Matthew K. McBride

Extended release of high molecular weight hydroxypropyl methylcellulose from molecularly imprinted, extended wear silicone hydrogel contact lenses.

Symptoms of contact lenses induced dry eye (CLIDE) are typically treated through application of macromolecular re-wetting agents via eye drops. Therapeutic soft contact lenses can be formulated to alleviate CLIDE symptoms by slowly releasing comfort agent from the lens. In this paper, we present an extended wear silicone hydrogel contact lens with extended, controllable release of 120 kDa hydroxypropyl methylcellulose (HPMC) using a molecular imprinting strategy. A commercial silicone hydrogel lens was tailored to release approximately 1000 μg of HPMC over a period of up to 60 days in a constant manner at a rate of 16 μg/day under physiological flowrates, releasing over the entire range of continuous wear. Release rates could be significantly varied by the imprinting effect and functional monomer to template ratio (M/T) with M/T values 0, 0.2, 2.8, 3.4 corresponding to HPMC release durations of 10, 13, 23, and 53 days, respectively. Lenses had high optical quality and adequate mechanical properties for contact lens use. This work highlights the potential of imprinting in the design and engineering of silicone hydrogel lenses to release macromolecules for the duration of wear, which may lead to decreased CLIDE symptoms and more comfortable contact lenses.

Sustained in vivo release from imprinted therapeutic contact lenses.

In this paper, we demonstrate the successful in vivo extended release of a small molecular weight therapeutic, ketotifen fumarate (MW=425), from molecularly imprinted, therapeutic contact lenses. This is the first time that a steady, effective concentration of drug is maintained in the tear film from a contact lens for an extended period of time for the entire duration of lens wear. Poly(HEMA-co-AA-co-AM-co-NVP-co-PEG200DMA) soft contact lenses were prepared (100±5 μm thickness, diameter 11.8 mm, power zero), and a constant tear film concentration of 170±30 μg/mL was measured for up to 26 hrs in a New Zealand white rabbit model. The results showed a dramatic increase in ketotifen mean residence time (MRT) and bioavailability compared to topical drop therapy and drug soaked lenses. The MRT for imprinted lenses was 12.47±3.99 hrs, ~4 and 50 fold greater than non-imprinted lenses and 0.035% eye drops (Zaditor®), respectively. Furthermore, AUC(0-26 hrs) was 9 and 94 fold greater for imprinted lenses than non-imprinted lenses and eye drops, respectively. The results indicate that molecular imprinting provides an exciting rational engineering strategy for sustained release. It is clear that imprinted lenses are very promising combination devices and are much more effective and efficient delivery devices than eye drops.

Photoinduced Plasticity in Cross-Linked Liquid Crystalline Networks

Photoactivated reversible addition fragmentation chain transfer (RAFT)-based dynamic covalent chemistry is incorporated into liquid crystalline networks (LCNs) to facilitate spatiotemporal control of alignment, domain structure, and birefringence. The RAFT-based bond exchange process, which leads to stress relaxation, is used in a variety of conditions, to enable the LCN to achieve a near-equilibrium structure and orientation upon irradiation. Once formed, and in the absence of subsequent triggering of the RAFT process, the (dis)order in the LCN and its associated birefringence are evidenced at all temperatures. Using this approach, the birefringence, including the formation of spatially patterned birefringent elements and surface-active topographical features, is selectively tuned by adjusting the light dose, temperature, and cross-linking density.

Initiatorless Photopolymerization of Liquid Crystal Monomers.

Liquid crystal monomers are widely employed in industry to prepare optical compensating films as well as extend or enhance the properties of certain display modes. Because of the thermotropic nature of liquid crystalline materials, polymerization of liquid crystalline monomers (sometimes referred to as reactive mesogens) is often initiated by radical photoinitiation (photopolymerization) of (meth)acrylate functional groups. Here, we report on the initiatorless photopolymerization of commercially available liquid crystalline monomers upon exposure to 365 nm UV light. Initiatorless polymerization is employed to prepare thin films as well as polymer stabilizing networks in mixtures with low-molar-mass liquid crystals. EPR and FTIR confirm radical generation upon exposure to 365 nm light and conversion of the acrylate functional groups. A potential mechanism is proposed, informed by control experiments that indicate that the monomers undergo a type II Norrish mechanism. The initiatorless polymerization of the liquid crystalline monomers yield liquid crystalline polymer networks with mechanical properties that can be equal to those prepared with conventional radical photoinitiators. We demonstrate that initiatorless polymerization of display modes significantly increases the voltage holding ratio, which could result in a reduction in drive voltages in flat-panel televisions and hand-held devices, extending battery life and reducing power consumption.

Bistable and photoswitchable states of matter

Classical materials readily switch phases (solid to fluid or fluid to gas) upon changes in pressure or heat; however, subsequent reversion of the stimulus returns the material to their original phase. Covalently cross-linked polymer networks, which are solids that do not flow when strained, do not change phase even upon changes in temperature and pressure. However, upon the addition of dynamic cross-links, they become stimuli responsive, capable of switching phase from solid to fluid, but quickly returning to the solid state once the stimulus is removed. Reported here is the first material capable of a bistable switching of phase. A permanent solid to fluid transition or vice versa is demonstrated at room temperature, with inherent, spatiotemporal control over this switch in either direction triggered by exposure to light.Polymers cross-linked with dynamic bonds can switch the phase from solid to fluid upon stimulus but return quickly to the solid state once the stimulus is removed. Here the authors report a light triggered permanent solid to fluid transition at room temperature with inherent spatiotemporal control in either direction

A readily programmable, fully reversible shape-switching material

Liquid crystalline elastomers programmed with light-activated bond exchange allowing controlled shape change. Liquid crystalline (LC) elastomers (LCEs) enable large-scale reversible shape changes in polymeric materials; however, they require intensive, irreversible programming approaches in order to facilitate controllable actuation. We have implemented photoinduced dynamic covalent chemistry (DCC) that chemically anneals the LCE toward an applied equilibrium only when and where the light-activated DCC is on. By using light as the stimulus that enables programming, the dynamic bond exchange is orthogonal to LC phase behavior, enabling the LCE to be annealed in any LC phase or in the isotropic phase with various manifestations of this capability explored here. In a photopolymerizable LCE network, we report the synthesis, characterization, and exploitation of readily shape-programmable DCC-functional LCEs to create predictable, complex, and fully reversible shape changes, thus enabling the literal square peg to fit into a round hole.

A user's guide to the thiol-thioester exchange in organic media: scope, limitations, and applications in material science

The exchange of thiolates and thiols has long been held as a nearly ideal reaction in dynamic covalent chemistry. The ability for the reaction to proceed smoothly in neutral aqueous media has propelled its widespread use in biochemistry, however, far fewer applications and studies have been directed towards its use in material science which primarily is performed in organic media. Herein, we present the exploration of this dynamic exchange in both small molecule and polymer settings with a wide sampling of thiols, thioesters, organic bases, and nucleophilic catalysts in various organic solvents. Effects of the character of the thiol and thioester, pKa or nucleophilicity of the catalyst, and heat on the reaction were investigated. The mechanism regarding the previously unexplored effectiveness of nucelophilic catalysts, such as quinuclidine or DABCO, to affect the thiol-thioester exchange was also explored. Finally, the use of the thiol-thioester exchange in a network polymer to reduce applied stresses or change shape of the material following polymerization was shown and the ability of basic and nucleophilic catalysts to promote these effects were benchmarked. The influence of polarity in these networks was also explored, with the rate of exchange shown to be easily tuned by the addition of diluents with varying polarities. Presented here is a so-called “users guide” to the thiol-thioester exchange; we hope that this guide is instructive to practitioners in the field of material science which seek to utilize the thiol-thioester exchange in both linear and network polymers.

Publisher Correction: Bistable and photoswitchable states of matter

The original version of this Article contained errors in Fig. 3. In Fig. 3a, the word ‘fluid’ in grey was incorrectly given as ‘solid’ in green, below that, ‘solid’ in green was previously ‘fluid’ in grey. Also, the label on the arrow incorrectly read ‘TMG (1 mol%) HABI-Cl (3 mol%) 455 nm, 1 min’; the correct version reads ‘TMG (1 mol%) HABI-O-n-oct (4 mol%) 455 nm, 4 min’. In the accompanying legend, the word ‘photobase’ was originally incorrectly given as ‘photoacid’. Additionally, in Fig. 3b, the label on the central image was ‘As is: solid’, rather than the correct ‘As is: fluid’. This has been corrected in both the PDF and HTML versions of the Article.

Recyclable and repolymerizable thiol–X photopolymers

We demonstrate a class of rapidly photopolymerizable step-growth cross-linked networks that incorporate thioesters into the backbone. The thioester functional groups enable complete degradation of the network into oligomers that can subsequently be recycled into a nearly indistinguishable material with no change in material behavior.

Dynamic and Responsive DNA-like Polymers

The synthesis of thiolactone monomers that mimic natural nucleosides and engage in robust ring opening polymerizations (ROP) is herein described. As each repeat unit contains a thioester functional group, dynamic rearrangement of the polymer is feasible via thiol-thioester exchange, demonstrated here by depolymerization of the polymers and coalescing of two polymers of different molecular weight or chemical composition. This approach constitutes the first step toward a platform that enables for the routine synthesis of sequence controlled polymers via dynamic template directed synthesis.