RAFT Emulsion Polymerization of Styrene Using a Poly((N,N-dimethyl acrylamide)-co-(N-isopropyl acrylamide)) mCTA: Synthesis and Thermosensitivity

Thermoresponsive poly((N,N-dimethyl acrylamide)-co-(N-isopropyl acrylamide)) (P(DMA-co-NIPAM)) copolymers were synthesized via reversible addition−fragmentation chain transfer (RAFT) polymerization. The monomer reactivity ratios were determined by the Kelen–Tüdős method to be rNIPAM = 0.83 and rDMA = 1.10. The thermoresponsive properties of these copo-lymers with varying molecular weights were characterized by visual turbidimetry and dynamic light scattering (DLS). The copolymers showed a lower critical solution temperature (LCST) in water with a dependence on the molar fraction of DMA in the copolymer. Chaotropic and kosmotropic salt anions of the Hofmeister series, known to affect the LCST of thermoresponsive polymers, were used as additives in the aqueous copolymer solutions and their influence on the LCST was demonstrated. Further on, in order to investigate the thermoresponsive behavior of P(DMA-co-NIPAM) in a confined state, P(DMA-co-NIPAM)-b-PS diblock copolymers were prepared via polymerization induced self-assembly (PISA) through surfactant-free RAFT mediated emulsion polymerization of styrene using P(DMA-co-NIPAM) as the macromolecular chain transfer agent (mCTA) of the polymerization. As confirmed by cryogenic transmission electron microscopy (cryoTEM), this approach yielded stabilized spherical micelles in aqueous dispersions where the PS block formed the hydrophobic core and the P(DMA-co-NIPAM) block formed the hydrophilic corona of the spherical micelle. The temperature-dependent behavior of the LCST-type diblock copolymers was further studied by examining the collapse of the P(DMA-co-NIPAM) minor block of the P(DMA-co-NIPAM)-b-PS diblock copolymers as a function of temperature in aqueous solution. The nanospheres were found to be thermosensitive by changing their hydrodynamic radii almost linearly as a function of temperature between 25 °C and 45 °C. The addition of kosmotropic salt anions, as a potentially useful tuning feature of micellar assemblies, was found to increase the hydrodynamic radius of the micelles and resulted in a faster collapse of the micelle corona upon heating.

Self-assembly of hydrophobic-amphiphilic diblock copolymers in solution

Thermoresponsive polymers are usually characterized by a locally amphiphilic chain structure and their self-assembly in solution is controlled, in particular, by the surface activity of the monomer units or side chains. We theoretically study the condensed state of a single diblock copolymer molecule consisting of a hydrophobic block and amphiphilic block with hydrophobic groups in the backbone and pendant polar groups. The equilibrium parameters of the polymer globules of different shapes are determined using the mean-field approach to determine the most favorable structure. Morphological diagrams of condensed macromolecules are presented depending on the chain length, amphiphilic block fraction, interaction parameters, and pendant volume and length. The diagrams are compared with those of a copolymer molecule with the same fraction of amphiphilic monomer units which are regularly distributed along the chain. The diblock copolymer molecule is found to form a single spherical or flattened particle, with the core from the hydrophobic block, or a granular micelle consisting of spherical or nearly spherical particles, in agreement with the experimental data in the literature. The optimal chain parameters for self-assembly into a stable single core-shell particle are predicted.

Synthesis and Characterization of Temperature-Responsive N-Cyanomethylacrylamide-Containing Diblock Copolymer Assemblies in Water

We have previously demonstrated that poly(N-cyanomethylacrylamide) (PCMAm) exhibits a typical upper-critical solution temperature (UCST)-type transition, as long as the molar mass of the polymer is limited, which was made possible through the use of reversible addition-fragmentation chain transfer (RAFT) radical polymerization. In this research article, we use for the first time N-cyanomethylacrylamide (CMAm) in a typical aqueous dispersion polymerization conducted in the presence of poly(N,N-dimethylacrylamide) (PDMAm) macroRAFT agents. After assessing that well-defined PDMAm-b-PCMAm diblock copolymers were formed through this aqueous synthesis pathway, we characterized in depth the colloidal stability, morphology and temperature-responsiveness of the dispersions, notably using cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and turbidimetry. The combined analyses revealed that stable nanometric spheres, worms and vesicles could be prepared when the PDMAm block was sufficiently long. Concerning the thermoresponsiveness, only diblocks with a PCMAm block of a low degree of polymerization (DPn,PCMAm < 100) exhibited a UCST-type dissolution upon heating at low concentration. In contrast, for higher DPn,PCMAm, the diblock copolymer nano-objects did not disassemble. At sufficiently high temperatures, they rather exhibited a temperature-induced secondary aggregation of primary particles. In summary, we demonstrated that various morphologies of nano-objects could be obtained via a typical polymerization-induced self-assembly (PISA) process using PCMAm as the hydrophobic block. We believe that the development of this aqueous synthesis pathway of novel PCMAm-based thermoresponsive polymers will pave the way towards various applications, notably as thermoresponsive coatings and in the biomedical field.

Chitosan-Based Biocompatible Copolymers for Thermoresponsive Drug Delivery Systems: On the Development of a Standardization System

Chitosan is a natural polysaccharide that is considered to be biocompatible, biodegradable and non-toxic. The polymer has been used in drug delivery applications for its positive charge, which allows for adhesion with and recognition of biological tissues via non-covalent interactions. In recent times, chitosan has been used for the preparation of graft copolymers with thermoresponsive polymers such as poly-N-vinylcaprolactam (PNVCL) and poly-N-isopropylamide (PNIPAM), allowing the combination of the biodegradability of the natural polymer with the ability to respond to changes in temperature. Due to the growing interest in the utilization of thermoresponsive polymers in the biological context, it is necessary to increase the knowledge of the key principles of thermoresponsivity in order to obtain comparable results between different studies or applications. In the present review, we provide an overview of the basic principles of thermoresponsivity, as well as a description of the main polysaccharides and thermoresponsive materials, with a special focus on chitosan and poly-N-Vinyl caprolactam (PNVCL) and their biomedical applications.

Hydrogen Bonds in Blends of Poly(N-isopropylacrylamide), Poly(N-ethylacrylamide) Homopolymers, and Carboxymethyl Cellulose

Recently, it was reported that the physical crosslinking exhibited by some biopolymers could provide multiple benefits to biomedical applications. In particular, grafting thermoresponsive polymers onto biopolymers may enhance the degradability or offer other features, as thermothickening behavior. Thus, different interactions will affect the different hydrogen bonds and interactions from the physical crosslinking of carboxymethyl cellulose, the lower critical solution temperatures (LCSTs), and the presence of the ions. This work focuses on the study of blends composed of poly(N-isopropylacrylamide), poly(N-ethylacrylamide), and carboxymethyl cellulose in water and water/methanol. The molecular features, thermoresponsive behavior, and gelation phenomena are deeply studied. The ratio defined by both homopolymers will alter the final properties and the gelation of the final structures, showing that the presence of the hydrophilic groups modifies the number and contributions of the diverse hydrogen bonds.