使用 PEG 修飾之生理吸附性膠原蛋白的眼用控釋劑型之研發
A Novel Approach to Ophthalmic Controlled Release:Biodefradable Adhesion via PEG Modified Collagen
中文摘要
為了增加膠原蛋白 (Collagen) 於眼中的生理吸附性，本實驗以 polyethylene glycol (PEG) 分子量 3000、4000、8000 及 methoxypolyethylene glycol (MPEG) 分 子量 5000 反應生成 PEG 活化物，並利用紅外光吸收光譜偵測鑑定產物。以活 化後的 (M)PEG 修飾膠原蛋白 (1000:1) 反應 30 分鐘，可得到最佳的修飾效 果。生成物 PEG-collagen 在電子顯微鏡的觀察下，與未修釋的膠原蛋白和經 glutaraldehyde 交錯連結 (cross-linked) 的修釋膠原蛋白作對照，發現由原來的纖 維狀被修飾改變成孔洞細密且呈網狀的結構。由 SDS-PAGE 電泳分析中膠原蛋 白次單位 (subunit) 的消失，證實有交錯連結的發生。將修飾後的膠原蛋白作為 基質，應用於眼用藥物 pilocarpine 控釋劑型的設計，於體外人工膜進行滲透實 驗顯示，於 10% pilocarpine 加入經修飾的膠原蛋白會有增加藥物控釋的效果，
其效果高達加入增稠劑或未經修飾者的三至五倍 。Pilocarpine 的釋離速度控制 組呈現零級的方式而修飾後的膠原蛋白會依 Higuchi 方程式釋離，其緩釋效果 的順序為 MPEG5000>PEG8000=PEG4000=PEG3000。
英文摘要
The objective of this research is to develop an ophthalmic controlled release dosage form using the biodegradable (M)PEG modified collagen as the vehicle. Collagen was first cross-linked with (M)PEGs as monitored by SDS-PAGE. SEM of the (M)PEG or glutaraldehyde modified collagens revealed they possessed tighter webbed structure than the native modified collagen. Hydrolysis of these (M)PEGs modified collagens by collagenase for 6hr had demonstrated a different patten of SDS-PAGE from that of the native one, indicating that these (M)PEG modified collagens were chemically different from the native collagen Pilocarpine release from solutions containing these PEG modified collagens followed Higuchi release behavoir, while the control
pilocarpine solution showed a zero-order fashion. This slow release effect is in the order of MPEG-5000> PEG-8000=PEG-4000=PEG-3000.
