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Article

A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies

1
Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
2
Faculty of Science, University of Split, 21000 Split, Croatia
3
Visage Technologies d.o.o., 10000 Zagreb, Croatia
4
Jadran-Galenski Laboratorij d.d., 51000 Rijeka, Croatia
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Department of Diagnostic and Interventional Radiology, University Hospital Center “Sestre milosrdnice”, University of Zagreb, 10000 Zagreb, Croatia
6
ORL/HNS Department, Zagreb School of Medicine, University Hospital Center “Sestre milosrdnice”, University of Zagreb, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Academic Editor: Piroska Szabó-Révész
Pharmaceutics 2021, 13(6), 795; https://doi.org/10.3390/pharmaceutics13060795
Received: 30 March 2021 / Revised: 11 May 2021 / Accepted: 20 May 2021 / Published: 26 May 2021
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. View Full-Text
Keywords: dexamethasone sodium phosphate; nose-to-brain delivery; spray-dried microspheres; pectin; hypromellose; mannitol; 3D nasal cavity model; in vitro nasal deposition dexamethasone sodium phosphate; nose-to-brain delivery; spray-dried microspheres; pectin; hypromellose; mannitol; 3D nasal cavity model; in vitro nasal deposition
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MDPI and ACS Style

Nižić Nodilo, L.; Ugrina, I.; Špoljarić, D.; Amidžić Klarić, D.; Jakobušić Brala, C.; Perkušić, M.; Pepić, I.; Lovrić, J.; Saršon, V.; Safundžić Kučuk, M.; Zadravec, D.; Kalogjera, L.; Hafner, A. A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies. Pharmaceutics 2021, 13, 795. https://doi.org/10.3390/pharmaceutics13060795

AMA Style

Nižić Nodilo L, Ugrina I, Špoljarić D, Amidžić Klarić D, Jakobušić Brala C, Perkušić M, Pepić I, Lovrić J, Saršon V, Safundžić Kučuk M, Zadravec D, Kalogjera L, Hafner A. A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies. Pharmaceutics. 2021; 13(6):795. https://doi.org/10.3390/pharmaceutics13060795

Chicago/Turabian Style

Nižić Nodilo, Laura, 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, and Anita Hafner. 2021. "A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies" Pharmaceutics 13, no. 6: 795. https://doi.org/10.3390/pharmaceutics13060795

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