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Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

ABSTRACT: The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf^®. We show that BUD facilitates the Curosurf^® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf^® dispersion is maintained for BUD < 10 wt% of the Curosurf^® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca²⁺ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf^® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant's lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide-enriched Curosurf^®.

SUBMITTER: Keshavarzi A

PROVIDER: S-EPMC10931555 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

Keshavarzi Atoosa A Asi Shirazi Ali A Korfanta Rastislav R Královič Nina N Klacsová Mária M Martínez Juan Carlos JC Teixeira José J Combet Sophie S Uhríková Daniela D

International journal of molecular sciences 20240304 5

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics an ...[more]

PMID: 38474237

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Project description:BackgroundRespiratory distress syndrome (RDS) is a common disease that seriously endangers the life and safety of newborns, especially premature infants. Exogenous pulmonary surfactant (PS) is the specific agent for the treatment of neonatal RDS. Lung ultrasound (LUS) has been successfully used in the diagnosis of RDS, but its value in guiding the application of PS is still unclear. This paper explored whether the application of PS under LUS monitoring has some advantages, including (1) decreasing the misdiagnosis rate of RDS and decreasing probability of using PS, and (2) reducing the dose of PS without reducing the therapeutic effect.MethodsThis study included two parts. Part 1: To decide whether the LUS is good to differentiate RDS from other lung diseases in the premature infants. All patients who were diagnosed with RDS and required PS treatment based on conventional criteria were routinely examined by LUS. Then, according to LUS findings, we decided whether they needed to receive PS treatment. Part 2: To see the dose reduction of surfactant is applicable. In RDS patients diagnosed based on LUS presentation and treated with Curosurf (Chiesi Pharmaceutical, Parma, Italy), the dose of Curosurf was compared with that recommended by the European RDS management guidelines.Results(1) Since March 2017, 385 newborn infants admitted to our neonatal intensive care unit met the traditional diagnostic criteria of RDS. Of these, only 269 cases were diagnosed with RDS and needed PS treatment according to LUS manifestations. The other 116 infants who did not meet the criteria for ultrasound diagnosis of RDS did not receive PS supplementation but obtained good outcomes, that is LUS findings decreased a misdiagnosis rate of RDS by 30.1% and subsequently resulted in a 30.1% reduction in PS use. (2) Among the 269 RDS patients diagnosed based on LUS findings, 148 were treated with Curosurf (another 121 RDS infants who received domestic PS treatment were not included in the study group), and the average dose was 105.4 ± 24.3 mg/kg per time, which is significantly lower than the dose of 200 mg/kg per time recommended by the European RDS guidelines. (3) The mortality rate of RDS patients was 0%, and no patients had ventilator-associated pneumonia or bronchopulmonary dysplasia in this study.ConclusionLUS can decrease the misdiagnosis rate of RDS, thereby decreasing the probability of using PS and decreasing the dose of PS, and can help RDS infants to achieve better outcomes.

Dataset Information

Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

Publications

Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

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