Diagnosis and therapy of brain diseases are often compromised by the difficulty to cross the blood brain barrier (BBB). Recently, the emerging field of nanotechnology has generated new promises to solve this problem. Nanoparticles (NPs) have several advantages in terms of biocompatibility, non-immunogenicity, non-toxicity and they can be functionalized to carry imaging agents and/or drugs, and to enhance theblood circulation residence time. Finally, the NPs surface can be modified with specific ligands in order to achieve site-specific delivery and successful penetration of the BBB. The objective of present investigation was to study the effect of surface characteristics of solid lipid nanoparticles (SLN) covalently coupled with the monomer of ApoE-residues (141-150) on cellular uptake in brain capillary endothelial cells. Radiolabelled and fluorescent (fluoroprobe strictly associated to SLN) have been used to evaluate the transcellular transport in in vitro BBB model based on human cerebral microvascular endothelial cells (hCMEC/D3). SLN made of tripalmitin, loaded with different fluorescent dyes (Bodipy, Tritc and Texas Red) and functionalized with phosphatidic acid (Aβ ligands) and DSPE-PEG(2000)-Maleimide have been investigated. SLN uptake was monitored byconfocal-laser-scanning microscopy and quantified by radiochemical techniques. The peptide mediated an efficient cellular uptake of SLN. SLN without surface-located peptide displayed less membrane accumulation and cellular uptake. In order to assess the ability of ApoE-SLN to enhance their transcellular transport, we studied the permeability through an in vitro BBB model. With respect to the un-functionalized SLN, the ApoE-SLN significantly enhanced their cellular uptake and permeability through the cell monolayer (PE = 0.6 • 10-5 cm/min vs PE = 6.95 • 10-5 cm/min, respectively; Student's t-test, p value. References: 1. Priano L, Zara GP, El-Assawy N, Cattaldo S, Muntoni E, Milano E, Serpe L, Musicanti C, Pérot C, Gasco MR, Miscio G, Mauro A. Baclofen-loaded solid lipid nanoparticles: preparation, electrophysiological assessment of efficacy, pharmacokinetic and tissue distribution in rats after intraperitoneal administration. Eur J Pharm Biopharm. 2011 Sep;79(1):135-41. doi: 10.1016/j.ejpb.2011.02.009. Epub 2011 Feb 23. Pub Med PMID: 21352914. 2. Gasco MR, Priano L, Zara GP. Chapter 10 - Solid lipid nanoparticles and microemulsions for drug delivery The CNS. Prog Brain Res. 2009;180:181-92. doi:10.1016/S0079-6123(08)80010-6. Epub 2009 Dec 8. Review. PubMed PMID: 20302835. 3. Gobbi M, Re F, Canovi M, Beeg M, Gregori M, Sesana S, Sonnino S, Brogioli D, Musicanti C, Gasco P, Salmona M, Masserini ME. Lipid-based nanoparticles with high binding affinity for amyloid-beta1-42 peptide. Biomaterials. 2010 Sep;31(25):6519-29. doi: 10.1016/j.biomaterials. 2010.04.044. Pub Med PMID:20553982. 4. Re F, Cambianica I, Zona C, Sesana S, Gregori M, Rigolio R, La Ferla B, Nicotra F, Forloni G, Cagnotto A, Salmona M, Masserini M, Sancini G. Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model. Nanomedicine. 2011 Oct;7(5):551-9. Epub 2011 May 20. Pub Med PMID: 21658472. 5. Re F, Cambianica I, Sesana S, Salvati E, Cagnotto A, Salmona M, Couraud PO, Moghimi SM, Masserini M, Sancini G. Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide. J Biotechnol. 2010 Dec 20;156(4):341-6. Epub 2011 Jul 6. Pub Med PMID: 21763360. Acknowledgement / funding: The research leading to these results received funding from the European Community’s Seventh Framework Program (FP7/2007-2013) under grant agreement n° 212043 (NAD). We thank Pierre-Olivier Couraud for providing the hCMEC/D3 cells.

Dal Magro, R., Ornaghi, F., Cambianica, I., Re, F., Barbero, F., Musicanti, C., et al. (2013). Solid Lipid Nanoparticles: a strategy to overcome the blood-brain barrier. In Solid Lipid Nanoparticles: a strategy to overcome the blood-brain barrier (pp.1-112).

Solid Lipid Nanoparticles: a strategy to overcome the blood-brain barrier

Dal Magro, R;Ornaghi, F;Cambianica, I;Re, F;Brambilla, A;Salvati, E;Masserini, M;Sancini, G
2013

Abstract

Diagnosis and therapy of brain diseases are often compromised by the difficulty to cross the blood brain barrier (BBB). Recently, the emerging field of nanotechnology has generated new promises to solve this problem. Nanoparticles (NPs) have several advantages in terms of biocompatibility, non-immunogenicity, non-toxicity and they can be functionalized to carry imaging agents and/or drugs, and to enhance theblood circulation residence time. Finally, the NPs surface can be modified with specific ligands in order to achieve site-specific delivery and successful penetration of the BBB. The objective of present investigation was to study the effect of surface characteristics of solid lipid nanoparticles (SLN) covalently coupled with the monomer of ApoE-residues (141-150) on cellular uptake in brain capillary endothelial cells. Radiolabelled and fluorescent (fluoroprobe strictly associated to SLN) have been used to evaluate the transcellular transport in in vitro BBB model based on human cerebral microvascular endothelial cells (hCMEC/D3). SLN made of tripalmitin, loaded with different fluorescent dyes (Bodipy, Tritc and Texas Red) and functionalized with phosphatidic acid (Aβ ligands) and DSPE-PEG(2000)-Maleimide have been investigated. SLN uptake was monitored byconfocal-laser-scanning microscopy and quantified by radiochemical techniques. The peptide mediated an efficient cellular uptake of SLN. SLN without surface-located peptide displayed less membrane accumulation and cellular uptake. In order to assess the ability of ApoE-SLN to enhance their transcellular transport, we studied the permeability through an in vitro BBB model. With respect to the un-functionalized SLN, the ApoE-SLN significantly enhanced their cellular uptake and permeability through the cell monolayer (PE = 0.6 • 10-5 cm/min vs PE = 6.95 • 10-5 cm/min, respectively; Student's t-test, p value. References: 1. Priano L, Zara GP, El-Assawy N, Cattaldo S, Muntoni E, Milano E, Serpe L, Musicanti C, Pérot C, Gasco MR, Miscio G, Mauro A. Baclofen-loaded solid lipid nanoparticles: preparation, electrophysiological assessment of efficacy, pharmacokinetic and tissue distribution in rats after intraperitoneal administration. Eur J Pharm Biopharm. 2011 Sep;79(1):135-41. doi: 10.1016/j.ejpb.2011.02.009. Epub 2011 Feb 23. Pub Med PMID: 21352914. 2. Gasco MR, Priano L, Zara GP. Chapter 10 - Solid lipid nanoparticles and microemulsions for drug delivery The CNS. Prog Brain Res. 2009;180:181-92. doi:10.1016/S0079-6123(08)80010-6. Epub 2009 Dec 8. Review. PubMed PMID: 20302835. 3. Gobbi M, Re F, Canovi M, Beeg M, Gregori M, Sesana S, Sonnino S, Brogioli D, Musicanti C, Gasco P, Salmona M, Masserini ME. Lipid-based nanoparticles with high binding affinity for amyloid-beta1-42 peptide. Biomaterials. 2010 Sep;31(25):6519-29. doi: 10.1016/j.biomaterials. 2010.04.044. Pub Med PMID:20553982. 4. Re F, Cambianica I, Zona C, Sesana S, Gregori M, Rigolio R, La Ferla B, Nicotra F, Forloni G, Cagnotto A, Salmona M, Masserini M, Sancini G. Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model. Nanomedicine. 2011 Oct;7(5):551-9. Epub 2011 May 20. Pub Med PMID: 21658472. 5. Re F, Cambianica I, Sesana S, Salvati E, Cagnotto A, Salmona M, Couraud PO, Moghimi SM, Masserini M, Sancini G. Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide. J Biotechnol. 2010 Dec 20;156(4):341-6. Epub 2011 Jul 6. Pub Med PMID: 21763360. Acknowledgement / funding: The research leading to these results received funding from the European Community’s Seventh Framework Program (FP7/2007-2013) under grant agreement n° 212043 (NAD). We thank Pierre-Olivier Couraud for providing the hCMEC/D3 cells.
No
abstract + poster
Scientifica
Solid Lipid Nanoparticles; Blood Brain Barrier, hCMEC/D3
English
International conference for NANOPARTICLES AND NANOTECHNOLOGIES IN MEDICINE - NPMED 2013
www.npmed13.eu
Dal Magro, R., Ornaghi, F., Cambianica, I., Re, F., Barbero, F., Musicanti, C., et al. (2013). Solid Lipid Nanoparticles: a strategy to overcome the blood-brain barrier. In Solid Lipid Nanoparticles: a strategy to overcome the blood-brain barrier (pp.1-112).
Dal Magro, R; Ornaghi, F; Cambianica, I; Re, F; Barbero, F; Musicanti, C; Brambilla, A; Salvati, E; Cagnotto, A; Masserini, M; Gasco, P; Sancini, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/73994
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