An Investigationon Microemulsion Of Norcantharidin

Microemulsions are stable, isotropic, transparent or semitransparent mixtures of oil, water and surfactant, frequently in combination with a consurfactant. Droplets of microemulsion are spheres or adopting the shape of a prolate ellipsoid which have characteristic dimensions of 10-100 nm. Advantages associated with microemulsions as drug delivery vehicles include their thermodynamically stability, aptical clarity, ease of preparation which not require a large input energy. Microemulsion systems have been proposed to enhance the bioavailability of drugs and developed time-release, fast-release and targeting administration of drugs and improvement of drug solubilization.Norcantharidin(NCTD), a derivative of cantharidin, is one of the most effective anticancer drugs against hepatogenic cancer, hepatocirrhosis, and other cancers. However, the successful treatment with NCTD of conventional formulation remains difficult because of several pharmacokinetic and formulation factors that affect its disposition and toxicity, especially kidneys. The high concentration of NCTD was attributed to the presence of the renal damage. Despite its side effects, NCTD is still largely used in advanced life-threatening tumors because of its high efficacy and low cost. Based on the clinical fact ,we prepared an alternative norcantharidin microemulsion to enhance it's bioavailability and reduce it's adverse effects .In this study, microemulsions prepared with lecithin, PEG, Brij-97,Pluronic-68 ,Tween as surfactants, ethano, isopropanol, butanol as consurfactant, ethyl oleate, soy bean oil, labrafaccc as oil were investigated by using the preduoternary phase diagram. We selected the system consisting of lecithin, ethanol, ethyl oleate, water as norcantharidin-loaded microemulsion for parenteral delivery. The effects of formation variables on the physicalchemical properties of microemulsion, solubility of norcantharidin in microemulsion system and stability of norcantharidin-loaded microemulsion were investigated .The GC method was set up to determine the concentration of norcantharidin in microemulsion and in the homogenate including heart, liver, spleen, lung, kidney, brain and plasma of the mice. The recovery and precision could satisfy the determination requirements about the bioample.The LD50 of norcantharidin microemulsion and norcantharidin injection was determined. The effects of biological reliability was not significance difference between norcantharidin microemulsion and norcantharidin injection in vivo.