Experiment Study Of Admorubicin Dolybutylcyanoacrylate Nanoparticles To Treat Transplanted Liver Cancer In Rat

Objective by histology examination one week post administration. The tumor growth inhibition with rat received therapy of Adriamycin-polybutylcyanoacrylate nanoparticles and adriamycin was remarkable necrosis more extensive in comparision with rat received therapy of normal Saline and adriamycin. The tumor tissue was replace of fibril tissue and non-structure tissue.Methods ADM-PBCA-NP was prepared by two-step methods.To measure the adriamycin envelopment rate and dosage by ultraviolet spectrophotometry and fluorospectrophotometry respectively. ADM-PBCA-NP with various ranges of diameter of the nanoparticles were produced by using the method of emulsior polymerization based on the carrier materials of a-polybutylcyanoacrylate. To extract the blood plasma samples, liver, kidney, spleen, heart and lung and to measure the density of ADM using high efficiency liquid chromatography;high performance liquid chromatography. To investigate the survivals of all the mice. Detect median lethal dose(LD₅0) of the tow drugs by the bliss method;Administration of ADM-PBCA-NP and exsanguinated 1ml in each time,then separated serum, distilled the Adriamycin with chloroform-carbinol, put it under High Performance Liquid Chromatography(HPLC)to examine the special htomatogram apex height. To account the concentration of the Adriamycin in serum according to the standard curve of the Adriamycin. Then analyse the test date with "spss" software and pharmacokinetic parameter in "3P87" and "MATLAB" software. Rat model of transplanted liver was established. The diameter of tumor was detected and a cannula was inserted into hepatic artery and fixed up it in order to record the survival datas. To measurethe growth rate, necrosis ranges and life extension rate of tumor after one weeks' abdominal incision.Results Highdrugcontent nanoparticles, DNA-ADM-PBCA-NP was prepared successfully. The ADM concentrations in the lever of rat in all the napariticles groups is markedly higher as compared to free ADM groups during 12h, with the excepting of the group with (22 + 6. 2)nm (P<0. 05) . whereas the concentration in the heart muscle was not determined or markedly lower than free ADM group (P<0. 05)high concentration in kidney did not keep long time , ADM concentration in the lung in the group of (194 + 28. 45)nm was higher than that of (48 + 9. 2)nm (P<0. 05). ADM concentration in the group of (101 + 18. 3)nm in the liver of the rats were remarkably higher than that in the other groups (P<0. 05), the second is (143 + 21.4)nm. ADM concentration in the group of (22 + 6.2)nm was not determined at all in the liver , kidney , heart , spleen and lung. The LD50 of ADM-PBCA-NP was 515. 5mg/kg, and the LD50 of ADM was 10. 38mg/kg. Compared to ADM, ADM-PBCA-NP effectively reduced the changes of the blood biochemistry and pathological damage such as cardiotoxicity, hepatotoxicity, nephrotoxicity and gastroenterotoxicity. The spleen remained the same in both. The large dose of ADM can make severe damage to the body. On the contrary ADM-PBCA-NP is not severe. The pharmacokinetic of Adriamycin and ADM-PBCA-NP in home rabbits were aaccording to the three chamber models. Compared to Adriamycin, the half life of ADM-PBCA-NP was prolonged about from 1. 9 to 3. 2 times; and the clearness of new drug from blood was 0.5369 times to Adriamycin, and the Area of Under the Curve(AUC)was 1.3697 times to Adriamycin. Before therapy , no statistic difference was found in each group volume of tumor (P>0.05). After therapy, statistic difference was found in each group volume of tumor (K0. 05). Normal Saline treated group, Survived time was 12.7days;Free adriamycin treated group, Survived time was 18. 7days. Adriamycin-polybutylcyanoacrylate nanoparticles treatedgroup Survived time was 32.5days . The survival rate of animals of every group was analyzed with increaseing longer surviaval. Tumor tissue of the animals was seen patch necrosis toxicity of adriamycin in the important organs of the body. ADM-PBCA-NP had a different distributing compared with Adriamycin; had a longer half life; and had a higher degree of biologic utilixation, Suctioned by the magnet at the right up quadrant, Adriamycin polybutylcyanoacrylate nanoparticles (ADM-PBCA-NP) can be assembling to a higher concentration at targeted organ liver. The survival rate of the animal given with free adriamycin was not improved compared to NS treated group, Using Adriamycin-polybutylcyanoacrylate nanoparticles in absence field can increase survival rate of animals, compared to NS treated animals or animals treated with free adriamycin. Using Adriamycin-polybutylcyanoacrylate nanoparticles in presence field can remarkablely increase survival rate of animals, compared to NS treated animals or animals treated with free adriamycin(fKO. 01).Conclusions ADM-PBCA-NP with some different ranges of diameters of the nanoparticles has the better liver targeting , and the characteristic of low releasing , which decrease the medicine distribution in the heart and other tissues. So it' s a good medicine-diverting system for treating liver cancers. ADM-PBCA-NP significantly diminished the To prepare ADM-PBCA-NP and investigate the determination factors and levels on procedures of adriamycin -polybutylcyanoacrylate nanoparticles(ADM-PBCA-NP) and to optimize preparation produres. To study the safety, pharmacokinetics and efficacy of the nanoparticles for transplanted liver cancer of ADM-PBCA-NP.