Biodegradable Polymeric Prodrugs

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DESCRIPTION (provided by applicant): Periodontal diseases comprise a group of related microbial-induced chronic inflammatory disorders that destroy the tissue supporting the teeth. The goals of this project are: to accelerate the recovery/restoration of new, healthy periodontal architecture by reducing inflammation; to reduce post-operative pain after periodontal surgery; and to create an unfavorable environment for periodontic bacteria. These goals are achieved using biodegradable (bioresorbable) polymers in which the polymer itself is a controlled-release system: the polymer serves as a temporary barrier that degrades into therapeutically active molecules such as non-steroidal anti-inflammatory drugs (NSAIDs) and concurrently releases admixed antimicrobials. We build upon our previous research with salicylate-based polymers, creating new NSAID-based polymers to simultaneously reduce inflammation, control pain, and eliminate bacteria while providing a biodegradable scaffold for restoring periodontal tissues. As a function of in vivo polymer degradation, we present the following questions: 1. Can NSAIDs be incorporated into a polymer backbone, such that hydrolytic degradation of the polymer directly releases the NSAID? 2. Does the localized release of NSAID promote localized bone growth? 3. Can antimicrobials that are physically admixed within the NSAID-based polymers be released concurrent to the chemically incorporated NSAID? 4. Will the combination of physically admixed antimicrobials and polymer degradation-dependent release of NSAID promote bone growth even further? The overall objective of this proposal is to determine if the local delivery of NSAIDs via degradable polymers will simultaneously reduce inflammation, eliminate bacteria and restore healthy periodontal architecture.