大黄酸聚乳酸纳米粒的制备及体外评价

Preparation and in Vitro Evaluation of Rhein- loaded Polylactic Acid Nanoparticles

目的：制备包载大黄酸的聚乳酸纳米粒（RH-PLA-NPs）,考察其理化性质,并评价其体外特性。方法：优选聚乳酸（PLA）为载体,采用自乳化溶剂扩散法来制备RH-PLA-NPs。在前期单因素考察的基础上,正交设计优化筛选RH-PLANPs制备处方并考察工艺稳定性,透射电镜观察其外观形态,激光粒度仪测定粒径及Zeta电位,超速离心法结合HPLC测定包封率及载药量,透析法考察其体外释药特性,MTT法评价其对Caco-2细胞的生物安全性。结果：最佳工艺制备的RH-PLA-NPs外观呈圆整球形,平均粒径为（134.37±3.61）nm,多分散系数为（0.099±0.023）,Zeta电位（-18.42±0.07）m V,包封率（60.38±1.51）%和载药量（1.33±0.08）%;体外释药呈缓释特性,在PBS缓冲液和含20%乙醇PBS缓冲液中24h累积释放百分率分别为87.08%和93.05%,释放行为均符合Weibull方程,分别为lnln（1/1-Q）=1.1317lnt-1.8613（R=0.9693）和lnln（1/1-Q）=1.0512lnt-1.6707（R=0.9873）;在0~200μg/m L范围内,对Caco-2细胞无明显的细胞毒性。结论：成功制备了RH-PLA-NPs,其粒径分布均匀,包封率及载药量较高,体外释药具有缓释特征,并且具有良好的生物安全性,是一种有开发前景的新制剂。

Objective： To investigate the optimal preparation and prepare of RH- PLA- NPs,and to evaluate its in vitro property. Methods： Using PLA as carriers and applying modified spontaneous emulsification solvent diffusion to prepare RH- PLA- NPs,optimizing and screening the prescription by orthogonal design optimization,ultra- high speed centrifugal combination with methanol extraction to determinate the encapsulation efficiency and drug loadings rate,transmission electron microscope to observe appearance,laser particle size tester to determine the average particle size and Zeta potential,and using dialysis method to investigate in vitro release characteristics,MTT method to investigate the cytotoxicity on Caco- 2 cells. Results： The results showed that RH- PLA- NPs were uniform size and round,and formed of（ 134. 37 ± 3. 61） nm in particle size with PDI of（ 0. 099 ± 0. 023）,Zeta potential of（- 18. 42 ± 0. 07）m V,entrapment efficiency of（ 60. 38 ± 1. 51） %,and drug loading of（ 1. 33 ± 0. 08） %. The in vitro release profiles in PBS and PBS with 20% Et OH conform to the Weibull equation： lnln（ 1 /1- Q） = 1. 1317lnt- 1. 8613（ R = 0. 9693） and lnln（ 1 /1- Q） = 1. 0512lnt- 1. 6707（ R = 0. 9873）,and 24 h release rate was 87. 08% and 93. 05%. Within the scope of the 0 200 μg / m L,RH- PLA- NPs had no obvious toxicity on Caco- 2 cells. Conclusion： Preparing RH- PLA- NPs successfully with uniform particle size,higher drug-loading rate and encapsulation efficiency,control release characteristics and good biocompatibility. RH- PLA- NPs have promising prospects for further development.