Physicochemical Characterization of Choline Amino Acid Ionic Liquid Solvated Linear–Dendritic Block Copolymers

Linear-dendritic block copolymers (LDBCs) have emerged as a promising material for assembling nanoparticles toward achieving targeted drug delivery; however, a major barrier to their success is that they can exhibit high dispersity, poor shelf life, and potentially high cytotoxicity to non-target interfacing blood cells during intravenous drug delivery. As an approach to bypass this barrier, ionic liquids (ILs) can electrostatically solvate LDBCs by direct dissolution and form stable and biocompatible IL-integrated LDBC nano-assemblies. This work is focused on the characterization of biocompatible amino acid ILs (AAILs) and AAIL-solvated LDBC nanoparticles (NPs). These experiments show that different amino acid ionic liquids increase the thermal and chemical stability of LDBC nanoparticles to different degrees. Stability studies show that Cho-dl-Ile 1:1 and Cho-l-Leu 1:1 LDBC NPs are stable for 19 days, while bare LDBC NPs quickly lose stability. Cho-l-Asn 1:1 LDBC NPs show the greatest increase in thermal stability on TGA despite performing the worst during stability studies. This work also suggests that anion stereochemistry plays a role in how ILs interact with the polymer, with Cho-dl-Ile 1:1 having much stronger interactions with the LDBC NPs than the very similar Cho-l-Leu 1:1. Quantification of AAIL associated with the LDBC NPs suggests that hydrophobicity of the anion and polymer of choice plays a role in how much AAIL is in the system. Unlike Cho-dl-Ile 1:1 and Cho-l-Leu 1:1, Cho-l-Asn 1:1 has a hydrophilic anion and shows an order of magnitude less anion associated with the LDBC NP system. These studies highlight how even small changes in IL chemistry can impact the nanoaggregation behavior of LDBCs and their eventual chemical and thermal stability.