| Abstract: | 本研究以帶正電之幾丁聚醣( Chitosan,CS,去乙醯度≧85% )及帶負電之三聚磷酸鈉( Sodium tripolyphosphate,TPP )，利用離子交聯作用之方式包覆鞣花酸( Ellagic acid,EA )製成奈米顆粒。先以臭氧降解幾丁聚醣(Original Mw,735 kDa )成高分子量(High Mw,約511 kDa )、中分子量(Medium Mw,約296 kDa )以及低分子量(Low Mw,約46 kDa )等不同分子量之CS，並分別溶於1 %醋酸溶液使濃度約為0.2 % (w/v)且將pH值調至4.7；將不同濃度(100~1000 μg/mL)之鞣花酸溶液，與上述之CS溶液充分混勻，接著滴入TPP( pH 9.0)溶液使CS/TPP重量比3/1、4/1、5/1、6/1，製備成幾丁聚醣–三聚磷酸鈉–鞣花酸(CS–TPP–ellagic acid)奈米顆粒，並探討鞣花酸濃度、幾丁聚醣分子量及CS/TPP重量比對於CS–TPP–ellagic acid奈米顆粒之包覆率、裝載率、產率、粒徑、表面電位等性質，以選定出較為適當的幾丁聚醣–三聚磷酸鈉–鞣花酸奈米顆粒。結果顯示，鞣花酸濃度600 μg/mL、幾丁聚醣分子量以原分子量(Original Mw,735 kDa ) 及CS/TPP 重量比3/1為最適選定的條件，其包覆率約45-50 %、裝載率3 %、產率約65 %、粒徑大小約300 nm、表面電位約35-40mV 。另外使用上述條件製出奈米顆粒放置於模擬腸胃道並探討其安定性，發現置於模擬胃液pH 1.2 之胃蛋白酶(Pepsin)作用2個小時之後發現約有20 % 鞣花酸釋放出奈米顆粒，表示此包覆有良好抗胃酸及胃酵素作用。繼續加入模擬腸液pH 7.4 之胰酶(Pancreatin)繼續作用6小時，則鞣花酸累積釋放率約從50 %到70 %，表示幾丁聚醣鞣花酸奈米顆粒在模擬腸液環境中，幾丁聚醣奈米顆粒結構變為蓬鬆，釋放出鞣花酸。
Chitosan (CS, original Mw 735 kDa, deacetylation ≧ 85%) were degraded by O3 oxidation into various molecular weights (High Mw 511 kDa, Medium Mw 296 kDa, and Low Mw 46 kDa), then dissolved into a 2 mg/mL concentration and adjusted to pH 4.7, then mixed individually with various concentrations of ellagic acid solution (100-1000 μg/mL). The mixed solutions were added dropwise with the sodium tripolyphosphate solution (TPP, pH 9.0) at different CS/TPP mass ratio of 3:1, 4:1, 5:1 and 6:1 to prepare CS-TPP- Ellagic acid nanoparticles. Such effective factors as ellagic acid concentration, chitosan molecular weight, and CS/TPP mass ratio on the encapsulation efficiency (EE) ,loading capacity, process yield, particle size and zeta potential of the nanoparticles were investigated.As a result, a suitable ellagic acid concentration 600 μg/mL, original Mw of 735 kDa and CS/TPP ratio of 3/1 that gave an encapsulation efficiency of 45-50 % , a loading capacity of 3 %, a process yield of about 65%, a nanoparticle size of about 300 nm and a zeta potential of +35～+40mV. Simulated gastrointestinal stability was carried out by mixing the CS-TPP-Ellagic acid nanoparticles in the simulated gastric fluid ( pH1.2,with pepsin )for 2 hours and then in the simulated intestinal fluid ( pH7.4,with pancreatin )for 6 hours,that showed about 20 % and 70 % ellagic acid released respectively . |
