Study On Docetaxel Loaded Poly(2-oxazoline)s Micelles And Its Anti-Breast Cancer Efficacy

At present,breast cancer is the leading cause of cancer death among women.In recent years,with the improvement of living conditions,the incidence of breast cancer in China has increased significantly.Taxanes is used as the most common drug for the therapy of breast cancer clinically.However,its present formulations suffer from two major drawbacks,namely their toxicity and resulting side effects and low drug loading capacity.Based on the present situation,it's time to find a suitable carrier,which can enhance the aqueous solubility of antitumor drugs and reduce the side effects of the clinical formulations.In this paper,we formulated docetaxel with amphiphilic poly(2-oxazoline)s(PO_x)to develop a novel drug delivery system with high drug loading capacity and low toxicity.Moreover,the activity of anti-breast cancer was studied in vitro and vivo.The first part of this study reported the preparation and characterization of the docetaxel(DTX)loaded PO_x micelles.Drug loaded PO_x based micelles were prepared using the thin film hydration method.The particle size,encapsulation efficiency and drug loading capacity of the obtained spherical micelles were about 50 nm,(88.81±2.93)% and(40.49±2.03)%,respectively.The cumulative release rate for obtained micelles was up to 80% at pH 5.5 in 24 h.The second part of this study reported the treatment of breast cancer by DTX loaded micelles in vitro.The cell uptake ability of C6 loaded micelles was detected via laser scanning confocal microscoly.CCK-8 method and Annexin V-FITC/PI double staining were used to investigate the cytotoxicity and apoptosis,respectively.The results showed that the MCF-7 cells had a higher uptake rate of coumarin 6 loaded micelles than that of free coumarin 6,which indicated the increased drug accumulation in cells.Compared with commercially available formulations,Docetaxel Injection,polymer micelle drug delivery system could significantly increase the cytotoxicity effect of docetaxel on MCF-7 cells and induce the apoptosis effectively.The third part of this study reported the effect of anti-breast cancer by DTX loaded micelles in vivo.Fluorescence DiR marked poly(2-oxazoline)s micelles can escape from reticuloendothelial system and achieve accumulation at tumor site on MCF-7 breast cancer xenografts mofel in nude mice.MTD for DTX loaded PO_x micelles were determined in a dose escalation method and the value was two times of Docetaxel Injection.When administration at MTD dose of micelles,the drug loaded PO_x micelles showed perfect anti-tumor effect observed by HE and TUNEL staining and tumor growth inhibition experiment.Safety evaluation showed that there was no systemic toxicity of poly(2-oxazoline)s micelles.In conclusion,the prepared PO_x micelle delivery system with high drug loading capacity and low toxicity in this paper has excellent anti-tumor activity both in vitro and vivo,showing a favorable application prospect and development potential for treatment of breast cancer.