【摘要】：目的為提高難溶性藥物多西他賽的水溶性,制備多西他賽-聚乙烯己內(nèi)酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(soluplus)-聚乙二醇-15-羥基硬脂酸酯(solutol HS15)混合膠束(docetaxel mixed micelles,DTX-MMs),并對(duì)其性質(zhì)進(jìn)行評(píng)價(jià)。方法以soluplus和solutol HS15作為兩親性載體材料,采用薄膜分散法制備DTX-MMs;利用馬爾文激光粒度儀測定膠束的粒徑及分布;采用透射電鏡觀察混合膠束的形態(tài);采用高效液相色譜法測定混合膠束的包封率和載藥量;采用芘熒光探針法測定混合膠束的臨界膠束濃度;以自制多西他賽注射液為對(duì)照,比較兩種制劑的體內(nèi)外性質(zhì)差異。結(jié)果由薄膜分散法制備的混合膠束的包封率和載藥量分別為89.91%和4.658%,平均粒徑為(72.54±2.2)nm,多分散系數(shù)為0.16±0.036;透射電鏡下觀察到混合膠束呈球形、分散良好;測得的臨界膠束質(zhì)量濃度值為(6.76×10~(-2))g·L~(-1);與多西他賽注射劑相比,混合膠束具有一定的緩釋能力,無溶血現(xiàn)象,藥時(shí)曲線下面積(AUC_(0-t))提高了2.638倍。結(jié)論采用薄膜分散法制備的混合膠束,粒徑小,包封率高,穩(wěn)定性好,可顯著提高多西他賽在水中的溶解度,具有良好的體內(nèi)外性能。
[Abstract]:Objective to improve the water solubility of docetaxel, an insoluble drug, The mixed micelle (docetaxel mixed micelles,DTX-MMs of docetase-polycaprolactam poly (vinyl acetate)-polyethylene glycol grafted copolymer (soluplus)-polyethylene glycol-15-hydroxystearate (solutol HS15) was prepared and its properties were evaluated. Methods soluplus and solutol HS15 were used as amphiphilic carrier materials, DTX-MMs; was prepared by thin-film dispersion method, the particle size and distribution of micelles were measured by Ma Erwen laser particle size analyzer, and the morphology of mixed micelles was observed by transmission electron microscope (TEM). The entrapment efficiency and drug loading of mixed micelles were determined by HPLC, the critical micelle concentration of mixed micelles was determined by pyrene fluorescence probe method, and the in vitro and in vivo properties of the two preparations were compared with those of docetaxel injection. Results the entrapment efficiency and drug loading of the mixed micelles prepared by the thin film dispersion method were 89.91% and 4.658, respectively. The average particle size was (72.54 鹵2.2) nm, polydispersity coefficient was 0.16 鹵0.036. Under transmission electron microscope, the mixed micelles were spherical and well dispersed. The critical micelle mass concentration was (6.76 脳 10 ~ (-2) g L ~ (-1). Compared with docetaxel injection, the mixed micelle had a certain sustained release ability, no hemolysis, and the area under the curve (AUC_ (0-t) increased 2.638 times. Conclusion the mixed micelles prepared by thin-film dispersion method have small particle size, high entrapment efficiency and good stability, which can significantly improve the solubility of docetaxel in water and have good properties in vivo and in vitro.
【作者單位】： 沈陽藥科大學(xué)藥學(xué)院;
【基金】：遼寧省自然科學(xué)基金資助項(xiàng)目(2015020749) 沈陽藥科大學(xué)創(chuàng)新創(chuàng)業(yè)訓(xùn)練計(jì)劃項(xiàng)目(201610163051)
【分類號(hào)】：R943
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本文編號(hào)：2259090