In vitro and in vivo characterization of poractant alfa supplemented with budesonide for safe and effective intratracheal administration.

Abstract

BackgroundThe intratracheal (IT) administration of budesonide using surfactant as a vehicle has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. The objective of this study was to characterize the in vitro characteristics and in vivo safety and efficacy of the extemporaneous combination of budesonide and poractant alfa.MethodsThe stability, minimum surface tension, and viscosity of the preparation were evaluated by means of high-performance liquid chromatography (HPLC), Wilhelmy balance, and Rheometer, respectively. The safety and efficacy of the IT administration of the mixture were tested in two respiratory distress syndrome (RDS) animal models: twenty-seventh day gestational age premature rabbits and surfactant-depleted adult rabbits.ResultsA pre-formulation trial identified a suitable procedure to ensure the homogeneity and stability of the formulation. Wilhelmy Balance tests clarified that budesonide supplementation has no detrimental effect on poractant alfa surface tension activity. The addition of budesonide to poractant alfa did not affect the physiological response to surfactant treatment in both RDS animal models, and was associated to a significant reduction of lung inflammation in surfactant-depleted rabbits.ConclusionOur in vitro and in vivo analysis suggests that the IT administration of a characterized extemporaneous combination of poractant alfa and budesonide is a safe and efficacious procedure in the context of RDS.

• Authors: Francesca Ricci, Chiara Catozzi, Francesca Ravanetti, Xabier Murgia, Francesco D'Aló, Natalia Macchidani, Elisa Sgarbi, Valentina Di Lallo, Federica Saccani, Marisa Pertile, Antonio Cacchioli, Silvia Catinella, Gino Villetti, Maurizio Civelli, Francesco Amadei, Fabio Franco Stellari, Barbara Pioselli, Fabrizio Salomone
• Journal: Pediatric research (Pediatr Res) Vol. 82 Issue 6 Pg. 1056-1063 (Dec 2017) ISSN: 1530-0447 [Electronic] United States
• PMID: 28723887 (Publication Type: Journal Article)

Chemical References

• Biological Products
• Bronchodilator Agents
• Phospholipids
• Pulmonary Surfactants
• Budesonide
• poractant alfa

Topics

• Animals
• Biological Products (administration & dosage, adverse effects)
• Bronchoalveolar Lavage Fluid
• Bronchodilator Agents (administration & dosage, adverse effects)
• Bronchopulmonary Dysplasia (drug therapy)
• Budesonide (administration & dosage, adverse effects)
• Disease Models, Animal
• Drug Administration Routes
• Female
• In Vitro Techniques
• Phospholipids (administration & dosage, adverse effects)
• Pregnancy
• Pulmonary Surfactants (administration & dosage)
• Rabbits
• Respiratory Distress Syndrome, Newborn (drug therapy)
• Surface Tension
• Trachea
• Viscosity