Supercritical CO2 emerges as a versatile platform for next-generation peptide formulations in cardiovascular disease

Despite their high specificity and potency, peptide-based drugs face significant hurdles in clinical translation due to poor stability, enzymatic degradation, and low bioavailability. This limits their effectiveness in treating widespread conditions like cardiovascular diseases (CVDs), which remain the leading cause of global morbidity and mortality. Current manufacturing techniques often fall short in producing stable, bioavailable peptide formulations, necessitating innovative approaches to drug delivery and processing.

This comprehensive review systematically discusses the application of supercritical carbon dioxide (scCO₂) technology for formulating peptide therapeutics targeting cardiovascular diseases. The authors summarized promising cardiovascular peptide candidates and analyzed key formulation strategies, including the development of polymeric and lipid nanoparticles and liposomes. They also detailed the limitations of conventional manufacturing methods and characterized various scCO₂-based processes, such as supercritical fluid extraction and rapid expansion of supercritical solutions, for peptide formulation development.

The review identifies scCO₂ as a superior alternative to conventional methods for peptide formulation, primarily due to its ability to enhance product quality and process thermosensitive compounds at low temperatures. A key advantage is the minimal to no use of organic solvents, which improves safety and environmental profiles. scCO₂ enables the creation of diverse advanced delivery systems, including polymeric nanoparticles, lipid nanoparticles, and liposomes, which can significantly improve peptide stability and bioavailability. These formulations are crucial for overcoming enzymatic degradation and poor absorption, which typically plague peptide therapeutics. The authors emphasize scCO₂'s potential to facilitate the development of next-generation peptide therapeutics for cardiovascular health by providing versatile and scalable manufacturing options. This technology offers a pathway to more effective and patient-friendly peptide drug products.

scCO₂ processing significantly enhances product quality and enables the formulation of thermosensitive peptides without harsh organic solvents, addressing critical limitations of current peptide drug development.