title: New chitosan derivatives for the preparation of rokitamycin loaded microspheres designed for ocular or nasal administration.
abstract: Acanthamoeba spp. are the causative agents of granulomatous amoebic encephalitis (GAE) and amoebic keratitis. Recent studies performed by Rassu et al. showed that, compared with the free drug, the loading of rokitamycin in chitosan microspheres improves and prolongs the in vitro antiamoebic activity of rokitamycin. This could be useful in transporting the drug for either ocular application to treat amoebic keratitis or nasal administration as an alternative route for the administration of the drug to the brain in GAE therapy. Starting from the previous study, our goal was to optimize the technological parameters in order to obtain chitosan microparticles loaded with rokitamycin and to evaluate the use of new quaternary ammonium chitosan derivatives in the preparation of spray dried microspheres containing the macrolide; these derivatives showed better characteristics (solubility, penetration enhancement) compared with chitosan itself. Toxicity studies on new polymers were performed. Spray dried loaded microspheres based on chitosan or chitosan derivatives were obtained by using appropriate preparative parameters. Microparticles containing chitosan derivatives showed similar or often better properties than formulations made of chitosan with respect to size, in vitro release behaviour and mucoadhesiveness thus making them more suitable for ocular or nasal administration. New polymers did not demonstrate cytotoxicity.
authors.affiliation: Department of Drug Sciences, University of Sassari, via Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.forename: Helene
authors.initials: H
authors.lastname: Jonassen
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Zambito
authors.forename: Stefano
authors.initials: S
authors.lastname: Fogli
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Breschi
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
mesh_terms: D000268:Adhesiveness; D000281:Administration, Intranasal; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004339:Drug Compounding; D042783:Endothelial Cells / Q000187:drug effects; D005079:Excipients; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D015644:Miocamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D009092:Mucous Membrane / Q000378:metabolism; D009883:Ophthalmic Solutions; D010316:Particle Size; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D000981:Antiprotozoal Agents; D005079:Excipients; D009883:Ophthalmic Solutions; D014867:Water; D015644:Miocamycin; D048271:Chitosan; C033383:rokitamycin