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Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation

Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood–brain barrier (BBB). The gro...

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Autores principales: Ilić, Tanja, Đoković, Jelena B., Nikolić, Ines, Mitrović, Jelena R., Pantelić, Ivana, Savić, Snežana D., Savić, Miroslav M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966342/
https://www.ncbi.nlm.nih.gov/pubmed/36839768
http://dx.doi.org/10.3390/pharmaceutics15020443
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author Ilić, Tanja
Đoković, Jelena B.
Nikolić, Ines
Mitrović, Jelena R.
Pantelić, Ivana
Savić, Snežana D.
Savić, Miroslav M.
author_facet Ilić, Tanja
Đoković, Jelena B.
Nikolić, Ines
Mitrović, Jelena R.
Pantelić, Ivana
Savić, Snežana D.
Savić, Miroslav M.
author_sort Ilić, Tanja
collection PubMed
description Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood–brain barrier (BBB). The growing availability of innovative excipients/ligands allowing improved brain targeting and controlled drug release makes the lipid nanocarriers a reasonable choice to overcome the factors impeding drug delivery through the BBB. However, a wide variety of methods, study designs and experimental conditions utilized in the literature hinder their systematic comparison, and thus slows the advances in brain-targeting by lipid-based nanoparticles. This review provides an overview of the methods most commonly utilized during the preclinical testing of liposomes, nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers intended for the treatment of various CNS disorders via the parenteral route. In order to fully elucidate the structure, stability, safety profiles, biodistribution, metabolism, pharmacokinetics and immunological effects of such lipid-based nanoparticles, a transdisciplinary approach to preclinical characterization is mandatory, covering a comprehensive set of physical, chemical, in vitro and in vivo biological testing.
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spelling pubmed-99663422023-02-26 Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation Ilić, Tanja Đoković, Jelena B. Nikolić, Ines Mitrović, Jelena R. Pantelić, Ivana Savić, Snežana D. Savić, Miroslav M. Pharmaceutics Review Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood–brain barrier (BBB). The growing availability of innovative excipients/ligands allowing improved brain targeting and controlled drug release makes the lipid nanocarriers a reasonable choice to overcome the factors impeding drug delivery through the BBB. However, a wide variety of methods, study designs and experimental conditions utilized in the literature hinder their systematic comparison, and thus slows the advances in brain-targeting by lipid-based nanoparticles. This review provides an overview of the methods most commonly utilized during the preclinical testing of liposomes, nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers intended for the treatment of various CNS disorders via the parenteral route. In order to fully elucidate the structure, stability, safety profiles, biodistribution, metabolism, pharmacokinetics and immunological effects of such lipid-based nanoparticles, a transdisciplinary approach to preclinical characterization is mandatory, covering a comprehensive set of physical, chemical, in vitro and in vivo biological testing. MDPI 2023-01-29 /pmc/articles/PMC9966342/ /pubmed/36839768 http://dx.doi.org/10.3390/pharmaceutics15020443 Text en © 2023 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
Ilić, Tanja
Đoković, Jelena B.
Nikolić, Ines
Mitrović, Jelena R.
Pantelić, Ivana
Savić, Snežana D.
Savić, Miroslav M.
Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation
title Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation
title_full Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation
title_fullStr Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation
title_full_unstemmed Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation
title_short Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation
title_sort parenteral lipid-based nanoparticles for cns disorders: integrating various facets of preclinical evaluation towards more effective clinical translation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966342/
https://www.ncbi.nlm.nih.gov/pubmed/36839768
http://dx.doi.org/10.3390/pharmaceutics15020443
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