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

doi:10.2745/dds.8.181

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 journal › Article › peer-review

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 language	English
Pages (from-to)	181-191
Number of pages	11
Journal	Drug Delivery System
Volume	8
Issue number	3
DOIs	https://doi.org/10.2745/dds.8.181
Publication status	Published - 1993

Keywords

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

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.2745/dds.8.181

Cite this

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

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.",

keywords = "1-adamantane, [D-Ala] Leu-enkephalin, brain-directed delivery, prodrug",

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

year = "1993",

doi = "10.2745/dds.8.181",

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AU - Kimura, Toshikiro

AU - Koike, Tomohiro

AU - Onogawa, Masahide

AU - Kurosaki, Yuji

AU - Nakayama, Taiji

AU - Konishi, Ryoji

AU - Mizobuchi, Noriko

AU - Kitagawa, Kouki

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

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