Preparation Of Drug-loaded PLA Nanoparticles And Study On The Inhibitory Effect On Gliomas

BCNU-loaded poly(D,L-lactic acid) nanoparticles ( BCNU-PLA NPs) wereprepared with spontaneous emulsification /solvent extraction method. SEM and TEMshowed that NPs with small particle size and narrow size distribution, which hadspherical geometry had been acquired. In order to find the optimum prepare condition,some factors that influence the formation of NPs such as preparation method, oilphase, concentration of PLA, emulsification concentration were studied.Bratton-Marshall colorimetric method was used to determine the drug content andthe influence of initial BCNU content, molecular weight of PLA and stirring time ondrug encapsulation efficiency were evaluated. The highest drug loaded ratio and drugencapsulation efficiency of NPs were 5.63% and 33.45%, respectively. Take intoaccount of the geometry, yield, size, and drug encapsulation efficiency of NPs, wedetermine the ratio of BCNU to PLA 1:5, MW of PLA 10 000, 30 000, 50 000,stirring time 5 hours as the optimum prepare condition. The study of in vitro drug release behavior demonstrated that BCNU-loaded PLANPs had shown certain sustained release characteristics. The NPs with low molecularweight of PLA showed higher burst effect and significantly faster release of drugfrom PLA samples. The results of cytotoxicity test demonstrated that drug-loadedNPs had higher antitumor activity, compared with free BCNU, and sustained drugrelease character was achieved as well. In addition, it appeared that the empty NPsbarely exerted effect on the growth of cells. This demonstrated that the matrix hadlow cytotoxicity and good biocompatibility.Inhibition of tumor growth in vivo of the nanoparticles was investigated bytumor-bearing animal model. The results showed that BCNU-loaded PLA NPs hadstronger cytotoxicity and prolonged the average survival time of rats. Especially whentreated at the early time with higher dosage of NPs, the average survival time of ratswere prolonged 88.37%, furthermore 1 rat kept normal behavior continuously up to 60days of observation period.PLA nanoparticles coated with transferrin were prepared with the same methodmentioned above. The activity of transferrin was remained and the NPs showedglioma cell-targeting ability. The biodistribution of Tf-coated nanoparticles wasfurther investigated by 99Tc-labeled SPECT. The results showed thatsurface-containing transferrin PLA nanoparticles were concentrated mainly at liverand spleen after intravenous injection. When administered with carotid injection, thebrain uptake of surface-containing transferrin PLA nanoparticles was remarkableincreased. After injected the nanoparticles stereotacticaly, the radioactivity could bedetected only in rat brain and no radioactive foci outside the brain could be found.