Boronic acids form weak to strong complexes with saccharides[1]: the degree of binding depends upon the structure of both partners. One important consequence of this is the affinity that boronic acids have for mucosal surfaces. Synthetic structures containing boronic acids ranging from polymers to nanoparticles[2] can be delivered to mucosal surfaces, e.g., by binding to mucin[3], as a preface to drug delivery, for example[4]. The same strategy has been used to stabilize tear film with guar in the presence of boric acid to treat dry eye[5].
Silicone elastomers are widely used in biomedical devices that may encounter mucosal surfaces. Perhaps the most common examples of such devices are the silicone hydrogel contact lenses that dominate the market. As part of a study to improve the biocompatibility of silicone, particularly in the eye, we report the development of boronic acid-modified silicones and their physical properties: surprisingly, the materials can be induced to form elastomeric structures without chemical crosslinks.
Both telechelic and pendant silicone boronates were readily prepared by hydrosilylation of protected boronates[6]. In the former case (Figure 1A), the molecular weight (MW) between boronates varied between 1000-7000 g/mol. In the latter case (Figure B), more important than MW was the content of pendant boronic acids, which ranged from 7-50% (average spacing between boronic acids of 14, 7 or 2 monomer units, respectively). When protected, the compounds were transparent, water clear oils.
Figure 1. Preparation of protected A: telechelic and B: pendant silicone boronic acids and models for their associative behaviour after hydrolysis. C: Model of mucin binding to the exposed surface of a silicone boronate.
Exposure to water immediately converted the materials to elastomers. Pendant molecules should only undergo chain extension via boronic acid dimers[7] to give viscous oils. However, the interaction of the trivalent boron with adjacent oxygen atoms provides secondary crosslinking through Lewis acid/base complexes (as with Silly Putty, Figure 2A). As a consequence, it is possible tune the modulus within a fairly narrow range. By contrast, the crosslink density is much higher with pendant boronic acids, which exhibit moduli that span an order of magnitude (Figure 2B).
Figure 2. Moduli after hydrolysis of A: telechelic and B: pendant silicone boronic acids.
These elastomers clearly present a surface of boronic acids, the concentration of which can be readily tuned. We will report the ability of mucin to bind to surface-bound boronic acids (Figure 1C) and describe the optimization of surface density of boronic acids on the silicone layer to facilitate monolayer coverage.
We thank the Natural Sciences and Engineering Council of Canada and 20/20 NSERC Ophthalmic Materials Network for financial support of this work.
References:
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