Conjugation, Prodrug, and Co-Administration Strategies in Support of Nanotechnologies to Improve the Therapeutic Efficacy of Phytochemicals in the Central Nervous System
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Published:2023-05-23
Issue:6
Volume:15
Page:1578
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ISSN:1999-4923
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Container-title:Pharmaceutics
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language:en
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Short-container-title:Pharmaceutics
Author:
Rassu Giovanna1ORCID, Sorrenti Milena2ORCID, Catenacci Laura2ORCID, Pavan Barbara3ORCID, Ferraro Luca4ORCID, Gavini Elisabetta1ORCID, Bonferoni Maria Cristina2ORCID, Giunchedi Paolo1ORCID, Dalpiaz Alessandro5ORCID
Affiliation:
1. Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23a, I-07100 Sassari, Italy 2. Department of Drug Sciences, University of Pavia, Viale Taramelli 12, I-27100 Pavia, Italy 3. Department of Neuroscience and Rehabilitation—Section of Physiology, University of Ferrara, Via Borsari 46, I-44121 Ferrara, Italy 4. Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, I-44121 Ferrara, Italy 5. Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 19, I-44121 Ferrara, Italy
Abstract
Phytochemicals, produced as secondary plant metabolites, have shown interesting potential therapeutic activities against neurodegenerative diseases and cancer. Unfortunately, poor bioavailability and rapid metabolic processes compromise their therapeutic use, and several strategies are currently proposed for overcoming these issues. The present review summarises strategies for enhancing the central nervous system’s phytochemical efficacy. Particular attention has been paid to the use of phytochemicals in combination with other drugs (co-administrations) or administration of phytochemicals as prodrugs or conjugates, particularly when these approaches are supported by nanotechnologies exploiting conjugation strategies with appropriate targeting molecules. These aspects are described for polyphenols and essential oil components, which can improve their loading as prodrugs in nanocarriers, or be part of nanocarriers designed for targeted co-delivery to achieve synergistic anti-glioma or anti-neurodegenerative effects. The use of in vitro models, able to simulate the blood–brain barrier, neurodegeneration or glioma, and useful for optimizing innovative formulations before their in vivo administration via intravenous, oral, or nasal routes, is also summarised. Among the described compounds, quercetin, curcumin, resveratrol, ferulic acid, geraniol, and cinnamaldehyde can be efficaciously formulated to attain brain-targeting characteristics, and may therefore be therapeutically useful against glioma or neurodegenerative diseases.
Subject
Pharmaceutical Science
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