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Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration

About 40 years ago the lipidization of hydrophilic drugs was proposed to induce their brain targeting by transforming them into lipophilic prodrugs. Unfortunately, lipidization often transforms a hydrophilic neuroactive agent into an active efflux transporter (AET) substrate, with consequent rejecti...

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Detalles Bibliográficos
Autores principales: Botti, Giada, Dalpiaz, Alessandro, Pavan, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399330/
https://www.ncbi.nlm.nih.gov/pubmed/34452105
http://dx.doi.org/10.3390/pharmaceutics13081144
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author Botti, Giada
Dalpiaz, Alessandro
Pavan, Barbara
author_facet Botti, Giada
Dalpiaz, Alessandro
Pavan, Barbara
author_sort Botti, Giada
collection PubMed
description About 40 years ago the lipidization of hydrophilic drugs was proposed to induce their brain targeting by transforming them into lipophilic prodrugs. Unfortunately, lipidization often transforms a hydrophilic neuroactive agent into an active efflux transporter (AET) substrate, with consequent rejection from the brain after permeation across the blood brain barrier (BBB). Currently, the prodrug approach has greatly evolved in comparison to lipidization. This review describes the evolution of the prodrug approach for brain targeting considering the design of prodrugs as active influx substrates or molecules able to inhibit or elude AETs. Moreover, the prodrug approach appears strategic in optimization of the encapsulation of neuroactive drugs in nanoparticulate systems that can be designed to induce their receptor-mediated transport (RMT) across the BBB by appropriate decorations on their surface. Nasal administration is described as a valuable alternative to obtain the brain targeting of drugs, evidencing that the prodrug approach can allow the optimization of micro or nanoparticulate nasal formulations of neuroactive agents in order to obtain this goal. Furthermore, nasal administration is also proposed for prodrugs characterized by peripheral instability but potentially able to induce their targeting inside cells of the brain.
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spelling pubmed-83993302021-08-29 Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration Botti, Giada Dalpiaz, Alessandro Pavan, Barbara Pharmaceutics Review About 40 years ago the lipidization of hydrophilic drugs was proposed to induce their brain targeting by transforming them into lipophilic prodrugs. Unfortunately, lipidization often transforms a hydrophilic neuroactive agent into an active efflux transporter (AET) substrate, with consequent rejection from the brain after permeation across the blood brain barrier (BBB). Currently, the prodrug approach has greatly evolved in comparison to lipidization. This review describes the evolution of the prodrug approach for brain targeting considering the design of prodrugs as active influx substrates or molecules able to inhibit or elude AETs. Moreover, the prodrug approach appears strategic in optimization of the encapsulation of neuroactive drugs in nanoparticulate systems that can be designed to induce their receptor-mediated transport (RMT) across the BBB by appropriate decorations on their surface. Nasal administration is described as a valuable alternative to obtain the brain targeting of drugs, evidencing that the prodrug approach can allow the optimization of micro or nanoparticulate nasal formulations of neuroactive agents in order to obtain this goal. Furthermore, nasal administration is also proposed for prodrugs characterized by peripheral instability but potentially able to induce their targeting inside cells of the brain. MDPI 2021-07-27 /pmc/articles/PMC8399330/ /pubmed/34452105 http://dx.doi.org/10.3390/pharmaceutics13081144 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Botti, Giada
Dalpiaz, Alessandro
Pavan, Barbara
Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
title Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
title_full Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
title_fullStr Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
title_full_unstemmed Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
title_short Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration
title_sort targeting systems to the brain obtained by merging prodrugs, nanoparticles, and nasal administration
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399330/
https://www.ncbi.nlm.nih.gov/pubmed/34452105
http://dx.doi.org/10.3390/pharmaceutics13081144
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