Systematic Design of PLGA Nanoparticles for Long-Acting Delivery of a Dual GLP-1/Glucagon Receptor Coagonist Peptide (SAR425899) via Phase Inversion Nanoencapsulation

Poly(lactic- co -glycolic) acid (PLGA) nanoparticles loaded with SAR425899, a dual glucagon-like peptide-1 (GLP-1)/glucagon receptor coagonist, were prepared and characterized using “phase inversion nanoencapsulation”. This study provides the mechanism of particle formation by supersaturation, nucleation, and growth by adding a soluble polymer or drug solution to a miscible nonsolvent. The Gibbs energy of mixing (Δ G mix ) was calculated using the UNIFAC method to determine the appropriate solvent and nonsolvent pairs. It was found that the size of PLGA particles tended to decrease with increasingly negative Δ G mix of the solvent and nonsolvent pairs used. The Δ G mix of solvent and nonsolvent pairs used in the phase inversion process correlated to the SAR425899 encapsulation and release behavior, with more negative Δ G mix increasing the degree of polymer supersaturation, which provided a decrease in particle size and an increased affinity of the polymer to encapsulate the SAR425899. Overall, these findings demonstrate the correlation between Δ G mix particle size, encapsulation, and release profile through the mechanism of supersaturation, nucleation, and growth.