| Summary: | 碩士 === 國立清華大學 === 化學工程學系 === 88 === 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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