Biodegradable Polymeric Prodrugs

描述(申请人提供)：牙周疾病包括一组相关的微生物引起的慢性炎症性疾病，破坏支持牙齿的组织。该项目的目标是：通过减少炎症，加速新的、健康的牙周结构的恢复/恢复；减少牙周手术后的疼痛；为牙周细菌创造一个不利的环境。这些目标是使用可生物降解(生物可再吸收)聚合物实现的，其中聚合物本身是一个控制释放系统：聚合物充当临时屏障，降解为治疗活性分子，如非类固醇抗炎药(NSAID)，并同时释放混合的抗菌剂。我们以我们之前的研究为基础，开发了基于非甾体抗炎药的新型聚合物，可同时减少炎症、控制疼痛和消除细菌，同时为修复牙周组织提供可生物降解的支架。作为体内聚合物降解的一个功能，我们提出了以下问题：1.非类固醇抗菌素能否被结合到聚合物骨架中，从而使聚合物的水解性降解直接释放非类固醇消炎药？2.非类固醇消炎药的局部释放是否促进局部骨生长？3.非类固醇消炎药聚合物中物理混合的抗菌剂能否与化学结合的非类固醇消炎药同时释放？4.物理混合的抗菌剂与聚合物降解相关的非类固醇抗菌素释放相结合是否会进一步促进骨生长？这项建议的总体目标是确定通过可降解聚合物局部给予非类固醇抗炎药是否能同时减少炎症、消除细菌和恢复健康的牙周结构。

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.