A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations

Area of Science:

• Pharmaceutical Sciences
• Biotechnology
• Materials Science

Background:

• Subcutaneous administration of therapeutic peptides offers patient benefits but faces challenges with high concentrations due to solubility, viscosity, and stability issues.
• Current methods for high-concentration peptide formulations often involve organic solvents or lipid excipients, leading to stability concerns.
• Limitations in dosing volume for subcutaneous injections necessitate the development of stable, high-concentration peptide formulations.

Purpose of the Study:

• To develop a novel method for preparing stable, high-concentration peptide nanosuspensions for subcutaneous administration.
• To investigate the use of low-shear resonant acoustic mixing as a generalizable technique for peptide nanoparticle formation.
• To evaluate the physicochemical stability and in vivo performance of peptide nanosuspensions.

Main Methods:

• Utilized low-shear resonant acoustic mixing to prepare peptide nanoparticles in aqueous solutions.
• Characterized the resulting nanosuspensions for viscosity, chemical stability, and physical stability.
• Formulated cyclosporine nanoparticles and evaluated their subcutaneous injection and release profile in rats.

Main Results:

• Low-shear resonant acoustic mixing successfully produced stable peptide nanoparticles across diverse molecular weights and structures.
• The resulting peptide nanosuspensions demonstrated low viscosity at high concentrations (>100 mg/mL) and maintained chemical and physical stability.
• Cyclosporine nanosuspensions showed sustained release behavior after subcutaneous injection in rats.

Conclusions:

• Low-shear resonant acoustic mixing is an effective and generalizable method for creating stable peptide nanosuspensions.
• This approach overcomes common challenges associated with high-concentration peptide formulations for subcutaneous delivery.
• Peptide nanosuspensions offer a promising strategy for enabling high-dose subcutaneous peptide therapeutics with sustained release profiles.