Antibiotic Resistance

Traditionally, free loading of drugs into hydrogels allows for release via first order diffusion. While this release strategy is generally simple to employ, drug release displays an initial burst effect due to the lack of molecular entrainment in the hydrogel matrix, and large initial concentration gradient. Many drawbacks exist in this scenario due to fast drug release, such as the disparity between drug release and degradation rate of the hydrogel; the drugs typically release more quickly. Most critically in the terms of implantable biomaterials, the residual hydrogel, now void of active drug, can become a harbor for bacteria to form a biofilm where the immune system has trouble accessing, creating grounds for infection. Utilizing acrylate-amine chemistry, certain drugs can be polymerized into the backbone of the structure while maintaining their respective activity. Two molecules being currently reviewed for this effect, as well as for combinatorial effects, are that of the antibiotic vancomycin and antioxidant curcumin. It is hypothesized that the addition of these two will show synergistic effects towards the antibiotic activity of the hydrogel degradation product (i.e. the drug(s) released). Multilayered polymeric self-assemblies as wound protective barriers in oral mucosal injuries:

Oral cavity possess a complex environment, including continual salivary flushing, fluid exuding from wounds, mastication, bacterial flora and digestive enzymes which poses significant treatment challenge for drug delivery and in developing an effective treatment strategy. While the current standards of therapy (e.g., gels and mouth rinses) provide temporary relief, there is still an unmet need for a robust, long acting barrier that can provide lubricating protection in oral wounds, thereby enhancing the wound healing response. Our current research is focused on developing modular treatment strategies using polymer based self-assembly for oral regenerative therapy; overcoming the inadequacies in current treatment approaches. As an alternative to the current treatment approaches, in situ multilayered barriers can be developed as a series of non-viscous mouth rinses, allowing for full coverage of all oral mucosal tissues. By providing a series of alternating streptavidin (or non-immunogenic neutravidin) and biotinylated polymer mouth rinses, multilayered polymeric barrier systems can be grown from the buccal surface in a layer-by-layer (LBL) process, as shown in Figure 1. Our research was intended towards understanding fundamental polymeric molecular properties and its effect on LBL growth. In order to realize such strategies for practical oral applications, functional property evaluation on stability of LBL under intra-oral chemical and mechanically conditions were critical. A lubricating surface that reduces adhesion to opposing tissue surfaces with significant stability against harsh intra-oral chemical conditions was observed, thus offering a potential treatment solution, which merits further investigation.

Active Polymeric Biomaterials, Drug Delivery, Functionalized Polymer Nanocarriers, Postsurgical Adhesions., Pro/antioxidant Biomaterials, Wound Healing

Cheryl Rabek, T.D. Dziubla and D.A. Puleo*. “The Effect of Plasticizers on the Erosion and Mechanical Properties of Polymeric Films” Journal of Biomaterials Application – (Accepted) S.P. Authimoolam, D.A. Puleo and T.D. Dziubla*. “Affinity Based Multilayered Polymeric Self-assemblies for Oral Wound Applications.” Advanced Healthcare Materials Epub ahead of Print (2013) Ramineni SK, Cunningham LL Jr, Dziubla TD, Puleo DA*. “Development of imiquimod-loaded mucoadhesive films for oral dysplasia.” J Pharm Sci. Nov 28. doi: 10.1002/jps.23386 (2012) Brown ME, Zou Y, Dziubla TD, Puleo DA*. “Effects of composition and setting environment on mechanical properties of a composite bone filler” J Biomed Mater Res A. Sep 10. doi: 10.1002/jbm.a.34399. (2012) Howard MD, Lu X, Rinehart JJ, Jay M, Dziubla TD*, “Carboxylesterase-triggered hydrolysis of nanoparticle PEGylating agents.” Langmuir. Aug 21;28(33):12030-7 (2012) J. Ambati, A.M. Lopez, D. Cochran, P. Wattamwar, K. Bean, T.D. Dziubla and S.E. Rankin*, “Loading and Protection of Antioxidant Enzyme on Engineered Silica” Acta Biomaterialia, 8(6):2069-103 PMID:22366223 (2012) P. P. Wattamwar, D. Biswal, D. B. Cochran, A. Lyvers, Eitel RE, Anderson, KW J. Z. Hilt, and T. D. Dziubla*, “Synthesis and Characterization of Poly(antioxidant β-amino esters) for Controlled Release of Polyphenolic Antioxidants” Acta Biomaterialia, 8(7):2529-37 PMID:22426289 (2012) D. Biswal, P.P. Wattamwar, T.D. Dziubla, J.Z. Hilt*. “Poly(β-amino ester) hydrogel synthesis by single-step polymerization method.” Polymer 52:5985-5992 (2011)