青藤碱聚乳酸羟基乙酸共聚物-水溶性维生素E纳米粒的质量评价

Quality Evaluation of Sinomenine-loaded Poly(Lactic-co-glycolic Acid)/D-α-tocopherol Polyethylene Glycol 1000 Succinate Nanoparticles

目的:对青藤碱聚乳酸羟基乙酸共聚物-水溶性维生素E(PLGA-TPGS)纳米粒(SPTN)的质量进行评价。方法:以PLGATPGS为载体,采用超声乳化-溶剂挥发法制备SPTN;另以PLGA为载体制备青藤碱PLGA纳米粒(SPN)作为对照。采用激光粒度仪测定2种纳米粒的粒径和Zeta电位;采用高效液相色谱法测定2种纳米粒中药物含量,计算其载药量、包封率、体外释放度和考察SPTN的体外稳定性,色谱柱为Hypersil C18,流动相为甲醇-10 mmol/L磷酸二氢钠(38∶62,V/V),流速为1.0 ml/min,检测波长为262 nm,进样量为20μl。结果:SPTN和SPN的平均粒径分别为(194.6±2.8)、(382.4±3.2)nm,Zeta电位分别为(-21.3±1.7)、(-13.9±2.3)m V;载药量分别为(9.5±0.7)%、(6.2±0.8)%,包封率分别为(41.3±1.6)%、(32.8±1.8)%;体外药物释放二者均呈两相释放,30 d时累积释放度分别为92.8%、71.3%;与0 d时比较,高温(40℃)、强光[(4 500±500)lx]、高湿[(90±5)%]条件下10 d内SPTN的外观性状、粒径、载药量均无明显变化,6个月的加速试验和12个月的长期试验中SPTN的外观性状、粒径、载药量也均无明显变化。结论:SPTN具有比SPN更小的粒径、更大的载药量和包封率,体外释放更完全,具有明显的缓释作用,体外稳定性好。

OBJECTIVE： To evaluate the quality of Sinomenine （SIN）-loaded poly （lactic-co-glycolic acid）/D-a-tocopherol polyethylene glycol 1000 succinate （PLGA-TPGS） nanoparticles （SPTN）. METHODS： SPTN was prepared by ultrasonic emulsifi- cation-solvent evaporation technique using PLGA-TPGS as cartier. SIN-loaded PLGA nanoparticles （SPN） was prepared as control using PLGA as carrier. Particle size and Zeta potential of 2 kinds of nanoparticles were determined by laser particle analyzer. Drug content was determied by HPLC, drug-loading amount, encapsulation ratio, in vitro release rate were calculated and stability of SPTN was surveyed. The determination was performed on Hypersil C18, column with mobile phase consisted of methanol-10 mmol/L NaH2PO4 （38：62, V/V） at the flow rate of 1.0 ml/min. The detection wavelength was set at 262 nm, and sample size was 20μ1. RESULTS： Mean particle size of SPTN and SPN were （194.6 ± 2.8） nm and （382.4 ± 3.2） nm; Zeta potential （-21.3 ± 1.7） mV and （ - 13.9 ± 2.3） mV; drug-loading amount （9.5 ± 0.7）% and （6.2 ± 0.8）% ; dissolution ratio （41.3 ± 1.6）% and （32.8 ± 1.8）%, respectively. The in vitro drug release profile showed diphasic release pattern, and the cumulative release rates of SPTN and SPN were 92.8% and 71.3% at 30 d. Compared with 0 d, there was no significant change in appearance, particle size and drug-loading amount of SPTN within 10 d under the condition of high temperature （40 ~C ）, high-lights [（4 500 ± 500） Ix] and high humidity [（90 ± 5）%]. There was no significant change in appearance, particle size, drug-loading amount of SPTN in 6 months acceleration test and 12 months long-term test. CONCLUSIONS： Compared with SPN, SPTN has smaller particle size and bigger drug-loading amount and dissolution ratio, releases in vitro more completely, and shows obvious sustained-release effect and good stability in vitro.