Lipid cubic phases for improved topical drug delivery in photodynamic therapy
Lipid cubic phases for improved topical drug delivery in photodynamic therapy
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DOI：
10.1016/j.jconrel.2005.05.010
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发表时间：
2005-09-02
影响因子：
10.8
通讯作者：
Moan, J
中科院分区：
文献类型：
--
作者：
Bender, J;Ericson, MB;Moan, J
我们已经评估了脂质立方相的功效，高度有序的自组装系统在纳米水平上，作为药物递送载体，用于在裸鼠皮肤上局部给药的δ-氨基乙酰丙酸（ALA）及其甲酯（m-ALA）。ALA是血红素的前体，在活组织中诱导光敏剂原卟啉IX（PpIX）的产生。局部给药后，测量皮肤表面的PpIX荧光，使得间接定量ALA渗透到组织中成为可能。立方相由脂质（单油酸甘油酯或植烷三醇）、水和药物形成。在某些情况下，丙二醇也包含在立方相中。所有研究溶剂中的药物浓度均为3%（w/w，基于样品总重量）。当制剂施用1小时时，在10小时的测量期间，与标准软膏相比，单油酸甘油酯立方体系和三组分植烷三醇样品显示出更高的荧光。ALA和m-ALA产生了类似的结果，尽管当使用m-ALA时，所研究的载体之间的差异更明显。对于24小时的应用，具有m-ALA的单油酸甘油酯立方体系统显示出比标准软膏更快的PpIX形成，这意味着在短的应用时间（小于4小时）下更高的PpIX水平。ALA的系统PpIX荧光通过使用脂质立方体制剂而升高。值得注意的是，对于具有m-ALA的单油酸甘油酯立方体样品也观察到小的全身效应。这些结果意味着当使用脂质立方体系统时改善的PpIX形成，最可能是由于增强的药物渗透。(c)2005 Elsevier B. V.保留所有权利。
We have evaluated the efficacy of lipid cubic phases, highly ordered self-assembly systems on the nanometer level, as drug delivery vehicles for in vivo topical administration of delta-aminolevulinic acid (ALA) and its methyl ester (m-ALA) on nude mice skin. ALA, a precursor of heme, induces the production of the photosensitizer protoporphyrin IX (PpIX) in living tissue. Measuring the PpIX fluorescence at the skin surface, after topical administration, makes indirect quantification of the penetration of ALA into the tissue possible. Cubic phases were formed of lipid (monoolein or phytantriol), water and drug. In some cases, propylene glycol was included in the cubic phase as well. The drug concentration was 3% (w/w, based on the total sample weight) in all investigated vehicles. When the formulations were applied for 1 h, the monoolein cubic systems and the three-component phytantriol sample showed higher fluorescence compared to the standard ointment during the 10 h of measurement. Both ALA and m-ALA yielded similar results, although the differences between the investigated vehicles were more pronounced when using m-ALA. For the 24-h applications, the monoolein cubic systems with m-ALA showed faster PpIX formation than the standard ointment, implying higher PpIX levels at short application times (less than 4 h). The systemic PpIX fluorescence of ALA was elevated by using the lipid cubic formulations. Notably, a small systemic effect was also observed for the monoolein cubic sample with m-ALA. These results imply improved PpIX formation when using the lipid cubic systems, most probably due to enhanced drug penetration. (c) 2005 Elsevier B.V. All rights reserved.