Naslov
Development and in vitro evaluation of dry powder platform for nose-to-brain delivery of dexamethasone

Autori
Nižić Nodilo, Laura ; Špoljarić, Drago ; Ugrina, Ivo ; Amidžić Klarić, Daniela ; Jakobušić Brala, Cvijeta ; Perkušić, Mirna ; Pepić, Ivan ; Lovrić, Jasmina ; Saršon, Vesna ; Safundžić Kučuk, Maša ; Zadravec, Dijana ; Kalogjera, Livije ; Hafner, Anita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, ostalo, znanstveni

Skup
2021 CRS Virtual Annual Meeting

Mjesto i datum
Online skup, 25.07.2021. - 29.07.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
nasal drug delivery ; spray drying ; microparticles ; in vitro nasal deposition ; 3D printed nasal cast

Sažetak
Introduction: Nasal route of administration offers a variety of therapeutic opportunities. Recently, it has been proposed as a route of choice for direct nose-to-brain glucocorticoid delivery to control neuroinflammation in patients with severe Covid-19 (1). Nasal powders have shown encouraging results in nose-to-brain drug delivery (2). This work presents the development of nasal powder delivery platform for dexamethasone sodium phosphate (DSP), employing Quality by Design (QbD) principles and including consideration of nasal deposition in the early phase of formulation development. Methods: QbD approach was employed in optimization of spray-dried DSP-loaded pectin and hypromellose microspheres. The optimized microspheres were blended with lactose monohydrate or mannitol at particle size of 45-63 µm as an inert carrier. Powder blends were characterized in terms of homogeneity, flow properties, spray cone angle, in vitro biocompatibility using Calu-3 cells and mucoadhesion using porcine nasal mucosa. Nasal deposition studies were performed using a 3D printed nasal cast connected to respiratory pump. Results: Swellable DSP-loaded polymeric microspheres (Dv50=2.88±0.01 mm) ensuring diffusion-controlled drug release completed in 90 minutes were developed based on QbD approach. Optimised microspheres/inert carrier powder blends were shown to be homogenous and suitable for administration by spraying. SEM micrographs of powder blends revealed microspheres adhered to carrier particles, fitting into the surface within the capsule upon device actuation (1.7-6.3% vs. 14.8%) and narrower spray cone angle (19.6-22.0° vs. 26.5°), which, coupled with appropriate paricle size range, resulted in improved nasal deposition profile. Microspheres were proven to be mucoadhesive showing 12-fold higher work of adhesion in relation to pure drug powder. Blending with inert carriers did not impair their mucoadhesive properties. Powder blends were shown to be biocompatible, inducing no decrease in cell viability. Conclusion/Impact: QbD approach enabled rational desing of spray-dried DSP-loaded polymeric microspheres. Optimised microspheres/inert carrier powder blends showed favourable biopharmaceutcal and sprayability properties. Nasal deposition studies revealed the potential of strategy employed to deliver drug to the targeted regions of nasal cavity.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA