Preparation And Biological Properties Of Heparin Self-assembled Nanoparticles

Cancer and thrombosis are two major diseases that seriously affect human health.A large number of studies have shown that the presence of cancer has greatly increased the incidence of thrombosis.Heparin is a pure natural substance that is ubiquitous in the animal body,has a strong water-solubility,and has anticoagulation and other functions,but it also causes bleeding and other side effects when applied.Paclitaxel plays a key role in the treatment of cancer as an anti-cancer drug.However,it has certain defects,namely its poor water solubility.In this paper,heparin and deoxycholic acid were constructed as carriers,and this vector was combined with paclitaxel to create a new drug system.The advantage is that when it is in the tumor tissue,it can enhance the penetration and retention(EPR).When it is used as a carrier and combined with paclitaxel,the solubility of the drug in water can be enhanced,the probability that the drug is used and the use rate thereof can be increased.The stability,to some extent reduce its side effects.The deoxycholic acid was grafted onto heparin with ethylenediamine to synthesize heparin-deoxycholic acid amphiphile(hep-DOCA).The micelles were prepared by ultrasonic method.The hydraulic diameter was about 191 nm and the zate potential was-21.3 m V,which indicated that the micelles were stable.The micelle drug loading and drug loading rate were determined by IMC model,which were 39% and 63%,respectively.Micelles can preferentially accumulate at the tumor site due to the EPR effect,releasing the drug.Using dialysis to release the drug,42% of IMC released at 25 h.Apoptotic cells were cultured for 24 h,and apoptosis was 35%.By characterizing the anticoagulant capacity of fresh rabbit blood,it was found that the BCI value was significantly lower than heparin,and the clotting time was also shorter than heparin,indicating that the anticoagulant ability was lower than that of heparin.Deoxycholic acid is grafted onto heparin using cystamine to synthesize sensitive heparin-deoxycholic acid amphiphilic compound(hep-ss-DOCA),which can occur under high concentration of glutathione in cancer cells.Degradation,promote drug release.Hep-ss-DOCA and lecithin were used to prepare micelles by ultrasonic at a ratio of 10:1.Thehydraulic diameter was about 269 nm,and the zate potential was-19.2 m V.The micelle drug loading and drug loading rate were determined by IMC model,which were 42% and 52%,respectively.When dialysis was used as a drug release experiment,70% of IMC was released after 14 h under the action of high concentration of glutathione,indicating that 20 m M glutathione can promote the disulfide bond cleavage and cause changes in the structure of micelles.To release the drug.Apoptotic cells were cultured for 24 h.Apoptosis of 72% was achieved by adding 20 m M glutathione,which was greatly improved compared to 35%without glutathione.By characterizing the anticoagulant capacity of fresh rabbit blood,it was found that the anticoagulant ability after adding 20 m M glutathione was similar to that of heparin,and that the anticoagulant ability without glutathione attenuates much.It shows that glutathione can degrade drugs,increase the anticoagulant activity of drugs around cancer cells,and then increase the therapeutic effect of cancer-induced thrombosis.