交聯劑與塑化劑對幾丁聚醣複合膜材性質之影響

Abstract

本研究以幾丁聚醣(C)為主成分並添加果膠(P)及阿拉伯膠(A)，再搭配交聯劑與塑化劑製成多成分複合膜材，期望藉此提升緻密膜材之機械性質，並同時達到改善膜材用於藥物釋放之成效。 首先將交聯劑與塑化劑與幾丁聚醣、果膠、阿拉伯膠均勻混合形成複合溶液，並經由熱風乾燥法形成緻密膜材。實驗所使用之交聯劑為戊二醛(GA)或EDC/NHS系統，用途為提升複合膜材之機械強度；實驗所使用之多元醇類塑化劑為甘油(Gly)或山梨醇(Sor)或木糖醇(Xyl)，用途為增進膜材延展性，並使膜材觸感變得柔軟。由膜材機械強度與延展性測定結果，初步挑選出延展性與機械強度皆符合設定門檻之組別，包含：代號為C-P-A-Gly (GA)及C-P-A-Sor (GA)，兩者皆以戊二醛作為交聯劑，並以甘油或山梨醇作為塑化劑之膜材組別進行後續的實驗測試。 根據材料崩解測試結果，選用戊二醛作為交聯劑可有效地提升膜材穩定性。此外，經由親水性質測試顯示：以山梨醇為塑化劑，相較於甘油，因其具有較多之羥基(-OH)，其構成之複合膜材所量得之接觸角較低、膨潤程度較高。在藥物釋放實驗，分別將四環黴素及牛血清白蛋白(BSA)作為小、大分子乘載藥物置於膜材中。C-P-A-Gly (GA)膜材擁有較為平緩的四環黴素釋放曲線，在延長小分子藥物之釋放時間有較佳的表現。在承載藥物為牛血清白蛋白之試驗中，C-P-A-Sor (GA)及C-P-A-Gly (GA)膜材均會減少此一大分子藥物釋放。而本研究所測得之膜材親水性質、短時間之膨潤效果、長時間之崩解程度均能與藥物釋放曲線趨勢一致。 總觀本研究將幾丁聚醣、果膠及阿拉伯膠經由交聯與塑化改質形成之複合緻密膜材，其機械性質與藥物釋放曲線均有所提升或改變，未來可進一步將此膜材應用在生醫相關領域。

In this research, cross-linking agents and plasticizers were added in order to improve both the mechanical properties and the drug release characteristics of the chitosan-based composite membranes. During the fabrication process, solutions containing chitosan, pectin and gum Arabic were added with different cross-linking agents and plasticizers, and the composite solutions were dried to form dense films. Cross-linking agents (glutaraldehyde or EDC/NHS) were used to enhance the tensile strength of this composite film. Moreover, polyol plasticizers (glycerol, sorbitol or xylitol) were also added to improve the ductility of the dense film. Based on the results of mechanical property test, glutaraldehyde, glycerol and sorbitol were chosen as the cross-linking agent and plasticizers to conduct the following tests. According to the results of disintegration test, the selected cross-linking agent, glutaraldehyde, enhanced the stability of dense films. Furthermore, owing to more hydroxyl groups that sorbitol has, dense films containing sorbitol showed greater hydrophilicity than that containing glycerol. This result was consistent with the measurements of water contact angles and swelling ratios of dense films. In drug release experiments, tetracycline hydrochloride and bovine serum albumin (BSA) functioned as small and large molecule drugs respectively. The cross-linked chitosan-based dense films with glycerol as the plasticizer could release the small molecule drug (tetracycline hydrochloride) in a steady and sustained manner. For the large molecule drug, the drug release from the cross-linked chitosan-based dense films with glycerol and that with sorbitol significantly decreased. In addition, the results of swelling ratio test and disintegration test of the films corresponded with the trends of the release profiles of the two drugs. In this study, the mechanical properties and the drug release characteristics of chitosan-based dense films had been improved or modified by using the cross-linking agents and the polyol plasticizers. These films can be utilized in biomedical-related areas in the future.