Surface Functionalization of Polymer Particles for Cell Targeting by Modifying Emulsifier Chemistry.

The oil in water emulsion/solvent extraction method is used to fabricate many FDA approved, polymer particle formulations for drug delivery. However, these formulations do not benefit from surface functionalization that can be achieved through tuning particle surface chemistry. Poly(vinyl alcohol) (PVA) is the emulsifier used for many FDA approved formulations and remains associated with the particle surface after fabrication. We hypothesized that the hydroxyl groups in PVA could be conjugated with biomolecules using isothiocyanate chemistry and that these modifications would endow the particle surface with additional functionality. We demonstrate that fluorescein isothiocyanate and an isothiocyanate derivatized mannose molecule can be covalently attached to PVA in a one-step reaction. The modified PVA polymers perform as well as unmodified PVA in acting as an emulsifier for fabrication of poly(lactide-co-glycolide) particles. Particles made with the fluorescein modified PVA exhibit fluorescence confined to the particle surface, while particles made with mannose modified PVA bind concanavalin A. In addition, mannose modified PVA increases particle association with primary macrophages by three-fold. Taken together, we present a facile method for modifying the surface reactivity of polymer particles widely used for drug delivery in basic research and clinical practice. Given that methods are established for conjugating the isothiocyanate functional group to a wide range of biomolecules, our approach may enable PVA based biomaterials to engage a multitude of biological systems.