Injection An Acridine Solid Lipid Nanoparticles

Solid lipid nanoparticles (SLN) is a promising drug delivery system with solid lipid as drug carriers, diameters ranging between 50 and 1000 nanometers, which has the advantages of high physical stability, slow speed of drug leakage and low toxicity etc. The objective of this thesis was to study amsacrine loaded solid lipid nanoparticles (SLN) for intravenous administration.Amsacrine is a ramification of acridine, which is insoluble. It can be used as an anticancer drug, an antivirus drug and an immunosuppressant. It is mainly used to treat an acute lymphocytic leucocythemia. Amsacrine is poorly assimilated by gastrointestinal tract and its oral administration has resulted in poor bioavailability, so intravenous administration is usually used. However, intravenous administration of AMSA has yielded a relatively short half-life and variable responses. Its curative effective is dissatisfactory. Therefore, it is so urgent to develop a new drug delivery system that the advantage of AMSA can be utilized in tumor therapy. The main aims of this research were to develop AMSA nanostructured lipid carrier (AMSA-SLN) with a long circulation in vivo. Meanwhile, we investigated its in vitro releasing characteristics, pharmacokinetics and tissue distribution.According to the results of the study before formulation, an improved emulsification solvent evaporation method was developed to prepare AMSA-SLN suspension, with Compritol 888 ATO as a lipid carrier. The optimal formulation was obtained by the orthogonal experiment. The method to determine its encapsulation efficiency and drug-loaded capacity was set up. Moreover, a freeze-drying method was investigated in order to improve the stability of the AMSA-SLN suspension, using 5% mannitol as a protector.The quality of the AMSA-SLN suspension was evaluated before and after freeze-drying. The AMSA-SLN suspension prepared by the optimal formulation was spheroidal shape through observing by transmission electron microscopy. Its encapsulation efficiency was 72.4 % , drug-loaded capacity was 7.24‰, the mean particle diameter was 119±15nm, the zeta potential was -32.5mv, the value of pH was close to 6.0, and it can be kept stable at 4℃ for one month only. However, the freeze-dried SLN showed an encapsulation efficiency of 73.3%, a drug-loaded capacity of 7.33‰, a zeta potential of -24.3mv, a mean particle diameter of 136±19nm, an unchanged pH, and the freeze-dried SLN can be stored at room temperature for 3 months with a...