In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin
The brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer’s disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13258 |
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| author | Hussein Akel Ildikó Csóka Rita Ambrus Alexandra Bocsik Ilona Gróf Mária Mészáros Anikó Szecskó Gábor Kozma Szilvia Veszelka Mária A. Deli Zoltán Kónya Gábor Katona |
| author_facet | Hussein Akel Ildikó Csóka Rita Ambrus Alexandra Bocsik Ilona Gróf Mária Mészáros Anikó Szecskó Gábor Kozma Szilvia Veszelka Mária A. Deli Zoltán Kónya Gábor Katona |
| author_sort | Hussein Akel |
| collection | DOAJ |
| description | The brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer’s disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics in AD suggests improved brain-targeting. Solid lipid nanoparticles (SLNs) and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising carriers to deliver the IN-administered insulin to the brain due to the enhancement of the drug permeability, which can even be improved by chitosan-coating. In the present study, uncoated and chitosan-coated insulin-loaded SLNs and PLGA NPs were formulated and characterized. The obtained NPs showed desirable physicochemical properties supporting IN applicability. The in vitro investigations revealed increased mucoadhesion, nasal diffusion, and drug release rate of both insulin-loaded nanocarriers over native insulin with the superiority of chitosan-coated SLNs. Cell-line studies on human nasal epithelial and brain endothelial cells proved the safety IN applicability of nanoparticles. Insulin-loaded nanoparticles showed improved insulin permeability through the nasal mucosa, which was promoted by chitosan-coating. However, native insulin exceeded the blood-brain barrier (BBB) permeation compared with nanoparticulate formulations. Encapsulating insulin into chitosan-coated NPs can be beneficial for ensuring structural stability, enhancing nasal absorption, followed by sustained drug release. |
| first_indexed | 2024-03-10T03:57:08Z |
| format | Article |
| id | doaj.art-fd757ba0629442a09b62974532acead4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:57:08Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fd757ba0629442a09b62974532acead42023-11-23T08:43:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241325810.3390/ijms222413258In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of InsulinHussein Akel0Ildikó Csóka1Rita Ambrus2Alexandra Bocsik3Ilona Gróf4Mária Mészáros5Anikó Szecskó6Gábor Kozma7Szilvia Veszelka8Mária A. Deli9Zoltán Kónya10Gábor Katona11Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös Str. 6, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös Str. 6, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös Str. 6, H-6720 Szeged, HungaryBiological Research Centre, Institute of Biophysics, Temesvári Blvd. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biophysics, Temesvári Blvd. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biophysics, Temesvári Blvd. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biophysics, Temesvári Blvd. 62, H-6726 Szeged, HungaryDepartment of Applied & Environmental Chemistry, Faculty of Science and Informatics, Rerrich Béla Sqr. 1, H-6720 Szeged, HungaryBiological Research Centre, Institute of Biophysics, Temesvári Blvd. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Biophysics, Temesvári Blvd. 62, H-6726 Szeged, HungaryDepartment of Applied & Environmental Chemistry, Faculty of Science and Informatics, Rerrich Béla Sqr. 1, H-6720 Szeged, HungaryFaculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös Str. 6, H-6720 Szeged, HungaryThe brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer’s disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics in AD suggests improved brain-targeting. Solid lipid nanoparticles (SLNs) and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising carriers to deliver the IN-administered insulin to the brain due to the enhancement of the drug permeability, which can even be improved by chitosan-coating. In the present study, uncoated and chitosan-coated insulin-loaded SLNs and PLGA NPs were formulated and characterized. The obtained NPs showed desirable physicochemical properties supporting IN applicability. The in vitro investigations revealed increased mucoadhesion, nasal diffusion, and drug release rate of both insulin-loaded nanocarriers over native insulin with the superiority of chitosan-coated SLNs. Cell-line studies on human nasal epithelial and brain endothelial cells proved the safety IN applicability of nanoparticles. Insulin-loaded nanoparticles showed improved insulin permeability through the nasal mucosa, which was promoted by chitosan-coating. However, native insulin exceeded the blood-brain barrier (BBB) permeation compared with nanoparticulate formulations. Encapsulating insulin into chitosan-coated NPs can be beneficial for ensuring structural stability, enhancing nasal absorption, followed by sustained drug release.https://www.mdpi.com/1422-0067/22/24/13258insulinnose-to-brain deliverysolid lipid nanoparticlesPLGA nanoparticleschitosan-coatingmucoadhesion |
| spellingShingle | Hussein Akel Ildikó Csóka Rita Ambrus Alexandra Bocsik Ilona Gróf Mária Mészáros Anikó Szecskó Gábor Kozma Szilvia Veszelka Mária A. Deli Zoltán Kónya Gábor Katona In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin International Journal of Molecular Sciences insulin nose-to-brain delivery solid lipid nanoparticles PLGA nanoparticles chitosan-coating mucoadhesion |
| title | In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin |
| title_full | In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin |
| title_fullStr | In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin |
| title_full_unstemmed | In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin |
| title_short | In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin |
| title_sort | in vitro comparative study of solid lipid and plga nanoparticles designed to facilitate nose to brain delivery of insulin |
| topic | insulin nose-to-brain delivery solid lipid nanoparticles PLGA nanoparticles chitosan-coating mucoadhesion |
| url | https://www.mdpi.com/1422-0067/22/24/13258 |
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