Abstract
Methotrexate (MTX)-loaded chitosan microspheres with a mean particle size of 5.0-5.5 μm and high drug encapsulation efficiencies (90.71-93.20 %) were prepared by spray-drying technique using chitosan with different molecular weights and degrees of deacetylation. MTX-loaded chitosan microspheres displayed a swift swelling property, a controlled manner of release, strong mucoadhesion and minor cilia irritation. MTX was found in rat brain tissues after nasal administration of MTX solution and MTX-loaded chitosan microspheres, the relative bioavailability of which was 118 % referring to MTX solution. In contrast, MTX cannot be detected in rat brain sections after intravenous administration of MTX. The MTX-loaded chitosan microspheres revealed a higher nose-to-brain transport as compared to MTX aqueous solution after nasal administration. Chitosan demonstrated its ability to be a safe and effective nasal absorption enhancer for poorly absorbed drugs, such as MTX, via the olfactory pathway.
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