Iron Oxide Nanoparticle-Based Magnetic Resonance Method to Monitor Release Kinetics from Polymeric Particles with High Resolution

A new method to precisely monitor rapid release kinetics from polymeric particles using super paramagnetic iron oxide nanoparticles, specifically by measuring spin–spin relaxation time (<i>T</i>₂), is reported. Previously, we have published the formulation of logic gate particles from an acid-sensitive poly-β-aminoester ketal-2 polymer. Here, a series of poly-β-aminoester ketal-2 polymers with varying hydrophobicities were synthesized and used to formulate particles. We attempted to measure fluorescence of released Nile red to determine whether the structural adjustments could finely tune the release kinetics in the range of minutes to hours; however, this standard technique did not differentiate each release rate of our series. Thus, a new method based on encapsulation of iron oxide nanoparticles was developed, which enabled us to resolve the release kinetics of our particles. Moreover, the kinetics matched the relative hydrophobicity order determined by octanol–water partition coefficients. To the best of our knowledge, this method provides the highest resolution of release kinetics to date

Biocompatible Polymeric Nanoparticles Degrade and Release Cargo in Response to Biologically Relevant Levels of Hydrogen Peroxide

Oxidative stress is caused predominantly by accumulation of hydrogen peroxide and distinguishes inflamed tissue from healthy tissue. Hydrogen peroxide could potentially be useful as a stimulus for targeted drug delivery to diseased tissue. However, current polymeric systems are not sensitive to biologically relevant concentrations of H₂O₂ (50–100 μM). Here we report a new biocompatible polymeric capsule capable of undergoing backbone degradation and thus release upon exposure to such concentrations of hydrogen peroxide. Two polymeric structures were developed differing with respect to the linkage between the boronic ester group and the polymeric backbone: either direct (<b>1</b>) or via an ether linkage (<b>2</b>). Both polymers are stable in aqueous solution at normal pH, and exposure to peroxide induces the removal of the boronic ester protecting groups at physiological pH and temperature, revealing phenols along the backbone, which undergo quinone methide rearrangement to lead to polymer degradation. Considerably faster backbone degradation was observed for polymer <b>2</b> over polymer <b>1</b> by NMR and GPC. Nanoparticles were formulated from these novel materials to analyze their oxidation triggered release properties. While nanoparticles formulated from polymer <b>1</b> only released 50% of the reporter dye after exposure to 1 mM H₂O₂ for 26 h, nanoparticles formulated from polymer <b>2</b> did so within 10 h and were able to release their cargo selectively in biologically relevant concentrations of H₂O₂. Nanoparticles formulated from polymer <b>2</b> showed a 2-fold enhancement of release upon incubation with activated neutrophils, while controls showed a nonspecific response to ROS producing cells. These polymers represent a novel, biologically relevant, and biocompatible approach to biodegradable H₂O₂-triggered release systems that can degrade into small molecules, release their cargo, and should be easily cleared by the body