Carboxymethylcellulose (CMC) and sodium alginate (ALG) gave inconsistent results, suggesting these polymers may interfere with binding, since it was the association rate constant kon that had the largest variability. Of the polymers tested, only HA has significant intrinsic biological activities, promoting cell motility and acting as cell assay a damage-associated molecular pattern upon degradation.36 Further research will be necessary to understand the influence of polymer chemistry and biochemistry on conjugate activities, but the approach utilizing negatively charged polymers in conjunction with antibody-based inhibitors appears to be quite general. Prospectus Challenges in developing antibody-polymer conjugates include validating them for use in treatment of autoimmune diseases that present with local manifestations of persistent inflammatory states, such as psoriasis and Crohn��s disease.
In addition, injuries in healing-impaired models, such as rodent models of diabetes, will provide an important test of whether intrinsic healing responses are sufficient to repair injuries if intense inflammation is modulated. Finally, a better understanding of the interplay between intrinsic biochemical activities of polymers and biopolymers used to conjugate to antibodies and their degradation rates will provide insight into the pharmacokinetics of this drug-delivery strategy and its overall biological activities. Ultimately, this therapeutic approach will need to be tested in humans to determine whether local cytokine neutralization is an effective treatment strategy.
Inhibitors of TNF-�� are currently the most promising formulation, but rapid development of next-generation inhibitors of mediators of inflammation could allow even more targeted treatment. Combined with improvements in polymer delivery vehicles, potentially offering time-dependent or stimulus-responsive delivery, and this approach could treat conditions for which there are very few effective options currently. Acknowledgments This work was supported by the Armed Forces Institute of Regenerative Medicine (W81XWH-08-2-0032), the National Institutes of Health (R43GM085897), and the Department of Defense (W81XWH-13-C-0050). NRW gratefully acknowledges support from a 3M Non-Tenured Faculty Grant, the Wallace H. Coulter Foundation Translational Research Award program, and the Heinz Endowments (C1747).
Disclosure of Potential Conflicts of Interest Disclosure of Potential Conflicts of Interest NRW has started a company to commercialize aspects of this research and acknowledges a potential conflict of interest. Footnotes Previously published online: www.landesbioscience.com/journals/biomatter/article/25597
Zinc oxide (ZnO) is a widely utilized commercial material that has recently garnered interest by medical and nanotechnology researchers due to its considerable antimicrobial1 and UV protection properties.2 In a review Cilengitide by Lansdown et al.