雙性共聚高分子面活性劑於陽離子性高分子微RNA傳送系統配方之應用

CNU IR > Pharmacy and Science > Dept. of Pharmacy > MOST Project > Item 310902800/33551

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Title:	雙性共聚高分子面活性劑於陽離子性高分子微RNA傳送系統配方之應用 Application of Amphiphilic Copolymers as Surfactants in the Formulation of Cationic Polymer/ Microrna Delivery Systems
Authors:	郭榮華
Contributors:	嘉藥學校財團法人嘉南藥理大學藥學系(含碩士班)
Keywords:	微RNA 雙性共聚高分子陽離子性高分子傳送系統 MicroRNA amphiphilic copolymers cationic polymer delivery systems
Date:	2020
Issue Date:	2022-01-13 16:20:25 (UTC+8)
Abstract:	最近蓬勃發展的核酸治療趨勢為microRNA (miRNA)治療，然而miRNA傳送系統之建立仍為其臨床成功的關鍵因素。非病毒性陽離子性高分子核酸載體由於安全性較高及製程簡單性，亦被廣泛應用於核酸傳送。目前PEO-PPO-PEO共聚高分子界面活性劑被使用於核酸傳送系統主要集中於增進plasmid DNA與silence RNA傳送之應用，而PEO-PPO-PEO共聚高分子較少應用於miRNA傳送而且對於影響細胞之分子機轉尚未建立。本計劃乃提出加入雙性共聚高分子PEO-PPO-PEO高分子界面活性劑於陽離子性高分子載體之miRNA傳送系統之配方，可提昇複合體之體外安定性、增加體?半衰期、屏障陽離子性高分子之正電荷以降低細胞毒性、增進陽離子性高分子傳送系統油性比例以利與細胞膜作用、降低非目標性基因作用機會、及更進一步發展為智慧?感性控制劑型之可能性。本計劃特色在於配方之彈性調配避免化學修飾既存陽離子性高分子載體分子結構以滿足臨床之實際需求，另外以全面性完整地調控傳送系統分子作用目標以降低不良之副作用，以提昇miRNA目標基因之精準度，透過本計劃能充分了解PEO-PPO-PEO共聚高分子影響細胞之分子機轉，並期許能發展成為高效率低毒性之陽離子性高分子/miRNA傳送系統。 The recent booming trend in nucleic acid therapy is microRNA (miRNA) therapy, but the establishment of miRNA delivery systems remains a key factor for its clinical success. Non-viral cationic polymer nucleic acid vectors are also widely used for nucleic acid delivery due to their high safety and simple process. Non-viral cationic polymer nucleic acid vectors are also widely used for nucleic acid delivery due to their high safety and simple process. At present, PEO(poly-ethylene oxide)-PPO(poly-propylene oxide)-PEO amphiphilic copolymers as surfactants are used in nucleic acid delivery systems, which are mainly used to improve the enhancing transfer of plasma DNA and silence RNA, while the applications in miRNA delivery are less used and its effect on the molecular mechanism of cells has not yet been established. This project proposes the formulation of PEO-PPO-PEO polymer surfactants in cationic polymer mediated miRNA delivery systems, which can improve the stability of the complexes in vitro, increase the half-life in vivo, shield the positive charges of cationic polymers to reduce cytotoxicity, increase the oily ratio of cationic polymer delivery systems to facilitate interaction with cell membranes, reduce the chance of off-target genes, and further develop into smart temperature- sensitive controlling dosage forms. The feature of this project is the flexible formulation of the formula to avoid chemical modification of the existing molecular structure of cationic polymers to meet the actual clinical needs, and to comprehensively and completely regulate the molecular target of the delivery system to reduce adverse side effects and enhance the miRNA target gene. Taken together, through this project, we can fully understand the molecular mechanism of cells affected by applying PEO-PPO-PEO copolymers into cationic polymer / miRNA delivery systems, and hope to develop into cationic polymer / miRNA delivery systems with high efficiency and low toxicity.
Relation:	計畫編號：MOST109-2637-E041-004 計畫年度：109 執行起迄：2020-08~2021-07
Appears in Collections:	[Dept. of Pharmacy] MOST Project

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