Small Angle Neutron Scattering Studies on the Internal Structure of Poly(lactide-co-glycolide)-block-poly(ethylene glycol) Nanoparticles as Drug Delivery Vehicles

Poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) nanoparticles are commonly used as drug carriers in controlled drug release and targeting. To achieve predictable and clinically relevant volumes of drug distribution, nanoparticle size, surface charge, and especially composition and structure must be controlled. Understanding the internal structures within the particles is fundamentally important to explain differences in drug loading and variations in drug release rate. We prepared nanoparticles from ester-terminated PLGA-PEG polymers via nanoprecipitation, and studied the effects of altering the solvent-water miscibility (THF, acetone, and acetonitrile). Morphology, size, polydispersity, and zeta-potential of PLGA-PEG nanoparticles were characterized. Small angle neutron scattering measurements and fitted models revealed the internal nanoparticle structure: PLGA blocks of 7-9 nm are encapsulated inside a fairly dense PEG/water network in a fractal geometry. Particles with a larger PLGA block volume and higher PEG volume fraction in the particle interior result in greater retention of the hydrophilic anticancer drug carboplatin.