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Article

Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution

1
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, 10124 Torino, Italy
2
Dipartimento di Oncologia, Università degli Studi di Torino, 10043 Orbassano, Italy
3
Dipartimento di Neuroscienze, Università degli Studi di Torino, 10126 Torino, Italy
*
Author to whom correspondence should be addressed.
Received: 20 November 2018 / Revised: 30 January 2019 / Accepted: 30 January 2019 / Published: 2 February 2019
(This article belongs to the Special Issue Advances in Solid Lipid Micro- and Nanoparticle Technology)
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. View Full-Text
Keywords: solid lipid nanoparticles; blood–brain barrier; methotrexate; insulin; transferrin solid lipid nanoparticles; blood–brain barrier; methotrexate; insulin; transferrin
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MDPI and ACS Style

Muntoni, E.; Martina, K.; Marini, E.; Giorgis, M.; Lazzarato, L.; Salaroglio, I.C.; Riganti, C.; Lanotte, M.; Battaglia, L. Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution. Pharmaceutics 2019, 11, 65. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11020065

AMA Style

Muntoni E, Martina K, Marini E, Giorgis M, Lazzarato L, Salaroglio IC, Riganti C, Lanotte M, Battaglia L. Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution. Pharmaceutics. 2019; 11(2):65. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11020065

Chicago/Turabian Style

Muntoni, Elisabetta, Katia Martina, Elisabetta Marini, Marta Giorgis, Loretta Lazzarato, Iris C. Salaroglio, Chiara Riganti, Michele Lanotte, and Luigi Battaglia. 2019. "Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution" Pharmaceutics 11, no. 2: 65. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11020065

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