團聯共聚物在小分子藥物中的自組裝與包覆行為

Abstract

雙親性團聯式共聚物可以於選擇性溶劑自組裝形成微胞已眾所皆知，其中喜 好溶劑的鏈段傾向和溶劑接觸，而不喜好溶劑的鏈段被屏蔽遠離溶劑，不同於傳 統的液態溶液微胞系統，我們發現團聯式共聚物PS-b-PEO 也可以自組裝形成各 種微胞結構於高溫熔融的PDP、benzoic acid 和Aspirin 小分子，因為熔融的小分 子猶如系統中的選擇性溶劑對PEO 鏈段具有選擇性，可以使PS-b-PEO 自組裝形 成微胞，並且自組裝結構可以被完整保留於固態樣品中當溫度降回室溫，我們進 一步發現，除了藉由熱退火的方式使PS-b-PEO 於大量的小分子中自組裝形成微 胞以外，也可以藉由溶劑退火獲得相同的自組裝結構於室溫下或45 ℃下，如此 一來可以防止不必要的化學反應在高溫發生，特別是當我們使用的小分子為藥物 小分子，而被保留於固態樣品中的自組裝結構可以被完整萃取出來經由適當的溶 劑，其中萃取出來的液胞結構具有充滿小分子的核心，包覆能力遠遠比在溶液系 統中所形成的傳統液胞結構高且具有應用於控制釋放的潛力，此外，不論藉由熱 退火的方式或溶劑退火的方式使PS-b-PEO 於大量的小分子中自組裝，其自組裝 結構皆取決於團聯式共聚物PS-b-PEO 的鏈段長度比和退火處理的時間，因為它 們會影響高分子鏈的堆疊情形與曲率。

It is well known that amphiphilic block copolymers in selective solvents self-assemble into micellar structures, where solvophilic blocks tend to contact with solvents while solvophobic blocks are shielded from the solvents. Different from the conventional micellization in liquid systems, we found that the block copolymers poly(styrene-block-ethylene oxide) (PS-b-PEO) can self-assemble into a variety of structures in melted 3-n-pentadecylphenol (PDP), benzoic acid and acetylsalicylic acid (Aspirin) at high temperature and the structures are retained in “solid state” after being cooled down to room temperature. We further found that such solid-state structures can be obtained by solvent annealing at room temperature or 45 ℃, which prevents unnecessary chemical reactions at high temperature especially for drug molecules. The structures that are trapped in solid state can be extracted entirely by using appropriate solvents. Compared with vesicles formed in liquid systems, the extracted vesicles, which are filled with small molecules in the core, are highly efficient to encapsulate substances and potential for the application of controlled release. Besides, the morphologies are dependent on the relative length of the block copolymers and the annealing time, which influence the packing of the copolymer chains and the inherent molecular curvature.