月桂氮卓酮对雌二醇皮肤渗透的促进作用及其机理

The mechanism of Azone-enhanced estradiol permeation across human skin in vitro

Ｖａｌｉａ－Ｃｈｉｅｎ双室渗透池及ＨＰＬＣ测定结果表明，月桂氮酮（Ａｚｏｎｅ）对雌二醇的皮肤渗透有良好的促进作用，当Ａｚｏｎｅ与丙二醇组成复合促透剂联合应用时，两者呈现协同作用。差示扫描量热计（ＤＳＣ）分析结果揭示了Ａｚｏｎｅ的促进机理是它瓦解了角质层的双分子脂质层的紧密结构，破坏了有序叠集排列，导致结构松散，流度（ｆｌｕｉｄｉｔｙ）增加，从而使药物分子易于转运。扫描电镜对皮肤表面的超微结构观察，进一步证实了Ａｚｏｎｅ对双分子脂质层的影响。皮肤表面不连续杜及裂隙的增加和毛囊口的拓宽，提示Ａｚｏｎｅ对角质层类脂质具有特异性的溶解作用，从而使屏障阻力降低，药物渗透速率增加。

Transdermal permeability of estradiol was investigated by using Valia-Chien dou-ble-compartment permeation cell,and amounts permeated were measured by HPLC. The resultsshowed Azone significantly increased estradiol flux. With 5%Azone in the vehicle ,estradiol fluxvalue increased 3.5 fold.With 41%propylene glycol and 5%Azone used conjunctly, they actedsynergistic effects on the penetration of estradiol, the flux value increased 30 fold greater com-pared to 40%PEG400/NS in the vehicle. In the result of DSC,a possible mechanism of Azone onestradiol permeation was revealed of follows : Azone dramatically disrupted the lipid bilayer struc-ture of stratum corneum and increased its fluidity,and this would permit estradiol permeationmore readily through this less rigid environment,yielding higher fluxes. The results of scanningelectron microscopy of skin ultrastructure also demonstrated that Azone influenced the lipid bilay-er structure of stratum corneum. The numerous small infolding lines divided the skin surface intosmall areas with vesiculation and numerous desquamated cells around the orifice of the hair werefractured, detached and widened. It is indicated that Azone could dissolve the lipid of stratumcorneum,and thus,it could reduce the barrier resistance and increase the permeation rate.