Neurodegenerative and cerebrovascular diseases exert a growing impact from the societal and economic point of view. Therefore the development of strategies for early detection as well as for effective and safe treatments of such diseases is becoming more important than ever. For these reasons, research the targeting of active molecules to CNS represents one of the most challenging drawbacks. The selectivity of blood-brain barrier (BBB) highly limits therapies for the cerebral diseases and in the recent years a great deal of efforts to develop strategies that aid drug passage across the BBB have been made. Nanotechnology-based approaches have gained increasing attention as the most promising strategies for CNS targeted drug delivery. Such approach involves the use of at least two components, one of which is a nanoparticle (NP), which serves as a carrier (nanocarrier), and the other is the therapeutic agent (cargo). Among NPs, those made of poly(lactic-co-glycolic acid) (PLGA) hold an uncommon biocompatibility and, when conjugated with an heptapeptide (g7) able to cross the BBB, they reach at high rate the cerebral tissue. Using in vitro cell models of lysosomal storage diseases, an heterogeneous group of rare inherited disorders characterized by the lysosomal accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities, with a strong neurological involvement, we demonstrate that PLGA-NPs loaded with the missing enzyme were able to reach lysosomes and to rescue 50% of the enzymatic deficiency after a single administration. Moreover the conjugation of the enzyme with NPs also might contribute to improve the stability/integrity of the enzyme thus prolonging its life span. Thus, g7-NPs seem to represent a promising tool for the treatment of diseases with neurological involvement. Work supported by ELA Foundation (Agreement n. 2011-037C1B: “Leading nanomedicine into the therapy for Leukodystrophies: nanoparticles overcoming the blood−brain barrier to treat the mouse model of Krabbe Disease”) and Fondazione Cassa di Risparmio di Perugia (Project n. 2010.011.0434: “Effetto sulla salute umana dell’esposizione a materiale nano strutturato: impiego di modelli cellulari per lo studio della nanotossicità”)

Derivatized nanoparticles for CNS-targeted drug delivery / B., Tancini; B., Bortot; D., Dolcetta; Tosi, Giovanni; A., Magini; Vandelli, Maria Angela; Forni, Flavio; G. M., Severini; C., Emiliani. - ELETTRONICO. - (2012), pp. 1-1. ((Intervento presentato al convegno Summer Symposium on Nanomaterials and their Application to Biology and Medicine. tenutosi a Poznan nel 20-24 June 2012.

Derivatized nanoparticles for CNS-targeted drug delivery

TOSI, Giovanni;VANDELLI, Maria Angela;FORNI, Flavio;
2012

Abstract

Neurodegenerative and cerebrovascular diseases exert a growing impact from the societal and economic point of view. Therefore the development of strategies for early detection as well as for effective and safe treatments of such diseases is becoming more important than ever. For these reasons, research the targeting of active molecules to CNS represents one of the most challenging drawbacks. The selectivity of blood-brain barrier (BBB) highly limits therapies for the cerebral diseases and in the recent years a great deal of efforts to develop strategies that aid drug passage across the BBB have been made. Nanotechnology-based approaches have gained increasing attention as the most promising strategies for CNS targeted drug delivery. Such approach involves the use of at least two components, one of which is a nanoparticle (NP), which serves as a carrier (nanocarrier), and the other is the therapeutic agent (cargo). Among NPs, those made of poly(lactic-co-glycolic acid) (PLGA) hold an uncommon biocompatibility and, when conjugated with an heptapeptide (g7) able to cross the BBB, they reach at high rate the cerebral tissue. Using in vitro cell models of lysosomal storage diseases, an heterogeneous group of rare inherited disorders characterized by the lysosomal accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities, with a strong neurological involvement, we demonstrate that PLGA-NPs loaded with the missing enzyme were able to reach lysosomes and to rescue 50% of the enzymatic deficiency after a single administration. Moreover the conjugation of the enzyme with NPs also might contribute to improve the stability/integrity of the enzyme thus prolonging its life span. Thus, g7-NPs seem to represent a promising tool for the treatment of diseases with neurological involvement. Work supported by ELA Foundation (Agreement n. 2011-037C1B: “Leading nanomedicine into the therapy for Leukodystrophies: nanoparticles overcoming the blood−brain barrier to treat the mouse model of Krabbe Disease”) and Fondazione Cassa di Risparmio di Perugia (Project n. 2010.011.0434: “Effetto sulla salute umana dell’esposizione a materiale nano strutturato: impiego di modelli cellulari per lo studio della nanotossicità”)
Summer Symposium on Nanomaterials and their Application to Biology and Medicine.
Poznan
20-24 June 2012
1
1
B., Tancini; B., Bortot; D., Dolcetta; Tosi, Giovanni; A., Magini; Vandelli, Maria Angela; Forni, Flavio; G. M., Severini; C., Emiliani
Derivatized nanoparticles for CNS-targeted drug delivery / B., Tancini; B., Bortot; D., Dolcetta; Tosi, Giovanni; A., Magini; Vandelli, Maria Angela; Forni, Flavio; G. M., Severini; C., Emiliani. - ELETTRONICO. - (2012), pp. 1-1. ((Intervento presentato al convegno Summer Symposium on Nanomaterials and their Application to Biology and Medicine. tenutosi a Poznan nel 20-24 June 2012.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/948891
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact