Self-assembled oligomeric procyanidin–insulin hybrid nanoparticles: a novel strategy for controllable insulin delivery

Abstract

Natural oligomeric procyanidin (OPC) with high biological and pharmacological activities was successfully used to synthesize OPC–insulin (OPC–INS) nanoparticles with different aggregation sizes for sustained and controlled delivery of hydrophilic insulin. The aggregation size of OPC–INS nanoparticles was regulated by OPC concentration, pH value, and incubation time. The fabrication mechanism would be that OPC and insulin self-assembled into a mixture of insulin aggregates via intermolecular interactions. In the self-assembly of insulin, OPC could serve both in the encompassing of insulin aggregates as a stabilizer and cross-linking different amounts of insulin aggregates into OPC–INS nanoparticles as interphase. OPC–INS nanoparticles not only demonstrated effective insulin drug loading but also exhibited aggregation-size-dependent and controlled insulin release performance in vitro. In the best case for OPC–INS nanoparticles, only ∼21% of insulin was released in 37 days. This study showed that the OPC–INS nanosystem is promising to serve as a long-acting insulin release formulation, and OPC has great potential as a drug carrier for nanomedicine.