Nasal Administration of Drug Loaded Chitosan Microparticles and Brain Uptake

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and muco-adhesiveness. The existence of direct pathways from the nasal cavity to the central nervous system (CNS) raises the possibility that intranasal drug administration may allow therapeutics that cannot penetrate the blood brain barrier (BBB) to be rapidly targeted to CNS using olfactory and trigeminal neural pathways. Our recent studies have shown the possibility to deliver directly to CNS an anti-ischemic drug, unable to cross the BBB, by nasal administration of microparticulate system prepared by using chitosan hydrochloride. The drug was found in the liquor at concentrations up to two order of magnitude higher than those obtained at systemic level. Based on these results, we have prepared and characterized new chitosan microparticles containing rokitamicin (RK) for nasal delivery. RK is a semisynthetic macrolide of the leucomycin group currently studied as alternative drug to the analogous macrolide antibiotics and for the treatment of granulomatous amoebic encephalitis caused by Acanthamoeba. The microparticles have been obtained by spray-drying with chitosan or chitosan glutamate. The powders have been investigated for particle size, morphology, in vitro drug release, mucoadhesive properties, and water uptake. In vivo studies were carried out in rats comparing the intravenous and the nasal administration of RK: the drug levels in blood and in liquor were followed for predetermined time periods after nasal administration of the microparticles. Only the microparticles obtained with chitosan glutamate allowed rokitamcyn to be absorbed in blood-stream and liquor.