids into natural and synthetic surfactants, (b) evaluate whether the presence of corticosteroids affects surfactant functionality, and (c) determine whether surfactant preparations enable the efficient spreading and distribution of BDP and BUD along the air-liquid interface. We have compared the performance of a purified surfactant from porcine lungs and two clinical surfactants: Poractant alfa, a natural surfactant of animal origin extensively used to treat premature babies, and CHF5633, a new synthetic surfactant preparation currently under clinical trials. Both, natural and clinical surfactants spontaneously incorporated corticosteroids up to at least 10% by mass with respect to phospholipid content. The presence of the drugs did not interfere with their ability to efficiently adsorb into air-liquid interfaces and form surface active films able to reach and sustain very low surface tensions (<2 mN/m) under compression-expansion cycling mimicking breathing dynamics. Furthermore, the combination of clinical surfactant with corticosteroids efficiently promoted the active diffusion of the drug to long distances along the air-liquid interface. This effect could not be mimicked by vehiculisation of corticosteroids in liposomes or in micellar emulsions similar to the formulations currently in use to deliver anti-inflammatory corticosteroids through inhalation.

show abstract

Section: Discussionsupporting

confidence: 55%

Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…For thin films, alternative approaches like the pressure balance technique can be used to directly measure the surface forces in terms of the disjoining pressure (e.g. Todorov et al, 2017).…”

Section: Experimental Methodsmentioning

confidence: 99%

A finite membrane element formulation for surfactants

Roohbakhshan

Sauer

2019

Colloids and Surfaces A: Physicochemical and Engineering Aspect

View full text Add to dashboard Cite

Surfactants play an important role in various physiological and biomechanical applications. An example is the respiratory system, where pulmonary surfactants facilitate the breathing and reduce the possibility of airway blocking by lowering the surface tension when the lung volume decreases during exhalation. This function is due to the dynamic surface tension of pulmonary surfactants, which depends on the concentration of surfactants spread on the liquid layer lining the interior surface of the airways and alveoli. Here, a finite membrane element formulation for liquids is introduced that allows for the dynamics of concentration-dependent surface tension, as is the particular case for pulmonary surfactants. A straightforward approach is suggested to model the contact line between liquid drops/menisci and planar solid substrates, which allows the presented framework to be easily used for drop shape analysis. It is further shown how line tension can be taken into account. Following an isogeometric approach, NURBSbased finite elements are used for the discretization of the membrane surface. The capabilities of the presented computational model is demonstrated by different numerical examples -such as the simulation of liquid films, constrained and unconstrained sessile drops, pendant drops and liquid bridges -and the results are compared with experimental data.

show abstract

“…In clinical practice, animalderived surfactant preparations, which contain relatively high amounts of DPPC as well as SP-B and SP-C, are still recommended over synthetic preparations. [6,7] The performance of Poractant alfa has been systematically compared, in vitro and in vivo, to that of other animalderived as well as synthetic surfactants, [10,11,22,33,34] and has been confronted to other preparations in several clinical trials. [13][14][15][16] Significant differences in clinical outcomes were found between Poractant alfa and other bovine preparations, both from minced lung and lung lavaged fluid.…”

Section: Plos Onementioning

confidence: 99%

“…Poractant alfa is extracted from porcine minced lungs and is licensed to be administered at phospholipid doses of 100 or 200 mg/kg, with salient pharmacodynamics and pharmacokinetic effects in the treatment of RDS. [10][11][12][13] Moreover, Poractant alfa has undergone large randomized clinical trials comparing its efficacy to other surfactant preparations. [13][14][15][16] On the other hand, little is known about Calsurf, which is extracted from lung washes of calves and is indicated for the treatment of RDS at an initial phospholipid dose of 40-100 (average 70) mg/kg (manufacturer information).…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization and in vivo comparison of the pulmonary outcomes of Poractant alfa and Calsurf in ventilated preterm rabbits

et al. 2020

Self Cite

View full text Add to dashboard Cite

Poractant alfa and Calsurf are two natural surfactants widely used in China for the treatment of neonatal respiratory distress syndrome, which are extracted from porcine and calf lungs, respectively. The purpose of this experimental study was to compare their in vitro characteristics and in vivo effects in the improvement of pulmonary function and protection of lung injury. The biophysical properties, ultrastructure, and lipid composition of both surfactant preparations were respectively analysed in vitro by means of Langmuir-Blodgett trough (LBT), atomic force microscopy (AFM), and liquid-chromatography mass-spectrometry (LC-MS). Then, as core pharmacological activity, both head-to-head (100 and 200 mg/kg for both surfactants) and licensed dose comparisons (70 mg/kg Calsurf vs. 200 mg/kg Poractant alfa) between the two surfactants were conducted as prophylaxis in preterm rabbits with primary surfactant deficiency, assessing survival time and rate and dynamic compliance of the respiratory system (C dyn ). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (V v ), and lung injury scores were determined post mortem. AFM and LC-MS analysis revealed qualitative differences in the ultrastructure as well as in the lipid composition of both preparations. Calsurf showed a longer plateau region of the LBT isotherm and lower film compressibility. In vivo, both surfactant preparations improved C dyn at any dose, although maximum benefits in terms of V v and intrapulmonary surfactant pools were seen with the 200 mg/kg dose in both surfactants. The group of animals treated with 200 mg/kg of Poractant alfa showed a prolonged survival time and rate compared to untreated but ventilated controls, and significantly ameliorated lung injury compared to Calsurf at any dose, including 200 mg/kg. The overall outcomes suggest the pulmonary effects to be dose dependent for both preparations. The group of animals treated with 200 mg/kg of Poractant alfa showed a significant reduction of mortality. Compared to Calsurf, Poractant

show abstract

Behavior of thin liquid films from aqueous solutions of a pulmonary surfactant in presence of corticosteroids

Cited by 6 publications

References 28 publications

Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant

Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant

A finite membrane element formulation for surfactants

In vitro characterization and in vivo comparison of the pulmonary outcomes of Poractant alfa and Calsurf in ventilated preterm rabbits

Contact Info

Product

Resources

About