ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier.
Solid lipid nanoparticles (SLN) are colloidal drug delivery systems characterized by higher entrapment efficiency, good scalability of the preparation process and increased sustained prolonged release of the payload compared to other nanocarriers. The possibility to functionalize the surface of SLN with ligands to achieve a site specific targeting makes them attractive to overcome the limited blood-brain barrier (BBB) penetration of therapeutic compounds. SLN are prepared for brain targeting by exploiting the adaptability of warm microemulsion process for the covalent surface modification with an Apolipoprotein E-derived peptide (SLN-mApoE). Furthermore, the influence of the administration route on SLN-mApoE brain bioavailability is here evaluated. SLN-mApoE are able to cross intact a BBB in vitro model. The pulmonary administration of SLN-mApoE is related to a higher confinement in the brain of Balb/c mice compared to the intravenous and intraperitoneal administration routes, without inducing any acute inflammatory reaction in the lungs. These results promote the pulmonary administration of brain-targeted SLN as a feasible strategy for improving brain delivery of therapeutics.
Nanomedicine Center, Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy. Electronic address: roberta.dalmagro@unimib.it.
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Dal Magro
School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Ornaghi
School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Cambianica
School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Beretta
Nanomedicine Center, Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Nanovector S.r.l., via Livorno, 60, 10144 Torino, TO, Italy.
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Musicanti
Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Rigolio
Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Donzelli
Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Canta
Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Ballarini
Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Cavaletti
Nanovector S.r.l., via Livorno, 60, 10144 Torino, TO, Italy.
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Gasco
Nanomedicine Center, Neuroscience Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
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Sancini
D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D041702:BALB 3T3 Cells; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties
D001057:Apolipoproteins E; D004337:Drug Carriers; D008055:Lipids
ApoE-derived peptide; Blood-brain barrier; Brain targeting; Pulmonary administration; Solid lipid nanoparticles