Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy
Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy
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DOI：
10.1016/j.jconrel.2008.05.002
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发表时间：
2008-08-07
影响因子：
10.8
通讯作者：
Moan, Johan
中科院分区：
文献类型：
--
作者：
Donnelly, Ryan F.;Morrow, Desmond I. J.;Moan, Johan
深部或结节性皮肤肿瘤的光动力疗法目前受到卟啉前体5-氨基乙酰丙酸（ALA）的不良组织渗透的限制。在这项研究中，硅微针阵列，第一次，以提高ALA在体外和体内的皮肤渗透。用高度为270 μ m、底部直径为240 μ m、间距为750 μ m的6 × 7微针阵列穿刺切除的小鼠皮肤，导致从含有19 mg ALA cm-2的生物粘附贴剂释放的ALA的经皮递送显著增加。双针穿刺增强了ALA向离体猪皮上部区域的递送，但在平均深度为1.875 mm时，ALA浓度与对照值相似，这可能反映了ALA与组织成分的结合。然而，重要的是，使用裸鼠的体内实验表明，微针穿刺可以减少皮肤中诱导高水平光敏剂原卟啉IX所需的应用时间和ALA剂量。这显然对临床实践有影响，因为更短的应用时间意味着改善患者和临床医生的便利性，并且可以在同一个疗程中治疗更多的患者。由于ALA价格昂贵并且通过二级反应快速降解，因此减少所需剂量也是一个显著的优点。(C)2008 Elsevier B. V.保留所有权利。
Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA). In this study, silicon microneedle arrays were used, for the first time, to enhance skin penetration of ALA in vitro and in vivo. Puncturing excised murine skin with 6 x 7 arrays of microneedles 270 pm in height, with a diameter of 240 mu m at the base and an interspacing of 750 pm led to a significant increase in transdermal delivery of ALA released from a bioadhesive patch containing 19 mg ALA cm(-2). Microneedle puncture enhanced ALA delivery to the upper regions of excised porcine skin but, at mean depths of 1.875 mm, ALA concentrations were similar to control values, possibly reflecting binding of ALA by tissue components. However, and importantly, in vivo experiments using nude mice showed that microneedle puncture could reduce application time and ALA dose required to induce high levels of the photosensitiser protoporphyrin IX in skin. This clearly has implications for clinical practice, as shorter application times would mean improved patient and clinician convenience and also that more patients could be treated in the same session. As ALA is expensive and degrades rapidly via a second order reaction, reducing the required dose is also a notable advantage. (C) 2008 Elsevier B.V. All rights reserved.