Biochemical enhancement of transdermal delivery with magainin peptide: modification of electrostatic interactions by changing pH.
Biochemical enhancement of transdermal delivery with magainin peptide: modification of electrostatic interactions by changing pH.
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DOI：
10.1016/j.ijpharm.2008.05.042
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发表时间：
2008-10
影响因子：
5.8
通讯作者：
Yeu‐Chun Kim;S. Late;A. Banga;P. Ludovice;M. Prausnitz
中科院分区：
文献类型：
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作者：
Yeu‐Chun Kim;S. Late;A. Banga;P. Ludovice;M. Prausnitz
爪蟾抗菌肽是一种天然存在的、形成毛孔的肽，最近已被证明可增加皮肤渗透性。本研究验证了爪蟾抗菌肽和药物之间的静电力介导药物通过皮肤转运的假设。带正电荷的爪蟾抗菌肽和带负电荷的模型药物荧光素之间的静电相互作用在pH 7.4下是有吸引力的，并且当与2%N-月桂酰肌氨酸在50%乙醇中配制时，在体外通过人表皮的递送增加了35倍。增加到pH 10或11在很大程度上中和爪蟾抗菌肽的电荷，这消除了由于爪蟾抗菌肽的增强。屏蔽静电相互作用与1- 2 M NaCl溶液类似地消除增强。显示相反的依赖于pH值，爪蟾抗菌肽和带正电荷的抗恶心药物，格拉司琼之间的静电相互作用，在很大程度上被中和在pH值10，并导致在92倍的增加，经皮给药。pH值降至5时，爪蟾抗菌肽的正电荷增加，从而排斥格拉司琼，并逐渐降低经皮通量。圆二色性分析，多光子显微镜，和FTIR光谱显示没有显着的pH值对爪蟾抗菌肽二级结构，爪蟾抗菌肽沉积在角质层，或角质层脂质顺序，分别影响。我们得出结论，爪蟾抗菌肽增加透皮给药的机制，涉及爪蟾抗菌肽和药物之间的静电相互作用。
Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35-fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin's charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1–2M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 92-fold increase in transdermal delivery. Decreasing to pH 5 increased magainin's positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs.