A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies
Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently propose...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/6/795 |
| _version_ | 1827691402124853248 |
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| author | Laura Nižić Nodilo Ivo Ugrina Drago Špoljarić Daniela Amidžić Klarić Cvijeta Jakobušić Brala Mirna Perkušić Ivan Pepić Jasmina Lovrić Vesna Saršon Maša Safundžić Kučuk Dijana Zadravec Livije Kalogjera Anita Hafner |
| author_facet | Laura Nižić Nodilo Ivo Ugrina Drago Špoljarić Daniela Amidžić Klarić Cvijeta Jakobušić Brala Mirna Perkušić Ivan Pepić Jasmina Lovrić Vesna Saršon Maša Safundžić Kučuk Dijana Zadravec Livije Kalogjera Anita Hafner |
| author_sort | Laura Nižić Nodilo |
| collection | DOAJ |
| description | Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region. |
| first_indexed | 2024-03-10T11:01:13Z |
| format | Article |
| id | doaj.art-2402e2f7e6e94012b89ba69157130479 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:01:13Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2402e2f7e6e94012b89ba691571304792023-11-21T21:29:39ZengMDPI AGPharmaceutics1999-49232021-05-0113679510.3390/pharmaceutics13060795A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition StudiesLaura Nižić Nodilo0Ivo Ugrina1Drago Špoljarić2Daniela Amidžić Klarić3Cvijeta Jakobušić Brala4Mirna Perkušić5Ivan Pepić6Jasmina Lovrić7Vesna Saršon8Maša Safundžić Kučuk9Dijana Zadravec10Livije Kalogjera11Anita Hafner12Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Science, University of Split, 21000 Split, CroatiaVisage Technologies d.o.o., 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaJadran-Galenski Laboratorij d.d., 51000 Rijeka, CroatiaJadran-Galenski Laboratorij d.d., 51000 Rijeka, CroatiaDepartment of Diagnostic and Interventional Radiology, University Hospital Center “Sestre milosrdnice”, University of Zagreb, 10000 Zagreb, CroatiaORL/HNS Department, Zagreb School of Medicine, University Hospital Center “Sestre milosrdnice”, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaNasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.https://www.mdpi.com/1999-4923/13/6/795dexamethasone sodium phosphatenose-to-brain deliveryspray-dried microspherespectinhypromellosemannitol |
| spellingShingle | Laura Nižić Nodilo Ivo Ugrina Drago Špoljarić Daniela Amidžić Klarić Cvijeta Jakobušić Brala Mirna Perkušić Ivan Pepić Jasmina Lovrić Vesna Saršon Maša Safundžić Kučuk Dijana Zadravec Livije Kalogjera Anita Hafner A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies Pharmaceutics dexamethasone sodium phosphate nose-to-brain delivery spray-dried microspheres pectin hypromellose mannitol |
| title | A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies |
| title_full | A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies |
| title_fullStr | A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies |
| title_full_unstemmed | A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies |
| title_short | A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies |
| title_sort | dry powder platform for nose to brain delivery of dexamethasone formulation development and nasal deposition studies |
| topic | dexamethasone sodium phosphate nose-to-brain delivery spray-dried microspheres pectin hypromellose mannitol |
| url | https://www.mdpi.com/1999-4923/13/6/795 |
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