Manosroi A, Kongkaneramit L, Manosroi J
Pharmaceutical-Cosmetics Raw Materials and Natural Products Research and Development Center, Faculty of Pharmacy, Institute for Science and Technology Research and Development, Chiang Mai University, Chiang Mai 50200, Thailand.
Int J Pharm. 2004 Feb 11;270(1-2):279-86. doi: 10.1016/j.ijpharm.2003.10.031.
The aim os this study was to characterize the stability and transdermal absorption of amphotericin B (AMB: 0.05 mg/mg lipid) in hydrogenated soya phosphatidylcholine/cholesterol/charged lipid [dicetyl phosphate (-) or stearylamine (+)] liposomes at molar ratios of 1:1:0, 7:2:0, 7:2:1(-) and 7:2:1(+). The AmB contents in liposomes were determined by HPLC with UV detection at 382 nm. Stabilities of AmB in liposome formulations were compared with those in solution and powder forms, during storage at 4, 30 and 45 degrees C for 90 days. Absorption studies of AmB across the rat skin were conducted, using vertical Franz diffusion cells at 37 degrees C for 24 h. The slowest degradation was observed in the positive liposome (7:2:1(+)AmB), with shelf life of approximately 1 year (30 degrees C). In comparison, the shelf lives of AmB in solution and powder were 4 and 14 days, respectively. AmB in positive liposomes seemed to demonstrate the highest flux in stratum corneum (58 ng/cm(2)/h), while the highest flux in viable epidermis (23 ng/cm(2)/h) was observed in negative liposomes. AmB entrapped in charged liposomes showed sustained skin absorption. The positively charged liposome might be the best formulation for AmB, due to its higher stability than other formulations.
本研究的目的是表征两性霉素B(AMB:0.05 mg/mg脂质)在氢化大豆磷脂酰胆碱/胆固醇/带电脂质[磷酸二鲸蜡酯(-)或硬脂胺(+)]脂质体中的稳定性和经皮吸收情况,脂质体的摩尔比为1:1:0、7:2:0、7:2:1(-)和7:2:1(+)。脂质体中的两性霉素B含量通过在382 nm处进行紫外检测的高效液相色谱法测定。将两性霉素B在脂质体制剂中的稳定性与溶液和粉末形式的稳定性进行比较,在4℃、30℃和45℃下储存90天。使用垂直Franz扩散池在37℃下进行两性霉素B经大鼠皮肤的吸收研究,持续24小时。在阳性脂质体(7:2:1(+)AmB)中观察到最慢的降解,保质期约为1年(30℃)。相比之下,两性霉素B在溶液和粉末中的保质期分别为4天和14天。阳性脂质体中的两性霉素B似乎在角质层中表现出最高通量(58 ng/cm²/h),而在活表皮中最高通量(23 ng/cm²/h)在阴性脂质体中观察到。包封在带电脂质体中的两性霉素B表现出持续的皮肤吸收。带正电荷的脂质体可能是两性霉素B的最佳制剂形式,因为它比其他制剂具有更高的稳定性。