Study On The Preparation Of PSO/DOX-NLC And The Reversal Effect On MDR In Leukemia Cells

Leukemia is a common malignant tumor. Doxorubicin as its clinical first-line antitumor drug, can effectively kill the tumor cell. However, it is easy to produce drug resistance, which is the main cause of chemotherapy failure. By adding a recersal agent or changing the drug formulation, through preparation of slow-controlled release and targeted agents, can change the transport pathway of drug and improve the concentration of tumor cells. It is one of the effective methods to solve MDR. In these new dosage forms, liposomes and nanoparticles is a research hotspot. The traditional liposomes and SLN can reverse MDR, but the drug loading and encapsulation rate are low, unstable and the drug easy to leak during storage. In recent years, the preparation of NLC can effectively resolve the problems of SLN, and is is suitable for variety of drug delivery routes.This paper takeing PSO and DOX as model drugs, with solid lipd precirol ATO 5, GM, and lipid LABRATAC LIPOPHIE WL1349 as carrier material, using soybean lecithin, F68 and tween-80 and emulsification evaporation and solidification method to prepare PSO/DOX-NLC.On the basis of single factor experiments, with the encapsulation efficiency of PSO and DOX as evaluation index, using central composite design and response surface method to optimize the prescription. Meanwhile this paper established the HPLC detection method of encapsulation efficiency of PSO and DOX. The optimal prescription of PSO/DOX-NLC as follow: the drug lipid ration was 1:10; the rate of phospholopid and lipospme was 1.97; and the concentration of tween-80 was 2.6%. The EE of PSO and DOX is more than 70 % and 80% respectively.In this paper, the nano morphology, particle size and zata potential were detemined by TEM and nano laser granulometer. Observing the stability at low temperature and screening the freeze-dried protective agent, the freeze-dried powder was analysised by DSC and FTIR. Using in vitro dissolution dialysis method to study the sustained release effect. PSO/DOX-NLC was round and oval solid ball, the particle size, polydispersity and zeta potential was(128.7±1.8) nm,(0.22±0.01),-(20.17±0.31) m V. The best storage temperature is 4 ℃ and the optimal freeze-drying protective agent was 5 % mannitol and trehalose mixtures. The DSC and FTIR scanning display PSO and DOX were encapsulated in the carrier material, the peaks of drugs disappeared. In vitro dialysis showed PSO/DOX-NLC burst in the former 5h and sustainedrelease effect is better than PSO/DOX solution.This paper respectively prepared PSO/DOX-NLC and DOX-NLC to study the reversal effect of multidrug resistance in drug-resistant leukemia cell. Leukemia sensitive strain K562/S and DOX resistant cell strain K562/ADR as the tested cells, DOX-NLC as the control object,using MTT determing the sensitivity of PSO/DOX-NLC on K562/ADR. The resules showed that the reversal fold of PSO/DOX-NLC is 2.55 times of DOX-NLC, and with PSO/DOX free drugs as comtrol, the reversal fold is 6.46.In summary, this study successfully prepared optimal physicochemical property of PSO/DOX-NLC, and the reversal of multidrug resistance on leukemia cell is significant.