Effects of amphiphilic diblock copolymer on drug nanoparticle formation and stability

This study systematically compares the effects of amphiphilic diblock copolymer (di-BCP) on stabilizing hydrophobic drug nanoparticles formed by flash nanoprecipitation (FNP), and provides a guideline on choosing suitable di-BCPs. Four widely used di-BCPs, i.e., polystyrene-block-poly(ethylene glycol) (PS-b-PEG), polycaprolactone-block-poly(ethylene glycol) (PCL-b-PEG), polylactide-block-poly(ethylene glycol) (PLA-b-PEG), and poly(lactic-co-glycolic acid) (PLGA-b-PEG), and β-carotene as a model drug were used. The study showed that PLGA-b-PEG was the most suitable one, whose hydrophobic block was biodegradable and noncrystallizable as well as had relatively high glass transition temperature (Tg) and a right solubility parameter (δ). The molecular weight of PLGA block over the range from 5k to 15k showed an insignificant effect on controlling the particle size. Amorphous drug particles with a high drug loading of over 83 wt% can be achieved. Much remarkable evidence supported the nanoparticles with kinetically frozen and non-equilibrium packing structures of polymer chains rather than either the micelles or micellar nanoparticles with two well segregated polymer blocks. The thermodynamic effects of the drug and BCP on the particle stability, size and structures were discussed by using solubility parameters.