Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives

The living cationic ring-opening polymerization of 2-oxazolines has been studied in great detail since its discovery in 1966. The versatility of this living polymerization method allows copolymerization of a variety of 2-oxazoline monomers to give a range of tunable polymer properties that enable, for example, hydrophilic, hydrophobic, fluorophilic, as well as hard and soft materials to be obtained. However, this class of polymers was almost forgotten in the 1980s and 1990s because of their long reaction times and limited application possibilities. In the new millennium, a revival of poly(2-oxazoline)s has arisen because of their potential use as biomaterials and thermoresponsive materials, as well as the easy access to defined amphiphilic structures for (hierarchical) self-assembly. Recent developments that illustrate the potential of poly(2-oxazoline)s are discussed in this Review. In addition, the promising combination of poly(2-oxazoline)s and click chemistry is illustrated.

Poly(2‐oxazoline)s: A Polymer Class with Numerous Potential Applications

Numerous non-ionic thermally responsive homopolymers phase separate from their aqueous solutions upon heating. Far fewer neutral homopolymers are known to phase separate upon cooling. A systematic compilation of the polymers reported to exhibit thermoresponsive behaviour is presented in this review, includ- ing N-substituted poly((meth)acrylamide)s, poly(N-vinylamide)s, poly(oxazoline)s, protein-related polymers, poly(ether)s, polymers based on amphiphilic balance, and elastin-like synthetic polymers. Basic properties of aqueous solutions of these poly- mers are briefly described.

/pdf/non-ionic-thermoresponsive-polymers-in-water-3t5btprqf5.pdf

Non-ionic Thermoresponsive Polymers in Water

https://www.repository.cam.ac.uk/bitstream/1810/194887/1/Poly(2-oxazoline)%20in%20biological%20and%20biomedical%20application%20contexts.pdf

Poly(2-oxazolines) in biological and biomedical application contexts

Poly(ethylene imine)s (PEIs) are widely used in different applications, but most extensively investigated as non-viral vector systems. The high ability of cationic PEIs to complex and condense negatively charged DNA and RNA combined with their inherent proton sponge behavior accounts for the excellent efficiency in gene delivery. Further chemical modifications of the polymer expand the application potential, primarily aiming at increased transfection efficiency, cell selectivity and reduced cytotoxicity. Improvements in the synthesis of tailor-made PEIs in combination with new in-depth analytical techniques offer the possibility to produce highly purified polymers with defined structures. The contemporary strategies towards linear and branched poly(ethylene imine)s with modified surface characteristics, PEI-based copolymers as well as conjugates with bioactive molecules will be discussed. In this regard, the versatile branched PEIs have been successfully modified in a statistical manner, whereas the linear counterparts open avenues to design and synthesize well-defined architectures, in order to exploit their high potential in gene delivery.

Branched and linear poly(ethylene imine)-based conjugates: synthetic modification, characterization, and application

2-Aryl- and 2-alkyl-2-oxazolines have been polymerized to poly-(N-aroyl)aziridines and poly(N-acyl)aziridines, respectively, in the presence of boron trifluoride. The polymers obtained were glassy, light yellow resins with molecular weights ranging from 3500 to 7500 (35–50 oxazoline units per chain). The polymerization rates have been determined for several of these monomers. A polymerization mechanism is proposed.

D. P. Sheetz

Papers

Homopolymerization of 2‐alkyl‐ and 2‐aryl‐2‐oxazolines