Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. It is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, we prepared PLGA NPs surface modified with a BBB-penetrating peptide (simil-opioid peptide) for BBB crossing and with a sialic acid residue (SA) for the interaction with brain receptors. This double coverage could allow to obtain novel targeted NPs with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. The central analgesic activity of Loperamide (opioid drug, unable to cross the BBB) loaded in these novel NPs was evaluated in order to point out the capability of the NPs to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded NPs administration remained significant over 24 hrs. Using confocal and fluorescent microscopy, the novel NPs were localized within the tissue parenchyma (brain, kidney, liver, spleen and lung). Finally, the biodistribution studies showed a localization of the 6% of the injected dose into the CNS over a prolonged time (24 hrs). Notwithstanding an increased accumulation of SA-covered NPs in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double targeted NPs to enter the brain allowing the drug to be released over a prolonged time. Moreover, electron microscopy of brain sections after iv administration of modified NPs, allowed us to hypothesize a multiple-pathway mechanism of BBB crossing of modified NPs. NPs surface interaction with BBB membrane without a clear involvement of specific receptors, but possibly based on “biousian conformation” of the surface of NPs, along with ruffles of the membrane produced near to modified-NPs, seemed to mediate a BBB crossing process based on endocytosis

Nanoparticles for brain delivery of drugs: in vivo experiments and mechanism of BBB crossing / Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio. - In: AMERICAN JOURNAL OF NEUROPROTECTION AND NEUROREGENERATION. - ISSN 1947-2951. - STAMPA. - 3:(2011), pp. 13-20.

Nanoparticles for brain delivery of drugs: in vivo experiments and mechanism of BBB crossing

TOSI, Giovanni;FANO, Rita Adriana;BADIALI, Luca;BONDIOLI, Lucia;RUOZI, Barbara;VERGONI, Anna Valeria;RIVASI, Francesco;BENASSI, Rois;VANDELLI, Maria Angela;FORNI, Flavio
2011

Abstract

Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. It is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, we prepared PLGA NPs surface modified with a BBB-penetrating peptide (simil-opioid peptide) for BBB crossing and with a sialic acid residue (SA) for the interaction with brain receptors. This double coverage could allow to obtain novel targeted NPs with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. The central analgesic activity of Loperamide (opioid drug, unable to cross the BBB) loaded in these novel NPs was evaluated in order to point out the capability of the NPs to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded NPs administration remained significant over 24 hrs. Using confocal and fluorescent microscopy, the novel NPs were localized within the tissue parenchyma (brain, kidney, liver, spleen and lung). Finally, the biodistribution studies showed a localization of the 6% of the injected dose into the CNS over a prolonged time (24 hrs). Notwithstanding an increased accumulation of SA-covered NPs in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double targeted NPs to enter the brain allowing the drug to be released over a prolonged time. Moreover, electron microscopy of brain sections after iv administration of modified NPs, allowed us to hypothesize a multiple-pathway mechanism of BBB crossing of modified NPs. NPs surface interaction with BBB membrane without a clear involvement of specific receptors, but possibly based on “biousian conformation” of the surface of NPs, along with ruffles of the membrane produced near to modified-NPs, seemed to mediate a BBB crossing process based on endocytosis
3
13
20
Nanoparticles for brain delivery of drugs: in vivo experiments and mechanism of BBB crossing / Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio. - In: AMERICAN JOURNAL OF NEUROPROTECTION AND NEUROREGENERATION. - ISSN 1947-2951. - STAMPA. - 3:(2011), pp. 13-20.
Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio
File in questo prodotto:
File Dimensione Formato  
tosi et al.AJNN.pdf

non disponibili

Tipologia: Post-print dell'autore (bozza post referaggio)
Dimensione 486.91 kB
Formato Adobe PDF
486.91 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
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: http://hdl.handle.net/11380/649195
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact