2 research outputs found
Interplay between Silk Fibroin’s Structure and Its Adhesive Properties
<i>Bombyx mori</i>-derived silk fibroin (SF) is a well-characterized
protein employed in numerous biomedical applications. Structurally,
SF consists of a heavy chain and a light chain connected via a single
disulfide bond. The HC sequence is organized into 12 crystalline domains
interspersed with amorphous regions that can transition between random
coil/α-helix and beta-sheet configurations, giving silk its
hallmark properties. SF has been reported to have adhesive properties
and shows promise for development of medical adhesives; however, the
mechanism of these interactions and the interplay between SF’s
structure and adhesion are not understood. In this context, the effects
of physical parameters (i.e., concentration, temperature, pH, and
ionic strength) and protein structural changes on adhesion were investigated
in this study. Our results suggest that amino acid side chains that
have functionalities capable of coordinate (dative) bond or hydrogen
bond formation (such as those of serine and tyrosine) might be important
determinants in SF’s adhesion to a given substrate. Additionally,
the data suggest that fibroin amino acids involved in beta-sheet formation
are also important in the protein’s adhesion to substrates
DataSheet1_Hyaluronic acid-ibuprofen conjugation: a novel ototherapeutic approach protecting inner ear cells from inflammation-mediated damage.PDF
There is a substantial need of effective drugs for the treatment of hearing loss, which affects nearly 500 million individuals globally. Hearing loss can be the result of intense or prolonged noise exposure, ototoxic drugs, infections, and trauma, which trigger inflammatory signaling cascades that lead to irreversible damage to cochlear structures. To address this, we developed and characterized a series of covalent conjugates of anti-inflammatory drugs to hyaluronic acid (HA), for potential use as topical ototherapeutics. These conjugates were tested in in vitro assays designed to mirror physiological processes typically observed with acoustic trauma. Intense noise exposure leads to macrophage recruitment to the cochlea and subsequent inflammatory damage to sensory cells. We therefore first tested our conjugates’ ability to reduce the release of inflammatory cytokines in macrophages. This anti-inflammatory effect on macrophages also translated to increased cochlear cell viability. In our initial screening, one conjugate, ibuprofen-HA, demonstrated significantly higher anti-inflammatory potential than its counterparts. Subsequent cytokine release profiling of ibuprofen-HA further confirmed its ability to reduce a wider range of inflammatory markers, to a greater extent than its equivalent unconjugated drug. The conjugate’s potential as a topical therapeutic was then assessed in previously developed tympanic and round window membrane tissue permeation models. As expected, our data indicate that the conjugate has limited tympanic membrane model permeability; however, it readily permeated the round window membrane model and to a greater extent than the unconjugated drug. Interestingly, our data also revealed that ibuprofen-HA was well tolerated in cellular and tissue cytocompatibility assays, whereas the unconjugated drug displayed significant cytotoxicity at equivalent concentrations. Moreover, our data highlighted the importance of chemical conjugation of ibuprofen to HA; the conjugate had improved anti-inflammatory effects, significantly reduced cytotoxicity, and is more suitable for therapeutic formulation. Overall, this work suggests that ibuprofen-HA could be a promising safe and effective topical ototherapeutic for inflammation-mediated cochlear damage.</p