Liposomal formulation containing poly ethylene glycol-phospholipid conjugated molecules with cytotoxic effects

Abstract

Abstract Over the last decades many drugs have been developed, however a high percentage of them failed due to adverse side effects and lack of selectivity. Therefore, development of new therapeutic agents that selectively act on the target tissue without side effects is necessary. Today, anticancer research is focusing on developing individualized targeted therapies. A class of compounds that have recently been considered as good candidates for development of different pharmaceutical agents are hydrazide- hydrazone derivatives. Therapeutic prominence of such compounds has been well established. In the present study, we report on the synthesis of Poly ethylene glycol-phospholipid conjugated molecules (mPEG2000-HZ-PE) using hydrazone bond capable of forming hetero-functional cross linkers. For this, liposome formulations containing mPEG2000-HZ-PE conjugate or conventional mPEG2000-DSPE molecules were prepared using lipid film hydration and extrusion methods. Then in vitro cytotoxic effect of liposome was evaluated using MTT assay and anti-tumor efficacy was assessed in a mouse 4 T1 Breast tumor model. For therapeutic efficacy study, TAT modification was done. After i.v. injection of liposome formulations, tumor size and survival were monitored on 3 occasions a week for 75 days. Results showed that there was significant difference in the half maximal inhibitory concentration (IC50) of liposome possessing mPEG2000-HZ-PE compared to liposome formulation bearing mPEG2000-DSPE during all incubation periods. In vivo, TAT modified mPEG2000-HZ-PE liposome significantly improved survival of animals. Conclusion The present results confirmed cytotoxic effect of the synthesized mPEG2000-HZ-PE conjugate which therefore can be used in different drug delivery systems with various platforms in combination drug therapy of cancer.