1008-1542 2021 42 4 389 399 10.7535/hbkd.2021yx04009 article 依托泊苷納米混合膠束的制備及其理化性質 Preparation and evaluation of physicochemical properties of etoposide nano-mixed micelles 為提高依托泊苷制劑的水溶性和穩定性,采用星點設計-效應面法優化依托泊苷納米混合膠束(ETP mPEG-PLA/P123)的處方工藝。在單因素試驗基礎上,以投藥量、mPEG-PLA所占質量比和水化體積為自變量,以依托泊苷包封率、載藥量以及粒徑為因變量,進行3因素5水平的星點設計-效應面法實驗,采用熒光探針法測定臨界膠束濃度(CMC),并對所制備的膠束制劑進行理化性質和釋放行為的評估。結果表明,ETP mPEG-PLA/P123膠束制劑的最優處方工藝如下:mPEG-PLA與P123質量比為38∶62,投藥量為5 mg,水化體積為6 mL;采用最優處方制得的混合膠束的包封率為87.4%,載藥量為4.19%,粒徑為115.6 nm,PDI為0.216,Zeta電位為-16.3 mV;熒光探針法測定的CMC值為1.7×10-3 g/L,mPEG-PLA/P123膠束穩定性良好;體外釋放實驗中,依托泊苷可從膠束中緩慢而持續地釋放,在48 h內釋放量可達80%。采用優化處方制得的ETP mPEG-PLA/P123納米混合膠束,能顯著增加依托泊苷的溶解度,膠束制劑穩定性好,且有一定的緩釋作用,可為進一步拓寬依托泊苷新型制劑的應用范圍提供理論依據。 In order to enhance the aqueous solubility and stability of etoposide preparation,the central composite design-response surface method was used to optimize the prescription technology of etoposide nano-mixed micelles (ETP mPEG-PLA/P123).Based on the results of single factor test,central composite design-response surface method of three factors and five levels was carried out to optimize the prescription technology with drug dosage,the mass ratio of mPEG-PLA and hydration volume as independent variables,and the entrapment efficiency,drug loading and particle size as dependent variables.The critical micelle concentration (CMC) was determined by fluorescence probe method,and the physicochemical properties and release behavior of the prepared micelle preparations were evaluated.The results showed that the optimal prescription of ETP mPEG-PLA/P123 micelle preparation was that mPEG-PLA∶P123=38∶62,the drug dosage was 5 mg,and the hydration volume was 6 mL.After optimization,the entrapment efficiency and drug loading were 874% and 419%,the particle size was 1156 nm,PDI was 0216,and Zeta potential was -163 mV.The CMC value was 17×10-3 g/L,so mPEG-PLA/P123 micelles had high stability.In vitro release experiments,etoposide could be released from micelles slowly and continuously,up to 80% within 48 h.The optimized ETP mPEG-PLA/P123 nano-mixed micelles were able to enormously improve the aqueous solubility of etoposide,and the micelle preparation had good stability and a certain slow-release effect.The results of this study could provide theoretical guidance for further broadening the range of application of new etoposide preparations. 藥劑學;依托泊苷;P123;膠束;UPLC;薄膜水化法;星點設計-效應面法 pharmaceutics; etoposide; P123; micelles; UPLC; thin film hydration method; central composite design-response surface method 張欣欣,許 潔,蔣 巖,趙麗艷,張萬明 ZHANG Xinxin, XU Jie, JIANG Yan, ZHAO Liyan, ZHANG Wanming hbkjdx/article/abstract/b202104009
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