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Surface-Modified Nanocarriers for Nose-To-Brain Delivery: From Bioadhesion to Targeting
Open accessPreprint — published as 10.3390/pharmaceutics10010034 · Paper page
Abstract
In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.
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![Figure 1 (a) Nasal innervation; (b) Nose-to-brain (N2B) pathways of drug delivery (modified from [15,16] with permission).](/paper-figures/9c694c8f77f047b09bbaac04caee4c5a/surface-modified-nanocarriers-for-nose-to-brain-delivery-from-bioadhesion-to-figure-1.jpg)
![Figure 2 Dynamics of Alexa-dextran in brain tissue following nasal administration of hydrophobic (STR–CH2R4H2C) and hydrophilic (MPEG–PCL–CH2R4H2C) surface nanocarriers in: (a) whole brain and (b) 2 mm-sliced brain sections (reprinted with permission from [76]).](/paper-figures/886e42a0e82b4857b274c7cec00214eb/surface-modified-nanocarriers-for-nose-to-brain-delivery-from-bioadhesion-to-figure-2.jpg)
![Figure 3 Surface chemistry of nanoparticles having an influence on mucoadhesion (modified with permission from [84]).](/paper-figures/23424b355fb4411ea266e4fdefb4472f/surface-modified-nanocarriers-for-nose-to-brain-delivery-from-bioadhesion-to-figure-3.jpg)
![Figure 4 Fraction of total radioactivity recovered per organ 90 min after nasal administration to rats of (a) 99mTc-labelled simvastatin-loaded nanoparticles; (b) 99mTc-labelled simvastatin suspension [113].](/paper-figures/71bc71326e494e2db3fb6f83612d196d/surface-modified-nanocarriers-for-nose-to-brain-delivery-from-bioadhesion-to-figure-4.jpg)
![Figure 5 Major mechanisms hindering particles from diffusing through mucus: (a) Size filtering, by which only particles smaller than the mesh pores of the mucin fiber network can cross, whereas larger objects are blocked; (b) Interaction filtering, when particles behavior is different according to their surface properties: orange particles interacting strongly with the components of the mucus gel are trapped, whereas green particles showing weak interactions are allowed to go across (reproduced with permission from [121]).](/paper-figures/2c6044d4feb24bb5a48e289ed92519c9/surface-modified-nanocarriers-for-nose-to-brain-delivery-from-bioadhesion-to-figure-5.jpg)
![Figure 6 Distribution of wheat germ agglutinin (WGA)-conjugated quantum dots-loaded nanoparticles in various organs, 3 h after intranasal administration: (a) optical image (b) quantification of luminescence signals (adapted with permission from [153]. Copyright 2008 American Chemical Society).](/paper-figures/7d9838aa121545f0b9d3362424f43f1f/surface-modified-nanocarriers-for-nose-to-brain-delivery-from-bioadhesion-to-figure-6.jpg)
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“According to the present literature, different kinds of nanocarriers are used to prepare nasal formulations able to target the brain, constituted by polymer-based and lipid-based nanoparticles [21,22,23].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [22]
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1 retracted
Ahmad, N., Ahmad, I., Umar, S., Iqbal, Z., Samim, M., & Ahmad, F. J. (2014) · Drug Delivery · doi:10.3109/10717544.2014.941076 · Cited by 70
RetractedMucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues
Lai, S. K., Wang, Y.-Y., & Hanes, J. S. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.11.002 · Cited by 1,863
Cone, R. A. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.09.008 · Cited by 1,459
Intranasal delivery to the central nervous system: Mechanisms and experimental considerations
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21924 · Cited by 1,239
Nasal drug delivery—possibilities, problems and solutions
Illum, L. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00363-2 · Cited by 1,139
Modern methods for delivery of drugs across the blood–brain barrier
Chen, Y., & Liu, L. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.11.010 · Cited by 1,036
Thorne, R. G., Pronk, G. J., Padmanabhan, V., & Frey, W. H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.029 · Cited by 958
Transport of drugs from the nasal cavity to the central nervous system
Illum, L. (2000) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(00)00087-7 · Cited by 907
Intranasal insulin improves cognition and modulates β-amyloid in early AD
Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Plymate, S. R., Breitner, J. C. S., DeGroodt, W., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000265401.62434.36 · Cited by 830
Approaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases
Gabathuler, R. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.028 · Cited by 829
Cited by
Sorted by citations
Evaluation of intranasal delivery route of drug administration for brain targeting
Erdő, F., Bors, L. A., Farkas, D., Bajza, Á., & Gizurarson, S. S. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.10.009 · Cited by 773
Drug delivery to the central nervous system
Nance, E. A., Pun, S. H., Saigal, R., & Sellers, D. L. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00394-w · Cited by 442
On a highway to the brain: A review on nose-to-brain drug delivery using nanoparticles
Formica, M. L., Real, D. A., Picchio, M. L., Catlin, E. J., Donnelly, R. F., & Paredes, A. J. (2022) · Applied Materials Today · doi:10.1016/j.apmt.2022.101631 · Cited by 282
Nanoemulsions for “Nose-to-Brain” Drug Delivery
Bonferoni, M. C., Rossi, S., Sandri, G., Ferrari, F., Gavini, E., Rassu, G., & Giunchedi, P. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11020084 · Cited by 269
Ceña, V., & Játiva, P. (2018) · Nanomedicine · doi:10.2217/nnm-2018-0139 · Cited by 232
Metadata
- Authors
- Sonvico, F., Clementino, A. R., Buttini, F., Colombo, G., Pescina, S., Stanisçuaski Guterres, S., Raffin Pohlmann, A., & Nicoli, S.
- Affiliations
- University of Parma (IT)
- University of Ferrara (IT)
- Corresponding author
- Sonvico, Fabio
- ORCID
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2018-02-09
- Volume
- 10
- Issue
- 1
- Pages
- 34-34
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC5874847
- OpenAlex
- W2786145144
- Cited by
- 306
- References
- 176
- Citations by year
- 2026: 16 · 2025: 36 · 2024: 35 · 2023: 35 · 2022: 49 · 2021: 54 · 2020: 45 · 2019: 24 · 2018: 11
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (401196/2014-3, PVE 401196/2014-3)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- nose-to-brain delivery, intranasal drug delivery, nanocarriers, surface modification, blood-brain barrier bypass, mucoadhesion, mucoadhesive polymers, static electricity, insulin, Alzheimer's disease, brain drug delivery, particle engineering
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