| Hepatocellular cancer(PLC)is one of most common cancer,which is also one of the most common cause of cancer death worldwide.The PLC could deteriorate rapialy and it’s difficult to be cured.Sorafenib,the only effective systemic therapeutic medicine that can significantly improve the survival rate of patients with advanced HCC,is a multikinase inhibitor that targets multiple signaling pathways.However,the water insolubility of sorafenib may reduce its orally bioavailability and the toxicity and drug resistance are also unneglected side effects,what make some sorafenib-related therapy regimens are not satisfactory.Indeed,regimens that have incorporated this drug is far from optimal because a marked refractoriness to sorafenib is an initial characteristic of liver tumors,as the lack of effective treatments for patients with advanced HCC who are intolerant to sorafenib or for whom sorafenib has failed represents an unmet medical need.Combinating sorafenib with other drugs is an effective method to reduce its toxicity.Curcumin(diferuloylmethane)is a major constituent of turmeric powder which is extracted from the rhizomes of Curcuma longa L which found in south and southeast tropical Asia.Clinical research showed that Curcumin,as a chemopreventive agent,is effective for a variety of cancers,including breast,prostate,colon and lung.Combinating with other drugs to enhance their antitumor and antimetastatic effects gets lots of attention.Polymeric micelles can improve the solubility and bioavailability of insoluble drugs.The polymer can protect the insoluble drugs in the core of micelles with the hydrophilic shell.The structure of micelles can send the drugs in core to the focus of cancer,this improves the bioavailability of drugs and enhance curative effect.Therefore,we designed a polymeric nano micelles formulation to combinate curcumin and sorafenib for the therapy of HCC,inder to synergistic augmentation of therapeutic efficacy,and reduce the toxic side effects of sorafenib.The self-assembled polymeric micelles were prepared with PCL30-PEG135-PCL30 by thin film-hydration method.Before the preparation of self-assembled polymeric nanoparticles,the pharmacy computer simulation was used to find the suitable triblock polymer firstly.It was found that the self-assembled polymeric micelles we prepared had the characteristics as follows,(a)the appearance of micelle system was clear and transparent;(b)the particle size of micelle was 194.9±4.6nm;(c)SEM showed that the size was about 100-160 nm,and the shape was core-shell concentric sphere;(d)the entrapment rates of curcumin and sorafenib were 75.62±1.08% and 91.20±0.41%,respectively;(e)the drug-loading rate of curcumin and sorafenib were 22.6±0.64% and 13.73±0.35%,respectively;(f)the stability of self-assembled polymeric nanoparticle could remain stable for 5 weeks in 4℃;(g)the inhibition rate of micelles against HepG-2 cell and SMMC-7721 cells increased time-dependently when compared with raw drug;(h)Study on Pharmacokinetics in Rats showed that the t1/2 of curcumin and sorafenib in micelles increased 13.75 and 1.116-fold,the AUC0-∞ increased 15.44 and 2.74-fold,the MRT0-∞ increased 15.3 and 1.26-fold,and the clearance rate decreased to 0.087 and 0.39-fold respectively when compared the rats injected with micelles with the rats injected with raw drug solution.All of the results showed that the micelles had the long circulating property. |
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