两性霉素B微乳的制备及体外经皮渗透研究

Preparation of Amphotericin B Microemulsion and Its Transdermal Absorption

目的制备水包油型两性霉素B微乳,并对其进行体外经皮渗透性能考察。方法用相转变温度法制备两性霉素B微乳,用光散射粒度仪测定微乳的粒径,电子透射电镜观察微乳的形态。用药物渗透扩散仪进行两性霉素B透皮吸收研究,高效液相色谱法测定两性霉素B含量。结果用相转变温度法制备了Tween80和异丙醇重量比为1∶1,IPM和混合表面活性剂之比为1∶9,水含量64.6%,载药量为0.247%的两性霉素B微乳。所制微乳符合微乳特征,调节pH值有助于两性霉素B由分散介质向微乳表面转移。水性月桂氮酮对两性霉素B的促渗效果最好,pH值为5.12,月桂氮酮浓度为1%时,两性霉素B微乳经离体兔皮的JS为4.627μg·cm-2·h-1,经离体大鼠皮肤的JS为4.484μg·cm-2·h-1。结论开发微乳透皮给药制剂有望提高两性霉素B的疗效,降低其毒副作用。

OBJECTIVE To prepare O/W microemulsion of amphotericin B and investigate its in vitro transdermal delivery ability. METHODS Amphotericin B microemulsion was prepared by phase transfer temperature （PIT） method. The mean droplet sizes of microemulsion were measured via dynamic light scattering （DLS） on a Zetasizer, their microstructures were observed by transmission electron microscope （TEM）. Amphotericin B diffusion studies were performed via excised rabbit skin using a drug diffusion apparatus. The contents of amphotericin B were measured by HPLC. RESULTS With mass ratio of Tween 80 and alcohol 1 ： 1, mass ratio of IPM and the mixture of surfactants 1 ： 9, content of water 64.6%, microemulsion containing 0.247% amphotericin B was prepared by PIT method, which was according with the characterization of microemulsion. The adjusting ofpH forced amphotericin B transferring from aqueous phase to interface of microdroplets. Azone was the best enhancer of amphotericin B At pH 5.12, the content of azone was 1%, the steady-state permeation rates of microemulsion through through excised rabbit skin and rat skin were 4.627 and 4.484μg.cm^-2.h^-1 CONCLUSION The further research of amphotericin B microemulsion transdermal delivery system maybe useful for increasing its therapeutic effect and reducing toxicity.