| Summary: | 碩士 === 國立雲林科技大學 === 化學工程與材料工程系碩士班 === 101 === In this study, we found that compound A can form nanoparticles by a modified ethanol injection method for the first time, In order to improve the stability of compound A nanoparticles, D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) was added into compound A nanoparticles. In addition, the effects of polyethylene glycol chain (PEG1000) on compound A dispertions were investigated by compared with mixed A/α-Tocopherol (VE) nanoparticles. Physicochemical characteristics of mixed A/TPGS and A/VE nanoparticles were investigated by multi-techniques including dynamic light scattering (DLS), transmission electron microscope (TEM), fluorescence spectrometer and differential scanning calorimetry (DSC). High performance liquid chromatography (HPLC) was used to study the chemical stability of mixed A/TPGS dispersionss in different concentrations of dithiothreitol (DTT). Transdermal absorption studies of A/TPGS nanoparticles across the rat skin were investigated by using Franz diffusion cells. Furthermore, behavior of mixed A/TPGS and A/VE monolayers at the air/water interface were measured at 24 ℃ by Langmuir trough system combined with fluorescence microscopy.
Adding TPGS into compound A nanoparticles decreased average particle size among the A/TPGS systems, and mixed A/TPGS 6:4 dispersions showed the smallest average particle size. Mixed A/TPGS (9.9:0.1, mol ratio) dispersionss exhibited better storage stability than pure compound A dispersions. Main phase transition temperature of A dispersionss was found at 59.4 ℃. The phase transition temperature remained constant, and the enthalpy of the observable gel to liquid-crystalline phase transition decreased with increasing XTPGS or XVE, and the phase change enthalpy was eliminated at XTPGS = 0.5 or XVE = 0.1. By Comparing results of mixed A/TPGS with A/VE systems at the same molar ratio, PEG-chains was found to enhance the intermolecular interactions. At room temperature (compound A is under gel state), the incorporation of TPGS or VE into compound A membrane reduced the mobility in hydrocarbon chain region, and the presence of TPGS generally increased the molecular mobility of the interfacial region of the membrane. This indicated that PEG-chain may soften compound A membrane structure. The most chemical stability was found as the mixed A/TPGS (9:1) dispersions in 0.01M concentration of DTT. Adding TPGS can improve compound A dispersions permeability, and mixed A/TPGS (9/1) dispersions exhibited better transdermal efficacy absorption than pure compound A dispersionss. Monolayer results showed that mixed A/TPGS monolayers were more expanded than mixed A/VE monolayers, possibly resulting from PEG-chains steric barrier. Excess area results showed that the mixed A/TPGS monolayers were negative deviation and mixed A/VE monolayers were positive deviation at low surface pressure, implying PEG-chain makes intermolecular arrangement tighter. In addition, the mixed A/TPGS and A/VE monolayers were positive deviation at high surface pressure, which maybe caused by steric repulsive of neighboring PEG-chains. Excess Gibbs free energy and the free Gibbs energy results showed that mixed A/TPGS monolayer molecules were more miscible and thermodynamic stable than mixed A/VE monolayer. Fluorescence imaging results showed that compound A molecules aggregated into dendritic domain, indicating that the impact of line tension was less than the dipole repulsion. At constant surface pressure, adding TPGS into compound A domain make compound A Domain become smaller and uniformly distributed, indicating TPGS will make intermolecular more expaned. On the other hand, adding VE, part of the domain become large, and turn into circular shape by the dendrimers. This indicates that steric repulsion of PEG-chain will make intermolecular no cohesive interaction in mixed monolayers.
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