Polymeric nanoparticles (Np) have been considered as strategic carriers for brain targeting. 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, in this paper, we prepared PLGA Np surface modified with a BBB-penetrating peptide (similopioid 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 Np 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 Np was evaluated in order to point out the capability of the Np to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded Np administration remained significant over 24 h. Using confocal and fluorescent microscopies, the novel Np 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 h). Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, and lung), the pharmacological and biodistribution results are proofs of the ability of double targeted Np to enter the brain allowing the drug to be released over a prolonged time.

Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: In vivo pharmacological evidence and biodistribution / Tosi, Giovanni; Vergoni, Anna Valeria; Ruozi, Barbara; Bondioli, Lucia; Badiali, Luca; Rivasi, Francesco; Costantino, Luca; Forni, Flavio; Vandelli, Maria Angela. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - STAMPA. - 145:1(2010), pp. 49-57. [10.1016/j.jconrel.2010.03.008]

Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: In vivo pharmacological evidence and biodistribution

TOSI, Giovanni;VERGONI, Anna Valeria;RUOZI, Barbara;BONDIOLI, Lucia;BADIALI, Luca;RIVASI, Francesco;COSTANTINO, Luca;FORNI, Flavio;VANDELLI, Maria Angela
2010

Abstract

Polymeric nanoparticles (Np) have been considered as strategic carriers for brain targeting. 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, in this paper, we prepared PLGA Np surface modified with a BBB-penetrating peptide (similopioid 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 Np 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 Np was evaluated in order to point out the capability of the Np to reach and to remain in the brain. The results showed that the pharmacological effect induced by loaded Np administration remained significant over 24 h. Using confocal and fluorescent microscopies, the novel Np 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 h). Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, and lung), the pharmacological and biodistribution results are proofs of the ability of double targeted Np to enter the brain allowing the drug to be released over a prolonged time.
2010
145
1
49
57
Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: In vivo pharmacological evidence and biodistribution / Tosi, Giovanni; Vergoni, Anna Valeria; Ruozi, Barbara; Bondioli, Lucia; Badiali, Luca; Rivasi, Francesco; Costantino, Luca; Forni, Flavio; Vandelli, Maria Angela. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - STAMPA. - 145:1(2010), pp. 49-57. [10.1016/j.jconrel.2010.03.008]
Tosi, Giovanni; Vergoni, Anna Valeria; Ruozi, Barbara; Bondioli, Lucia; Badiali, Luca; Rivasi, Francesco; Costantino, Luca; Forni, Flavio; Vandelli, M...espandi
File in questo prodotto:
File Dimensione Formato  
Tosi et al., JCR 2010.pdf

Solo gestori archivio

Tipologia: Versione pubblicata dall'editore
Dimensione 972.25 kB
Formato Adobe PDF
972.25 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
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/11380/642502
Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 117
  • ???jsp.display-item.citation.isi??? 103
social impact