以幾丁聚醣包覆四環素對藥物控制釋放之研究

Controlled Release Characteristics of Tetracycline Loaded Chitosan Microspheres

王雅琪(Ya-Chi Wang)

指導教授 ： 鍾次文 ； 王士豪

中原大學/工學院/醫學工程研究所/碩士(2002年)

https://doi.org/10.6840/cycu200200541

摘要

本文以改良式滴入法應用各種製備條件製備符合治療牙周病所需之幾丁聚醣-四環素微小球，並以二次乳化法將聚乳酸-甘醇酸共聚物（PLGA 50：50），及褐藻酸（Alginate）乳化具有幾丁聚醣-四環素溶液之微小球，並探討微小球的特性。
結果顯示以乾式法製備，經戊二醛（濃度2.5%）交聯六十分鐘的條件為最佳，其包覆效率為67.4%±5.6%（n=3），釋放時間可達11天，仍能達到抑菌的最低有效濃度（1~2μg/ml），且無突釋（initial burst）的現象。經細菌抑菌測定試驗，確定微小球所釋出的四環素仍保有抑菌活性。
以濕式法製備之微小球，四環素於製備過程中即大量損失，包覆效率幾乎不超過50%，釋放結果也不理想，經改變不同條件如：戊二醛交聯時間增加及濃度提昇，也無法達到要求。
以二次乳化製備之聚乳酸-甘醇酸共聚物-幾丁聚醣微小球發現，外部水相中加入0.05%褐藻酸可有效的提昇包覆效率達19.6%±4.3%，且釋放時間達至9天。

關鍵字

二次乳化法 ； ,聚乳酸-甘醇酸共聚物 ； 改良式滴入法 ； 微小球 ； 四環素 ； 幾丁聚醣

並列摘要

In this study, we fabricated tetracycline (Tc) loaded chitosan microspheres by using different preparing process, conditions and methods for therapy of periodontal disease. Modified orifice and double emulsion method have been applied to fabricate chitosan microspheres. The results showed that pre-dried microspheres prior to cross-linking by 2.5% glutaraldehyde at 60 minutes would be the best conditions for microspheres, fabricated by modified orifice method. The encapsulation efficiency were 67.4%±5.6% (n=3) and could maintain 11 days of in-vitro release characteristics test. The efficacy of encapsulated Tc has been confirmed by bacteriostatic tests.
Double emulsion (w/o/w) technique can also fabricate Tc loaded alginate / poly(d,l-lactide-co-glycolide) / chitosan multilayered microspheres. They could also release Tc (in vitro test ) up to 9 days although the encapsulation efficiency was only 19.6%±4.3% (n=3).
Through the study, we found the best conditions for fabricating Tc loaded microspheres, which can be applied for therapy of periodontal disease, by modified orifice and double emulsion method.

並列關鍵字

microspheres ； tetracycline ； chitosan ； modified orifice ； l-lactide-co-glycolide) ； Poly(d ； double emulsion

參考文獻

[41]Fwu-Long Mi et. al., The adsorption of copper(II) ion on chitosan-tripolyphosphate chelating resin, Chemistry, 57(1), 11-24, 1999.

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