College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Eur J Pharm Sci. 2011 Sep 18;44(1-2):149-57. doi: 10.1016/j.ejps.2011.07.003. Epub 2011 Jul 12.
5-Aminolevulinic acid (5-ALA), inducing photodynamic protoporphyrin (PpIX), is a hydrophilic molecule, resulting in leashing the capacity to cross tissue barriers like stratum corneum (SC) of skin. Here, we aimed to develop 5-ALA loaded ultradeformable liposomes (UDL) with different surface charges, and to investigate their physicochemical characteristics and capability for the skin penetration and retention of 5-ALA for topical photodynamic therapy (PDT). The effects of surface charges of UDL on in vitro permeation of 5-ALA and in vivo accumulation of 5-ALA-induced PpIX in viable skin were determined and then compared with conventional neutral liposomes (nLiposome). All UDL showed smaller particle size and better deformability than nLiposome. However, entrapment efficiency of 5-ALA was similar to each vesicle. Among vesicles, the cationic UDL (cUDL) demonstrated higher stability and permeability, and could deliver 5-ALA into deep skin tissue by topical application. Moreover, the 5-ALA loaded in cUDL was long retained, and induced more amount of PpIX in viable skin than those in other UDL and nLiposome. Considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, these results suggested that topical delivery of 5-ALA loaded in cUDL could be an interesting proposal to optimize PDT related to 5-ALA.
5-氨基酮戊酸（5-ALA），诱导原卟啉 IX（PpIX），是一种亲水性分子，能够束缚穿越组织屏障的能力，如皮肤的角质层（SC）。在这里，我们旨在开发具有不同表面电荷的 5-ALA 负载超变形脂质体（UDL），并研究其物理化学特性以及用于局部光动力疗法（PDT）的 5-ALA 皮肤穿透和保留能力。确定了 UDL 的表面电荷对 5-ALA 的体外渗透和 5-ALA 诱导的 PpIX 在活皮中的体内积累的影响，并与常规中性脂质体（nLiposome）进行了比较。所有 UDL 均显示出比 nLiposome 更小的粒径和更好的变形性。然而，5-ALA 的包封效率与每种囊泡相似。在囊泡中，阳离子 UDL（cUDL）表现出更高的稳定性和渗透性，并可通过局部应用将 5-ALA 递送至深层皮肤组织。此外，负载在 cUDL 中的 5-ALA 保留时间更长，并在活皮中诱导出比其他 UDL 和 nLiposome 更多的 PpIX。考虑到 5-ALA 转化为 PpIX 优先发生在表皮中，这些结果表明，局部递送负载在 cUDL 中的 5-ALA 可能是优化与 5-ALA 相关的 PDT 的一个有趣建议。
