Maximizing dermal targeting and minimizing transdermal penetration by magnolol/honokiol methoxylation

Chwan Fwu Lin, Tsong Long Hwang, Saleh A. Al-Suwayeh, Yu Ling Huang, Yi Yun Hung, Jia You Fang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

32 Scopus citations

Abstract

Magnolol and honokiol, predominant active compounds in the family Magnoliaceae, are known to exhibit strong anti-inflammatory activities against dermal disorders. We attempted to modify the structures of magnolol and honokiol by methoxylation to optimize the skin delivery ability. Absorption of these permeants into and through the skin was performed at both an infinite dose and saturated solubility. Superoxide anion and elastase released from human neutrophils were the biomarkers used to examine anti-inflammatory potencies of these permeants. The safety of the permeants was evaluated by keratinocyte viability and in vivo bioengineering techniques. Topical magnolol and honokiol at an infinite dose (7.5 mM) showed skin accumulations of 0.22 and 0.16 nmol/mg, respectively. Methoxylation significantly enhanced their skin absorption. Deposition amounts of dimethylmagnolol and dimethylhonokiol were respectively 15- and 7-fold greater than those of magnolol and honokiol. Contrary to the skin accumulation results, the transdermal penetration across skin decreased following methoxylation. No transdermal delivery occurred for dimethylhonokiol. Skin uptake of 4′-O-methylhonokiol was 2-fold higher than that of 2-O-methylhonokiol, although they are isomers. Methoxylated permeants demonstrated selective absorption into follicles, which showed 3-5-fold higher follicular amounts compared to magnolol and honokiol. The relative order of anti-inflammatory activities was honokiol > 2-O-methylmagnolol > dimethylhonokiol > magnolol. The other compounds exhibited negligible or negative responses in activated neutrophils. Magnolol and honokiol induced slight but significant keratinocyte cytotoxicity and stratum corneum disruption. Daily administration of methoxylated permeants, especially dimethylhonokiol, produced no skin irritation for up to 7 days. Methoxylated magnolol and honokiol can be efficient and safe candidates for treating inflammatory skin disorders.

Original languageEnglish
Pages (from-to)153-162
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume445
Issue number1-2
DOIs
StatePublished - 10 03 2013

Keywords

  • Anti-inflammation
  • Honokiol
  • Magnolol
  • Methoxylation
  • Skin permeation

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