Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study
Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the intestinal mucosal barrier, resist enzymatic degradati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/1/5 |
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| author | Chiara Migone Letizia Mattii Martina Giannasi Stefania Moscato Andrea Cesari Ylenia Zambito Anna Maria Piras |
| author_facet | Chiara Migone Letizia Mattii Martina Giannasi Stefania Moscato Andrea Cesari Ylenia Zambito Anna Maria Piras |
| author_sort | Chiara Migone |
| collection | DOAJ |
| description | Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the intestinal mucosal barrier, resist enzymatic degradation, and transport drugs to the brain after crossing the blood–brain barrier. Therefore, a chitosan quaternary ammonium derivative was synthesized and conjugated with methyl-β-cyclodextrin to prepare DAL-medicated nanoparticles (DAL-NP). DAL-NP particle size was 227.7 nm, zeta potential +8.60 mV, encapsulation efficiency 89%. DAL-NP protected DAL from degradation by chymotrypsin or pancreatin and tripled DAL degradation time compared to non-encapsulated DAL. Use of DAL-NP was safe for either Caco-2 or bEnd.3 cells, with the latter selected as a blood–brain barrier model. DAL-NP could also cross either the Caco-2 or bEnd.3 monolayer by the transepithelial route. The results suggest a potential DAL-NP ability to transport to the brain a DAL dose fraction administered orally, although in vivo experiments will be needed to confirm the present data obtained in vitro. |
| first_indexed | 2024-03-10T13:52:45Z |
| format | Article |
| id | doaj.art-e2d22364c5cc43eb93d548a9c9afb3af |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T13:52:45Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e2d22364c5cc43eb93d548a9c9afb3af2023-11-21T02:01:59ZengMDPI AGPharmaceutics1999-49232020-12-01131510.3390/pharmaceutics13010005Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro StudyChiara Migone0Letizia Mattii1Martina Giannasi2Stefania Moscato3Andrea Cesari4Ylenia Zambito5Anna Maria Piras6Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, INSTM—University of Pisa Research Unit (UdR Pisa), University of Pisa, Via Moruzzi 13, 56124 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, ItalyPeptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the intestinal mucosal barrier, resist enzymatic degradation, and transport drugs to the brain after crossing the blood–brain barrier. Therefore, a chitosan quaternary ammonium derivative was synthesized and conjugated with methyl-β-cyclodextrin to prepare DAL-medicated nanoparticles (DAL-NP). DAL-NP particle size was 227.7 nm, zeta potential +8.60 mV, encapsulation efficiency 89%. DAL-NP protected DAL from degradation by chymotrypsin or pancreatin and tripled DAL degradation time compared to non-encapsulated DAL. Use of DAL-NP was safe for either Caco-2 or bEnd.3 cells, with the latter selected as a blood–brain barrier model. DAL-NP could also cross either the Caco-2 or bEnd.3 monolayer by the transepithelial route. The results suggest a potential DAL-NP ability to transport to the brain a DAL dose fraction administered orally, although in vivo experiments will be needed to confirm the present data obtained in vitro.https://www.mdpi.com/1999-4923/13/1/5mucoadhesive nanoparticlesCaco-2 monolayer permeationbEnd.3 monolayer permeationblood–brain barrier permeationpeptide brain targeting |
| spellingShingle | Chiara Migone Letizia Mattii Martina Giannasi Stefania Moscato Andrea Cesari Ylenia Zambito Anna Maria Piras Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study Pharmaceutics mucoadhesive nanoparticles Caco-2 monolayer permeation bEnd.3 monolayer permeation blood–brain barrier permeation peptide brain targeting |
| title | Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study |
| title_full | Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study |
| title_fullStr | Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study |
| title_full_unstemmed | Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study |
| title_short | Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study |
| title_sort | nanoparticles based on quaternary ammonium chitosan methyl β cyclodextrin conjugate for the neuropeptide dalargin delivery to the central nervous system an in vitro study |
| topic | mucoadhesive nanoparticles Caco-2 monolayer permeation bEnd.3 monolayer permeation blood–brain barrier permeation peptide brain targeting |
| url | https://www.mdpi.com/1999-4923/13/1/5 |
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