Stimuli‐responsive amphiphilic PDMAEMA‐b‐PLMA copolymers and their cationic and zwitterionic analogs

Abstract

In this work, the synthesis and characterization of novel amphiphilic diblock copolymers of poly(2-dimethylamino ethyl methacrylate)-b-poly(lauryl methacrylate), PDMAEMA-b-PLMA, using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique, are reported. The diblocks were successfully derivatized to cationic and zwitterionic block polyelectrolytes by quaternization and sulfobetainization of the PDMAEMA block, respectively. Furthermore, their molecular and physicochemical characterization was performed by using characterization techniques such as NMR and FTIR, size exclusion chromatography, light scattering techniques, and transmission electron microscopy. The structure of the diblock micelles, their behavior, and properties in aqueous solution were investigated under the effect of pH, temperature, and ionic strength, as PDMAEMA and its derivatives are stimuliresponsive polymers and exhibit responses to variations of at least one of these physicochemical parameters. These new families of stimuli-responsive block copolymers respond to changes of their environment giving interesting nanostructures, behavioral motifs, and properties, rendering them useful as nanocarriers for drug delivery and gene therapy.

Effects of Chemical Modifications on the Thermoresponsive Behavior of a PDMAEA-b-PNIPAM-b-POEGA Triblock Terpolymer

“…It has been reported in the literature [62,65,67] that the quaternization reactions utilized here are quantitative, and the tertiary amine groups convert to the quaternary amine group at almost 100% yields, as confirmed after conducting 1 H-NMR measurements. Consequently, the successful chemical modifications of the amine group on the side chain of PDMAEA block with quaternizing or sulfobetanizing agents were confirmed by the above-mentioned 1 H-NMR experiments.…”

“…As a result, it becomes less hydrophilic (lessened hydrogen bonding interactions with water molecules), leading to the formation of more compact aggregates. Moreover, it should be noted that at 25 • C, the obtained R h value is rather similar compared to the calculated length (L = 12) of the completely extended macromolecular chain (L = the number of the monomeric units of each block multiplied by 0.254, which corresponds to nearly the half micellar diameter for spherical core-shell micelles) [65], indicating that the formed aggregates may have micellar-like core-shell structures.…”

“…Its hydrophilicity decreases in the case of quaternization with iodohexane because of the existence of hydrophobic alkyl side chains on the Q 6 PDMAEA block [64]. Upon sulfobetainization reaction with 1,3-propanesultone, the solubility of the PDMAEA block in aqueous media decreases, as it is known from the literature that polyampholytes are less soluble in water [65]. Nevertheless, in all types of functionalization, the solubility of PDMAEA block is independent of solution pH.…”

Synthesis of (AB)n‐, AnBn‐, and AxBy‐type amphiphilic and double‐hydrophilic star copolymers by RAFT polymerization

“…The molecularweight control was achieved by using CDTP as the RAFT agent as was established from previous works. 40,42 AIBN was the radical initiator and the reaction took place in dioxane for 18 h. Subsequently, the PDMAEMA linear arms were reacted with the difunctional monomer EGDM leading to the formation of a crosslinked core in dioxane at 70 C for 24 h and the preparation of a PDMAEMA homostar. In this way, the CTA active groups were placed inside the crosslinked core of the star.…”

Poly(2‐[dimethylamino]ethyl methacrylate)‐b‐poly(hydroxypropyl methacrylate)/DNA polyplexes in aqueous solutions

“…[9][10][11][12] One of the most common nanocarriers used for such purpose is poly(2-[dimethylamino]ethyl methacrylate), a cationic pH and thermoresponsive polymer. [13,14] Cherng et al were one of the first to have successfully formed PMDAEMA-plasmid polyplexes via electrostatic interactions, [15] while others followed focusing on the optimal balance between transfection and toxicity by modifying molecular weight and/or copolymerization with biocompatible monomers. [16][17][18] Furthermore, new architectures were synthesized, such as diblocks, [19] triblocks, [20] grafted corona-shell-corona, [21] and stars [22] in order to provide proper DNA shielding, efficient complexation, and compaction and targeted delivery to the cells.…”