Pure Insulin Nanoparticle Agglomerates for Pulmonary Delivery

Abstract

Diabetes is a disease characterized by defects in insulin utilization, either through autoimmune destruction of insulin-producing cells (Type I) or insulin resistance (Type II). Treatment includes regular insulin injections, which can be painful and inconvenient, often leading to low patient compliance. To overcome this problem, novel formulations of insulin are being investigated, such as inhaled aerosols. Sufficient deposition of powder in the distal regions of the lung to maximize systemic absorption requires precise control over particle size, with particles between 1 and 5 microns in aerodynamic diameter being within the respirable range. Insulin nanoparticles were produced by titrating insulin dissolved at low pH to the pI of the native protein, and were then processed into microparticles using solvent displacement. Particle size, crystallinity, dissolution properties, stability, and powder density were characterized. This work demonstrates that pure insulin microparticles can be produced from nanosuspensions with minimal processing steps and with suitable properties for deposition in the peripheral lung.