Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes
| العنوان: | Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes |
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| المؤلفون: | Anh D. Lê, Alexandrine L. Martel, Leila Mousavifar, Jordan D. Lewicky, Hoang-Thanh Le, Thi M.-D. Nguyen, René Roy, Douglas Funk, Nya L. Fraleigh, Peter W. Schiller |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 15 International Journal of Molecular Sciences, Vol 22, Iss 7996, p 7996 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | kappa opioid receptor antagonist, QH301-705.5, dynantin, Dynorphin, Pharmacology, Blood–brain barrier, blood–brain barrier, Dynorphins, κ-opioid receptor, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, In vivo, glycoliposome, Humans, Medicine, Distribution (pharmacology), Biology (General), Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Spectroscopy, 030304 developmental biology, 0303 health sciences, business.industry, Receptors, Opioid, kappa, Organic Chemistry, Antagonist, targeted delivery, General Medicine, Corpus Striatum, peptide, 3. Good health, Computer Science Applications, Chemistry, medicine.anatomical_structure, Targeted drug delivery, CNS therapeutic, Liposomes, Nasal administration, addiction, dopamine, Peptides, business, 030217 neurology & neurosurgery, neurotransmitter |
| الوصف: | Peptide therapeutics offer numerous advantages in the treatment of diseases and disorders of the central nervous system (CNS). However, they are not without limitations, especially in terms of their pharmacokinetics where their metabolic lability and low blood–brain barrier penetration hinder their application. Targeted nanoparticle delivery systems are being tapped for their ability to improve the delivery of therapeutics into the brain non-invasively. We have developed a family of mannosylated glycoliposome delivery systems for targeted drug delivery applications. Herein, we demonstrate via in vivo distribution studies the potential of these glycoliposomes to improve the utility of CNS active therapeutics using dynantin, a potent and selective dynorphin peptide analogue antagonist of the kappa opioid receptor (KOR). Glycoliposomal entrapment protected dynantin against known rapid metabolic degradation and ultimately improved brain levels of the peptide by approximately 3–3.5-fold. Moreover, we linked this improved brain delivery with improved KOR antagonist activity by way of an approximately 30–40% positive modulation of striatal dopamine levels 20 min after intranasal administration. Overall, the results clearly highlight the potential of our glycoliposomes as a targeted delivery system for therapeutic agents of the CNS. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| DOI: | 10.3390/ijms22157996 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c96bed9f96be01a94d61a9d016a901c6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c96bed9f96be01a94d61a9d016a901c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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| DOI: | 10.3390/ijms22157996 |