Biochemical enhancement of transdermal delivery with magainin peptide: Modification of electrostatic interactions by changing pH

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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 1-2 M 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, orstratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs. (C) 2008 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2008-10
Language
English
Article Type
Article
Keywords

HUMAN STRATUM-CORNEUM; PORE-FORMING PEPTIDE; ANTIMICROBIAL PEPTIDES; PENETRATION ENHANCERS; DIELECTRIC CONSTANT; DRUG-DELIVERY; IN-VIVO; SKIN; PERMEABILITY; POLYPEPTIDES

Citation

INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.362, no.1-2, pp.20 - 28

ISSN
0378-5173
DOI
10.1016/j.ijpharm.2008.05.042
URI
http://hdl.handle.net/10203/93066
Appears in Collection
CBE-Journal Papers(저널논문)
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