The Basis Studies Of Ultrasonic Locating And Targeting Drug Microcapsule

Ultrasonic locating and targeting drug microcapsule is a kind of targeting drug system (TDS) to release drug under the ultrasonic physical effect. The shell of microcapsule is made from biodegradable high molecular polymer and the microcapsule is prepared using a compound emulsion-dispersion solvent evaporation method. The interior of microcapsule is filled with air. Reflection and scattering phenomenon is going to take place when the microcapsules are irradiated by ultrasonic, so we can see the image of them on the screen and locate them in vivo. Gas in the microcapsule will expand and contract periodically under ultrasonic influence, at last the microcapsule will burst and release drug in the area that irradiated by ultrasonic. Ultrasonic locating and targeting drug microcapsule could increase the drug concentration in targeting area and reduce the blood concentration, it is helpful to increase therapy effect and decrease adverse reaction. It is a novel physical targeting drug system and it will play a good part in thrombus and tumor therapy.Part one: Using the compound emulsion-dispersion solvent evaporation method which is widely used in microcapsules preparation, we prepared the microcapsules and improved the preparation method. We used ultrasonic to prepare compound emulsion and changed the outer-water phase to gelatin-PVA mixed solution. Single factor experiments were used for filtering the better preparation method. The effects of different variables on the preparation of microcapsules were studied according to a L9(34)orthogonal design of experiments. UV spectrophotometer was used to detect the dosage of microcapsules. After filtering the methods and prescriptions, we got the better method and the best formulation. Following them we prepared a set of microcapsules. The dosage of them is 3.02±0.03%, envelope rate is 40.81±0.13%.Part two: We used the DSC to analyze the form of microcapsules and used the optical microscope as well as scanning electronic microscope to observe the microcapsules. Laser scattering equipment was used to analyze the size and the scope of microcapsules. We watched the ultrasonic diagnostic image of microcapsules in vitro, established HPLC method to detect the drug concentration of microcapsules released in vitro. A part of results were evaluated with the equation of Higuchi. After the detection, we got the result, the microcapsules had good figure, the average size was 1.15μm and scope size was between 0.79-1.48μm. The drug loaded in the microcapsules could be released quickly in the pH7.4 PBS under ultrasonic effect.Part three: Ultrasonic image and drug release of microcapsules in vivo were studied. We established the method of HPLC to detect drug concentration in the plasma and kidney homogenate under the different experimental conditions. GCV concentration in plasma and kidney homogenate had a good linearity ranged from 0.2-8.0μg/ml. The method recoveries varied from 90%-110%, the extraction recoveries were all higher than 70%. The RSD of within-day and between-day were all less than 5%. The drug concentration in plasma and kidney homogenate under the different experimental conditions had statistics differences.Ultrasonic targeting drug release can increase the drug concentration in targeting area and decrease the concentration in blood obviously. Ultrasonic locating and targeting drug microcapsule is worth researching deeply in the future.