Influence of Chitosan Glutamate on the In Vivo Intranasal Absorption of Rokitamycin from Microspheres

Intranasal delivery is an alternative method to target therapeutics in central nervous system (CNS). In the study here described, mucoadhesive microspheres based on chitosan glutamate (CG) and containing rokitamycin were prepared by spray drying and in vitro characterized. Moreover, the influence of chitosan glutamate on rokitamycin 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 loaded rokitamycin chitosan (CH) microparticles and after intravenous administration of the free drug. The concentrations of feed solution or kind of chitosan 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 rokitamycin 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 intravenous administration, rokitamycin is not able to cross the blood-brain barrier and to reach the CSF from the bloodstream. On the contrary, drug goes to the cerebrospinal fluid and the bloodstream only after nasal administration of CG microparticles.