Polymerization of benzoxazines and thermal degradation mechanisms of polybenzoxazines were investigated using the direct pyrolysis mass spectrometry (DP-MS) technique. The benzoxazine structures were based on phenol and aniline and on bisphenol-A and methylamine or aniline. Polymerizations of the benzoxazines were carried out by curing them at elevated temperatures without addition of initiator or catalyst. DP-MS data showed the presence of chains generated by opposing polymerization reaction pathways indicating quite complex structures for the polybenzoxazines under investigation. Thermal decomposition of polybenzoxazines was started by the cleavage of methylamine or aniline linkages. It was determined that polybenzoxazines based on phenol were more stable than the corresponding bisphenol-A-based polybenzoxazines, while those based on methylamine were more stable than the corresponding polybenzoxazines incorporating aniline. Thus, it can be concluded that the presence of bulky groups decreased the extent of crosslinking which in return decreased the thermal stability. © 2012 Society of Chemical Industry

Background Reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, trigger biodegradation of polymer-based nanoparticles (NPs) bearing pinacol-type boronic ester groups. These NPs may selectively release their cargo, in this case paclitaxel (PTX), at the high levels of ROS present in the intracellular environment of inflamed tissues and most tumors. Purpose The main objective was to determine anti-tumor efficacy of PTX-loaded ROS-sensitive NPs and to examine whether macrophage infiltration had any impact on treatment efficacy. Methods NPs were synthesized and their characteristics in the presence of H 2 O 2 were demonstrated. Both confocal microscopy as well as flow cytometry approaches were used to determine degradation of ROS-sensitive NPs. HeLa cells were cultured in vitro and used to establish tumor xenografts in nude mice. In vivo experiments were performed to understand toxicity, biodistribution and anti-tumor efficacy of the NPs. Moreover, we performed immunohistochemistry on tumor sections to study infiltration of M1 and M2 subsets of macrophages. Results We demonstrated that PTX delivered in NPs containing a ROS-sensitive polymer exhibits a better anti-tumor efficacy than PTX in NPs containing ROS-non-sensitive polymer, free PTX or Abraxane ® (nab-PTX). The biodistribution revealed that ROS-sensitive NPs exhibit retention in liver, spleen and lungs, suggesting a potential to target cancer metastasizing to these organs. Finally, we demonstrated a correlation between infiltrated macrophage subsets and treatment efficacy, possibly contributing to the efficient anti-tumor effects. Conclusion Treatment with ROS-sensitive NPs containing PTX gave an improved therapeutic effect in HeLa xenografts than their counterpart, free PTX or nab-PTX. Our data revealed a correlation between macrophage infiltration and efficiency of the different antitumor treatments, as the most effective NPs resulted in the highest infiltration of the anti-tumorigenic M1 macrophages.