本研究應用油/水脂質乳化液包覆抗癌藥物紫杉醇(paclitaxel)，以tricaprylin (C8:0)為油相，磷脂基膽鹼(egg PC)和非離子型界面活性劑Tween 80為乳化劑，輔以PEG-DSPE 或folate-PEG-DSPE，製備長循環半生期型以及專一標的型油/水脂質乳化液。由於tricaprylin (C8:0)碳鏈較tricaproin (C6:0)長，且毒性較低，故本研究藉由將原配方中之混合油相組成[tricaproin (C6:0): tricaprylin (C8:0) (3:1, w/w)]改為單一油相組成tricaprylin (C8:0)，期能發展毒性較低、穩定性與原配方相若之藥物載體。研究結果顯示，兩種不同油相組成之脂質乳化液，液滴粒徑與包覆效率相似；且經過三個月的儲存時間，粒徑皆可維持不變；而除未經PEG-DSPE或folate-PEG-DSPE改質之脂質乳化液外，包覆效率皆可維持二至三個月以上不變。利用黏度計進行之血液實驗結果亦證實兩種不同油相組成之脂質乳化液與血液作用情形相仿。由此可知，單一油相組成脂質乳化液確能取代混合油相組成脂質乳化液，成為較合適之藥物載體。
為更進一步探討油/水脂質乳化液之界面現象，吾人利用表面張力之測量結果，配合Gibbs吸附公式，計算出單一界面活性劑分子於空氣/水界面所佔據之表面積(A2/molecule)，並進而估計佔據一乳化液滴表面所需之界面活性劑分子個數。由計算結果發現，乳化液系統中含有過剩之乳化劑，其作用可能與乳化液之穩定性有關。此外，由單分子之表面積與表面張力之關係，可知PEG-DSPE 分子的PEG長鏈是以brush的型態接枝於乳化液液滴表面，形成立體屏障(steric barrier)，以增加乳化液之穩定性。

此外，為深入了解egg PC與Tween 80、PEG-DSPE分子在界面上相互作用的情形，吾人亦應用Motomura等人所推導之熱力學公式，求得混合界面活性劑在界面吸附層(adsorbed film)與微胞(micelle)中之過剩自由能(excess Gibbs free energy)。其結果顯示，當總濃度低於臨界微胞濃度(CMC)時，egg PC與Tween 80分子間的作用力小於同分子間作用力，其過剩自由能大於零；而當總濃度增加至臨界微胞濃度， egg PC在界面上的濃度增加，與Tween 80分子形成均勻混合的微胞。至於PEG-DSPE，則由於其與egg PC、Tween 80分子之間的作用力較小，傾向溶於水中；若吸附至界面，亦容易對egg PC/Tween 80之混合單分子層結構造成擾動。故可推測在脂質乳化液液滴的油/水界面上，egg PC與Tween 80可形成排列緊密之單分子層，而PEG-DSPE雖有可能對單分子層之結構造成破壞，卻仍能藉由其PEG長碳鏈之立體障礙，發揮穩定作用。

In this study, paclitaxel, a promising anticancer drug, was entrapped in oil-in-water lipid emulsion droplets with tricaprylin (C8:0) as the oil core, egg phosphatidylcholine (egg PC) and a nonionic surfactant, Tween 80, as the principal emulsifier. The lipid emulsion was modified with polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) and folate-polyethylene glycol-distearoyl phosphatidylethanolamine (folate-PEG-DSPE), respectively, to obtain the steric-stabilizing type and specific-targeting type lipid emulsions.
On the basis of a formulation which has been developed in our laboratory, a less cytotoxic lipid emulsion is being sought by substituting the originally more toxic oil core, tricaproin (C6:0): tricaprylin (C8:0) (3:1, w/w), with tricaprylin (C8:0), which is expected to be less cytotoxic because of its longer alkyl chain. The results showed similar particle diameters and paclitaxel encapsulation efficiencies of the two lipid emulsions with different oil contents. After three months of storage, the particle sizes remained unchanged, and the encapsulation efficiencies of paclitaxel, except for that of the conventional-type lipid emulsions, remained in the initial level for at least two months. The effect of blood constituents on the tricaprylin-in-water lipid emulsions is also similar to that on the tricaproin: tricaprylin (3:1, w/w)-in-water lipid emulsions.

In an attempt to investigate the interfacial phenomenon of lipid emulsions, the surface tensions of egg PC, Tween 80, and PEG-DSPE are measured as a function of the concentration. With the application of the Gibbs adsorption equation, the molecular area of an individual surfactant molecule (A2/molecule) at the air/water interface is determined such that the number of molecules necessary to occupy the oil/water interface of a lipid emulsion droplet can be estimated. It was discovered that excess amount of surfactant is present in the lipid emulsion system which may result in micelles or suspension of surfactant molecules in the aqueous media, and is considered to be related to emulsion stabilization.

On the other hand, with the application of the thermodynamic equations derived by Motomura et al., the composition of surfactants in the mixed adsorbed film and mixed micelle can be estimated directly from the results of surface tension measurements such that the interaction between surfactant molecules can be evaluated. The results show that the egg PC and Tween 80 molecules are not miscible with each other in the adsorbed film but form homogeneous mixed micelle when the CMC is reached. As for the PEG-DSPE molecule, it can interfere with the close packing of egg PC and Tween 80 molecules when adsorbs to the air/water interface, or dissolve in the bulk solution when it is rejected by the mixed egg PC/Tween 80 monomolecular film. It is thus inferred that when the oil/water interface of the lipid emulsion droplet is under consideration, a close-packed monomolecular film is produced by egg PC and Tween 80 molecules. Though PEG-DSPE molecules can result in structural perturbation in this mixed egg PC/Tween 80 film, the steric-stabilization of the PEG-chain is expected to compensate for the instability caused by its incorporation.

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