Alkanethiol Molecular Barriers for Controlling Small Molecule Release Kinetics from a Microgel-Based Reservoir Device

Abstract

Poly­(N-isopropylacrylamide)-co-acrylic acid microgel-based reservoir devices were constructed by “sandwiching” a single layer of microgels between two thin Au layers (all on a glass support). The microgels were loaded with the model drug crystal violet (CV) utilizing the electrostatic interactions between deprotonated acrylic acid (AAc) and the positively charged CV; release can be triggered from the microgels by neutralizing the deprotonated AAc groups at acidic conditions. Alkanethiols of different alkyl chain lengths and polarities were immobilized on the upper Au layer of the device, and the release rate of the model drug CV from the microgel layer, after acid neutralization, was assessed. We found that the CV release rate was the highest when the alkyl chain length was short and contained a hydrophilic moiety. Conversely, the release rate was hindered by the presence of thiols with long alkyl chain lengths and with no hydrophilic moiety. We explain this phenomenon by quantifying the thiol’s ability to hinder acid penetration into the microgel layer, and the ability of free CV to pass through the upper Au layer and into the solution. Utilizing various thiols and mixed thiol layers, we are able to tune release profiles from these reservoir devices to potentially achieve array devices with precisely tuned small molecule release profiles.

Surface‐Bound Microgels for Separation, Sensing, and Biomedical Applications

“…Guo et al followed this study by adding a self-assembled alkane-thiol coating on the gold overlayer to reduce the CV diffusion rate and enable accurate monitoring of the CV transport. [230] The team found that short alkane chains (C-2 to C-6) displaying hydrophilic terminal groups increased the diffusion rate up to 5-fold compared to unmodified etalons. At the same time, long-chain hydrocarbons (C-11 to C-15) slowed CV diffusion from the sensor by nearly 10-fold.…”

A pH and Temperature Dual-Responsive Microgel-Embedded, Adhesive, and Tough Hydrogel for Drug Delivery and Wound Healing

“…At pH < 4.25, the PAAc chains are protonated and become neutralized. 44,45 The anionic charge property of the microgels also enables their interaction with cationic proteins. 46 For example, high protein drug (cytochrome c) loading capacity (more than 9.7 × 10 5 protein molecules/ microgel particle) has been achieved in a previous study due to the formation of the polymer (PNIPAAm-co-AAc)−protein complexes and the porous structure of the microgels.…”