Glucose-Responsive Nanoparticles for Rapid and Extended Self-Regulated Insulin Delivery.

To mimic native insulin activity, materials have been developed that encapsulate insulin, glucose oxidase, and catalase for glucose-responsive insulin delivery. A major challenge, however, has been achieving the desired kinetics of both rapid and extended release. Here, we tune insulin release profiles from polymeric nanoparticles by altering the degree of modification of acid-degradable, acetalated-dextran polymers.

Dual-responsive nanoparticles release cargo upon exposure to matrix metalloproteinase and reactive oxygen species.

Micellar nanoparticles were designed to be responsive to matrix metalloproteinases (MMPs) and reactive oxygen species (ROS), each of which is upregulated in the pathology of inflammatory diseases. The amphiphilic polymer-based nanoparticle system consists of a hydrophilic shell responsible for particle morphology change and aggregation, together with a hydrophobic block designed to release cargo in the presence of ROS.

Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release.

Histone deacetylase inhibitors (HDACi) target abnormal epigenetic states associated with a variety of pathologies, including cancer. Here, the development of a prodrug of the canonical broad-spectrum HDACi suberoylanilide hydroxamic acid (SAHA) is described. Although hydroxamic acids are utilized universally in the development of metalloenzyme inhibitors, they are considered to be poor pharmacophores with reduced activity in vivo.

Evaluating prodrug strategies for esterase-triggered release of alcohols.

Prodrugs are effective tools in overcoming drawbacks typically associated with drug formulation and delivery. Those employing esterase-triggered functional groups are frequently utilized to mask polar carboxylic acids and phenols, increasing drug-like properties such as lipophilicity. Herein we detail a comprehensive assessment for strategies that effectively release hydroxy and phenolic moieties in the presence of an esterase.

Readily accessible fluorescent probes for sensitive biological imaging of hydrogen peroxide.

Hydrogen peroxide is a major component of oxygen metabolism in biological systems that, when present in high concentrations, can lead to oxidative stress in cells. Noninvasive molecular imaging of H(2)O(2) using fluorogenic systems represents an effective way to detect and measure the accumulation of this metabolite. Herein, we detail the development of robust H(2)O(2)-sensitive fluorescent probes using a boronic ester trigger appended to the fluorophore through a benzyl ether linkage.

Investigation of self-immolative linkers in the design of hydrogen peroxide activated metalloprotein inhibitors.

A series of self-immolative boronic ester protected methyl salicylates and metal-binding groups with various linking strategies have been investigated for their use in the design of matrix metalloproteinase proinhibitors.

Probing presynaptic regulation of extracellular dopamine with iontophoresis.

Iontophoresis allows for localized drug ejections directly into brain regions of interest driven by the application of current. Our lab has previously adapted a method to quantitatively monitor iontophoretic ejections. Here those principles have been applied in vivo to modulate electrically evoked release of dopamine in anesthetized rats.

Activation of sulfonate ester based matrix metalloproteinase proinhibitors by hydrogen peroxide.

This study details the development of matrix metalloproteinase inhibitor prodrugs (proMMPi) that are activated in the presence of reactive-oxygen species (ROS). Conventional matrix metalloproteinase inhibitors (MMPi) utilize a zinc-binding group (ZBG) that chelates to the catalytic zinc(II) ion of matrix metalloproteinases (MMPs) to inhibit their activity. To create ROS-sensitive prodrugs, sulfonate esters were used as a protecting group for the ZBG to block their metal binding ability.