论文部分内容阅读
目的:以紫杉醇(PTX)为模型药物,构建K237修饰的热敏脂质体(K237-PTX-TSL),系统研究K237-PTX-TSL的制备工艺、理化性质,处方优化和体外释放特性。方法:采用NH2末端PEG化技术合成靶向磷脂材料DSPE-PEG-K237,采用薄膜分散法制备K237修饰的紫杉醇热敏脂质体(K237-PTX-TSL),HPLC法测量药物的包封率和载药量;采用马尔文激光粒度仪测定K237-PTX-TSL的粒径及粒径分布和Zeta电位;利用差示扫描量热法(DSC)测量相变温度(Tm);采用透析袋法测量相变温度下的释药规律并拟合释放曲线。结果:优化的处方为:DPPC∶DSPG∶MSPC∶DSPE-PEG-NHS=9∶1∶1∶1,药脂比为1/20,磷脂浓度为5.0%,DSPE-PEG-K237占处方磷脂总量为1%。制备得到的K237-PTX-TSL包封率为(94.23±0.76)%;粒测得K237-PTX-TSL粒径为(88.3±4.7)nm,电荷为-4.5 mv,PDI值为0.13±0.01;K237-PTX-TSL的相变温度为40.805℃,K237-PTX-TSL在42℃时的体外释放最优拟合为一级动力学模型,方程为In(100-Q)=-0.063 8t+4.713 0(r=0.994 4)。42℃时20 min内紫杉醇累计释放度为72.45%,60 min的累计释放度为98.84%。结论:K237修饰的热敏脂质体载药量和包封率较高、粒径较小,热敏释药性质良好,1 h内药物基本释放完全。
OBJECTIVE: To study the preparation process, physicochemical properties, formulation optimization and in vitro release characteristics of K237-PTX-TSL using K237 modified thermosensitive liposomes as a model drug with paclitaxel (PTX) as a model drug. METHODS: Targeted phospholipid material DSPE-PEG-K237 was synthesized by NH2 terminal PEGylation technique. K237 modified paclitaxel thermosensitive liposome (K237-PTX-TSL) was prepared by membrane dispersion method. The entrapment efficiency of the drug was measured by HPLC. The particle size, particle size distribution and Zeta potential of K237-PTX-TSL were measured by Malvern laser particle sizer. The phase transition temperature (Tm) was measured by differential scanning calorimetry (DSC) Phase transition temperature of drug release law and fitting release curve. Results: The optimized prescription was: DPPC: DSPG: MSPC: DSPE-PEG-NHS = 9:1:1:1, the lipid-lipid ratio was 1/20, the phospholipid concentration was 5.0%, DSPE-PEG- The amount is 1%. The encapsulation efficiency of K237-PTX-TSL was (94.23 ± 0.76)%. The particle size of K237-PTX-TSL was (88.3 ± 4.7) nm and the charge was -4.5 mV. The PDI value was 0.13 ± 0.01. The phase transition temperature of K237-PTX-TSL was 40.805 ℃, and the best in vitro release of K237-PTX-TSL at 42 ℃ was the first-order kinetic model. The equation was In (100-Q) = -0.063 8t + 4.713 0 (r = 0.994 4). The cumulative release of paclitaxel was 72.45% within 20 min at 42 ° C and 98.84% at 60 min. Conclusion: The thermosensitive liposomes modified by K237 have higher drug loading and entrapment efficiency, smaller particle size and good thermal release properties, and the drug released completely within 1 h.