Distribution of nobiletin chitosan-based microemulsions in brain following i.v. injection in mice

The purpose of this study was to characterize the in vitro properties of a number of chitosan-based microemulsions containing nobiletin and determine its distribution in mice brain following i.v. administration. The phase behavior and properties of chitosan-based microemulsions were investigated in a pseudo-ternary system composed of polyoxyethylene 35 castor oil/benzyl alcohol/medium-chain triglyceride/tea oil/water with the chitosan. The droplet sizes were found to be smaller than 25 nm by photo correlation spectrometer. The nobiletin-loaded hyaluronic acid chitosan-based microemulsion (HAC-ME) carried negative charge and nobiletin-loaded hydrochlorate chitosan-based microemulsion (HCC-ME) carried positive charge. The concentrations of nobiletin in tissues were determined by HPLC after i.v. administration of HAC-ME, nobiletin-loaded microemulsion (ME), HCC-ME and nobiletin solution. Based on AUC(0-t), MRT and C(max), HAC-ME delivered more nobiletin to the brain compared to nobiletin solution, ME and HCC-ME. The long-circulation effect might contribute to the higher AUC(0-t) for HAC-ME in brain. On the other hand, the AUC(0-t) in plasma and brain after i.v. administration of HCC-ME were not significantly increased relative to ME. These results indicate that HAC-ME may be presented as potential candidates for delivering more drugs into the brain.