Role of physicochemical parameters associated with the hydrophobic vs. amphiphilic biodegradable polymer nanoparticles formation

Abstract

Polymer nanoparticles formed from polymers with biodegradable and biocompatible properties are promising candidates for biomedical applications. Herein, the role of different physicochemical parameters associated with the formation of hydrophobic [Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL)] and amphiphilic [Poly(ethylene glycol) methyl ether-block-poly(l-lactide-co-glycolide) (PEG-PLGA)] polymer nanoparticles has been studied by Small-Angle Neutron Scattering (SANS). We show that the changes in size and the number density of hydrophobic polymer nanoparticles are associated with the polymer concentration or solvent-to-nonsolvent ratio or the synergetic effect of these parameters. These results support the formation of the hydrophobic PLGA nanoparticles as the nucleation of small molecules followed by the coalescence-induced growth process. PCL nanoparticles follow a similar pathway as observed for PLGA nanoparticles. Contrarily, any significant changes in the size and the number density of PEG-PLGA nanoparticles associated with the polymer concentration or solvent-to-nonsolvent ratio have not been observed. In amphiphilic PEG-PLGA nanoparticles, the PLGA cores follow the nucleation process while PEG molecules stay around the core with random conformation. The coalescence-induced growth, unlike hydrophobic polymer nanoparticles, is suppressed due to the hydrated steric barrier of PEG chains. This distinct difference in the formation mechanism of the hydrophobic and amphiphilic polymers could be utilized for applications associated with the different length scales of nanoparticles.