The pathogenicity of periodontal disease is linked mainly with gram-negative anaerobic bacteria and with tissue damage caused by the host response to infection. Therefore, adjuvant to conventional antimicrobial therapies, the modulation of host response to infection (termed as host modulatory therapy;HMT) must also be accompanied for its complete therapy. None of the current local and sustained periodontal therapies include this aspect. Thus, the goal of this work is to evolve a system of controlled/sustained dual delivery of antibacterial &HMT agents in periodontal pockets from biodegradable/biocompatible cross-linked chitosan formulations. This SBIR phase-I application proposes to develop a xerogel, film/sheet formulation of a cross-linked chitosan with a model antibacterial agent and a HMT agent and to optimize it for sustained dual-drug release in their respective effective doses for about 30 days. The released components from the optimized formulations would be investigated to prove their efficacy in controlling the formation and growth of periodontal biofilm in an in-vitro mouth model;the same components will also tested to verify their contribution to HMT through a fibroblast repopulation study in a periodontal wound healing model and through their effect on modulation of fibroblastic cytokines related to periodontal problems. If successful, besides incorporation of HMT in the local sustained delivery periodontal treatment device, the proposed product will also allow ease of placement of device in periodontal pockets and its better retention at the site of placement due to know mucoadhesive properties of the device matrix. Thus, the smart polymer properties of the used ingredients will also be exploited in this proposed study. Information from this phase-I study will provide a basis for future studies to be proposed in its phase-II, which will include optimization of formulation procedures, followed by the establishment of standard operating procedures (SOPs) for quality control of each batch of product, and scale-up of optimized formulations procedures. The product will also be investigated for in-vivo periodontal pocket studies in animal models and also in toxicity and biocompatibility studied. All of these studies are mandated for FDA's Investigational New Device (IND) certification before its upgrade for clinical studies in future. B the end of Phase- II, it is hoped that a marketable product will be identified and the application for pre-market (510 K) notifications will be filed. The long term objective is to commercialize ths product for a complete local sustained therapy of periodontal disease through antibacterial as well as HMT. The device has a huge potential to help the society, as almost 80% of adult Americans have periodontal problems and these problems claim more than $60 billion in expenses yearly.
This proposal seeks to evolve a cross-linked mucoadhesive formulation for the extended release of a model antibacterial agent and a host inflammation modulator (commonly referred to as Host Modulation Therapy;HMT) in periodontal pockets. The combination of antibacterial action and HMT would provide a complete local and sustained therapy for periodontal disease. This formulation addresses few issues that have been under-focused so far in current local periodontal therapies, e.g.: 1. incorporation of HMT;2. retention of drug delivery device after its placement;3. enhancement of period for sustained delivery of active ingredients beyond 7 days. The device will be designed as a xerogel for the ease of placement in to periodontal pockets;it would then become mucoadhesive to improve the chances of retention in periodontal tissue. Finally it would concomitantly deliver agents for microbial control and for HMT for up to a month or so, performing all tasks at the same time. Thus, the chances of success of this product in successfully treating the periodontal disease are high.