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Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution
Glioblastoma is the most common and invasive primary tumor of the central nervous system and normally has a negative prognosis. Biodistribution in healthy animal models is an important preliminary study aimed at investigating the efficacy of chemotherapy, as it is mainly addressed towards residual c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409770/ https://www.ncbi.nlm.nih.gov/pubmed/30717376 http://dx.doi.org/10.3390/pharmaceutics11020065 |
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author | Muntoni, Elisabetta Martina, Katia Marini, Elisabetta Giorgis, Marta Lazzarato, Loretta Salaroglio, Iris Chiara Riganti, Chiara Lanotte, Michele Battaglia, Luigi |
author_facet | Muntoni, Elisabetta Martina, Katia Marini, Elisabetta Giorgis, Marta Lazzarato, Loretta Salaroglio, Iris Chiara Riganti, Chiara Lanotte, Michele Battaglia, Luigi |
author_sort | Muntoni, Elisabetta |
collection | PubMed |
description | Glioblastoma is the most common and invasive primary tumor of the central nervous system and normally has a negative prognosis. Biodistribution in healthy animal models is an important preliminary study aimed at investigating the efficacy of chemotherapy, as it is mainly addressed towards residual cells after surgery in a region with an intact blood–brain barrier. Nanoparticles have emerged as versatile vectors that can overcome the blood–brain barrier. In this experimental work, solid lipid nanoparticles, prepared using fatty acid coacervation, have been loaded with an active lipophilic ester of cytotoxic drug methotrexate, and functionalized with either transferrin or insulin, two proteins whose receptors are abundantly expressed on the blood–brain barrier. Functionalization has been achieved by grafting a maleimide moiety onto the nanoparticle’s surface and exploiting its reactivity towards thiolated proteins. The nanoparticles have been tested in vitro on a blood–brain barrier cellular model and in vivo for biodistribution in Wistar rats. Drug metabolites, in particular 7-hydroxymethotrexate, have also been investigated in the animal model. The data obtained indicate that the functionalization of the nanoparticles improved their ability to overcome the blood–brain barrier when a PEG spacer between the proteins and the nanoparticle’s surface was used. This is probably because this method provided improved ligand–receptor interactions and selectivity for the target tissue. |
format | Online Article Text |
id | pubmed-6409770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64097702019-03-29 Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution Muntoni, Elisabetta Martina, Katia Marini, Elisabetta Giorgis, Marta Lazzarato, Loretta Salaroglio, Iris Chiara Riganti, Chiara Lanotte, Michele Battaglia, Luigi Pharmaceutics Article Glioblastoma is the most common and invasive primary tumor of the central nervous system and normally has a negative prognosis. Biodistribution in healthy animal models is an important preliminary study aimed at investigating the efficacy of chemotherapy, as it is mainly addressed towards residual cells after surgery in a region with an intact blood–brain barrier. Nanoparticles have emerged as versatile vectors that can overcome the blood–brain barrier. In this experimental work, solid lipid nanoparticles, prepared using fatty acid coacervation, have been loaded with an active lipophilic ester of cytotoxic drug methotrexate, and functionalized with either transferrin or insulin, two proteins whose receptors are abundantly expressed on the blood–brain barrier. Functionalization has been achieved by grafting a maleimide moiety onto the nanoparticle’s surface and exploiting its reactivity towards thiolated proteins. The nanoparticles have been tested in vitro on a blood–brain barrier cellular model and in vivo for biodistribution in Wistar rats. Drug metabolites, in particular 7-hydroxymethotrexate, have also been investigated in the animal model. The data obtained indicate that the functionalization of the nanoparticles improved their ability to overcome the blood–brain barrier when a PEG spacer between the proteins and the nanoparticle’s surface was used. This is probably because this method provided improved ligand–receptor interactions and selectivity for the target tissue. MDPI 2019-02-02 /pmc/articles/PMC6409770/ /pubmed/30717376 http://dx.doi.org/10.3390/pharmaceutics11020065 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Muntoni, Elisabetta Martina, Katia Marini, Elisabetta Giorgis, Marta Lazzarato, Loretta Salaroglio, Iris Chiara Riganti, Chiara Lanotte, Michele Battaglia, Luigi Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution |
title | Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution |
title_full | Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution |
title_fullStr | Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution |
title_full_unstemmed | Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution |
title_short | Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution |
title_sort | methotrexate-loaded solid lipid nanoparticles: protein functionalization to improve brain biodistribution |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409770/ https://www.ncbi.nlm.nih.gov/pubmed/30717376 http://dx.doi.org/10.3390/pharmaceutics11020065 |
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