Preparation And Application In The Joint Treatment Of Antineoplastic Drugs Of A Novel Embolic Nanoparticles-embedded Microcapsules

In the present study, calcium alginate nanospheres were prepared by emulsion-gelation at the very start and then calcium alginate gel-beads embedding the nanospheres were produced by means of high-voltage electrostatic droplet generator. Using chitosan as wall material, a novel nanoparticles-embedded microcapsules (NEMs) were prepared at last. The NEMs'morphology, particle size distribution, and the loading properties and the release properties in vitro were studied. Furthermore, the cancer cell inhibition activity of the NEMs were also investigated.Firstly, the calcium alginate nanospheres with a size distribution from 100 to 1000 nm and an average size of 505 nm were prepared by emulsion-gelation. And the NEMs with a size distribution from 150 to 250μm and an average size of 210μm were generated by high-voltage electrostatic droplet generator. The FITC fluorescent labelling test proved the nano-in-micro structure of NEMs was successfully constructed.Secondly, capecitabine was taken as model drug with low molecular weight. The drug loading properties and the release properties in vitro of the NEMs were investigated. Specifically, the effect of chitosan concentration, chitosan molecular weight and the initial concentration of CAP on drug loading properties and release properties in vitro of NEMs were studied. The results showed that the drug loading rate and the encapsulation efficiency was higher with the increase of chitosan concentration, meanwhile, the release properties in vitro of NEMs performed better sustained release behavior. The NEMs with 100 kDa chitosan showed better drug loading properties and the in vitro release properties. And with the increase of the initial concentration of CAP, the drug loading rate and the encapsulation efficiency were all increasing. In the initial 0.5 h, the cumulative release rate was not more than 20%, and over 90% in 240 h. It showed that there was no initial burst release and the release was completely.Thirdly, usingγ-globulin as a protein model drug, the drug loading properties and the release performance in vitro of the NEMs were investigated. Specifically, the effect of chitosan concentration, chitosan molecular weight and the initial concentration ofγ-globulin on drug loading properties and release performances in vitro of NEMs were studied. The results showed that the drug loading rate was higher with the increase of chitosan concentration, and also showed better sustained release behavior in vitro. The NEMs with 100 kDa chitosan showed better drug loading properties and the in vitro sustained release performances. With the lncrease of the initial concentration ofγ-globulin, there was little change in the drug loading rate and the trends of sustained release was almost consistent. In the initial 0.5 h, the cumulative release rate was not more than 10%, which showed the NEMs inhibit the burst release behavior significantly.Fourthly, the effect of the drug loading in different spatial of NEMs on the loading properties and release performances in vitro were studied. The results in this study demonstrated that the outer was higher than the inner in drug loading rate, for the two model drugs: capecitabine andγ-globulin. For release performances, the inner was slower than the outer in the former time and the inner showed a phenomenon of delayed release, especially for theγ-globulin.Fifthly, co-loading two drugs in the NEMs, the release properties of drugs were investigated. The results showed that co-loading capecitabine andγ-globulin (Bevacizumab/ Papain), the NEMs'multi-spatial structure could delay the capecitabine's release, and the proteins'cumulative release rate was higher in the release process. In the middle and later release processes, the NEMs of co-loading drugs exhibited an orderly release. But co-loading capecitabine and methotrexatum, the release trends was almost consistent.Finally, the cancer cell inhibition activity of drug loading NEMs was studied. The results demonstrated that capecitabine had significant inhibition to the cancer cells, the inhibition rate becoming from 60% to 80% approximately in 168 h. The blank NEMs and the single loading capecitabine NEMs also showed inhibition activity to the cancer cells, and with the increase of dose, the inhibition rate increased slowly. Co-loading capecitabine and methotrexatum, the NEMs had the inhibition capacity to the cancer cells, too. But the inhibition rate decreased with the time going, probably because the two drugs antagonism each other.