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

Autor: Guo X; Departments of Pediatrics and Neonatology, Children's Hospital of Fudan University, Shanghai, China., Luo S; Departments of Pediatrics and Neonatology, Children's Hospital of Fudan University, Shanghai, China., Amidani D; Department of Research and Development, Chiesi Farmaceutici, Parma, Italy., Rivetti C; Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy., Pieraccini G; CISM Mass Spectrometry Centre, Department of Health Sciences, University of Florence, Firenze, Italy., Pioselli B; Department of Research and Development, Chiesi Farmaceutici, Parma, Italy., Catinella S; Department of Research and Development, Chiesi Farmaceutici, Parma, Italy., Murgia X; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research, Saarbrücken, Saarland, Germany., Salomone F; Department of Research and Development, Chiesi Farmaceutici, Parma, Italy., Xu Y; Departments of Pediatrics and Neonatology, Children's Hospital of Fudan University, Shanghai, China., Dong Y; Departments of Pediatrics and Neonatology, Children's Hospital of Fudan University, Shanghai, China., Sun B; Departments of Pediatrics and Neonatology, Children's Hospital of Fudan University, Shanghai, China.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Mar 13; Vol. 15 (3), pp. e0230229. Date of Electronic Publication: 2020 Mar 13 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0230229
Abstrakt: 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 (Cdyn). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (Vv), 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 Cdyn at any dose, although maximum benefits in terms of Vv 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 alfa exerted better effects if licensed doses were compared, which requires further investigation.
Competing Interests: The study was supported by Chiesi Farmaceutici S.p.A, which owns the marketing rights for Poractant alfa. The company contributed to the study design but had neither influence on the performance, analysis, and interpretation of experimental data nor in writing the manuscript. BP, SC, and FS are employees of Chiesi Farmaceutici S.p.A. XM served as consultant for Chiesi in this study. YD is a recipient of research grants from the National Natural Science Foundation (No. 81501288) and Shanghai Municipal Commission of Health (Project Young Physician Investigator). This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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