Optimization of transdermal delivery using magainin pore-forming peptide

Abstract

The skin's outer layer of stratum corneum, which is a thin tissue containing multilamellar lipid bilayers, is the main barrier to drug delivery to the skin. To increase skin permeability, our previous work has shown large enhancement of transdermal permeation using a pore-forming peptide, magainin, which was formulated with N-lauroyl sarcosine (NLS) in 50% ethanol-in-PBS. Mechanistic analysis suggested that magainin and NLS can increase skin permeability by disrupting stratum corneum lipid structure. In this study, our goal was to improve conditions that increase skin permeability by magainin by further optimizing the pretreatment time and concentration of magainin exposure. We found that skin permeability increased with increasing pretreatment time. Skin permeability also increased with increasing magainin concentration up to 1 mM, but was reduced at a magainin concentration of 2 mM. Enhancement of skin permeability to fluorescein (323 Da) up to 35-fold was observed. In contrast, this formulation did not enhance skin permeability to larger molecules, such as calcein (623 Da) and dextran (3,000 Da).

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

“…The screening of the attractive electrostatic interaction by such a small change in the Debye length implies that the fluorescein molecule must be close to the edge of this pathway. This is consistent with our previous finding that magainin did not enhance transdermal transport of molecules larger than fluorescein (Kim et al,2008), such as calcein (623 Da, r = 6 Å and dextran (3,000 Da, r = 16 Å (Oliver et al, 1992). This is also consistent with previous studies of magainin in simpler lipid bilayer systems, in which the pores are believed to be of Angstrom dimensions (Ludtke et al, 1995, Matsuzaki et al, 1996.…”

Basics and Recent Advances in Peptide and Protein Drug Delivery

“…One such peptide used to enhance skin permeability is magainin, a 23-amino acid peptide known to form pores in bacterial cell membranes [151,152]. While previously demonstrated to increase the permeability of small molecules, its use for peptide delivery enhancement still requires optimization [153]. In addition, recent, work by Ruan et al .…”

Transdermal Delivery Enhanced by Antimicrobial Peptides

“…For example, we previously observed that increased skin permeability was strongly dependent on magainin concentration. 23 As shown in Figure 6(A), increasing magainin concentration up to 1 mM increased skin permeability (ANOVA, p < 0 05). However, further increase in magainin concentration to 2 mM reduced enhancement below that of the NLS control, as reported previously.…”

“…However, further increase in magainin concentration to 2 mM reduced enhancement below that of the NLS control, as reported previously. 23 This effect may be explained by aggregation of high-concentration magainin in the stratum corneum lipids, which may disrupt and occlude the expected pore structures formed by lower-concentration magainin. 24 Transdermal Delivery Enhanced by Antimicrobial Peptides Kim et al In order to investigate the correlation of enhancement with lipid structure disruption, we measure FTIR spectra to assess lipid fluidity.…”