Improvement of peptide delivery to brain by chemical modification: [D-Ala2] Leu-enkephalin conjugated with 1-adamantane

Toshikiro Kimura, Tomohiro Koike, Masahide Onogawa, Yuji Kurosaki, Taiji Nakayama, Ryoji Konishi, Noriko Mizobuchi, Kouki Kitagawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

An ester compound (Ada-Enk) of [D-Ala2] Leuenkephalin (Enk) with 1-adamantanol was evaluated as a prodrug for the improved brain delivery using rats as the experimental animal. The tissue-to-plasma concentration ratio(Kp)of Ada-Enk at steady state dining the intravenous infusion was 4.5 times larger than that of Enk, indicating the improved delivery to the brain. The distribution of Ada-Enk to the other organs was also increased in comparison with Enk, but the degree of the enhanced distribution was much higher in the brain. The distribution of Ada-Enk was similar in all the regions in the brain. In addition, Enk was found in the brain during the intravenous infusion of Ada-Enk. The in vitro metabolic study showed that Ada-Enk was metabolized in both plasma and brain while Enk was formed in the brain homogenates much more than in the plasma.

Original languageEnglish
Pages (from-to)181-191
Number of pages11
JournalDrug Delivery System
Volume8
Issue number3
DOIs
Publication statusPublished - Jan 1 1993

Keywords

  • 1-adamantane
  • [D-Ala] Leu-enkephalin
  • brain-directed delivery
  • prodrug

ASJC Scopus subject areas

  • Pharmaceutical Science

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