Development of a Nanoparticle-Based Approach for the Blood-Brain Barrier Passage in a Murine Model of Amyotrophic Lateral Sclerosis.

Autor: Violatto MB; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Pasetto L; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Casarin E; Ananas Nanotech S.r.l., 35131 Padua, Italy., Tondello C; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padua, Italy.; Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital Frankfurt, 60596 Frankfurt am Main, Germany., Schiavon E; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padua, Italy., Talamini L; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Marchini G; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Cagnotto A; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Morelli A; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Lanno A; Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Passoni A; Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Bigini P; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy., Morpurgo M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padua, Italy., Bonetto V; Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri' IRCCS, 20133 Milan, Italy.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Dec 10; Vol. 11 (24). Date of Electronic Publication: 2022 Dec 10.
DOI: 10.3390/cells11244003
Abstrakt: The development of nanoparticles (NPs) to enable the passage of drugs across blood-brain barrier (BBB) represents one of the main challenges in neuropharmacology. In recent years, NPs that are able to transport drugs and interact with brain endothelial cells have been tested. Here, we investigated whether the functionalization of avidin-nucleic-acid-nanoassembly (ANANAS) with apolipoprotein E (ApoE) would allow BBB passage in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Our results demonstrated that ANANAS was able to transiently cross BBB to reach the central nervous system (CNS), and ApoE did not enhance this property. Next, we investigated if ANANAS could improve CNS drug delivery. To this aim, the steroid dexamethasone was covalently linked to ANANAS through an acid-reversible hydrazone bond. Our data showed that the steroid levels in CNS tissues of SOD1 G93A mice treated with nanoformulation were below the detection limit. This result demonstrates that the passage of BBB is not sufficient to guarantee the release of the cargo in CNS and that a different strategy for drug tethering should be devised. The present study furthermore highlights that NPs can be useful in improving the passage through biological barriers but may limit the interaction of the therapeutic compound with the specific target.
Databáze: MEDLINE
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