In Vitro And In Vivo Evaluation Of Redox-responsive Sorafenib Carrier Nanomicelles Synthesized From Poly (Acrylic Acid)-cystamine Hydrochloride-D-?-tocopherol Succinate

In recent years,chemotherapy is the main treatment of cancer.However,the anticancer chemotherapy drugs have been restricting the application in the clinical due to the low solubility and poor selectivity in the body.Therefore,it is very critical to design a new nano drug delivery system to solve the problem of the solubility and selectivity.Nano micelle is a novel drug delivery system,which has attracted great interest in recent years because of its ability to self-assemble into micelles with a core-shell structure.The hydrophobic core can be used as a reservoir of poorly soluble anticancer drugs.Furthermore,the nanomicelles can also be modified with the target molecular to achieve the targeting of the micelles.For example,the introduce of the disulfide bonds to the structure achieve the redox responsive of the micelles,so as to achieve the control drug release of from the micelles.In the experiment,the redox responsive polymer micelle was designed and constructed which has many functions such as solubilization of anticancer drugs,release of drugs.This system was established by linking D-?-tocopherol succinate(VES)with poly(acrylic acid)(PAA)by a disulfide bond linker(ss).This polymer(PAAssVES)was successfully synthesized.The chemical structure was also demonstrated by FT-IR analyses and 1H-NMR analyses.This carrier can self-assemble into nanomicelles,and the CMC value is 6.3 ?g/m L.The drug loaded micelles were prepared by solvent evaporation method using the two PAA-CYS-VES as a drug carrier and SFN as the model drug.The drug loaded micelles were characterized and the particle size was about 200 nm by Malvern laser particle size analyzer.The Zeta potential was-24 mV and the encapsulation efficiency could reach about 87%.From the transmission electron microscopy,SFN-loaded nanomicelles(SFN-NM)were almost spherical.SFN is as an amorphous or molecular state in the micelles from the DSC curve.Moreover,in the vitro release studies,the SFN-NM has the redox responsive properties that the release amount was dependence with the GSH concentration.BGC-823 cells were used as the cell model,and the cell viability was studied by MTT method.The results showed that the blank micelles had almost no toxicity to cancer cells,which demonstrate the safety of the carrier material was good,the SFN-NM shows a stronger toxic(81.1%)with the SFN(69.2%).On the other hand,in vivo studies,SFN-NM has increased 2.8 fold compared with the SFN-sol in the pharmacokinetics study.This demonstrated that the polymeric micelles as a drug carrier can obviously improve the bioavailability of free drugs.The results indicated that PAA-CYS-VES could be used as a delivery system for anticancer drugs.