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Study for Zedoary Turmeric Oil Nanostructued Lipid Carrier Delivery System

Author: YangKaiLiang
Tutor: ChenDaWei
School: Shenyang Pharmaceutical University
Course: Pharmacy
Keywords: Zedoary Turmeric Oil Solid lipid nanoparticles Nanostructured lipid carrier system In vitro drug release Lyophilization Pharmacokinetics Pharmacodynamics
CLC: R283
Type: Master's thesis
Year: 2007
Downloads: 54
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Abstract


Zedoary Turmeric Oil （ZTO）, was chosen as a model drug and was encapsulated into ananostructured lipid carder system（NLC）, with the aim of enhancing its physical and chemicalstabilities, increasing its target ability, diminishing its adverse reactions, and studying thepotentiality of the traditional Chinease volatile oil medicine to be encapsulated into NLC. Theformula and preparation process were investigated, and some phamarceutical characteristicswere studied, as well as the pharmacokinetics and tissue distribution.In this study the ZTO content was detected using RP-HPLC method, which was consideredas a sensitive and reproducible way to determine the content of ZTO in NLC. The recovery ismore than 99% and the RSD value of less than 1% denoted a good resproducibility.A novel hot dispersion-cool solidification method was developed to prepare ZTO-NLC.Asshown in results, ultrasonic time and intensity affected the particle size of NLC significantly. Ahigh drug loading NLC could be acquired, if solid lipid Crodamol SS and liquid lipid Miglyol812N were employed as lipid cartier, and Soybean lecithin/Solutol HS 15 as emulsifiers.Subsequently orthogonal design experiments, with the criteria of particle size and long-termstability, were performed to optimize the process parameters. The appearance of NLC wasspheric with mean particle size of （1264±19） nm, andζpotential of -24.5 inV. The encapsulationefficiency of Curcumol and Germacrone were （96.664±1.38）% and （94.994±1.49）% respectively. Drugloading of Curcumol and Germacrone were （38.664±1.38）% and （38.004±1.49）% respectively. Resultsof the release experiments indicated that the release rate of ZTO from ZTO-NLC was coincidentwith Weibull equation, which showed an initial burst effect followed by a slower rate stage.Some drug might be adsorbed onto the surface, while others be embedded in the NLC.NLC were successfully lyophilized in order to increase their stability. The effects of differentcryoprotectants on the appearance, mean particle size and drug entrapment efficiency in NLCafter lyophilization and reconstitution were investigated to select the optimal cryoprotectant. Theconfiguration of the freeze-dried cake was analyzed by electron microscopy. The freeze-driedZTO-NLC powers were investigated by DSC and X-ray scatter. The results showed thatcomparing with the bulk lipid, the solidification temperature decreased, and the crystallizationcharacteristic of ZTO-NLC was amorphous. The RP-HPLC methods were developed for the determination of Germacrone in rat plasmaand in different biological samples respectively. The results of ZTO-Inj and ZTO-NLC after tailiv administration were compared. The pharmacokinetic parameters of ZTO-NLC were obtainedas:T1/2 8.88 h, AUC0-∞ 11.47μg·h·mL-1, MRT 7.73 h. And their weight-mean targeting content inheart, liver, spleen, lung, kidney and brain were 0.07%, 50.80%, 3.27%, 3.14%, 0.88%, 0.60%, respectively, according to which, ZTO-NLC could increase the hepatic targeting efficiency ofzedoary turmeric oil in rats and decrease the heart and kidney distribution in some extend.Transplation tumor model of hepatoma in mice were used to observe the inhibitory effectsof ZTO-NLC and ZTO-Inj on H22 cells in mice. The results showed that comparing withZTO-Inj, the survival, antitumor activity has been enhanced in mice after iv ZTO-NLC.Vascular irritation testing, Active systemic anaphylaxis testing, RBC tolerance testing wereused to evaluation the security after iv ZTO-NLC, and the results meet the requirement of theSFDA related guidance for new drug.

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CLC: > Medicine, health > Chinese Medicine > Of Pharmacy > Chinese medicine processing,preparation
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