Poly(ethylene glycol) Conjugated Poly(lactide)-Based Polyelectrolytes: Synthesis and Formation of Stable Self-Assemblies Induced by Stereocomplexation

A series of pH-responsive amphiphilic poly(N,N-dimethylaminoethyl methacrylate)-block-poly(d-lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) conjugated with poly(ethylene glycol) (D-PDLA-D@PEG) and D-PLLA-D@PEG copolymers were synthesized using a combination of ring-opening polymerization and atom-transfer radical polymerization followed by sequential quaternization of PDMAEMA chains and azide-alkyne click reaction with alkyne-end PEG. Gel permeation chromatography, nuclear magnetic resonance, and Fourier transform infrared spectroscopy results demonstrate the successful synthesis of the copolymers, and the conjugated PEG percentages in the copolymers can be tuned by the feeding ratios in the quaternization reaction. Conjugating PEG onto the PDMAEMA segments also successfully facilitated the D-PDLA-D@PEG, D-PLLA-D@PEG, and its corresponding 1:1 D/L mixtures to be dissolved directly in aqueous solution at the desired concentration range without using any organic solvents unlike the copolymers without PEG conjugation (D-PDLA-D and D-PLLA-D). We demonstrate control over micellar size, charge, and stability via three different preparation pathways, i.e., solution pH, percentages of PEG conjugation in the copolymers, and formation of PLA stereocomplex in micellar core. Static and dynamic light scattering studies demonstrate that the size of the core-shell micelles increases when the solution pH is reduced due to the protonation of the PDMAEMA segments that caused the osmotic pressure within the micelle to increase until the micelles reached a maximum size. It is interesting to note that the micelles formed by 1:1 D/L mixtures have larger swelling ratios as well as aggregation number and hydrodynamic radius that do not change significantly with pH and dilution, respectively, as compared to micelles formed from individual D or L forms of the copolymers. The enhanced stability of the pH-responsive micelles prepared by direct dissolution of the 1:1 D/L mixtures of the PEG conjugated PLA-based polyelectrolytes in aqueous medium is attributed to the stereocomplex formation between PLLA and PDLA in the micellar core as confirmed by wide-angle X-ray scattering measurements.