| Nanoparticles delivery system(NPDs) is the new field of pharmaceutical research in recent years. It includes the size range of10～1000nm. The Nano-agents show excellent performance and many new features with a unique small size effect and a certain surface effects and other features. As a delivery and controlled release carriers, it has many advantages, such as extending the time of medical action, improving the stability of drugs, avoiding the drug degradations before reaching the lesion site. As the nano-size effects, nanoparticles in vivo have specificity of distribution. It can be absorbed by the reticuloendothelial system, mainly distributed in the liver by intravenous injection of certain size nanoparticles. Preparating nano-drugs by nano-technology targeting the liver is gradually taken seriously.In this study, the nanoparticles containing NAC and chitosan were prepared by solvent diffusion method. Preparation investigated from physical and chemical properties of nanoparticles, including particle size, encapsulation efficiency, drug loading influence and Zeta potential. After process optimization, NAC chitosan nanoparticles were prepared, which appeared round, no adhesion, uniform spherical particles in the transmission electron microscope. The average particle size was (163.0±12.8)nm while drug encapsulation efficiency was (81.2±1.2)%. The preparation process was simple with high encapsulation efficiency, narrow size distribution. The obtained system was relatively stable. It met the desired objectives.Release results in vitro showed that acetylcysteine chitosan nanoparticles in pH7.4PBS cumulated drug release74.5%in24h. NAC released faster from the nanoparticles in the previous2h, but the release slowed down after4h. NAC release had stabilized after6h. NAC nanoparticles had obviously sustained release effect compared with NAC injection. The nanoparticles stability in the release medium was improved due to the package effect.Two groups of NAC nanoparticles and free drug groups were injected into mouse tail vein. NAC was detected in plasma and different organs at10min,20min,30min,1h,2h,4h. The results of distribution in vivo showed that the nanoparticles significantly changed the biodistribution of the drug in mice. Compared with the NAC injection, the nanoparticles significantly increased the concentration of NAC in liver tissue,while obviously reducing the drug concentration in the blood, heart and kidneys. The certain size nanoparticles wrapped the drug had the passive liver targeting effect,which provided a theorial basis for the NAC nanoparticles to treat liver diseases.Chronic liver injury model was established by subcutaneous injection of carbon tetrachloride in rats. Different doses of NAC nanoparticles were administrated by tail vein injection. The results showed that the model of serum alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde were strikingly higher than the normal group while glutathione and superoxide dismutase significantly reduced. The difference was statistically significant (p<0.05). Serological indicators and MDA of NAC nanoparticles treatment groups reduced, GSH and SOD increased in contrast with model group. Liver biopsy showed that the nanoparticle treatment groups ameliorated hepatic steatosis, inflammatory and necrosis, which confirmed the NAC nanoparticles markedly inhibited the oxidative stress and lipid peroxidation. The nanoparticle groups had better treatments than the NAC control group. Compared with NAC group, nanoparticles had a significant dose advantage, and the efficacy of the dose was significantly better than the control group. Nanoparticles with passive targeting made NAC enriched in the liver. It significantly reduced the use of dose, improved treatment outcomes. |
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