PEGylation strategies for active targeting of PLA/PLGA nanoparticles.

This work evaluates various techniques for the incorporation of poly(ethylene glycol) (PEG) onto biodegradable nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) or poly(lactic acid) (PLA) with the purpose of providing a functional site for surface conjugation of targeting agents and for improving surface properties. The techniques compared were based on NP preparation with blends of PLGA and poloxamer or with block copolymers of PLGA/PLA with PEG. Blending of PLGA with poloxamer 407 resulted in the incorporation of the latter to up to a 43 wt % content. Direct conjugation of heterofunctional NH2-PEG-COOH to the surface of premade NPs was not highly effective. Preparation of copolymers of PLGA with PEG was determined to be more effective and versatile by polymerization of lactide and glycolide dimers onto the hydroxyl group of heterofunctional OH-PEG-COOH than by conjugation of the premade polymers with carbodiimide chemistry. NPs prepared with these copolymers confirmed the surface localization of PEG and proved to be useful for conjugation of mouse immumoglobulin as a model targeting agent.