Chitosan/Fucoidan Nanoparticles---Characterization and Application in Pulmonary Delivery System

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基本資料

Project title

Code/計畫編號

MOST103-2221-E019-064

Translated Name/計畫中文名

幾丁聚醣/褐藻醣膠奈米粒性質探討及在肺部傳輸系統的應用

Project Coordinator/計畫主持人

Yi-Cheng Huang

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Food Science

Website

https://www.grb.gov.tw/search/planDetail?id=8357007

Year

2014

Start date/計畫起

01-08-2014

Expected Completion/計畫迄

01-07-2015

Bugetid/研究經費

753千元

ResearchField/研究領域

醫學工程
藥學

"本計畫書擬以幾丁聚醣 (Chitosan) 與褐藻醣膠 (Fucoidan) 製備具抗氧化特性載體，應用於肺部傳輸系統，並選取臨床上常用之胺基醣苷類抗生素－健大黴素 (Gentamicin)－為模型藥物，探討由幾丁聚醣/褐藻醣膠奈米粒釋放之健大黴素，對於抑制克雷伯氏肺炎桿菌之最低抑菌濃度的影響，並評估由肺部給藥之健大黴素的生物利用率，以期提高肺炎治療的功效。申請者基於前兩年的研究計畫，以幾丁聚醣與褐藻醣膠製備奈米級傳輸載體，其可釋放基質細胞衍生因子調控幹細胞的遷移；釋放鹼性纖維母細胞生長因子幫助神經修復；亦可應用於口服傳輸系統，提高薑黃素的穩定性及口服利用率。本計畫將擴大幾丁聚醣/褐藻醣膠奈米粒的應用層面，評估其為肺部傳輸載體的潛力，結合申請者先前的研究成果及肺部傳輸、肺炎治療、抗生素給藥的問題探討，以期對臨床醫學中肺炎的治療有所助益。在此專題研究計畫中，第一年：探討幾丁聚醣/褐藻醣膠奈米粒的性質，以評估其在肺部模擬液中的穩定性、細胞相容性、抗發炎及抗氧化特性。目前肺炎的治療大多投以抗生素，然而抗生素的使用會導致自由基的生成而造成副作用，以致臨床上肺炎的治療面臨挑戰。已知褐藻醣膠、幾丁聚醣具有抗氧化的生理活性，能抑制自由基的生成，因此，此計畫的目的為製備具抗氧化能力的幾丁聚醣/褐藻醣膠載體，應用於肺部傳輸給藥。第二年：延續第一年的實驗結果，以最適之幾丁聚醣/褐藻醣膠奈米粒攜帶健大黴素，探討健大黴素的包覆率、攜帶量及釋放行為，並評估其最低抑菌濃度。第三年：建立肺部氣管內 (Intratracheal, IT) 給藥的動物實驗模式，以液相層析-電灑游離-串聯質譜儀 (LC/ESI-MS/MS) 系統分析健大黴素在血液中的濃度，評估其生物利用率及對肺功能的影響。此計畫結合海洋資源與醫學工程，利用萃取自褐藻的褐藻醣膠與萃取自蝦蟹殼的幾丁聚醣，製備奈米載體攜帶健大黴素，直接於肺部給藥，期待能提高治療肺炎的效果。此外，對於海洋資源的開發及利用，亦提供一個新的方向。 " "In the current proposal, we will develop chitosan/fucoidan nanoparticles (CS/F NPs) as antioxidant carriers for pulmonary delivery system. Gentamicin (GM), a commonly used aminoglycoside antibiotic, is used as a model drug to discuss the in vitro release behavior of drugs from CS/F NPs. Furthermore, the minimum inhibitory concentrations (MICs) in resisting Klebsiella pneumonia, and bioavailability of released GM through pulmonary delivery will be evaluated. Hopefully, the results will be an improvement for pneumonia treatment. In the last two-year investigations, the applicant has developed CS/F NPs as nano-carriers. The stromal cell-derived factor-1 released from CS/F NPs can mobilize mesenchymal stem cells; the basic fibroblast growth factor released from CS/F NPs is effective on neurite extension. In addition, the CS/F NPs can be used as oral delivery carrier to control the release of curcumin and increase its bioavailability. This proposal is intended to extent the application of CS/F NPs to pulmonary delivery system. Combination the previous experimental results with the challenge of antibiotic therapy in pneumonia, we hope the results would be helpful for clinical pneumonia treatment. This project includes three-year research programs. In the first year, we will discuss the properties of CS/F NPs, including stability in stimulated lung fluids, biocompatibility, anti-inflammatory and anti-oxidant activities and so on. We try to utilize the anti-oxidant bioactivities of fucoidan and chitosan to inhibit the free radicals produced by antibiotics which have been wide used in pneumonia treatment. The aim in this year is to fabricate anti-oxidant CS/F NPs as pulmonary delivery carriers. In the second year, the most suitable CS/F NPs got from the results of the first year will be used to carry GM. The encapsulation efficiency, loading content and release behavior of GM from CS/F NPs will be discussed. Furthermore, we will also evaluate the MIC value of GM in resisting Klebsiella pneumonia. In the third year, we will establish the SD (Sprague Dawley) rat animal model for intratracheal (IT) treatment. The LC/ESI-MS/MS system will be used to analyze the concentration of GM in blood for bioavailability evaluation. The impact of CS/F NPs on pulmonary function will also be examined and discussed. This proposal combine marine resources with the concept of biomedical engineering, using fucoidan extracted from brown algae and chitosan extracted from crab and shrimp to fabricate nanoparticles to carry GM for pneumonia treatment. We expect that this pulmonary delivery system could be effective in pneumonia therapy and provide a new direction for the development and use of marine resources. "

Keyword(s)

幾丁聚醣
褐藻醣膠
奈米粒
肺部傳輸
chitosan
fucoidan
nanoparticles
pulmonary delivery

DSpace CRIS

Chitosan/Fucoidan Nanoparticles---Characterization and Application in Pulmonary Delivery System

基本資料

Description