Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase Activity, While Driving Potency and Aqueous Solubility.

An unmet medical need remains for patients suffering from dry eye disease (DED). A fast-acting, better-tolerated noncorticosteroid anti-inflammatory eye drop could improve patient outcomes and quality of life. Herein, we describe a small-molecule drug discovery effort to identify novel, potent, and water-soluble JAK inhibitors as immunomodulating agents for topical ocular disposition.

Discovery and Preclinical Development of Novel Intraocular Pressure-Lowering Rho Kinase Inhibitor: Corticosteroid Conjugates.

A new class of ocular steroids designed to mitigate steroid-induced intraocular pressure (IOP) elevation while maintaining anti-inflammatory activity was developed. Herein is described the discovery and preclinical characterization of ROCK'Ster compound . Codrugs consisting of a Rho kinase inhibitor (ROCKi) and a corticosteroid were synthesized.

High-resolution PFPE-based molding techniques for nanofabrication of high-pattern density, sub-20 nm features: a fundamental materials approach.

Several perfluoropolyether (PFPE)-based elastomers for high-resolution replica molding applications are explored. The modulus of the elastomeric materials was increased through synthetic and additive approaches while maintaining relatively low surface tension values (<25 mN/m). Using large area (>4 in.

The pursuit of a scalable nanofabrication platform for use in material and life science applications.

In this Account, we describe the use of perfluoropolyether (PFPE)-based materials that are able to accurately mold and replicate micro- and nanosized features using traditional techniques such as embossing as well as new techniques that we developed to exploit the exceptional surface characteristics of fluorinated substrates. Because of the unique partial wetting and nonwetting characteristics of PFPEs, we were able to go beyond the usual molding and imprint lithography approaches and have created a technique called PRINT (Particle [or Pattern] Replication In Nonwetting Templates). PRINT is a distinctive "top-down" fabrication technique capable of generating isolated particles, arrays of particles, and arrays of patterned features for a plethora of applications in both nanomedicine and materials science.

The Patterning of Sub-500 nm Inorganic Oxide Structures.

Elastomeric perfluoropolyether molds are applied to pattern arrays of sub-500 nm inorganic oxide features. This versatile soft-lithography technique can be used to pattern a wide range of materials; in this work inorganic oxides including TiO2 , SnO2 , ZnO, ITO, and BaTiO3 are patterned on a variety of substrates with different aspect ratios. An example of TiO2 posts is shown in the figure.