Preparation Of Protein-Encapsulated Nanoparticles Using Polysuccinimide-Oleylamine For Sustained Protein Release

The clinical use of biologics for acute disease management is constrained by rapid clearance and systemic accumulation, which may compromise therapeutic outcomes. While sustained release nanoparticles are well-established for chronic conditions, analogous strategies for acute indications─particularly those requiring controlled release within 48 h─remain insufficiently developed. This study explores polysuccinimide-oleylamine (PSI-OA), a polymer with a tunable dissolution profile, for protein delivery. Using inverse flash nanoprecipitation and a herringbone T-shaped microfluidic mixer, PSI-OA nanoparticles encapsulating bovine serum albumin and lipase were fabricated. Optimized synthesis parameters yielded nanoparticles with less than 200 nm, with encapsulation efficiencies of roughly 75 and 98%, respectively, while retaining enzymatic activity. Both systems demonstrated ∼50% release at 24 h and full release by 48 h. These findings underscore the potential of PSI-OA nanoparticles for short-term sustained delivery of protein therapeutics in acute care settings.