Polymer Nanospheres for Improved Drug Delivery Of Protein Therapeutics and Vaccine Antigens

摘要

Biologically adherent polymeric microsphere carriers have been shown to be effective in the oral delivery of proteins such as insulin and DNA plasmids. These microspheres are comprised of hydrophobic copolymers that appear to have a significantly longer residence time in the gastrointestinal tract as compared to conventional microspheres. While highly promising, the hydrophobic microspheres still present challenges in terms of manufacturing and formulation of clinically acceptable products. Typically, the microspheres are produced from an organic solvent solution, which raises concerns about deleterious effects on the therapeutic proteins and residual organic solvent in the final product. These difficulties can be averted by utilizing SuperFluids~(TM), supercritical, critical or near-critical fluids with or without polar cosolvents such as ethanol. Conditions were established for the formation of Super-Fluids~(TM) polymer nanospheres. These include polymer solubility, nozzle size and type, excipients and polymer/drug ratio. SuperFluids~(TM) polymer nanospheres made with PLGA had narrow size distributions, around 200 to 400 nanometers. These nanospheres were used to encapsulate insulin and control its release into PBS. In vivo studies with diabetic mice indicated that Super-Fluids~(TM) polymer nanoencapsulated insulin caused a statistical reduction in glucose levels after oral administration.