Cell-Penetrating Peptide-Modified Block Copolymer Micelles Promote Direct Brain Delivery via Intranasal Administration
Abstract
Purpose In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(ε-caprolactone) (PCL) amphiphilic block copolymers through the ester bond.Methods We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. Finally, we determined the brain distribution and biodistribution after intranasal administration of coumarin-loaded MPEG-PCL-Tat.Results The amount of coumarin in the brain after intranasal administration was significantly higher than that after intravenous administration. In addition, cellular uptake of coumarin using MPEG-PCL was the lowest, while cellular uptake of coumarin using Tat-modified MPEG-PCL (MPEG-PCL-Tat) was higher than that of MPEG-PCL. Therefore, the brain distribution of coumarin administered using MPEG-PCL-Tat was significantly greater than that using MPEG-PCL. Then, the coumarin distribution after MPEG-PCL-Tat administration in non-targeted tissues (lung, liver, heart, kidney and spleen) was lower than that after coumarin administration without nanomicelles.Conclusion We have demonstrated that utilization of nano-sized micelles modified with Tat can facilitate direct intranasal brain delivery.
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- Authors
- Kanazawa, T., Taki, H., Tanaka, K., Takashima, Y., & Okada, H.
- Affiliations
- Tokyo University of Pharmacy and Life Sciences (JP)
- Corresponding author
- Kanazawa, Takanori
- Venue
- Pharmaceutical Research
- Published
- 2011-04-16
- Volume
- 28
- Issue
- 9
- Pages
- 2130-2139
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1963832082
- Cited by
- 166
- References
- 15
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 18 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 13 · 2016: 12 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 11
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- cell-penetrating peptides, TAT peptide, block copolymer micelles, mPEG-PCL, nose-to-brain delivery, intranasal drug delivery, brain distribution, coumarins, glioma cells, cellular uptake, tissue distribution
- MeSH terms
- Administration, Intranasal, Animals, Brain, Brain Neoplasms, Coumarins, Drug Carriers, Glioma, Injections, Intravenous, Micelles, Neoplasm Transplantation, Particle Size, Peptide Fragments, Polyesters, Polyethylene Glycols, Tissue Distribution, Rats, Sprague-Dawley, Cell Line, Tumor, Rats, tat Gene Products, Human Immunodeficiency Virus, Cell-Penetrating Peptides
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