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

Abstract

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.

Using Swellable Polymers as Structure Directing Scaffolds in Mesoporous Titania Synthesis

“…Bands at 2935 cm [26]. The band at 500 -800 cm −1 was assigned to Ti-O-Ti asymmetric stretching [19] [27] [28].…”

How Can We fine-tune Nanoparticles to Improve Drug delivery?

“…Magnetic nanoparticles attached to drug molecules can also be integrated with thermosresponsive materials which can be induced to release its therapeutic contents upon exposure to AMF. In another aspect, in a diseased cell, the pathological microenvironment changes in pH, concentration of glucose and reductive reagents, and the presence of specific enzyme [13,14]. These changes are manipulated in vivo to stimulate a trigger for drug release [15].…”

Micro- and nanostructures of polylactide stereocomplexes and their biomedical applications

“…48 PLA-based polyelectrolyte systems grafted with watersoluble PEG were synthesized by He and co-workers. 49 Poly (dimethylaminoethyl methacrylate) (PDMAEMA) was used as a building block of copolymers which are cationic polyelectrolytes and have antibacterial, haemostatic and anticancer activity. Micelles prepared from these copolymers and their stereocomplexes show a pH-dependent size.…”