Optimization and characterization of deoxypodophyllotoxin loaded mPEG-PDLLA micelles by central composite design with response surface methodology

作     者：YU Ying-Lan LI Ya-Nan ZHANG Yong SUN Ru-Ning TU Jia-Sheng SHEN Yan 

作者机构：Department of PharmaceuticsSchool of PharmacyChina Pharmaceutical UniversityNanjing 210009China Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of Professional InstituteChina Pharmaceutical UniversityNanjing 210009China 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2018年第16卷第6期

页      面：471-480页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1005[医学-中医学] 1002[医学-临床医学] 0703[理学-化学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：supported by the Ministry of Science and Technology of China(No.2014ZX09507001006) the National Natural Science Foundation of China(No.81501579) the Natural Science Foundation of Jiangsu Province(No.BK20150702) the Science and Technology Development Fund of Nanjing Medical University(No.2016NJMU105) the Priority Academic Program Development of Jiangsu Higher Education Institutions 

主　　题：Deoxypodophyllotoxin Central composite design Micelles Cytotoxicity 

摘      要：The therapeutic application of deoxypodophyllotoxin(DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers(m PEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg m PEG-PDLLA, the weight ratio of 1 : 4(m PEG-PDLLA : DPT), 30 m L hydration volume and the hydration temperature at 40 oC. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles(DPT-PM) were about(20 ± 2.84)% and(98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10^(-7) mol·L^(-1), which showed significant difference from free DPT(P 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.