Antibiotic ResistanceTraditionally, 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.
Figure 1: Scheme showing overall proposed application of LBL self- assemblies in oral drug delivery