Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration.
active efflux transporters
brain targeting
influx transporters
lipidization
micro and nanoparticles
nasal administration
prodrug
receptor-mediated transport
self-assembled nanoparticles
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
27 Jul 2021
27 Jul 2021
Historique:
received:
11
06
2021
revised:
13
07
2021
accepted:
23
07
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
29
8
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34452105
pii: pharmaceutics13081144
doi: 10.3390/pharmaceutics13081144
pmc: PMC8399330
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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