Synthesis and Characterization of Polymeric Antioxidant microparticles for the pr

描述（由申请人提供）：每年在美国，大约有132,000名接受抗癌治疗的患者发生口腔黏膜炎（OM），这是一种痛苦的、使人衰弱的口腔伤口状况，据估计，这将增加患者的护理成本17,000-43,000美元。大多数治疗方法都侧重于姑息治疗或通过应用生长因子（GF）加速伤口愈合过程。尽管生长因子，如Palifermin，已经显示出愈合OM的希望，但它们携带肿瘤生长的潜力，并且不能针对OM的根本原因。最常报道的发生OM的分子机制是由于抗癌化学辐射制度产生过多的活性氧（ROS）。一种有效的抗氧化剂，如姜黄素，可能是一种令人兴奋的治疗药物，可以直接抑制OM发展的早期阶段，即氧化应激。事实上，它可以应用于抗癌制度之前，以防止OM的发生。此外，姜黄素：1)已被证明能够抑制癌细胞的生长，而不会引发肿瘤的生长，2)已被证明具有伤口愈合能力，3)已被证明具有抗炎和抗菌特性，4)口服耐受性良好，5)非常便宜。然而，由于姜黄素在生理环境中的半衰期短，生理上的传递是一个挑战

DESCRIPTION (provided by applicant): Every year in the United States, approximately 132,000 patients undergoing anti-cancer therapy develop oral mucositis (OM), a painful, debilitating oral wound condition, which is estimated to increase the patient's cost of care by $17,000-43,000. Most treatments have focused on either palliative care or accelerating the wound healing process through the application of growth factors (GF). Although growth factors, such as Palifermin, have shown promise in healing OM, they carrying the potential for neoplastic growths, and do not target the root cause of OM. The most commonly reported molecular mechanism for occurrence of OM is the excessive generation of reactive oxygen species (ROS) due to the anti-cancer chemo- radiation regimes. A potent antioxidant, such as curcumin, may represent an exciting therapeutic agent in OM prevention as a direct inhibitor of the earliest phase of OM development, i.e. oxidative stress. In fact, it can be applied before the anti-cancer regimes to prevent the occurrence of OM altogether. Additionally, curcumin: 1) has demonstrated ability to inhibit the growth of cancer cells and not trigger neoplastic growths, 2) has demonstrated wound healing capacity, 3) has proven anti-inflammatory and antimicrobial properties, 4) is well tolerated orally, and 5) is very inexpensive. However, delivery of curcumin physiologically represents a challenge due to its short half-life in physiological environments and poor aqueous solubility. The central hypothesis of this project is that curcumin-based polymers composed of natural antioxidants (C-PoNA) can be synthesized into tissue adhesive microparticles, and applied prophylactically to oral mucosal surfaces to decrease local cellular oxidative stress, and thereby decrease the likelihood of developing chemo/radio-therapy induced OM. As part of fulfilling this hypothesis, the research plan has been separated into two specific aims, Aim 1: C-PoNA microparticles provide controlled release of curcumin, and Aim 2: C-PoNA microparticles adhere to oral mucosal tissues. The first aim focuses on development and characterization of antioxidant polymer formulations, while the second aim focuses on demonstrating the ability to deliver select formulations to oral mucosal surfaces via an in vitro model. After the execution of this proposal, C-PoNA microparticle formulation(s) will be identified that can overcome the primary limitations of current curcumin delivery strategies. Microparticles that bond strongly to mucin while permitting long term local release will be obtained. In short, completion of this proposal will inform design of preclinical animal trials as e progress into phase II.