Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration
Alzheimer’s disease is characterized by a progressive deterioration of neurons resulting in a steady loss of cognitive functions and memory. Many treatments encounter the challenge of overcoming the blood–brain barrier, thus the intranasal route is a non-invasive effective alternative that enhances...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/2310-2861/8/11/715 |
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| author | Lupe Carolina Espinoza Diana Guaya Ana Cristina Calpena Rodolfo Miguel Perotti Lyda Halbaut Lilian Sosa Adriel Brito-Llera Mireia Mallandrich |
| author_facet | Lupe Carolina Espinoza Diana Guaya Ana Cristina Calpena Rodolfo Miguel Perotti Lyda Halbaut Lilian Sosa Adriel Brito-Llera Mireia Mallandrich |
| author_sort | Lupe Carolina Espinoza |
| collection | DOAJ |
| description | Alzheimer’s disease is characterized by a progressive deterioration of neurons resulting in a steady loss of cognitive functions and memory. Many treatments encounter the challenge of overcoming the blood–brain barrier, thus the intranasal route is a non-invasive effective alternative that enhances the drug delivery in the target organ–the brain–and reduces the side effects associated with systemic administration. This study aimed at developing intranasal gels of donepezil as an approach to Alzheimer’s disease. Three different gels were elaborated and characterized in terms of pH, morphology, gelation temperature, rheology, and swelling. An in vitro release study and an ex vivo permeation in porcine nasal mucosa were conducted on Franz diffusion cells. The tolerability of the formulations was determined by the cytotoxicity in human nasal cells RPMI 2650. Results showed that pluronic gels exhibit the higher release rate and enhanced permeation compared to chitosan gel. Moreover, the combination of Pluronic F-127 and Transcutol<sup>®</sup> P exerted a synergic effect on the permeation of donepezil through the nasal mucosa. The resulting gels showed suitable tolerance in the RPMI 2650 cell line and physicochemical characteristics for intranasal delivery, and thus gel formulations administered by nasal mucosa could be an alternative strategy to improve the bioavailability of donepezil. |
| first_indexed | 2024-03-09T19:03:08Z |
| format | Article |
| id | doaj.art-01eae98a62d94c6888f6d04ea94b1606 |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-09T19:03:08Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj.art-01eae98a62d94c6888f6d04ea94b16062023-11-24T04:46:37ZengMDPI AGGels2310-28612022-11-0181171510.3390/gels8110715Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal AdministrationLupe Carolina Espinoza0Diana Guaya1Ana Cristina Calpena2Rodolfo Miguel Perotti3Lyda Halbaut4Lilian Sosa5Adriel Brito-Llera6Mireia Mallandrich7Departamento de Química, Universidad Técnica Particular de Loja, Loja 1101608, EcuadorDepartamento de Química, Universidad Técnica Particular de Loja, Loja 1101608, EcuadorInstitute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, SpainPharmaceutical Technology Research Group, Faculty of Chemical Sciences and Pharmacy, National Autonomous University of Honduras (UNAH), Tegucigalpa 11101, HondurasDirección de Ciencia, Tecnología e Innovación, Universidad de la Habana, Calle M entre 19 y 21 #255, Vedado, La Habana 10400, CubaInstitute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainAlzheimer’s disease is characterized by a progressive deterioration of neurons resulting in a steady loss of cognitive functions and memory. Many treatments encounter the challenge of overcoming the blood–brain barrier, thus the intranasal route is a non-invasive effective alternative that enhances the drug delivery in the target organ–the brain–and reduces the side effects associated with systemic administration. This study aimed at developing intranasal gels of donepezil as an approach to Alzheimer’s disease. Three different gels were elaborated and characterized in terms of pH, morphology, gelation temperature, rheology, and swelling. An in vitro release study and an ex vivo permeation in porcine nasal mucosa were conducted on Franz diffusion cells. The tolerability of the formulations was determined by the cytotoxicity in human nasal cells RPMI 2650. Results showed that pluronic gels exhibit the higher release rate and enhanced permeation compared to chitosan gel. Moreover, the combination of Pluronic F-127 and Transcutol<sup>®</sup> P exerted a synergic effect on the permeation of donepezil through the nasal mucosa. The resulting gels showed suitable tolerance in the RPMI 2650 cell line and physicochemical characteristics for intranasal delivery, and thus gel formulations administered by nasal mucosa could be an alternative strategy to improve the bioavailability of donepezil.https://www.mdpi.com/2310-2861/8/11/715Alzheimer’s diseasegelintranasal administrationdonepezil |
| spellingShingle | Lupe Carolina Espinoza Diana Guaya Ana Cristina Calpena Rodolfo Miguel Perotti Lyda Halbaut Lilian Sosa Adriel Brito-Llera Mireia Mallandrich Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration Gels Alzheimer’s disease gel intranasal administration donepezil |
| title | Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration |
| title_full | Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration |
| title_fullStr | Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration |
| title_full_unstemmed | Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration |
| title_short | Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration |
| title_sort | comparative study of donepezil loaded formulations for the treatment of alzheimer s disease by nasal administration |
| topic | Alzheimer’s disease gel intranasal administration donepezil |
| url | https://www.mdpi.com/2310-2861/8/11/715 |
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