Martina H. Stenzel

Synthesis of glycopolymers and their multivalent recognitions with lectins

Synthetic carbohydrate ligands – also widely known as glycopolymers – are known to undergo numerous recognition events when interacting with their corresponding lectins. Interactions are greatly enhanced due to the multivalent character displayed by the large number of repeating carbohydrate units along the polymers (pendant glycopolymers); therefore, resulting what is called the “glycocluster effect”. Moreover, the strength and the availability of these multivalent recognitions can be tuned via the architecture of the glycopolymers. Hence, understanding the mechanistic interactions between the types of lectins (plant, animal, toxin and bacteria) with their synthetic ligands is crucial. This review focuses on the synthesis of pendant glycopolymers via various synthetic pathways (free radical polymerization, NMP, RAFT, ATRP, cyanoxyl mediated polymerization, ROP, ROMP and post-polymerization modification) and their interactions with their respectively lectins.

Acid-degradable polymers for drug delivery: a decade of innovation

Polymers that start degrading under acidic conditions are increasingly investigated as a pathway to trigger the release of drugs once the drug carrier reached the slightly acidic tumour environment or after the drug carrier has been taken up by cells, resulting in the localization of the polymer in the acidic endosomes and lysosomes. The advances in the design of acid-degradable polymers and drug delivery systems have been summarized and discussed in this review article. Various acid-labile groups such as acetals, orthoester, hydrazones, imines and cis-aconityl, that can undergo cleavage in slightly acidic conditions, have been employed to create polymer architectures or polymer-drug conjugates that can degrade under lysosomal and endosomal conditions, triggering the fast release of drugs or DNA.

Ultrafast click conjugation of macromolecular building blocks at ambient temperature.

Block copolymers in seconds: Catalyst-free, ambient-temperature click conjugation of individual polymer strands becomes possible using novel ATRP-derived cyclopentadienyl-capped polymers in an extremely rapid hetero-Diels-Alder cycloaddition with macromolecules equipped with electron-deficient dithioester end groups prepared by the RAFT process.

Honeycomb structured polymer films via breath figures

Among various structuring techniques, a water-driven ‘templating’ method for the fabrication of highly ordered porous membranes has been widely exploited for the past 17 years due to its versatility and robustness. This simple method relies on the formation of “breath figures” and the assembly of a polymer around them, resulting in the production of membranes with hexagonally arranged pores known as honeycomb structured porous polymer films/membranes. Herein, we present a review of relevant literature to stress on the advantages of this simple templating method compared with the wide range of conventional templating and lithographic techniques that have been previously used in the field. Furthermore, we present a comprehensive review on the progress in the field including the study of relevant variables, the materials that have been used, the combination of the method with other techniques, some current and potential applications for the membranes as well as characterization techniques.

Honeycomb structured porous films prepared from carbohydrate based polymers synthesized via the RAFT process

Carbohydrate based polystyrene was synthesized via RAFT polymerization. The RAFT agents were based on α-D-glucose, β-cyclodextrin and modified cellulose to obtain polystyrene with a polar head or polystyrene with a star or comb structure, respectively. The polymerizations were carried out in different solvents. The molecular weight of the linear polymer was found to develop according to the expected values, but the synthesis of the carbohydrate based polymers was influenced by other parameters. The molecular weight for the star polymer synthesis showed a pronounced deviation due to the reduced accessibility of the RAFT group at higher conversions of the polymerization. Films of these carbohydrate containing polystyrenes were cast from carbon disulfide and dichloromethane producing highly regular honeycomb structured films with pore diameters between 0.5 and 4 µm. The pore size was influenced by the polymers used as well as by the casting conditions.

Modification of polysaccharides through controlled/living radical polymerization grafting - Towards the generation of high performance hybrids

This review covers the literature concerning the modification of polysaccharides through controlled radical polymerizations (NMP, ATRP and RAFT). The different routes to well-defined polysaccharide-based macromolecules (block and graft copolymers) and graft-functionalized polysaccharide surfaces as well as the applications of these polysaccharide-based hybrids are extensively discussed.

Thiol–yne and Thiol–ene “Click” Chemistry as a Tool for a Variety of Platinum Drug Delivery Carriers, from Statistical Copolymers to Crosslinked Micelles

Statistical and block copolymers based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly[oligo(ethylene glycol) methylether methacrylate] (POEGMEMA) were modified with 4-pentenoic anhydride or 4-oxo-4-(prop-2-ynyloxy)butanoic anhydride to generate polymers with pendant vinyl or acetylene, respectively. Subsequent thiol-ene or thiol-yne reaction with thioglycolic acid or 2-mercaptosuccinic acid leads to polymers with carboxylate functionalities, which were conjugated with cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) to generate a drug carrier for Pt-drugs. Only the polymers modified with 2-mercaptosuccinic acid resulted in the formation of soluble well-defined polymers with gel formation being prevented. Due to the hydrophobicity of the drug, the block copolymers took on amphiphilic character leading to micelle formation. The micelles were in addition crosslinked to further stabilize their structure. Pt-containing statistical copolymer, micelles, and crosslinked micelles were then tested regarding their cellular uptake by the A549 lung cancer cell line to show a superior uptake of crosslinked micelles. However, due to the better Pt release of the statistical copolymer, the highest cytotoxicity was observed with this type of polymer architecture.

Microgel stars viaReversible Addition Fragmentation Chain Transfer (RAFT) polymerisation — a facile route to macroporous membranes, honeycomb patterned thin films and inverse opal substrates

Arm first microgel polymers were successfully synthesised utilising Reversible Addition Fragmentation Chain Transfer (RAFT) polymerisation techniques. A functional prearm linear AB block copolymer intermediate, (polystyrene)-block-(polydivinylbenzene), was prepared via RAFT by simple one pot chain extension and arm coupling of a preprepared polystyrene macromer. The arms are coupled together via the residual unsaturation present in the polydivinylbenzene block by free radical means to form core-crosslinked microgels. It was found that the arm coupling process could be described by invoking a two-stage coupling system. The initial induction period consists of the formation of largely two-arm (on average) species. This is followed by a latter growth period, where true core-crosslinked microgels are formed consisting of polyarm clusters having 16 arms (on average) per cluster. These microgel materials were cast under specific conditions to form porous polymer films of varying quality. Image analysis of these films demonstrated the importance of the linear component : microgel component ratio in determining both a uniform pore size and the formation of a hexagonal close packed array of pores.

Synthesis of Star Polymers using RAFT Polymerization: What is Possible?

Various pathways to generate star polymers using reversible addition?fragmentation transfer (RAFT) are discussed. Similar to other polymerization techniques, star polymers can be generated using arm-first and core-first approaches. Unique to the RAFT process is the subdivision of the core-first approach into the R-group and Z-group approaches, depending on the attachment of the RAFT agent to the multifunctional core. The mechanism of the R- and Z-group approaches are discussed in detail and it is shown that both techniques have to overcome difficulties arising from termination reactions. Termination reactions were found to broaden the molecular weight. However, these side reactions can be limited by careful design of the synthesis. Considerations include RAFT and radical concentration, number of arms, type of RAFT agent and monomer. Despite obvious challenges, the RAFT process is highly versatile, allowing the synthesis of novel polymer architectures such as poly(vinyl acetate) and poly(vinyl pyrrolidone) star polymers.

Drug Carriers for the Delivery of Therapeutic Peptides

Peptides take on an increasingly important role as therapeutics in areas including diabetes, oncology, and metabolic, cardiovascular, and infectious diseases. In addition, many peptides such as insulin have been employed for many years. A challenge in the administration of peptide drugs is their often low hydrolytic stability, as well as other problems that are common to any drug treatment such as systemic distribution. There is a significant attention in the literature of protein drugs and their delivery strategies, but not many overviews are specifically dedicated to peptides. In this review, the different approaches to deliver peptides have been summarized where the focus is only on drug carriers based on organic materials. Initial discussion is on different methods of polymer-peptide conjugation before being followed by physical encapsulation techniques, which is divided into surfactant-based techniques and polymer carriers. Surfactant-based techniques are dominated by liposome, microemulsions and solid-lipid nanoparticles. The field widens further in the polymer field. The delivery of peptides has been enhanced using polymer-decorated liposomes, solid microspheres, polyelectrolyte complex, emulsions, hydrogels, and injectable polymers. The aim of this article is to give the reader an overview over the different types of carriers.