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

Abstract

Introduction 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.

Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders

“…In the development of intranasal drug delivery systems for brain targeting, it is necessary to assess its cytotoxicity through the nasal epithelium. Concerning the biological evaluation of the investigated SLNs, the RPMI 2650 cell line was herein adopted as they represent a cell model widely explored for mimicking human nasal epithelium [30][31][32][33]. When RPMI 2650 cells were exposed to the cryoprotectant free-SLN formulations, no toxic effect appeared at the different concentrations and time points tested (Figures 9 and 10).…”

What Are the Key Anatomical Features for the Success of Nose-to-Brain Delivery? A Study of Powder Deposition in 3D-Printed Nasal Casts

“…We used a deposition test protocol described in our previous works [ 35 , 37 ]. For each experiment, we first coated each part of the nasal cast with an artificial mucus (5% w / w of Poloxamer ® 407 and solution in Simulated Nasal Electrolyte Solution (SNES)).…”

Design, Development, Evaluation, and In Vivo Performance of Buccal Films Embedded with Paliperidone-Loaded Nanostructured Lipid Carriers

“…Formulation techniques such as cocrystallization [10], lipid nanoconstructs [8], and ion-exchange resin complexes [11] were attempted. Similarly, transdermal and nose-to-brain routes were also assessed [4,9,12,13].…”