利用耗散粒子動力學模擬pH敏性MPEG-b-(PLA-co-PAE)嵌段共聚物之藥物輸送系統

本研究是利用耗散粒子動力學，模擬研究以嵌段共聚物MPEG-b-(PLA-co-PAE)為載體，裝載藥物DOX所形成之平衡形態，並且改變嵌段比例、高分子濃度及藥物濃度，觀察平衡形態的變化，計算在不同條件下，藥物的乘載效率以及藥物載體內的分布狀況，接著模擬在弱酸性環境下，載體的平衡形態變化。本篇使用的載體是雙親性的嵌段共聚物MPEG-b-(PLA-co-PAE)，poly(ethylene glycol)(PEG)具有生物相容性而poly(β-amino ester)(PAE)具有無毒性及生物可分解性質，poly(lactide)(PLA)則是有生物可分解性及生物可吸收性；此載體是一種pH敏性的高分子，再弱酸性環境下，PAE會被質子化變成PAEH，而從疏水性轉變為親水性，使載體結構解體，進行藥物釋放，因此，MPEG-b-(PLA-co-PAE)被認為是具有發展性的藥物載體。研究結果發現，嵌段共聚物的PEG比例較大時，會增加藥物裝載能力以及裝載效率，而在弱酸性環境下時，藥物載體的微胞大小會變大，並且變大的幅度會隨著PAE嵌段比例增加而增加，這也表示會有更快的藥物釋放速率。

關鍵字

耗散粒子動力學； pH敏性嵌段共聚物；藥物輸送

並列摘要

This work uses dissipative particle dynamic simulation to study on morphology of drug carrier MPEG-b-(PLA-co-PAE) with different block ratio, copolymer concentration and drug concentration. In different condition, drug loading efficiency and drug distribution in drug carrier are investigated. Finally ,in weakly acidic environment, drug carrier morphology and drug releasing situation will also be discussed. In this work, we use amphiphilic pH-sensitive copolymer as drug carrier, composed of hydrophobic poly(β-amino ester)(PAE) and hydrophilic poly(ethylene glycol)(PEG). Because of its tertiary amine, PAE has a weak basic character and can be protonated at low pH. Therefore, PAE becoming hydrophilic causes the aggregation structure broken and drug releasing. Poly(β-amino ester)(PAE) is non-toxic and biodegradable, poly(ethylene glycol)(PEG) is biocompatible, and poly(lactide)(PLA) is biodegradable and bioabsorbable, thus PEG(-PAE)4 copolymer is promising candidate for drug delivery. The results indicate that drug loading efficiency and drug loading capability will increase while ratio of PEG block is increasing. In weakly acidic environment, the drug carrier size will become larger. And the larger ratio of PAE block, the larger size the drug carrier will become. It’s also represent faster drug releasing rate.

並列關鍵字

Dissipative particle dynamics ； pH-sensitive block copolymer ； Drug delivery

參考文獻

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利用耗散粒子動力學模擬pH敏性MPEG-b-(PLA-co-PAE)嵌段共聚物之藥物輸送系統

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