Study Of Lung Targeting Of Adriamycin Lactic Acid-glyoclic Acid Microspheres

Adriamycin is a broad-spectrum anti-cancer drug impeding the synthesis of DNA in cancer cells. It has powerful anti-cancer effect together with great side effects after injection:bone marrow suppression, cardiac toxicity, nausea, vomiting and hair loss, which results into limited clinical application, so it is necessary to be made into targeting preparations.The study aims at creating lung-targeting preparations of adriamycin-glycolic acid microspheres. The drug-loaded microspheres are intaken by lung capillary vessel s automatically via the blood circulation after intravenous injection, then drug concentration may be found in the lung capillaries of mechanical intake, thereby increasing pulmonary blood concentration, enhancing drug efficacy and reducing systemic drug concentration and side effects so as to achieve a better clinical effect.In this paper, the determination of drug loading and drug encapsulation were detected by HPLC; and a UV-Vis spectrophotometry for the determination of microspheres release in vitro was also available:From the angle of detection methods, UV spectrophotometry was adopted to investigate release properties and release mechanism of drug-loaded microspheres in vitro. A cumulative release percentage of the time for drug release curve was achieved, and the results showed that Adriamycin-lactic acid-glycolic acid microspheres release properties in vitro was superior to doxorubicin solution, and drug release pattern accorded with Higuchi equation. Methodological studies had shown that the analysis method was sensitive, reproducible, consistent with sample analysis requirements for prescription drug design, and also preparation evaluation offered a reliable method.Adriamycin lactic acid-glycolic acid microspheres (ADM-PLGA) were prepared by emulsion solvent diffusion-adsorption. Quality indicators were particle size, drug loading and entrapment rate. And single factor study was carried on about adriamycin lactic acid-glycolic acid microspheres formulation and process factors, on the basis of which, the optimal prescription was achieved by orthogonal design. The properties of microspheres were tested through the investigation on micro-particle size, size distribution, surface morphology, mobility, electric, determination and other items inspected. It turned out to be of proper-sized obtained microsphere, good distribution and stability, and appropriate drug loading and drug encapsulation.From the preliminary investigation on the stability of drug-loaded microspheres, including inflence factor test (temperature test, humidity test, and light exposure test), accelerated testing, and long-term test, focusing on the microspheres morphology, mobility, drug loading and release properties of other indicators, the results of which conveyed that high temperature and high humidity influenced microsphere morphology greatly and the remaining inspection items were stable, indicating that microspheres were kept appropriateyl in a cool, dry storage under sealed conditionHPLC was used in Adriamycin-lactic acid-glycolic acid microspheres tests in animals in vivo as the main detection method, preliminarily researching drug concentration in heart, liver, spleen, lung, kidney and plasma in reference to equal concentration of the standard solution, investigating targeting effect on the tissues and organs in mice intravenously injected microspheres suspension in 0.25-72h. The test results showed that ADM lactic acid-glycolic acid microspheres significantly increased lung targeting, and could improve the drug concentration in lung and change the drug concentration in vivo distribution of tissues and organs, thereby reducing the side effects of drugs and improving treatment.