Idebenone (IDE) is a synthetic short-chain analogue of coenzyme Q10 that has been proved to be active at the level of the central nervous system against cerebral disorders elicited by both vascular lesions and neurodegenerative processes. It is a highly lipophilic drug with a very low water solubility and the only marketed pharmaceutical formulation is an oral dosage form. The drug solubility and the binding with serum proteins determine a reduced absorption and a poor bioavailability at the level of the CNS (0.4% of the dose reaches the brain). Cyclodextrin was successfully used to increase IDE solubility. Particularly, two of the most popular cyclodextrin (CD) derivatives, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CD) are able to solubilize several poorly water soluble drugs and are approved by FDA for parenteral use. Moreover, SBE-beta-CD showed to be a good polyanionic crosslinker for chitosan. In this study, we prepared chitosan nanoparticles by ionic gelation with SBE-beta-CD. IDE was loaded into hydrophylic nanoparticles by a previous complexation with SBE-beta-CD, moreover, an overloading of the system was made adding to chitosan solution a soluble complex of IDE with HP-beta-CD. Morfological analysis showed spherical particles with a smooth surface. All systems had sizes in the nanometrical range and high drug loading %, particularly for the nanoparticles prepared in the presence of IDE/HP-beta-CD complex (about 10%). Both simple and overloaded systems showed a sustained release of IDE. In vitro studies are in progress to evaluate the ability of chitosan nanoparticles to increase the permeation of the drug through nasal mucosa.
CHITOSAN/SULFOBUTHYL ETHER BETA-CYCLODEXTRIN NANOPARTICLES FOR IDEBENONE DELIVERY
GUARDO, MARTA;TOMMASINI, Silvana;STANCANELLI, Rosanna;VENTURA, Cinzia Anna
2012-01-01
Abstract
Idebenone (IDE) is a synthetic short-chain analogue of coenzyme Q10 that has been proved to be active at the level of the central nervous system against cerebral disorders elicited by both vascular lesions and neurodegenerative processes. It is a highly lipophilic drug with a very low water solubility and the only marketed pharmaceutical formulation is an oral dosage form. The drug solubility and the binding with serum proteins determine a reduced absorption and a poor bioavailability at the level of the CNS (0.4% of the dose reaches the brain). Cyclodextrin was successfully used to increase IDE solubility. Particularly, two of the most popular cyclodextrin (CD) derivatives, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CD) are able to solubilize several poorly water soluble drugs and are approved by FDA for parenteral use. Moreover, SBE-beta-CD showed to be a good polyanionic crosslinker for chitosan. In this study, we prepared chitosan nanoparticles by ionic gelation with SBE-beta-CD. IDE was loaded into hydrophylic nanoparticles by a previous complexation with SBE-beta-CD, moreover, an overloading of the system was made adding to chitosan solution a soluble complex of IDE with HP-beta-CD. Morfological analysis showed spherical particles with a smooth surface. All systems had sizes in the nanometrical range and high drug loading %, particularly for the nanoparticles prepared in the presence of IDE/HP-beta-CD complex (about 10%). Both simple and overloaded systems showed a sustained release of IDE. In vitro studies are in progress to evaluate the ability of chitosan nanoparticles to increase the permeation of the drug through nasal mucosa.Pubblicazioni consigliate
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