Optimizing PEG Length for Enhanced In Vivo Pharmacokinetics of a Micellar siRNA Carrier

摘要

Mixed micelles containing varied molar percentages and molecular weight of PEG in the corona have been synthesized and characterized in vitro and in vivo. Increasing PEG length in the corona of micelles reduces in vivo biodistribution in the kidneys and lungs, which suggests a significant improvement in stability and decreased blood cell aggregation, respectively. The 50D/20k PEG micelles result in a 17.7 minute blood circulation half-life value that can be utilized for delivery to highly-vascularized tumors via the EPR effect. This platform demonstrates the potential for biocompatible siRNA delivery, and ongoing studies will assess the 50D/20k formulation for siRNA delivery to orthotopic breast cancer tumors.