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Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs

[Image: see text] Nanoparticles are promising mediators to enable nasal systemic and brain delivery of active compounds. However, the possibility of reaching therapeutically relevant levels of exogenous molecules in the body is strongly reliant on the ability of the nanoparticles to overcome biologi...

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Autores principales: Clementino, Adryana Rocha, Pellegrini, Giulia, Banella, Sabrina, Colombo, Gaia, Cantù, Laura, Sonvico, Fabio, Del Favero, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335725/
https://www.ncbi.nlm.nih.gov/pubmed/34259534
http://dx.doi.org/10.1021/acs.molpharmaceut.1c00366
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author Clementino, Adryana Rocha
Pellegrini, Giulia
Banella, Sabrina
Colombo, Gaia
Cantù, Laura
Sonvico, Fabio
Del Favero, Elena
author_facet Clementino, Adryana Rocha
Pellegrini, Giulia
Banella, Sabrina
Colombo, Gaia
Cantù, Laura
Sonvico, Fabio
Del Favero, Elena
author_sort Clementino, Adryana Rocha
collection PubMed
description [Image: see text] Nanoparticles are promising mediators to enable nasal systemic and brain delivery of active compounds. However, the possibility of reaching therapeutically relevant levels of exogenous molecules in the body is strongly reliant on the ability of the nanoparticles to overcome biological barriers. In this work, three paradigmatic nanoformulations vehiculating the poorly soluble model drug simvastatin were addressed: (i) hybrid lecithin/chitosan nanoparticles (LCNs), (ii) polymeric poly-ε-caprolactone nanocapsules stabilized with the nonionic surfactant polysorbate 80 (PCL_P80), and (iii) polymeric poly-ε-caprolactone nanocapsules stabilized with a polysaccharide-based surfactant, i.e., sodium caproyl hyaluronate (PCL_SCH). The three nanosystems were investigated for their physicochemical and structural properties and for their impact on the biopharmaceutical aspects critical for nasal and nose-to-brain delivery: biocompatibility, drug release, mucoadhesion, and permeation across the nasal mucosa. All three nanoformulations were highly reproducible, with small particle size (∼200 nm), narrow size distribution (polydispersity index (PI) < 0.2), and high drug encapsulation efficiency (>97%). Nanoparticle composition, surface charge, and internal structure (multilayered, core–shell or raspberry-like, as assessed by small-angle neutron scattering, SANS) were demonstrated to have an impact on both the drug-release profile and, strikingly, its behavior at the biological interface. The interaction with the mucus layer and the kinetics and extent of transport of the drug across the excised animal nasal epithelium were modulated by nanoparticle structure and surface. In fact, all of the produced nanoparticles improved simvastatin transport across the epithelial barrier of the nasal cavity as compared to a traditional formulation. Interestingly, however, the permeation enhancement was achieved via two distinct pathways: (a) enhanced mucoadhesion for hybrid LCN accompanied by fast mucosal permeation of the model drug, or (b) mucopenetration and an improved uptake and potential transport of whole PCL_P80 and PCL_SCH nanocapsules with delayed boost of permeation across the nasal mucosa. The correlation between nanoparticle structure and its biopharmaceutical properties appears to be a pivotal point for the development of novel platforms suitable for systemic and brain delivery of pharmaceutical compounds via intranasal administration.
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spelling pubmed-83357252021-08-05 Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs Clementino, Adryana Rocha Pellegrini, Giulia Banella, Sabrina Colombo, Gaia Cantù, Laura Sonvico, Fabio Del Favero, Elena Mol Pharm [Image: see text] Nanoparticles are promising mediators to enable nasal systemic and brain delivery of active compounds. However, the possibility of reaching therapeutically relevant levels of exogenous molecules in the body is strongly reliant on the ability of the nanoparticles to overcome biological barriers. In this work, three paradigmatic nanoformulations vehiculating the poorly soluble model drug simvastatin were addressed: (i) hybrid lecithin/chitosan nanoparticles (LCNs), (ii) polymeric poly-ε-caprolactone nanocapsules stabilized with the nonionic surfactant polysorbate 80 (PCL_P80), and (iii) polymeric poly-ε-caprolactone nanocapsules stabilized with a polysaccharide-based surfactant, i.e., sodium caproyl hyaluronate (PCL_SCH). The three nanosystems were investigated for their physicochemical and structural properties and for their impact on the biopharmaceutical aspects critical for nasal and nose-to-brain delivery: biocompatibility, drug release, mucoadhesion, and permeation across the nasal mucosa. All three nanoformulations were highly reproducible, with small particle size (∼200 nm), narrow size distribution (polydispersity index (PI) < 0.2), and high drug encapsulation efficiency (>97%). Nanoparticle composition, surface charge, and internal structure (multilayered, core–shell or raspberry-like, as assessed by small-angle neutron scattering, SANS) were demonstrated to have an impact on both the drug-release profile and, strikingly, its behavior at the biological interface. The interaction with the mucus layer and the kinetics and extent of transport of the drug across the excised animal nasal epithelium were modulated by nanoparticle structure and surface. In fact, all of the produced nanoparticles improved simvastatin transport across the epithelial barrier of the nasal cavity as compared to a traditional formulation. Interestingly, however, the permeation enhancement was achieved via two distinct pathways: (a) enhanced mucoadhesion for hybrid LCN accompanied by fast mucosal permeation of the model drug, or (b) mucopenetration and an improved uptake and potential transport of whole PCL_P80 and PCL_SCH nanocapsules with delayed boost of permeation across the nasal mucosa. The correlation between nanoparticle structure and its biopharmaceutical properties appears to be a pivotal point for the development of novel platforms suitable for systemic and brain delivery of pharmaceutical compounds via intranasal administration. American Chemical Society 2021-07-14 2021-08-02 /pmc/articles/PMC8335725/ /pubmed/34259534 http://dx.doi.org/10.1021/acs.molpharmaceut.1c00366 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Clementino, Adryana Rocha
Pellegrini, Giulia
Banella, Sabrina
Colombo, Gaia
Cantù, Laura
Sonvico, Fabio
Del Favero, Elena
Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs
title Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs
title_full Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs
title_fullStr Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs
title_full_unstemmed Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs
title_short Structure and Fate of Nanoparticles Designed for the Nasal Delivery of Poorly Soluble Drugs
title_sort structure and fate of nanoparticles designed for the nasal delivery of poorly soluble drugs
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335725/
https://www.ncbi.nlm.nih.gov/pubmed/34259534
http://dx.doi.org/10.1021/acs.molpharmaceut.1c00366
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