A Fe₃O₄/Octreotide Modified Dual-targeting Nano Liposomes And Its Pharmacodynamics Study

Targeted formulations,also known as targeting drug delivery systems,could improve the concentration of drugs in the target tissue and enhance the treatment effect of drugs.The purpose of this project is to prepare a dual-targeted nano-drug delivery system in order to improve drug treatment effects and reduce side effects.Firstly,specific targeting drug delivery systems was prepared.Oleanolic acid?OA?was encapsulated into liposomes by ethanol injection method,and the ligand octreotide?Oct?,which has a specific interaction with tumor-specific somatostatin receptors?SSTR?,was used for modification OA liposomes.The sizes of OA liposomes and Oct modified OA liposomes were between 100²00 nm and Zeta potentials were-20.73 ± 0.27 mV and-1.42 ± 0.08 mV,respectively.TEM showed that the liposomes were smooth and free from agglomerations.The FTIR and UV-vis test results showed that OA liposomes were modified by Oct successfully.Stability study proved that low temperature was helpful for liposomal preparations storage and stability.The studies of in vitro anti-tumor effect,cell uptake and competitive inhibition found that Oct-modified OA liposomes could be delivered to the cells through receptor-ligand interactions,and improved anti-tumor effect.Based on the specific targeting OA liposomes,Fe₃O₄ nanoparticles were used to modify the single-targeted liposomes to obtain double-targeted liposomes.Fe₃O₄ nanoparticles achieved rapid aggregation in tumor and increased drug content.The Fe₃O₄ nanoparticles were prepared by coprecipitation method,and the size were 10²0 nm.The structure of Fe₃O₄ nanoparticles was spinel.The Fe₃O₄/Oct modified double-targeted nano-liposomes were optimized and prepared by co-incubation method.In addition,Oxford Link-ISIS X-ray energy spectrum study showed that the Fe₃O₄/Oct-modified liposomes contained five elements: C,O,P,Cu,Fe,which proved that Fe₃O₄ nanoparticles were modified to the surface of liposomes.In vivo pharmacodynamic studies have shown that different OA liposomes can improve the accumulation of OA in the tumor site through targeting,and non-toxic and side effects for the tissues.For all liposomal preparations,Fe₃O₄/Oct-modified liposomes showed best tumor inhibition,which proved that the synergistic effect of Oct and Fe₃O₄ nanoparticles could not only improve the therapeutic effect of OA on tumor,but also reduce the damage to normal tissue.This study has provided a new targeted nanometer delivery system for tumor therapy,and laid a good theoretical foundation for the development of drug delivery system.