In vitro Evaluation of Paliperidone Palmitate Loaded Cubosomes Effective for Nasal-to-Brain Delivery

• Published in: International journal of nanomedicine 2023-01, Vol.18, p.1085-1106
• Main Authors: Deruyver, Laura, Rigaut, Clément, Gomez-Perez, Alejandro, Lambert, Pierre, Haut, Benoit, Goole, Jonathan
• Format: Article
• Language: English
• Subjects: Antipsychotics; Bioavailability; Brain; charged nanoparticles; Chitosan; Comparative analysis; cubosomes; Drugs; Lipids; Mucins; Nanoparticles; nasal cast; nasal powder formulation; Nose; nose-to-brain delivery; Original Research; Paliperidone Palmitate; Permeability; Powders; Psychotropic drugs; rpmi 2650 cell line; Schizophrenia
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S397650

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. 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. 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. 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.