Design of surface-modified poly(D,L-lactide-co-glycolide) nanoparticles for targeted drug delivery to bone.

Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles, modified with both alendronate and polyethylene glycol (PEG), were prepared by dialysis method without additional surfactant to evaluate the potency of the bone-targeted drug delivery. Alendronate, a targeting moiety that has a strong affinity for bone, was conjugated to PLGA polymer via carbodiimide chemistry. Monomethoxy PEG(mPEG)-PLGA block copolymers with different molecular weights of mPEG (M(n) 550, 750, and 2000) were synthesized and used for a hydrophilic layer on the surface of the nanoparticles to avoid reticuloendothelial system (RES). The surface-modified PLGA nanoparticles with various ratios of alendronate and mPEG densities on their surface were evaluated by adsorption study onto hydroxyapatite (HA). It was confirmed that alendronate-modified nanoparticles had a strong and specific adsorption to HA. The amount of nanoparticles absorbed onto HA tended to be smaller when the content of alendronate was decreased and the large block length of mPEG was found to reduce the potency of alendronate.