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In this report we demonstrate methanol as an effective degenerative chain transfer agent to control the cationic polymerisation (initiated by triflic acid) of electron rich p-alkoxy-styrenes, such as p-methoxystyrene (p-MOS). Kinetic analysis revealed that an induction period occurs initially during which free cationic polymerisation occurs at low monomer conversion before proceeding through the pseudo first order rate, analogous to the RAFT mechanism. Ethanol and isopropanol also demonstrated excellent control (Đ > 1.30), however, with an apparent increase in experimental molecular weight. Furthermore, methanol controlled polymers were successfully chain extended upon sequential monomer addition, demonstrating the ‘livingness’ of the alcohol mediated cationic polymerisation.

Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.

The synthesis of single-chain nanoparticles by palladium-catalyzed Sonogashira coupling between a terminal alkyne and a di-halo aryl cross-linker is reported. Statistical copolymers with trimethylsilyl protected alkyne groups pendent to the linear methacrylate back bones were synthesized using reversible addition-fragmentation chain transfer polymerization post polymerization de-protection providing terminal alkyne functionalized linear polymer chains. These linear polymer chains were intramolecularly cross-linked via bifunctional cross-linkers. The resulting well-defined covalently bonded nanoparticles were characterized via triple-detection size exclusion chromatography where MALS detector provided molecular weight information and viscometric detection characterizes particle size and conformations. The particle size could be readily tuned through polymer molecular weight and by degree of cross-linking. © 2015 Wiley Periodicals.

In this review we outline the various methods that have been explored to synthesize architecturally defined nanoparticles from discrete polymer chains, summarize the methods of characterization that are required to prove their formation and probe their morphology, and introduce a number of potential applications that are being explored currently. Given the small size of the nanostructures produced by these methods and the relative ease with which they can be tailored to specific end use applications it is likely such efforts will intensify in the coming years. So far, simple chemistry has been utilized and high-level characterization and modeling studies have been applied to understand the process by which these particles form and how they behave, both in the bulk and in solution. Although impossible to predict where this work will lead, we hope this “user's guide” will prove useful to the community as research on single-chain nanoparticles continues to evolve.

An efficient route to architecturally defined, sub-20 nm soft nanoparticles fabricated from single polymer chains via intramolecular photodimerization of pendant anthracene units is presented. Photodimerization is confirmed by the disappearance of the characteristic anthracene π-π* absorption peak at ≈360 nm measured by UV-vis spectroscopy. Size exclusion chromatography (SEC) with UV, multi-angle light scattering (MALS), and viscometric detection confirms that as photodimers form, the chains fold to form nanoparticles, demonstrated by shifts in the SEC traces to longer retention times as a function of increased irradiation time. These shifts indicate a reduction in hydrodynamic radius, corroborated and quantified by viscometric data. MALS detector traces reveal the presence of a small amount of chain-chain coupling during this process, but confirm that this is primarily a single-chain phenomenon. Electron microscopy provides visual confirmation of nanoparticle formation. The intra-chain photodimerization of anthracene-functionalized polymers in dilute solution is presented as an efficient route to architecturally defined nanoparticles. UV-vis spectroscopy confirms anthracene photodimerization, triple detection SEC confirms that these intramolecular linkages induce chains to fold into nanoparticles. TEM images reveal architecturally defined, oblong nanoparticles in the sub-20 nm size regime. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

We highlight here recent work from our laboratory on the subject of fabricating nanostructures from single polymer chains. These so-called single-chain nanoparticles are synthesized by inducing intra-molecular cross-linking on discrete macromolecules in dilute solution. Among the biggest challenges in this rapidly expanding area of research is reliable and accurate means to characterize this process. In this paper, we review our preferred method of characterization: size exclusion chromatography featuring multiple modes of detection. Multi-angle light scattering in conjunction with a concentration detector can provide absolute molecular weight data; viscometric detection can provide information about solution size and conformation. Correlation of these data provides a simple and robust way to quantify the process by which we fold single polymer coils into architecturally defined unimolecular nanostructures.