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 - 1993

Fingerprint

Adamantane
Leucine Enkephalin
Peptides
Brain
Intravenous Infusions
Prodrugs
Esters

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Improvement of peptide delivery to brain by chemical modification : [D-Ala2] Leu-enkephalin conjugated with 1-adamantane. / Kimura, Toshikiro; Koike, Tomohiro; Onogawa, Masahide; Kurosaki, Yuji; Nakayama, Taiji; Konishi, Ryoji; Mizobuchi, Noriko; Kitagawa, Kouki.

In: Drug Delivery System, Vol. 8, No. 3, 1993, p. 181-191.

Research output: Contribution to journalArticle

Kimura, T, Koike, T, Onogawa, M, Kurosaki, Y, Nakayama, T, Konishi, R, Mizobuchi, N & Kitagawa, K 1993, 'Improvement of peptide delivery to brain by chemical modification: [D-Ala2] Leu-enkephalin conjugated with 1-adamantane', Drug Delivery System, vol. 8, no. 3, pp. 181-191. https://doi.org/10.2745/dds.8.181
Kimura, Toshikiro ; Koike, Tomohiro ; Onogawa, Masahide ; Kurosaki, Yuji ; Nakayama, Taiji ; Konishi, Ryoji ; Mizobuchi, Noriko ; Kitagawa, Kouki. / Improvement of peptide delivery to brain by chemical modification : [D-Ala2] Leu-enkephalin conjugated with 1-adamantane. In: Drug Delivery System. 1993 ; Vol. 8, No. 3. pp. 181-191.
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