From an epoxide monomer toolkit to functional PEG copolymers with adjustable LCST behavior.

The lower critical solution temperature (LCST) behavior of novel poly(ethylene glycol) (PEG)-based copolymers bearing multiple functional groups, obtained by anionic ring-opening (co)polymerization (AROP), has been investigated. Variable comonomer ratios of ethylene oxide (EO) and the corresponding oxiranes isopropylidene glyceryl glycidyl ether (IGG), ethoxyl vinyl glycidyl ether (EVGE), allyl glycidyl ether (AGE), or N,N-dibenzyl amino glycidyl (DBAG), particularly designed to implement functional groups at the PEG backbone, were found to influence the LCST behavior. Sharp transitions from translucent to opaque solutions, comparable to other well-established stimuli-responsive polymers, were observed at temperatures ranging from 9 to 82 °C. The influence of the side group hydrophobicity could be quantified by the comparison of the different copolymer systems observed.

Introducing an amine functionality at the block junction of amphiphilic block copolymers by anionic polymerization strategies.

A series of block copolymers bearing a single amino in-chain functionality was synthesized via anionic polymerization of styrene and ethylene oxide. By means of both a conventional and a continuous setup, living polystyrene was quantitatively end functionalized with an oxirane (DBAG) prior to the polymerization of the poly(ethylene oxide) segment. The in-chain amine was conjugated with a fluorescent dye.

Multifunctional Poly(ethylene glycol)s.

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and defined with state-of-the-art characterization techniques-for example real-time (1)H NMR spectroscopy monitoring of the EO polymerization kinetics-this emerging class of polymers embodies a powerful platform for bio- and drug conjugation.

Poly(ethylene glycol-co-allyl glycidyl ether)s: a PEG-based modular synthetic platform for multiple bioconjugation.

A series of random copolymers comprising ethylene oxide (EO) and 0-100% allyl glycidyl ether (AGE) has been prepared by anionic ring-opening polymerization with molecular weights between 5000 and 13,600 g/mol and polydispersity indices in the range of 1.04-1.19. As key for the homogeneity of the PEG conjugates, real-time ¹H NMR polymerization kinetics, ¹³C NMR analysis of triad sequence distribution, and analysis of the thermal behavior by differential scanning calorimetry (DSC) revealed a distinctive random copolymer structure. Via thiol-ene coupling (TEC), showing mainly "click" characteristics and nearly quantitative yields, PEG derivatives with multiple amino, carboxy, or hydroxy functionalities have been prepared, providing suitable reactivities for further attachment. Without further modification, P(EO-co-AGE)s were conjugated with cysteine or the tripeptide glutathione (GSH) via TEC, resulting in well-defined hybrid materials with multiple peptide units conjugated to the PEG backbone. The results demonstrate superior loading capacity of the copolymers in comparison to the PEG homopolymer.

Partially quarternized amino functional poly(methacrylate) terpolymers: versatile drug permeability modifiers.

Partially quarternized poly(methacrylate) terpolymers (Q-BBMCs) have been synthesized, based on the basic butylated methacrylate copolymer (BBMC/EUDRAGIT E), an excipient approved by the Food and Drug Administration (FDA) and to date mainly applied for tablet coatings. Via straightforward polymer modification reactions, a series of Q-BBMCs with quarternization degrees of 22%, 42%, and 65% has been prepared. Apical to basolateral transport across Caco-2 cell monolayers was investigated, employing the paracellular transported compounds trospium and mannitol. At pH 6.5 quarternization resulted in increased permeation enhancement up to 2.8-fold compared to BBMC, that is, up to 7.3-fold compared to control. Moreover, measurements of the transepithelial electrical resistance (TEER) revealed a special advantage of the quarternized poly(methacrylate) terpolymers with respect to the pH range, in which the polymers exhibit biological activity as permeation enhancers. Whereas at pH 6.5 TEER dropped within 30 min below 30% of the initial value for all polymers, at pH 7.4 this effect solely occurred for Q-BBMCs, meaning a significant extension of the pH range relevant for drug permeation. In a subsequent period of 6 h, also excellent recovery was observed.

Hetero-Multifunctional Poly(ethylene glycol) Copolymers with Multiple Hydroxyl Groups and a Single Terminal Functionality.

Hetero-multifunctional poly(ethylene glycol-co-glycerol) random copolymers with multiple hydroxyl functionalities and a single terminal functionality have been prepared by copolymerization of ethylene oxide (EO) and ethoxy ethyl glycidyl ether (EEGE) with the use of a suitable initiator, introducing a protected amino group or a double bond, respectively. Acidic deprotection was used for removal of the acetal protecting groups in the chain, and the terminal amino group was regenerated by catalytic hydrogenation. A series of copolymers with narrow polydispersity was obtained, varying comonomer fractions from 3 to 67% and molecular weights in the range of 5 000-32 000 g · mol(-1) (1.05 < $\overline M _{\rm w} /\overline M _{\rm n}$ < 1.25). Molecular and thermal characterization was carried out using (1) H- and (13) C NMR, SEC and differential scanning calorimetry (DSC).