| 摘要: | [1]研究計畫目的：本計畫目的為為達成有效地消滅存在於孔洞介質(如人工植體)內的細菌，研製開發結合光敏劑靛氰綠(Indocyanine green；ICG)與利福黴素(Rifampicin；RIF)之多功能聚乳酸-聚甘醇酸奈米粒子(ICG-RIF-Loaded PLGA Nanoparticles; IRPNPs)，並探索其在1)光動力，2)光熱力，以及3)抗生素三重治療上的效能與應用性。[2]研究計畫背景/緣起：當醫療植體置入人體內發生細菌感染時，常會面臨到細菌因處於死角而容易生成生物膜，進而牢固粘附在器材上而難以清除，如此必須進行手術清創並更換新的材料，其會耗費大量時間、金錢並造成患者極大痛苦。另外細菌對抗生素產生抗藥性則又是另一難解的問題。而在臨床殺菌技術上，光治療由於能提供有效破壞生物膜與高通用性(不受限於細菌種類)，目前已廣泛地測試於學術及臨床研究上。其中ICG是目前少數已獲得臨床認證可用於人體的光敏劑。然而，由於其本身不足的光/熱穩定性，使得該物質在實際應用上受到極大的限制。綜合以上，研製開發一穩定及高效能的奈米光-化學製劑預期對於消滅介質內細菌具有高度的應用價值。[3]研究方法與特點：所製作出的IRPNP預期有以下特點：1)相較於抗生素，IRPNP所產生之高溫與自由基能有更多機會接觸並破壞死角細菌團外的生物膜，進而提升殺菌效果；2) ICG及RIF分子可同時獲得載體保護，如此可改善ICG易受光/熱影響而降解之缺點並提供適切的RIF釋放效果；3)粒子可同時提供光熱力、光動力與抗生素等三種滅菌方式，因此預期能獲得顯著提升的治療成效；4)在光治療的配合下，抗生素的有效劑量可望降低，如此得以減輕病人的化療副作用以及患部細菌的抗藥性程度。[4]計畫執行優勢：本計畫主持人過去在奈米醫學領域上有長期的關注與研究發展，並對於奈米藥物載體設計上有實務的開發經驗。合作廠商-宇格材料企業有限公司熟稔市場上各類抗菌材料或技術，並對於計畫中IRPNP的組成材料特性與抗菌分析具備專業知識與完整技術支援能力。因此該研究組合足以執行此產學合作計劃案。[5]預期完成研究工作項目：整體研究工作分為四個階段：本期計畫將進行1)第一階段：完成IRPNP的製備，性質與功能性檢測以及產品最佳化(1-7月)與2)第二階段：以體外細菌模型評估IRPNP的抗菌效果(8-12月)。 ;[1] Specific Aim: We aim to design and fabricate multifunctional indocyanine green (ICG)-rifampicin (RIF) loaded poly(lactic-co-glycolic acid) nanoparticles (IRPNPEs), and explore their potential of photochemo-therapeutics on treatment of microbial infection happened in porous medium such as implants.[2] Background: For the treatment of implant infection, one of the most difficulties is that the bacteria adhere to the equipment tightly due to protection by biofilm in the dead space and thus hard to be removed. To solve this situation, surgical debridement and replacement of a new material is necessary but it is often time- and money consuming and may cause great pain to the patient. In addition, the drug resistance of bacteria to antibiotics may raise another issue to be concerned. In terms of adjuvant antimicrobial therapeutics, phototherapy has been extensively investigated in both academic and clinical aspects since it can provide several advantages such as exceptional bactericidal effect and high versatility, and ICG, a water-soluble tricarbocyanine dye, is one of few clinically proved photosensitizers. However, due to its inherent lack of light / thermal stability, the material is greatly limited in practical application. Taken all together, it is desired to develop an ICG-stable nanoagent with photo-chemotherapeutic functionality for treatment of bacterial infection in implants.[3] Advantages: The developed IRPNPs may provide following advantages in clinical use: 1) Compared with antibiotics alone, the high temperature and singlet oxygen generated by the IRPNPs may provide more chances to destroy the biofilms located in the dead space and thereby enhance the bactericidal effect. 2) Both ICG and RIF are encapsulated in the particles and that may prevent ICG degradation and provide a desired RIF release efficiency through an appropriate drug carrier design. 3) The IRPNP can simultaneously provide photothermal-, photodynamic-, and chemical treatments whereby the efficacy of antimicrobial therapy may be dramatically enhanced. 4) Since the IRPNP can offer adjuvant phototherapy, the effective dose of RIF provided by the IRPNP is supposedly lower than that performed in normal antibiotic treatment, and therefore the level of chemotherapy-induced side effect on patients and drug-resistance of bacteria can be reduced. [4] Qualification/Capability: The project PI (YH Lee) has robust research background in the fields of nanomedicine and drug delivery, and has practical hands-on experience on design and manufacture of nano-drug carrier in the past 5 years. The partner company; Yu Green Co. Ltd., is a well-established biotech/material company with strong knowledge/professions in fundamental material sciences, applications of antibacterial biomaterials, and instrumental analysis. Therefore, such partnership is perfectly qualified to conduct this industry-academia collaboration project.[5] Research Schedule: The overall task in this IRPNP study can be divided into four phases. In this project, we will finish 1) the 1st section of “To fabricate, characterize and optimize the IRPNP” (1 - 7 Month) and 2) the 2nd section of “To assess the antibacterial capability and dose efficacy of the IRPNP through an in vitro microbial assay” (8 - 12 Month). |
