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.
Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Jing
J
Yao
Jian Ping
JP
Zhou
Qi Neng
QN
Ping
Yun
Y
Lu
Liang
L
Chen
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D019905:Benzyl Alcohol / Q000737:chemistry; D001921:Brain / Q000378:metabolism*; D002368:Castor Oil / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D047309:Flavones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006820:Hyaluronic Acid / Q000737:chemistry; D007275:Injections, Intravenous; D051379:Mice; D010316:Particle Size; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D020947:Tea Tree Oil / Q000737:chemistry; D014018:Tissue Distribution; D014280:Triglycerides / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D004655:Emulsions; D047309:Flavones; D013501:Surface-Active Agents; D014280:Triglycerides; C023040:polyethoxylated castor oil; D020947:Tea Tree Oil; D002368:Castor Oil; D006820:Hyaluronic Acid; D048271:Chitosan; C008661:nobiletin; D019905:Benzyl Alcohol