Evaluating Novel SP-B and SP-C Synthetic Analogues for Pulmonary Surfactant Efficacy

Int J Med Sci. 2024 Feb 25;21(5):775-783. doi: 10.7150/ijms.92920. eCollection 2024.

Abstract

Pulmonary surfactants, a complex assembly of phospholipids and surfactant proteins such as SP-B and SP-C, are critical for maintaining respiratory system functionality by lowering surface tension (ST) and preventing alveolar collapse. Our study introduced five synthetic SP-B peptides and one SP-C peptide, leading to the synthesis of CHAsurf candidates (CHAsurf-1 to CHAsurf-5) for evaluation. We utilized a modified Wilhelmy balance test to assess the surface tension properties of the surfactants, measuring spreading rate, surface adsorption, and ST-area diagrams to comprehensively evaluate their performance. Animal experiments were performed on New Zealand white rabbits to test the efficacy of CHAsurf-4B, a variant chosen for its economic viability and promising ST reduction properties, comparable to Curosurf®. The study confirmed that higher doses of SP-B in CHAsurf-4 are associated with improved ST reduction. However, due to cost constraints, CHAsurf-4B was selected for in vivo assessment. The animal model revealed that CHAsurf-4B could restore alveolar structure and improve lung elasticity, akin to Curosurf®. Our research highlights the significance of cysteine residues and disulfide bonds in the structural integrity and function of synthetic SP-B analogues, offering a foundation for future surfactant therapy in respiratory disorders. This study's findings support the potential of CHAsurf-4B as a therapeutic agent, meriting further investigation to solidify its role in clinical applications.

Keywords: disulfide bond; pulmonary surfactant-associated protein B; pulmonary surfactants; surface tension; synthetic.

MeSH terms

  • Animals
  • Cysteine
  • Elasticity
  • Pulmonary Surfactants* / pharmacology
  • Rabbits
  • Surface-Active Agents

Substances

  • Cysteine
  • Pulmonary Surfactants
  • Surface-Active Agents