Mucoadhesive in situ gelling fluticasone propionate nanosuspension for nasal delivery by nebulization

INTRODUCTION Strategies to improve nasal drug delivery include development of formulations which reduce mucociliary clearance [1] and careful selection of nasal delivery device [2]. In situ gelling nanosuspensions present combined approach to increase mucoadhesion and prolong drug retention at nasal mucosa [1]. The aim of this study is to develop an in situ gelling fluticasone propionate nanosuspension and assess its nasal deposition after spraying with jet-flow nebulizer. MATERIALS AND METHODS Fluticasone propionate nanosuspensions prepared by wet media milling, were mixed with pectin and sodium hyaluronate solutions at different ratios. Formulations were characterised in terms of particle size, zeta- potential, surface tension, rheological properties, in vitro biocompatibility using Calu-3 cells, mucoadhesiveness with porcine mucosa and nasal deposition pattern using a jet- flow nebulizer and a 3D printed nasal cast. RESULTS In situ gelling fluticasone propionate nanosuspensions were characterised by particle diameter between 140.3 to 166.8 nm, zeta-potential between –89.5 and –83.2 mV and surface tension of about 37 mN m-1 at 25 °C. Rheological studies confirmed the gelation of formulations when mixed with simulated nasal fluid. The formed gel showed appropriate strength and stability profile. All formulations were biocompatible (cell viability > 90%) and mucoadhesive. Spraying the formulations with jet-flow nebulizer resulted in targeted deposition within the 3D printed nasal cast. CONCLUSION Biocompatible in situ gelling fluticasone propionate nanosuspensions have been successfully prepared. Their rheological properties imply instant gelling in contact with nasal fluid, which, combined with mucoadhesive properties, indicate the potential for extended residence time at nasal mucosa. Nasal deposition profiles proved the suitability of jet-flow nebulizer for nasal delivery of in situ gelling nanosuspensions. Acknowledgement This work has been supported in part by Croatian Science Foundation under the project UIP-2017-05-4592 and European Social Fund under the Croatian Science Foundation project DOK- 2020-01-2473. REFERENCES 1. Alshweiat, A, et al. Int J Pharm (2020) 579:119-166 2. Xi, J, et al. Pharm Res (2016) 33:1527- 1541