Preparation And Characterization Of Chitosan/5-fluorouracil Nanoparticles

Nanoparticle now is considered as a perspective drug-loaded system. It can improve the curative effect of the drugs with poor dissolubility or low absorptivity. The most important two contents of nanoparticle are the preparation technology and low toxicity. Chitosan (CS) is a natural polymer with an excellent biocompatibility and degradation. It also can inhibit the metastasis of tumour cells. All these chacteristics make CS a very interesting material for drug delivery systems. This research focused on 5- fluorouracil, which is a kind of representative antitumor drug and widely used in many kinds of tumor therapy,. In this research, we prepared Chitosan/5- fluorouracil nanoparticles (CS/5-Fu NPs) by micro-emulsion method.When glutaraldehyde (GA) was used as crosslinker, more than ten influential factors including the use amount of oil phase, water phase, and preparation temperature et al., were investigated to optimize the preparation conditions. The NPs were mono-dispersed and size distributing 50 ¹00nm, also with ideal drug loading efficiency (LE) and encapsulation efficiency (EE). Furtherly, CS/5-Fu NPs were prepared by substituting GA with NaCl, Na₂SO₄, Na₃C₆H₅O₇ and Na₅P₃O₁₀, respectively. And NPs with size distributing 50 ¹50nm can be obtained by adjusting the salt concentrations and preparation temperature. These results indicated that the optimized parameters of micro-emulsion could be a generalization, and that the valence of anion can influence the size, LE and EE of the NPs prepared. Na₂SO₄ was considered as the best choice.The detection of in vitro release effect of NPs prepared by using the five crosslinker mentioned above were carried out by testing both the release effect in buffer solution and apoptosis rate of K562 cells cultured with these NPs. These NPs shows slow release effect and NPs prepared by Na2SO4 were the best. The apoptosis experiment of K562 cells indicated that the survival time of these cells reduced remarkably, especially cells cultured with NPs prepared by GA. So it could be unsuitable for GA to be used in sustained- release preparations for K562 cells, for this preparation may be harmful to normal cells in body.Still with the optimized parameters of micro-emulsion, and introducingγ-Fe₂O₃ as magnetism target, the CS/5-Fu NPs with magnetism (CS/5-Fu MNPs) were prepared. These MNPs were also mono-dispersed and with size distributing ⁸0nm, also nice magnetism behaviour. The apoptosis experiment of K562 cells indicated that the survival time of these cells were reduced remarkably.This research will be beneficial to establish a platform of sustained-release preparation and magnetism targeting preparation. Also it is significative to tumor therapy.