Tracking immune-related cell responses to drug delivery microparticles in 3D dense collagen matrix.

Beyond the therapeutic purpose, the impact of drug delivery microparticles on the local tissue and inflammatory responses remains to be further elucidated specifically for reactions mediated by the host immune cells. Such immediate and prolonged reactions may adversely influence the release efficacy and intended therapeutic pathway. The lack of suitable in vitro platforms limits our ability to gain insight into the nature of immune responses at a single cell level. In order to establish an in vitro 3D system mimicking the connective host tissue counterpart, we utilized reproducible, compressed, rat-tail collagen polymerized matrices. THP1 cells (human acute monocytic leukaemia cells) differentiated into macrophage-like cells were chosen as cell model and their functionality was retained in the dense rat-tail collagen matrix. Placebo microparticles were later combined in the immune cell seeded system during collagen polymerization and secreted pro-inflammatory factors: TNFα and IL-8 were used as immune response readout (ELISA). Our data showed an elevated TNFα and IL-8 secretion by macrophage THP1 cells indicating that Placebo microparticles trigger certain immune cell responses under 3D in vivo like conditions. Furthermore, we have shown that the system is sensitive to measure the differences in THP1 macrophage pro-inflammatory responses to Active Pharmaceutical Ingredient (API) microparticles with different API release kinetics. We have successfully developed a tissue-like, advanced, in vitro system enabling selective "readouts" of specific responses of immune-related cells. Such system may provide the basis of an advanced toolbox enabling systemic evaluation and prediction of in vivo microparticle reactions on human immune-related cells.

Hemostatic polymers: the concept, state of the art and perspectives.

This article presents a critical overview of the most significant developments in the use of polymers as hemostatic agents. The materials have been divided into two groups, which are, naturally occurring and synthetic. Remarkable examples include collagen, chitosan, bovine serum albumin/glutaraldehyde hydrogels, poly(cyanoacrylate)s and poly(alkylene oxide)s. The different mechanisms for their modes of action as well as the structural features that are believed to induce hemostasis are discussed. Finally, an overview of the future challenges is given.

PolyPEGA with predetermined molecular weights from enzyme-mediated radical polymerization in water.

The preparation of acrylic polymers with predetermined molecular weights using metalloenzymes as catalysts, ascorbic acid as reducing agent and alkyl halides as initiators is reported. The mechanism of polymerization resembles an ARGET ATRP process.

Investigation of metal ligand affinities of atom transfer radical polymerization catalysts with a quadrupole ion trap.

An electrospray ionization mass spectrometer equipped with a quadrupole ion trap as the mass analyzer provided a powerful tool for the investigation of metal ligand affinities of catalysts for atom transfer radical polymerization. It allowed, in particular, (i) the identification, in a library of ligands, of the most stable, and thus active, copper catalysts; (ii) the assessment of the effects of the reaction medium on the relative stabilities of the catalyst complexes; and (iii) the evaluation of the influence of the nature of the ligand on both the complex halogenophilicity and the metal-ligand stabilities in the gas-phase.

Rapid screening of atom transfer radical polymerization catalysts by electrospray ionization mass spectrometry.

An ESI-MS-based methodology allows for a rapid assay of ATRP catalyst performance without prior polymerization experiments.

Fourier transform ion mobility measurement of chain branching in mass-selected, chemically trapped oligomers from methylalumoxane-activated, metallocene-catalyzed polymerization of ethylene.

Fourier transform ion mobility spectrometry is used to determine the branching in mass-selected, chemically trapped oligomers produced in the polymerization of ethylene by a metallocene catalyst activated by methylalumoxane. The measured branching is included in a kinetic analysis to extract the activation energies for the elementary steps in polyethylene formation. Propagation, chain transfer, and chain walking have activation energies of 4.1, 11, and 11 kcal/mol.

Chain transfer to aluminium in MAO-activated metallocene-catalyzed polymerization reactions.

Chemical trapping of metal-bound oligomeric chains during the MAO-activated, metallocene-catalyzed polymerization of ethylene identify the two observed chain-bearing species to be alkylzirconocenium species and higher alkyl aluminiums, consistent with a proposed mechanism.

Measuring rate constants for active species in the polymerization of ethylene by MAO-activated metallocene catalysts by electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) of MAO-activated metallocene-catalyzed polymerizations quenched with carbodiimides provides a method for the determination of rate constants in Ziegler-Natta polymerizations.