Long Cycle Aclarubicin Of Pelge Nanoparticles,

The leukaemia is the extensive infiltration in bone marrow and other organs of unusual leucocyte, cause the malignant disease of the going on reduction of normal blood cell. Leukaemia is one of the ten major malignant tumour which endanger the life of human , and it is one of the main cause of disease of the death of the young one under the age of 20. The chemotherapy medicine given intravenously by way of the tradition dosages would present some adverse effects, such as phlebitis, doing harm to liver etc. This has limited the clinical application of the chemotherapy medicine.In the present study, aclarubicin A(ACRB) was taken as the model drug and loaded by the polymer of PELGE having the long characteristic of detention time in the blood. And through preparing the ACRB PELGE nanoparticles(ACRB-PELGE-NP) having the long-ciculating time in the blood, make the detention time in the blood of ACRB lengthen , the concentration of ACRB in the blood rises, and could achieve the goal of strengthening the curative effects and reducing the adverse effects.All aspect of ACRB- PLGA- NP/ ACRB- PELGE-NP were investigated in detail and systematically in the present study , including the process of the preparation, drug loading ,entrapment efficiency, diameter , the lyophilization of the nanoparticles , the releasing kinetics in vitro , the preliminary stability and the biodistribution and the pharmacokinetics of ACRB- PLGA- NP/ ACRB- PELGE-NP in the body etc.According to the characteristics that the ACRB can't be solved in water but could be solved in acidic solution, we have prepared ACRB- PLGA- NP/ ACRB- PELGE-NP with double emulsification and nanoprecipitation separately. Comparing the process and the prescription of the two kinds of methods, we observed the diameter of nanoparticles prepared by the nanoprecipitation was relatively small (about 130nm ), entrapment efficiency is relatively high (about 85%), the process is simple and the reappearing is good, so in the present present the ACRB- PLGA- NP/ ACRB- PELGE-NP was prepared by the nanoprecipitation. The Central Composite Design was applied to the optimization of the formulation based on the size , entrapment efficiency etc. The size of the resulting ACRB-PLGA- NP was 127.3 nm, and the entrapment efficiency and drug loading were 86.99% and 8.70% respectively. The optimal formulation was simple, the reappearing was good and the entrapment efficiency was high which implied ACRB could be in full use in this formulation.Consulting the optimal formulation of the ACRB- PLGA-NP,we have prepared the ACRES- PELGE- NP, and have investigated the molecular weight of PEG and the percent of PEG impact on the diameter, drug loading, entrapment efficiency and the Zeta potential of the the ACRB- PELGE- NP. As the molecular weight of PEG and the percent of PEG increase, the variation tendency of the diameter , the absolute Zeta potential , entrapment efficiency and the drug loading of the ACRB- PELGE- NP is not obvious, furthermore, we prepared the ACRB- PLGA- NP/ ACRB-PELGE-NP lyophilization injection and carrying on the overall quality evaluation to the lyophilization injection, the result showed that the lyophilization didn't influence the quality index of the ACRB- PLGA- NP/ ACRB- PELGE-NP , such as size, drug loading, PH etc. The result of hdroscopicity showed that the relative humidity of the ACRB- PLGA- NP/ ACRB- PELGE-NP lyophilization injection was 73.92%-75.40%, there was no difference among the hdroscopicity of the four kinds of nanoparticles.The result of the releasing kinetics in vitro of the ACRB-PLGA- NP/ ACRB- PELGE-NP lyophilization injection showed that the releasing profile had the burst releasing partes and the sustained releasing partes. The releasing profile of ACRB- PLGA-NP/ ACRB- PELGE-NP lyophilization injection could be well characterized by the two phase dynamic equation (weibull equation and monoexponential equation). There was no obviousdifference among the releasing rates of the four kinds of nanoparticles.In the present experiment , ACRB- PLGA- NP lyophilization injection taken as reference , the biodistribution and the pharmacokinetics of the ACRB- PELGE- NP was studied.The concentration and the percent of ACRB of ACRB- PELGE- NP in the liver was lower than that of ACRB-PLGA-NP in the liver at the same time, while, the concentration and the percent of ACRB of ACRB- PELGE - NP in the blood was higher than that of ACRB-PLGA-NP in the blood at the same time. This shows that the ACRB- ACRB-PELGE - NP has the long circulating time in the blood. Compared with ACRB-PLGA-NP, in the kidney , heart , spleen, the concentration and the percent of ACRB of the ACRB- PELGE- NP didn't change obviously. The half-life (61. 80h) of ACRB- PELGE-NP was longer than the half-life (23. 94h) of ACRB-PLGA-NP. DTI and DSI were applied to the evaluation of the liver-targeting, blood-target > lung-targeting , spleen-targeting , kidney-targeting and heart-targeting of the ACRB- PELGE- NP. Compared with ACRB-PLGA-NP, the ACRB- PELGE- NP could greatly increase the detention time of ACRB in the blood and reduce the concentration of ACRB in the liver. This indicates the subject has achieved the anticipated purpose-preparing the long-circulating ACRB- PELGE- NP.