ArticlePharmaceutics2021
Investigation of the Transport Pathways Associated with Enhanced Brain Delivery of Peptide Drugs by Intranasal Coadministration with Penetratin.
Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery.Drug delivery and translational research · 2026Review
- New Insights into Drug Development via the Nose-to-Brain Pathway: Exemplification Through Dodecyl Creatine Ester for Neuronal Disorders.Pharmaceutics · 2026Review
- Micro/Nanoparticles in the Nose-Brain Axis: Implications for Pathogenesis and Therapeutic Interventions.International journal of nanomedicine · 2026Review
- Modulation of antibody transport in the brain and spinal cord through the intranasal pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Intranasal Drug Delivery Technology in the Treatment of Central Nervous System Diseases: Challenges, Advances, and Future Research Directions.Pharmaceutics · 2025Review
- Distribution of Intranasally Administered rIL-10 Along the Olfactory Nerve and Perivascular Space After Intracerebral Hemorrhage.CNS neuroscience & therapeutics · 2025Article
- Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood-brain barrier.Exploration (Beijing, China) · 2025Review
- Insulin-inspired peptides may open new pathways to treat Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Insulin-inspired hippocampal neuron-targeting technology for protein drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Modified Cell-Penetrating Peptide Enhances Insulin and Oxytocin Delivery across an RPMI 2650 Nasal Epithelial Cell Barrier In Vitro.Pharmaceutics · 2024Article
- Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer's Disease Therapy.Drug delivery and translational research · 2024Review
- Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway.Pharmaceutics · 2023Article
- Research progress in brain-targeted nasal drug delivery.Frontiers in aging neuroscience · 2023Review
- Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared the concentrations of Exendin-4 in plasma and brain after intranasal and subcutaneous administration and suggested that coadministration with L-penetratin facilitated the direct nose-to-brain transport of Exendin-4. Second, we demonstrated that L-penetratin did not stimulate the transport of Cy7-labeled Exendin-4 and insulin through the trigeminal nerves but shifted their distribution to the olfactory mucosal pathway. Third, we investigated the distribution of insulin into the deeper regions of the brain after delivery via the olfactory pathway and suggested that insulin had entered the olfactory bulb, bottom part of the brain, and perivascular space through the cerebrospinal fluid and had diffused throughout the brain. We further demonstrated that intranasally delivered insulin with L-penetratin specifically accumulated on the hippocampus neuronal cells. Thus, this study suggested that administrating peptide drugs intranasally with L-penetratin allows direct transport to the olfactory bulb, bottom part of the brain, and perivascular space of the cerebral artery. This technique also potentially allows targeting of specific brain areas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.