Visualization and Quantitative Assessment of the Brain Distribution of Insulin through Nose-to-Brain Delivery Based on the Cell-Penetrating Peptide Noncovalent Strategy

Molecular Pharmaceutics
Noriyasu KameiMariko Takeda-Morishita

Abstract

Our recent work suggested that intranasal coadministration with the cell-penetrating peptide (CPP) penetratin increased the brain distribution of the peptide drug insulin. The present study aimed to distinctly certify the ability of penetratin to facilitate the nose-to-brain delivery of insulin by quantitatively evaluating the distribution characteristics in brain using radioactive (64)Cu-NODAGA-insulin. Autoradiography and analysis using a gamma counter of brain areas demonstrated that the accumulation of radioactivity was greatest in the olfactory bulb, the anterior part of the brain closest to the administration site, at 15 min after intranasal administration of (64)Cu-NODAGA-insulin with l- or d-penetratin. The brain accumulation of (64)Cu-NODAGA-insulin with penetratin was confirmed by ELISA using unlabeled insulin in which intact insulin was delivered to the brain after intranasal coadministration with l- or d-penetratin. By contrast, quantification of cerebrospinal fluid (CSF) samples showed increased insulin concentration in only the anterior portion of the CSF at 15 min after intranasal coadministration with l-penetratin. This study gives the first concrete proof that penetratin can accelerate the direct transport of i...Continue Reading

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Citations

Apr 3, 2018·Biological & Pharmaceutical Bulletin·Noriyasu KameiMariko Takeda-Morishita
Oct 3, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Noriyasu Kamei
Sep 12, 2017·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Mariko Takeda
Jan 1, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Michael J MajcherTodd Hoare
Aug 25, 2019·International Journal of Pharmaceutics·Patricia P MartinsZhengrong Cui
Jul 15, 2020·Nuclear Medicine and Biology·Hidefumi Mukai, Yasuyoshi Watanabe
Aug 30, 2019·The Journal of Physical Chemistry. B·Lucas Rodrigues de MelloEmerson Rodrigo da Silva
Nov 4, 2021·Drug Delivery and Translational Research·Mireya L Borrajo, María José Alonso

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