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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/8/1144 |
| _version_ | 1797522450900058112 |
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| author | Giada Botti Alessandro Dalpiaz Barbara Pavan |
| author_facet | Giada Botti Alessandro Dalpiaz Barbara Pavan |
| author_sort | Giada Botti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T08:29:34Z |
| format | Article |
| id | doaj.art-bc066b5044cd47e7aea201825df8b121 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T08:29:34Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-bc066b5044cd47e7aea201825df8b1212023-11-22T09:13:08ZengMDPI AGPharmaceutics1999-49232021-07-01138114410.3390/pharmaceutics13081144Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal AdministrationGiada Botti0Alessandro Dalpiaz1Barbara Pavan2Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 19, I-44121 Ferrara, ItalyDepartment of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 19, I-44121 Ferrara, ItalyDepartment of Neuroscience and Rehabilitation—Section of Physiology, University of Ferrara, Via L. Borsari 46, I-44121 Ferrara, ItalyAbout 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.https://www.mdpi.com/1999-4923/13/8/1144lipidizationprodruginflux transportersactive efflux transportersreceptor-mediated transportmicro and nanoparticles |
| spellingShingle | Giada Botti Alessandro Dalpiaz Barbara Pavan Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration Pharmaceutics lipidization prodrug influx transporters active efflux transporters receptor-mediated transport micro and nanoparticles |
| 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 | lipidization prodrug influx transporters active efflux transporters receptor-mediated transport micro and nanoparticles |
| url | https://www.mdpi.com/1999-4923/13/8/1144 |
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