A click chemistry-based, free radical-initiated delivery system for the capture and release of payloads

AbstractClick chemistries are efficient and selective reactions that have been leveraged for multi-stage drug delivery. A multi-stage system allows independent delivery of targeting molecules and drug payloads, but targeting first-phase materials specifically to disease sites remains a challenge. Stimuli-responsive systems are an emerging strategy where common pathophysiological triggers are used to target payloads. Oxidative stress is widely implicated in disease, and we have previously demonstrated that reactive oxygen species (ROS) can crosslink and immobilize polyethylene glycol diacrylate (PEGDA) in tissue mimics. To build on these promising results, we present a two-step, catch-and-release system using azide-DBCO click chemistry and demonstrate the capture and eventual release of a fluorescent payload at defined times after the formation of a PEGDA capturing net. The azide component is included with radical-sensitive PEGDA, and the payload is conjugated to the DBCO group. In cell-free and cell-based tissue mimic models, azides were incorporated at 0–30% in the first-phase polymer net, and DBCO was delivered at 2.5–10 µM in the second phase to control payload delivery. The payload could be captured at multiple timepoints after initial net formation, yielding a flexible and versatile targeting system. Matrix metalloproteinase (MMP)-degradable peptides were incorporated into the polymer backbone to engineer fluorescent payload release by MMPs, which are broadly upregulated in diseases, through degradation of the capture net and directly from the DBCO. Taken together, this research demonstrates proof-of-principle for a responsive and clickable biomaterial to serve as a multi-potent agent for the treatment of diseases compounded by high free radicals

Efficient electrospray deposition of surfaces smaller than the spray plume

Abstract Electrospray deposition (ESD) is a promising technique for depositing micro-/nano-scale droplets and particles with high quality and repeatability. It is particularly attractive for surface coating of costly and delicate biomaterials and bioactive compounds. While high efficiency of ESD has only been successfully demonstrated for spraying surfaces larger than the spray plume, this work extends its utility to smaller surfaces. It is shown that by architecting the local “charge landscape”, ESD coatings of surfaces smaller than plume size can be achieved. Efficiency approaching 100% is demonstrated with multiple model materials, including biocompatible polymers, proteins, and bioactive small molecules, on both flat and microneedle array targets. UV-visible spectroscopy and high-performance liquid chromatography measurements validate the high efficiency and quality of the sprayed material. Here, we show how this process is an efficient and more competitive alternative to other conformal coating mechanisms, such as dip coating or inkjet printing, for micro-engineered applications