Kirjavainen M, Urtti A, Jääskeläinen I, Suhonen T M, Paronen P, Valjakka-Koskela R, Kiesvaara J, Mönkkönen J
Department of Pharmaceutics, University of Kuopio, Finland.
Biochim Biophys Acta. 1996 Dec 13;1304(3):179-89. doi: 10.1016/s0005-2760(96)00126-9.
Liposomes have been suggested as a vehicle for dermal and transdermal drug delivery, but the knowledge about the interaction between lipid vesicles and human skin is poor. Therefore, we visualized liposome penetration into the human skin by confocal laser scanning microscopy (CLSM) in vitro. Liposomes were prepared from phospholipids in different compositions and labeled with a fluorescent lipid bilayer marker, N-Rh-PE (L-alpha-phosphatidylethanolamine-N-lissamine rhodamine B sulfonyl). Fluorescently labelled liposomes were not able to penetrate into the granular layers of epidermis. However, the fluorescence from liposome compositions containing DOPE (dioleylphosphatidyl ethanolamine) was able to penetrate deeper into the stratum corneum than that from liposomes without DOPE. Pretreatment of skin with unlabeled liposomes containing DOPE or lyso-phosphatidyl choline (lyso-PC) enhanced the subsequent penetration of the fluorescent markers, N-Rh-PE and sulforhodamine B into the skin, suggesting possible enhancer activity, while most liposomes did not show such enhancement. Resonance energy transfer (RET) and calcein release assay between stratum corneum lipid liposomes (SCLLs) and the phospholipid vesicles suggested that the liposomes containing DOPE may fuse or mix with skin lipids in vitro and loosen the SCLL bilayers, respectively. Among the factors not affecting stratum corneum penetration were: negative charge, cholesterol inclusion and acyl chain length of the phospholipids. In conclusion, fusogenicity of the liposome composition appears to be a prerequisite for the skin penetration.
脂质体已被提议作为一种用于皮肤和透皮给药的载体，但关于脂质囊泡与人体皮肤之间相互作用的了解却很少。因此，我们通过体外共聚焦激光扫描显微镜（CLSM）观察了脂质体渗透进入人体皮肤的情况。脂质体由不同组成的磷脂制备而成，并用荧光脂质双层标记物N-Rh-PE（L-α-磷脂酰乙醇胺-N-丽丝胺罗丹明B磺酰）进行标记。荧光标记的脂质体无法渗透进入表皮的颗粒层。然而，含有二油酰磷脂酰乙醇胺（DOPE）的脂质体组合物发出的荧光比不含DOPE的脂质体发出的荧光能够更深地渗透进入角质层。用含有DOPE或溶血磷脂酰胆碱（lyso-PC）的未标记脂质体对皮肤进行预处理，可增强随后荧光标记物N-Rh-PE和磺基罗丹明B渗透进入皮肤的能力，这表明可能具有增强活性，而大多数脂质体并未表现出这种增强作用。角质层脂质脂质体（SCLL）与磷脂囊泡之间的共振能量转移（RET）和钙黄绿素释放试验表明，含有DOPE的脂质体在体外可能分别与皮肤脂质融合或混合，并使SCLL双层结构松弛。不影响角质层渗透的因素包括：磷脂的负电荷、胆固醇的掺入以及酰基链长度。总之，脂质体组合物的融合性似乎是皮肤渗透的一个先决条件。
