Synthesis and unimolecular micelles of amphiphilic dendrimer-like star polymer with various functional surface groups

摘要

We report the synthesis and functionalization of amphiphilic dendrimer-like star polymers (DLSPs) with a hydrophobic star-shaped poly(l-lactide) (PLLA) core and a hydrophilic poly(amidoamine) (PAMAM) dendron shell. First, carboxylic acid-functionalized PLLA star polymer was synthesized by ring-opening polymerization of l-lactide followed by functionalization with succinic anhydride. Second, 1-, 2-, and 3-generation PAMAM dendrons with a primary amine at the dendron root and benzyl ester protections at the periphery were prepared via a divergent method. By amide coupling between the carboxylic acid-terminated PLLA star polymer and six PAMAM dendrons, amphiphilic DLSPs were successfully synthesized. To enhance bioactivity and bioconjugation capability, the benzyl ester surface groups in these DLSPs were converted to carboxylic acid, primary amine, and triethylene glycol functional groups, respectively. Nuclear magnetic resonance spectroscopy and size-exclusion chromatography were used to confirm quantitative functionalization. These functional DLSPs exhibited a unique unimolecular micelle (14-28 nm) behavior in aqueous solution with a small amount of aggregation (205-344 nm), as studied by dynamic light scattering. In addition, they also exhibited large differences in thermal behaviors depending on the nature of different surface groups. Experimental results showed that these DLSPs had good solubility in aqueous solutions (ca. 10-25 mg/mL) and could greatly enhance the water solubility of hydrophobic drugs. Therefore, these amphiphilic DLSPs are promising candidates for controlled hydrophobic drug delivery.