Nanoparticles for drug delivery are potentially an ideal treatment solution for numerous diseases. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully used biodegradable polymers as structural material for drug delivery systems. However, it is well known that when administered to the bloodstream, the adsorption of plasma proteins on the nanoparticle surface (protein corona) leads to immune system recognition and rapid clearance to the liver and spleen, preventing its reach to the intended target tissues. Surface modification of the nanoparticles with polyethylene glycol (PEG) is proven to increase the half-life of circulation time of the nanoparticles by creating a hydrophilic steric barrier via hydrogen bonding with water which prevent the protein corona formation. Nevertheless, chemical modifications onto the nanoparticle surface will impact the interaction with targeted cells, and therefore engineering of these nanoparticles is a compromise between circulation time to reach targeted tissues and favorable interaction and uptake with targeted cells. Our approach based on the preparation of the nanoparticles using block copolymers PLGA-PEG allows us to prepare tunable nanoparticles with various sizes, surface densities, and architectures. These parameters will have a direct effect on the 3D arrangement of the PEG chains on the surface and the amount of OH groups exposed which in turn will mediate the interaction with plasma proteins and with the intended cells. Furthermore the possibility of giving the nanoparticles fluorescent properties is being explored adding fluorescent-label PLGA to our formulations. This will allow us to analyze the behavior of the nanoparticles in blood in a novel way via nanoparticle tracking analysis (NTA). This technique enables the visualization and imaging of the nanoparticles in pure blood plasma. The size distribution is obtained by measuring the motion of the particles via Stokes-Einstein relation. Using this technique, we can not only explore the protein corona formation but also we can retrieve information about the heterogeneous aggregation behavior of the particles, which cannot be efficiently studied with classical particle size measurement techniques such as dynamic light scattering.

Surface modification of polymeric nanoparticles for drug delivery applications

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.