【摘要】：目的制備一種基于生物可降解殼聚糖中空納米球的紫杉醇納米給藥系統(tǒng),旨在改善難溶性藥物的水溶性、調節(jié)藥物釋放,增加其療效。以人肺癌細胞A549為模型,研究殼聚糖中空納米球(CHN)載藥后促進藥物吸收作用,為肺癌治療提供支持。方法本研究以抗癌藥物紫杉醇(PTX)為模型藥物,通過吸附平衡法將PTX吸附到CHN的中空結構中。通過透射電子顯微鏡(TEM)和掃描電子顯微鏡(SEM)研究CHN的形態(tài)結構。通過差示掃描量熱法(DSC),粉末X射線衍射法(PXRD)和傅里葉紅外光譜法(FTIR)對PTX進行固體狀態(tài)的表征。通過體外釋放度實驗研究紫杉醇的釋放行為。通過細胞毒性試驗和細胞攝取實驗探究了殼聚糖中空納米球的紫杉醇納米給藥系統(tǒng)對肺癌細胞A549的影響。進行了載藥樣品(PTX-CHN)在家兔體內(nèi)的藥代動力學實驗。結果本研究成功制備了生物可降解殼聚糖中空納米球。在PTX-CHN藥物釋放中,PTX呈緩釋釋放。通過DSC、PXRD和FTIR對PTX在載體中的固體狀態(tài)進行表征,結果表明PTX在CHN中以非晶型狀態(tài)存在。體外毒性試驗表明CHN具有良好的生物安全性。PTX-CHN能夠顯著抑制肺癌細胞A549的增殖并促進其凋亡。細胞攝取實驗表明PTX-CHN能夠被肺癌細胞A549攝取。降解實驗表明CHN是生物可降解的。體內(nèi)藥代動力學實驗結果表明PTX-CHN能夠提高紫杉醇在家兔體內(nèi)的療效。結論CHN能夠提高水難溶性藥物PTX的水溶性,調節(jié)藥物釋放速率,提高療效,CHN作為一種生物可降解的生物材料,能夠被肺癌細胞A549攝取,促進藥物吸收,在肺癌治療中具有良好的應用前景。
[Abstract]:Objective to prepare a paclitaxel nano-drug delivery system based on biodegradable chitosan hollow nanosphere in order to improve the water solubility of insoluble drugs, regulate drug release and increase its curative effect. Human lung cancer cell line A549 was used as a model to study the effect of chitosan hollow nanosphere (CHN) on promoting drug absorption and providing support for the treatment of lung cancer. Methods the anticancer drug paclitaxel (PTX) was used as the model drug to adsorb PTX into the hollow structure of CHN by adsorption equilibrium method. The morphology and structure of CHN were studied by transmission electron microscope (TEM) and scanning electron microscope (SEM). The solid state of PTX was characterized by differential scanning Calorimeter (DSC),) powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). The release behavior of paclitaxel was studied by in vitro release test. The effect of paclitaxel nano-delivery system on lung cancer cell line A549 was studied by cytotoxicity test and cell uptake test. The pharmacokinetics of drug-loaded samples (PTX-CHN) in rabbits was studied. Results Biodegradable chitosan hollow nanoparticles were successfully prepared. In the drug release of PTX-CHN, PTX was released slowly. The solid state of PTX in the carrier was characterized by DSC,PXRD and FTIR. The results showed that PTX existed in amorphous state in CHN. In vitro toxicity test showed that CHN had good biosafety. PTX-CHN could significantly inhibit the proliferation and promote apoptosis of lung cancer cell line A549. Cell uptake assay showed that PTX-CHN could be ingested by lung cancer cell line A549. The degradation experiment showed that CHN was biodegradable. The results of pharmacokinetics in vivo showed that PTX-CHN could improve the efficacy of paclitaxel in rabbits. Conclusion CHN can improve the water solubility of water insoluble drug PTX, regulate the drug release rate and improve the curative effect. CHN, as a biodegradable biomaterial, can be ingested by lung cancer cell line A549 and promote drug absorption. CHN has a good application prospect in the treatment of lung cancer.
【學位授予單位】：錦州醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R943;R96

【相似文獻】

相關期刊論文 前8條

1 余欣尉;吳謙;呂望;王彥;馬小瓊;陳U，

本文編號：2508248