Michael Kather

Functional Isoeugenol‐Modified Nanogel Coatings for the Design of Biointerfaces

A new route for the synthesis of functional aqueous nanogels decorated with a controlled amount of surface-drafted isoeugenol molecules has been developed. Obtained nanogels exhibit two key functions: a) antibacterial activity against different oral pathogens and b) cell-adhesive and -growth-promoting properties. Functional nanogels can be potentially used as building blocks in the design of bioactive coatings on various implants preventing infections and accelerating tissue regeneration.

In-line Monitoring of Monomer and Polymer Content During Microgel Synthesis Using Precipitation Polymerization via Raman Spectroscopy and Indirect Hard Modeling

This contribution presents in-line monitoring of microgel synthesis by precipitation polymerization based on Raman spectroscopy. The spectra are evaluated via multivariate Indirect Hard Modeling (IHM) regression. Therefore, mechanistic models of the pure component spectra for solvent, monomer, and microgel are created by a sum of adaptable parameterized peak functions (Gaussian–Lorentzian). Instead of individual calibrations for each analyte, one comprehensive model is calibrated to predict both the monomer and microgel fraction while ensuring a consistent mass balance. As a novelty, this leads to an in-line microgel quantification based on an interactive spectral model. The results show cross-validation errors (RMSECV) of monomer and microgel fractions as low as 0.028 wt % and 0.084 wt %, respectively. The ability of IHM to account for non-linear spectral changes was found to reduce the microgel RMSECV by a factor of two compared to linear CLS regression. The calibration model allows simultaneous observation of the decrease in monomer content and the formation of microgels. Long as well as short focus immersion optics reveal characteristic vibrations of the turbid microgel suspension, although long focus optics are influenced by scattering particles to a greater extent. Precise examination of the model proves that the prediction is robust against changes in microgel particle size or temperature, which opens up the application of Raman spectroscopy as a comprehensive process analytical technology in microgel synthesis.

Stimuli-responsive poly(N-vinylcaprolactam-co-2-methoxyethyl acrylate) core–shell microgels: facile synthesis, modulation of surface properties and controlled internalisation into cells†

Herein we report the synthesis of biocompatible stimuli-responsive core-shell microgels consisting of a poly(N-vinylcaprolactam) (PVCL) core and a poly(2-methoxyethyl acrylate) (PMEA) corona via one-step surfactant-free precipitation copolymerization. The copolymerization process was investigated by reaction calorimetry, microgel growth was monitored by in situ dynamic light scattering and the chemical structure of core-shell microgels was characterized by Raman spectroscopy. It was possible to incorporate up to 32 mol% MEA into the PVCL/MEA microgels without loss of colloidal stability and broadening of the size distribution. The core-shell morphology of microgels was confirmed by transverse magnetization relaxation 1H-NMR, dynamic light scattering (DLS), atomic force microscopy (AFM) and viscosimetry. By means of the NMR data, calorimetry and viscosity measurements it could be shown that MEA is mainly located in the microgel shell. This leads to hindered temperature-induced swelling and collapsing of the PVCL-core, as demonstrated by DLS measurements, due to the fact that the PMEA-shell exhibits a very low LCST around 5 °C. These results could also be confirmed by AFM: an increasing MEA-content leads to the formation of dense and compact core-shell microgels and results in a loss of their softness and deformability. Due to the presence of the PMEA-shell these microgels can be endocytosed much faster by HeLa cells maintaining their viability and can be suitable candidates for the design of drug carriers or imaging/diagnostic systems.

The next step in precipitation polymerization of N-isopropylacrylamide: particle number density control by monochain globule surface charge modulation

Many applications of poly(N-isopropylacrylamide) microgels necessitate robust control over particle size. Here we derive a scaling law for the particle size in precipitation polymerization of N-isopropylacrylamide. The average particle volume in the collapsed state is proportional to the monomer ([M]) and initiator ([I]) concentration according to p ∝ [M]5/3[I]−4/3. The derived power law agrees well with the experimentally observed particle volume. The derivation assumes the particle number density to depend on the initiation rate and the surface charge density of monochain globules generated during the nucleation phase. The model also qualitatively predicts the experimentally observed particle size trends when reaction temperature or chain transfer agent concentrations are varied. Reaction rate measurements show that the reaction proceeds initially as radical solution polymerization, therefore justifying the use of Flory–Schulz approximation for the globule surface charge density in this work.

From Batch to Continuous Precipitation Polymerization of Thermoresponsive Microgels

Microgels are commonly synthesized in batch experiments, yielding quantities sufficient to perform characterization experiments for physical property studies. With increasing attention on the application potential of microgels, little attention is yet paid to the questions (a) whether they can be produced continuously on a larger scale, (b) whether synthesis routes can be easily transferred from batch to continuous synthesis, and (c) whether their properties can be precisely controlled as a function of synthesis parameters under continuous flow reaction conditions. We present a new continuous synthesis process of two typical but different microgel systems. Their size, size distribution, and temperature-responsive behavior are compared in depth to those of microgels synthesized using batch processes, and the influence of premixing and surfactant is also investigated. For the surfactant-free poly( N-vinylcaprolactam) and poly( N-isopropylacrylamide) systems, microgels are systematically smaller, while the actual size is depending on the premixing of the reaction solutions. However, by the use of a surfactant, the size difference between batch and continuous preparation diminishes, resulting in equal-sized microgels. Temperature-induced swelling-deswelling of microgels synthesized under continuous flow conditions was similar to that of their analogues synthesized using the batch polymerization process. Additionally, investigation of the internal microgel structure using static light scattering showed no significant changes between microgels prepared under batch and continuous conditions. The work encourages synthesis concepts of sequential chemical conditions in continuous flow reactors to prepare precisely tuned new microgel systems.

Kinetic Modeling of Precipitation Terpolymerization for Functional Microgels

Abstract Microgels based on poly(N-isopropylacrylamide)- and poly(N-vinylcaprolactam) can be synthesized by precipitation polymerization. To get a better insight into the kinetics of the microgel synthesis, a model-based approach is pursued. Herein, the approach proposed by Janssen et al. (2017) is extended to the terpolymerization system. The kinetic model for a two-phase terpolymerization is combined with parameter values from quantum mechanical calculations. The remaining unknown parameter values are estimated from experimental data using reaction calorimetry and Raman spectroscopy. Acceptable agreement of simulation and experimental measurements is obtained. The prediction of the gel phase growth is combined with the consumption of comonomers and the cross-linker N,N’-methylenebis(acrylamide) to predict the average distribution of comonomers, thus giving insight into the microgel structure. The resulting particle structures indicate uniform N-vinylcaprolactam and N-isopropylacrylamide compositions in the core and an outer layer with a high N-vinylcaprolactam fraction, while the cross-linker distribution decreases from core to shell.