Four ionic liquid(IL, gold)-modified polymer platforms were disrupted via electrostatics and hydrogen bonding using sodium-sulfate salt & hydrochloric acid. Salt fluidizes IL-LDBC NPs (middle), releasing cation (+,red). Acid causes most anion (-,red)/total IL loss, exposing dendritic-PAMAM (black). On DPP NPs (bottom), sodium deposits (+,green) with PEG expansion (blue), equally releasing cation/anion. Acid releases remaining IL and degrades PLGA (pink).

Abstract

Ionic liquids (ILs) have emerged as promising biomaterials for enhancing drug delivery by functionalizing polymeric nanoparticles (NPs). Despite the biocompatibility and biofunctionalization they confer upon the NPs, little is understood regarding the degree in which non-covalent interactions, particularly hydrogen bonding and electrostatic interactions, govern IL-NP supramolecular assembly. Herein, we use salt (0-1 M sodium sulfate) and acid (0.25 M hydrochloric acid at pH 4.8) titrations to disrupt IL-functionalized nanoassembly for four different polymeric platforms during synthesis. Through quantitative ¹H-nuclear magnetic resonance spectroscopy and dynamic light scattering, we demonstrate that the driving force of choline trans-2-hexenoate (CA2HA 1:1) IL assembly varies with either hydrogen bonding or electrostatics dominating, depending on the structure of the polymeric platform. In particular, the covalently bound or branched 50:50 block co-polymer systems (diblock PEG-PLGA [DPP] and polycaprolactone [PCl]-poly[amidoamine] amine-based linear-dendritic block co-polymer) are predominantly affected by hydrogen bonding disruption. In contrast, a purely linear block co-polymer system (carboxylic acid terminated poly[lactic-co-glycolic acid]) necessitates both electrostatics and hydrogen bonding to assemble with IL and a two-component electrostatically bound system (electrostatic PEG-PLGA [EPP]) favors hydrogen-bonding with electrostatics serving as a secondary role.