Noncovalent Strategy with Cell-Penetrating Peptides to Facilitate the Brain Delivery of Insulin through the Blood-Brain Barrier
| Autor: | Rei Itokazu, Ai Yamaoka, Noriyasu Kamei, Mariko Takeda-Morishita, Yukiko Fukuyama |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cell Survival medicine.medical_treatment Cell Pharmaceutical Science Hippocampus Cell-Penetrating Peptides Pharmacology Blood–brain barrier Rats Sprague-Dawley 03 medical and health sciences Mice In vivo Cell Line Tumor medicine Animals Hypoglycemic Agents Insulin Tissue Distribution biology Chemistry Brain Biological Transport General Medicine 030104 developmental biology medicine.anatomical_structure Gene Products tat Cell-penetrating peptide biology.protein Antibody Peptide drug Carrier Proteins Oligopeptides |
| Zdroj: | Biologicalpharmaceutical bulletin. 41(4) |
| ISSN: | 1347-5215 |
| Popis: | To overcome the difficulty in delivery of biopharmaceuticals such as peptides and proteins to the brain, several approaches combining the ligands and antibodies targeting the blood-brain barrier (BBB) have been tried. However, these are inefficient in terms of their permeability through the BBB and structural modification of bioactive drugs. In the present study, we therefore examined the usefulness of a noncovalent method using the cell-penetrating peptides (CPPs) such as octaarginine (R8) as a suitable brain delivery strategy for biopharmaceuticals. A safety examination using microvascular endothelial model bEnd.3 cells clarified that R8 was the safest among the CPPs tested in this study. The cellular uptake study demonstrated that coincubation with R8 enhanced the uptake of model peptide drug insulin by bEnd.3 cells in a concentration-dependent and a temperature-independent manner. Furthermore, an in vivo study with rats showed that the accumulation of insulin in the deeper region of the brain, i.e., hippocampus, significantly increased after the intravenous coadministration of insulin with D-R8 without altering the insulin disposition in plasma. Thus, the present study provided the first evidence suggesting that the noncovalent method with CPPs is one of the strategic options for brain delivery of biopharmaceuticals via intravenous injection. |
| Databáze: | OpenAIRE |
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