Richard Hoogenboom

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

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(2-oxazoline)s: A polymer class with numerous potential applications

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.

Polymeric multilayer capsules for drug delivery

The advent of Layer-by-Layer (LbL) assembly to fabricate polymeric as well as hybrid multilayer thin films has opened exciting avenues for the design of multifunctional drug carriers with extreme control over their physico-chemical properties. These polymeric multilayer capsules (PMLC) are typically fabricated by sequential adsorption of polymers onto a spherical substrate with dimensions varying from 10 nm to several microns and larger. In this critical review, we give an overview of the recent advances in the field of PMLC with respect to drug delivery and point out how sophisticated capsule engineering can lead to well-defined drug carriers with unique properties (139 references).

Responsive biomimetic networks from polyisocyanopeptide hydrogels

Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells. The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen. As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum. Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model, we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications, in particular in the biomedical field.

Poly(2-Oxazoline)s – Are They More Advantageous for Biomedical Applications Than Other Polymers?

Poly(2-alkyl-2-oxazoline)s are biocompatible polymers with polypeptide-isomeric structures that are attracting increasing interest as biomaterials for drug, gene, protein, and radionuclide delivery. They are, however, still relatively new in comparison to other classes of hydrophilic water-soluble polymers already established for such use, including poly(ethylene oxide), polyvinylpyrrolidone, and polymethacrylamides such as poly[N-(2-hydroxypropyl)methacrylamide]. This feature article critically compares the synthetic aspects and physicochemical and biological properties of poly(2-alkyl-2-oxazoline)s and these commonly studied polymers in terms of their suitability for biomedical applications.

Layer-by-layer preparation of polyelectrolyte multilayer membranes for separation

Polymer membranes provide a highly promising platform for the development of an efficient and sustainable technique for separation. Ideally such membranes combine a high flux with a high selectivity requiring thin defect-free membranes. The layer by layer (LBL) assembly technique has proven to be a versatile and simple method for the fabrication of very thin polyelectrolyte multilayers making it highly suitable for the preparation of separation membranes. Recent developments in this field related to membrane preparation and their applications in separation processes are presented and discussed in this review. An overview of the different fabrication techniques of such membranes will be first provided. In addition, the formation mechanism and the parameters that can be varied to tune the properties of the membranes will be discussed. Finally, the potential applications of these membranes in different separation areas such as pervaporation, nanofiltration, solvent resistant nanofiltration, reverse osmosis, gas separation and forward osmosis will be addressed.

Synthesis of star-shaped poly(ε-caprolactone) via‘click’ chemistry and ‘supramolecular click’ chemistry

The synthesis of star-shaped poly(e-caprolactone) is described via azide–alkyne cycloaddition (‘click’ chemistry) and via self-assembly of polymeric ligands into [2 × 2] grid-like metal complexes (‘supramolecular click’ chemistry)

Soluble polymeric dual sensor for temperature and pH value

Two birds with one stone: A thermoresponsive copolymer (see picture, blue beads) bearing a pH-responsive solvatochromic dye (red beads) acts as the first dual sensor for temperature and pH value (black curve). When the hydrophilicity of the copolymer is increased by using a monomer with more hydrophilic side chains, the dual sensing capabilities are lost (red curve), thus providing new insights into the hydration of thermoresponsive polymers.

Aqueous polymeric sensors based on temperature-induced polymer phase transitions and solvatochromic dyes

This feature article provides, for the first time, an overview of the research that guided the way from fundamental studies of the thermo-responsive phase separation of aqueous polymer solutions to polymeric sensor systems. The incorporation of solvatochromic dyes into thermoresponsive polymers as well as the concepts of polymeric sensors are presented and discussed in detail.

Microwave-assisted synthesis and properties of a series of poly(2-alkyl-2-oxazoline)s

Microwave-assisted organic synthesis is a quickly expanding field of research. The fast non-contact (super)heating of the reaction mixtures has already resulted in many examples of increased reaction rates and improved yields. However, the number of investigations focusing on microwave-assisted polymerizations, and especially living/controlled polymerizations, is still limited. Following our recent success in accelerating the cationic ring-opening polymerization of 2-oxazolines, we report here our studies on the cationic polymerization of a series of linear 2-alkyl-2-oxazolines under microwave irradiation. The effect of chain length on the polymerization kinetics was investigated. Moreover, the microwave polymerization of 2-ethyl-2-oxazoline was further investigated by 1H-NMR spectroscopy to determine the active species during the polymerization. Besides the microwave polymerization of the linear 2-alkyl-2-oxazoline monomers, the thermal and surface properties of the resulting polymers were investigated by DSC and contact-angle measurements to study the effect of side-chain length on the polymer properties.