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Influence of chitosan glutamate on the in vivo intranasal absorption of rokitamycin from microspheres

Gavini, Elisabetta and Rassu, Giovanna and Ferraro, Luca and Generosi, Amanda and Rau, Jiulietta V. and Brunetti, Antonio and Giunchedi, Paolo and Dalpiaz, Alessandro (2011) Influence of chitosan glutamate on the in vivo intranasal absorption of rokitamycin from microspheres. Journal of Pharmaceutical Sciences, Vol. 100 (4), p. 1488-1502. eISSN 1520-6017. Article.

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DOI: 10.1002/jps.22382

Abstract

Intranasal delivery is an alternative method to target therapeutics to the central nervous system. In the present study, chitosan glutamate (CG)-based mucoadhesive microspheres containing rokitamycin (RK) were prepared by spray-drying and in vitro characterization. Moreover, the influence of CG on RK absorption in bloodstream and cerebrospinal fluid (CSF) was evaluated after nasal administration to rats. The in vivo results were compared with those obtained after nasal administration of chitosan (CH)-based microparticles containing RK and after intravenous (IV) administration of the free drug. The in vitro results indicate that the concentrations of feed solution or kind of CH influence the RK entrapment and size of microspheres. All formulations increase the solubility of this poorly water-soluble drug, but CG is more able to increase the in vitro dissolution rate of RK than CH. CG microspheres absorb water quickly and then dissolve, whereas CH particles need more volume of water for swelling and gelling. In vivo studies showed that, after IV administration, RK is not able to cross the blood–brain barrier and to reach the CSF from the bloodstream. On the contrary, drug goes to the CSF and the bloodstream only after nasal administration of CG microparticles.

Item Type:Article
ID Code:5467
Status:Published
Refereed:Yes
Uncontrolled Keywords:Rokitamycin, chitosan, microspheres, nasal drug delivery, brain targeting, in vivo studies, spray drying, controlled release/delivery, site-specific delivery, CNS
Subjects:Area 03 - Scienze chimiche > CHIM/09 Farmaceutico tecnologico applicativo
Area 02 - Scienze fisiche > FIS/07 Fisica applicata (a beni culturali, ambientali, biologia e medicina)
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
001 Università di Sassari > 03 Istituti > Matematica e fisica
Publisher:Blackwell / Wiley
eISSN:1520-6017
Copyright Holders:© 2010 Wiley-Liss, Inc. and the American Pharmacists Association
Deposited On:10 Feb 2011 12:28

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