Sheu Ming-Thau, Chen Shin-Yi, Chen Ling-Chun, Ho Hsiu-O
Graduate Institute of Pharmaceutical Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan, 110, Taiwan, ROC.
J Control Release. 2003 Mar 26;88(3):355-68. doi: 10.1016/s0168-3659(02)00492-3.
The effect of micellar solubilization on the enhancement of the solubility and percutaneous penetration of estradiol by the surface-active agent, tocopheryl polyethylene glycol succinate (TPGS) was characterized in this study. Results show that the solubility of estradiol was improved in the presence of TPGS through micellar solubilization. The critical micelle concentration (CMC) of TPGS increased with increasing ethanol concentration in the medium. With the flux corrected to the saturated level (J(corrected)) of the free form of estradiol, an increase in the alcohol content of the medium resulted in an increase in J(corrected) for all levels of TPGS examined. For the same level of alcohol content, an increase in the TPGS concentration mostly led to a small extent of decrease in J(corrected). However, the extent of decrease was more obvious in media containing more than 60% alcohol. We also confirmed that only an insignificant amount of TPGS was transported across the skin (below the detection limit of 2 microg/ml). Permeabilities (P(eff)), which describe the overall effects (DK/H) on the stratum corneum (SC), decreased with increasing TPGS concentration for media containing 0, 40, 60, and 80% alcohol, whereas they increased then decreased with increasing TPGS concentration for media containing 10 and 20% alcohol. The enhancement ratios based on P(eff) assuming that the medium contained 0% TPGS and alcohol as unity did not increase accordingly with increases in TPGS concentration at the same level as alcohol. Likewise, the enhancement ratios for the same level of TPGS increased with low alcohol content, but then decreased with increasing alcohol content. We concluded that micellar solubilization by TPGS was able to improve the solubility of estradiol, but it only had an insignificant influence on the skin. Interfacial coverage of TPGS with increasing TPGS concentration and hindrance of the partitioning of estradiol by the increasing alcohol content might play a role in influencing the permeability of estradiol.
本研究对胶束增溶作用进行了表征，该作用可增强表面活性剂生育酚聚乙二醇琥珀酸酯（TPGS）对雌二醇溶解度和经皮渗透的影响。结果表明，在TPGS存在下，通过胶束增溶作用，雌二醇的溶解度得到了提高。TPGS的临界胶束浓度（CMC）随着介质中乙醇浓度的增加而升高。以雌二醇游离形式的饱和水平校正通量（J（校正））后，介质中乙醇含量的增加导致所有检测水平的TPGS的J（校正）均增加。对于相同的乙醇含量水平，TPGS浓度的增加大多导致J（校正）略有下降。然而，在含醇量超过60%的介质中，下降程度更为明显。我们还证实，仅有极少量的TPGS透过皮肤转运（低于2μg/ml的检测限）。描述对角质层（SC）总体影响（DK/H）的渗透率（P（eff）），对于含0%、40%、60%和80%乙醇的介质，随着TPGS浓度的增加而降低，而对于含10%和20%乙醇的介质，随着TPGS浓度的增加先升高后降低。假设介质中TPGS和乙醇含量为0%时，基于P（eff）的增强比并未随TPGS浓度的增加而相应增加，与乙醇含量处于同一水平。同样，相同水平TPGS的增强比在低乙醇含量时增加，但随后随着乙醇含量的增加而降低。我们得出结论，TPGS的胶束增溶作用能够提高雌二醇的溶解度，但对皮肤仅有微不足道的影响。TPGS界面覆盖率随TPGS浓度的增加以及乙醇含量增加对雌二醇分配的阻碍可能在影响雌二醇的渗透率方面发挥作用。
