| Summary: | 碩士 === 高雄醫學院 === 藥學研究所 === 87 === During the menstrual cycle, estradiol, the predominant estrogen, is secreted by ovaries. In clinical, estradiol has been used not only to alleviate menopausal systems such as vasomotor flushes but also to prevent cardiovascular deterioration. The oral does of estradiol is large because most of the estradiol would be decreased by the inactivation of estradiol within the gastrointestinal and liver during first-pass metabolism.
Using the transdermal route could solve the problem, the first-pass effect by oral route. Free estradiol had a slowly transdermal effect and a common way to solve the problem is using enhancer to increase the delivery. However, using enhancer might induce the skin damage and an unexpected release rate. Proniosome would be hydrated to form niosome spontaneously in the aqueous media. The advantages of proniosome were a lot such as increase the delivery and make the delivery rate constantly Niosome is the derivative of liposome by adding surfactant to increase the stability of liposome ( formed by phospholipid only).
In this study, proniosome containing Span series or mixed system containing Span and Tween all had higher encapsulation percentage more than 90%. The encapsulation percentage of Tween series was lower than the Span series, but the particle size of Tween series was smaller than the Span series. However, changing the ratio of Span 40 and lecithin did not seem like a factor to influence the encapsulation percentage or particle size. It still earned the similar result when adding different amount of cholesterol.
Comparing the effect of transdermal delivery, proniosome appeared better transdermal effect than the free form of estradiol in the same concentration. The differences between various types of surfactants were important factors to change the delivery rate. The ratio between Span 40 and lecithin might influence the delivery effect. Proniosome with high ratio of Span 40 had a large flux than the proniosome with low ratio of Span 40. The amount of cholesterol did not show a obvious influence in delivery effect. Proniosome prepared by Span 85 : Tween 20 = 1 : 1 had a higher flux than proniosome prepared by Span 85 or Tween 20. However, proniosome prepared by Span 40 : Tween 20 = 1 : 1 showed a lower flux than proniosome prepared by Span 40 or Tween 20. The transdermal mechanism of proniosome was also studied. Compared not only the release rate of proniosome preparing by different kinds of surfactants or different ratio between Span 40 and lecithin but also the enhancer effect by different kinds of surfactants or different ratio of Span 40, the transdermal mechanism was seemed like the sum of release rate of proniosome and the enhancer effect by different kinds of surfactants. The transdermal effect of niosome was different with the transdermal effect of proniosome. Using different transdermal route like de SC method or open method would change the flux of estradiol.
Finally, the in vivo study was developed by using microdialysis to detect the concentration under the skin. Proniosome formulations showed a higher AUC in skin and serum than free estradiol. Proniosome prepared by Span 60 might be a better formulation because it had not only higher Cmax and Css(steady state) but also shorter Tmax and Tss than proniosome prepared by Span 40.
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