Nasal administration of micropspheres containing a new antiamoebic drug

Purpose: To evaluate the in-vitro and in-vivo properties of chitosan microspheres as the drug delivery system able to obtain the direct nose-to-brain transport of a new macrolide, Rokitamycin. Methods: From our recent studies resulted that drug-loaded microspheres, prepared by spray-drying of the 0.25% (w/v) feed-solution and with drug-polymer ratio of 1-4 (w/w) were characterised by morphology, dimension and size distribution suitable for nasal administration. These formulations increase the drug dissolution rate, quickly absorb water and swell. The microspheres were chosen for ex-vivo and in-vivo studies. An extraction method from blood and cerebral-spinal fluid and a HPLC analysis method of Rokitamycin was expressly set up. In-vitro and in-vivo blood stability of the drug was evaluated. Preliminary tests of in-vivo nasal administration of microspheres on rats, compared with drug alone, were carried out. Results: The Rokitamycin encapsulation into the chitosan microspheres increases its poor ex-vivo permeability through nasal sheep mucosa. The drug is stable in human whole blood till 8 hour of incubation. On the contrary, after intravenous injection in rats, the Rokitamycin is widely degraded such to determine a half-life of 14 min. In-vivo results of nasal administration of microspheres show (se ci sono, altrimenti eliminare). Conclusions: These preliminary results show that the new antiamoebic drug, Rokitamycin, can be encapsulated into microspheres that can be administrated by nasal route as potential delivery system for obtaining the brain targeting of the drug. This work was supported by MIUR through grant PRIN05. The authors thank “Farmaceutici Formenti S.p.A” for the donation of Rokitamycin.