Experimental Study On Preparation Of Oral Albendazole Nanoparticles And Its Organ Tissue Targets

Experimental study on preparation of oral albendazole nanoparticles and its organ tissue targets Abstracts IObjictivel Echinococcosis is one of the worldwide distribution in humans and zoic parasitic diseases. It is also one of major endemic diseases which can cause the death of the herdsmen in the pastoral areas in northwest China including Xinjiang. According to the relative papers data report, the infection rate of echinococcosis is 31.5% and the morbidity rate is about 5% in high epidemic areas in Xinjiang. Albendazole (methyl[5-(propylthio)-LH-benzimidazole-2-yl] carbamate, ABZ) is a broad-spectrum antihelminthic drug and first choice for the treatment of human cystic echinococcosis which has also been considered as effective drug against human echinococcosis and neurocysticercosis. However, its therapeutical effect was unsatisfactory due to poor solubility , less gastrointestinal absorption and lower targeting effect after oral administration. The purpose of this study is to improve the therapeutic effect of albendazole by making new dosage forms, and studing so called nanoparticle the drug targeting function and increasing ABZ concentration in liver, spleen and lung in humans. Firstly, Albendazole physichemical characteristics were determined for change drug dosage form including the solubility in water and some organic solvents, oil-water partition coefficient, the pK~. The better solubilizers were experimentally selected for increasing its solubility. Secondly, for improvement its bioavailability and absorption in humans, albendazole-polybutycyanocrylate-nanoparticle (ABZ-PBCA-NP) was made 8 by three kinds of emulsification-polymerized methods. The satisfied prescription and the best techniques were selected for increase of drug-load, entrapment efficiency, size control and the distribution for nanoparticle. Thirdly, for the confirmation of the stability and safety, ABZ-PBCA-NP stability and fluxion had been studied as follows: (1) to look into released rule for nanoparticle, the released test of albendazole was processed in different medium in vitro; (2) to investigate the relationship between albendazole release and its absorption in stomach and intestine, the albendazole absorption rate in different pH solutions have been determined by using rat抯 intestinal infusion suit; (3) to examine free albendazole concentration in body, the serum protein binding rate had been compared between albendazole and ABZ-PBCA-NP. Finally, to validate nanopartilce targeting features time-course in blood and tissue distributions were compared with albendazole suspension and ABZ-PBCA- NP after single dose with oral and peritoneal injection in rats. Pharmacokinetics parameters of non-targeting drug (albendazole suspension) and targeting drug (ABZ-PBCA-NP ) in sera and liver were dealt with 3p8? computer programs. To ascertain targeting organs of nanoparticles multi-parameters index was introduce as the estimating standard. LMethodl Albendazole pKa values were determined by oil-water partition method. The concentration of 3H-albendazole was measured by the liquid scintillation counting. The serum protein binding rate of ABZ and ABZ-PBCA-NP was determined by the equlibrium dialysis method(ED). Making procedure for entrapment efficiency , loading drug and size as synthesis index, t...