Preparation Of 5-Fu Loaded PLA Immunonanoparticles And Their Application On The Field Of Ophthalmic And Tumour Therapy

5-fluorouracil (5-Fu) loaded Poly(actic acid) Nanoparticles (PLA NPs) wereprepared by improved double emulsion (water-in-oil-in-water, W/O/W) method usingbovine serum albumin(BSA) as emulsification. The characters of the NPs were measuredby SEM, TEM and MSD, the results showed that the NPs were spherical in shape, andthe particles diameters ranged from 100~200nm. The drug content and loading efficiency of5-Fu loaded PLA NPs was investigated via UV method. The drug content and loadingefficiency increased with the increase of the concentrations of 5-Fu and BSA.The release behavior of 5-Fu from PLA NPs was investigated via UV method. Itwas found that the release of 5-Fu from NPs had three periods, i.e., burst release,sustained release and last release period, the release speed increased with the decrease ofthe PLA molecular weight and the diameter of the NPs. Moreover, the release rate of thedrug also depended on the drug loading ratio and the pH of the release medium.Immunonanoparticles (INPs) were prepared through conjugating monoclonalantibody HILE6 onto the surface of NPs using EDC as catalyst, 84% of theimmunological activity of antibody could keep after conjugation reaction. The targetability of the INPs to the lens epithelial cells was studied in vitro. The results suggestedthat the INPs adhered the lens epithelial cells(LECs) in 30 minutes and enter thecytoplasm or/and nucleus in 4 hours, and the nucleus were the major compartment oftheir distribution. The LECs were sensitive to INPs and 68.42% growth inhibition wasachieved with a concentration of 240μg/ml after 24 hours of exposure. No cytotoxicity ofdrug-free INPs on LECs and cornea stroma cells (CSCs) was found following 72 hoursof exposure.Using same conjugation method mentioned above, VEGF monoclonal antibodyimmunonanoparticles (VEGF-INPs) were prepared. The tumor inhibition of VEGF-INPswas investigated using SCID rats as animal model. SPECT measurement showed that theINPs could reach the target cells, and the high inhibition activity of VEGF-INPs to tumorcells was achieved after 11 days.