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Laura Deruyver,1 Clément Rigaut,2 Alejandro Gomez-Perez,3 Pierre Lambert,2 Benoit Haut,2 Jonathan Goole1 1Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de pharmacie, Université libre de Bruxelles, Brussels, Belgium; 2Transfers, Interfaces and Processes (TIPs), École Polytechnique de Bruxelles, Université libre de Bruxelles, Brussels, Belgium; 3NanoMegas SRPL, Brussels, 1050, BelgiumCorrespondence: Laura Deruyver, Boulevard du triomphe, CP207, accès 2, Campus Plaine, Bâtiment BC – 1B6 117, Brussels, 1050, Belgium, Tel +3226505221, Fax +3226505269, Email Laura.Deruyver@ulb.beIntroduction: This work aimed to develop chitosan-coated cubosomal nanoparticles intended for nose-to-brain delivery of paliperidone palmitate. They were compared with standard and cationic cubosomal nanoparticles. This comparison relies on numerous classical in vitro tests and powder deposition within a 3D-printed nasal cast.Methods: Cubosomal nanoparticles were prepared by a Bottom-up method followed by a spray drying process. We evaluated their particle size, polydispersity index, zeta-potential, encapsulation efficiency, drug loading, mucoaffinity properties and morphology. The RPMI 2650 cell line was used to assess the cytotoxicity and cellular permeation. An in vitro deposition test within a nasal cast completed these measurements.Results: The selected chitosan-coated cubosomal nanoparticles loaded with paliperidone palmitate had a size of 305.7 ± 22.54 nm, their polydispersity index was 0.166 ± 0.022 and their zeta potential was +42.4 ± 0.2 mV. This formulation had a drug loading of 70% and an encapsulation efficiency of 99.7 ± 0.1%. Its affinity with mucins was characterized by a ΔZP of 20.93 ± 0.31. Its apparent permeability coefficient thought the RPMI 2650 cell line was 3.00E-05 ± 0.24E-05 cm/s. After instillation in a 3D-printed nasal cast, the fraction of the injected powder deposited in the olfactory region reached 51.47 ± 9.30% in the right nostril and 41.20 ± 4.59% in the left nostril, respectively.Conclusion: The chitosan coated cubosomal formulation seems to be the most promising formulation for nose-to-brain delivery. Indeed, it has a high mucoaffinity and a significantly higher apparent permeability coefficient than the two other formulations. Finally, it reaches well the olfactory region.Graphical Abstract: Keywords: cubosomes, nasal cast, charged nanoparticles, RPMI 2650 cell line, nose-to-brain delivery, nasal powder formulation, chitosan |
