Synthesis of pH-responsive core-shell nanoparticles of different sizes and with different shell compositions

摘要

The endosome-disrupting and pH-responsive poly(2-diethylamino ethyl methacrylate)-core/poly(2- aminoethyl methacrylate)-shell nanoparticles could potentially increase the efficacy of transcutaneous administered vaccines and facilitate the cytosolic delivery of a wide variety of therapeutic macromolecules. One of the goals of this study was to reduce the size of these core-shell nanoparticles to improve their permeation into the skin. Separate nanoparticle syntheses using reduced durations, decreased monomer concentrations, and decreased monomer solubility did not cause a significant decrease in the particle diameter compared to those previously reported. Manipulation of the reaction kinetics did not stabilize smaller particles leaving them susceptible to coagulation. Synthesis of poly(2-diethylamino ethyl methacrylate)/ Poly(ethylene glycol) methacrylate copolymer nanoparticles were sterically stabilized by the amphiphilic polymer brush at the particle surface and exhibited slightly smaller hydrodynamic diameter measured by dynamic light scattering. Manipulation of the reaction kinetics and the monomer ratio could lead to significantly smaller chains. Another goal for this study was to create core-shell nanoparticles with different charged shells to see if the shell could be modified to electrostatically adsorb a wider range of drugs. In addition, the different charges of the shell could affect the nanoparticles' endosome-disrupting abilities and/or their permeation through the skin.