Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Franciele Aline Bruinsmann; Stefania Pigana; Tanira Aguirre; Gabriele Dadalt Souto; Gabriele Garrastazu Pereira; Annalisa Bianchera; Laura Tiozzo Fasiolo; Gaia Colombo; Magno Marques; Adriana Raffin Pohlmann; Silvia Stanisçuaski Guterres; Fabio Sonvico

doi:10.20944/preprints201902.0034.v1

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preprints.org > chemistry and materials science > biomaterials > doi: 10.20944/preprints201902.0034.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Franciele Aline Bruinsmann

Stefania Pigana

Tanira Aguirre

Gabriele Dadalt Souto

Gabriele Garrastazu Pereira

Adriana Raffin Pohlmann

Silvia Stanisçuaski Guterres

Fabio Sonvico

Version 1 : Received: 1 February 2019 / Approved: 4 February 2019 / Online: 4 February 2019 (13:27:10 CET)

A peer-reviewed article of this Preprint also exists.

Bruinsmann, F.A.; Pigana, S.; Aguirre, T.; Souto, G.D.; Pereira, G.G.; Bianchera, A.; Fasiolo, L.T.; Colombo, G.; Marques, M.; Pohlmann, A.R.; Guterres, S.S.; Sonvico, F. Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery. Pharmaceutics 2019, 11, 86. Bruinsmann, F.A.; Pigana, S.; Aguirre, T.; Souto, G.D.; Pereira, G.G.; Bianchera, A.; Fasiolo, L.T.; Colombo, G.; Marques, M.; Pohlmann, A.R.; Guterres, S.S.; Sonvico, F. Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery. Pharmaceutics 2019, 11, 86.

Abstract

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

Keywords

nasal permeability; nose-to-brain; simvastatin; nanocapsules; mucoadhesion; CNS disorders; chitosan

Subject

Chemistry and Materials Science, Biomaterials

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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