Optimization of Formulation of Co-loaded Docetaxel and Gambogic Acid Albumin Nanoparticles and Evaluation of Its Quality

Yu ZHENG; Xiao-fang LI; Chao-qun WU; Tian-tian ZHAO; Zu-bing MA; Qiang SUN

doi:10.13422/j.cnki.syfjx.20190846

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Optimization of Formulation of Co-loaded Docetaxel and Gambogic Acid Albumin Nanoparticles and Evaluation of Its Quality

Pharmacy and Processing | 更新时间：2021-02-09

- Optimization of Formulation of Co-loaded Docetaxel and Gambogic Acid Albumin Nanoparticles and Evaluation of Its Quality
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 16, Pages: 104-110(2019)
- 作者机构：
  
  1.成都中医药大学　药学院，中药材标准化教育部重点实验室，四川省中药资源系统研究与开发利用重点实验室——省部共建国家重点实验室培育基地，成都　 611137；
  2.凯里学院，贵州　凯里　 556000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190846
  CLC： R22; R28; R94; Q2; C37
- Received：31 October 2018，
  
  Published Online：04 January 2019，
  
  Published：20 August 2019
- 稿件说明：
移动端阅览
Yu ZHENG, Xiao-fang LI, Chao-qun WU, et al. Optimization of Formulation of Co-loaded Docetaxel and Gambogic Acid Albumin Nanoparticles and Evaluation of Its Quality[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 104-110.
DOI：

Yu ZHENG, Xiao-fang LI, Chao-qun WU, et al. Optimization of Formulation of Co-loaded Docetaxel and Gambogic Acid Albumin Nanoparticles and Evaluation of Its Quality[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 104-110. DOI： 10.13422/j.cnki.syfjx.20190846.

摘要

目的：

利用星点设计-效应面法优化共载多西他赛(DTX)和藤黄酸(GA)白蛋白纳米粒(DTX-GA-BSA NPs)的处方，制备DTX-GA-BSA NPs并评价其质量。采用两药相互作用指数(CDI)筛选DTX和GA的最佳协同配比，为该纳米粒的应用与推广提供实验依据。

方法：

采用Nab™法制备DTX-GA-BSA NPs，以牛血清白蛋白(BSA)为载体材料。利用Design-Expert 8.0.6软件设计实验和处理数据，以粒径和多分散性指数(PDI)的总评“归一值”(OD)以及包封率为评价指标，测定DTX-GA-BSA NPs的粒径，PDI，包封率和Zeta电位。利用噻唑蓝比色法分别测定DTX和GA对MGC-803和HGC-27细胞增殖的单独和协同抑制作用。

结果：

DTX-GA-BSA NPs的最优处方为BSA质量浓度5 g·L

－1

，水油体积比(水相与油相的体积比)1∶17，药载比(药物与载体的质量比)1∶10；模型预测值与实测值偏差较小，具有优良的预测性。DTX-GA-BSA NPs的平均粒径135.8 nm，PDI＝0.09，Zeta电位－21.4 mV。当DTX和GA浓度分别为0.004，0.12 μmol·L

－1

时，二者对MGC-803细胞的协同增殖抑制作用最显著；当DTX和GA浓度分别为0.004，1 μmol·L

－1

时，二者对HGC-27细胞的协同增殖抑制作用最显著。

结论：

优选的DTX-GA-BSA NPs处方工艺稳定可靠，建立的数学模型具有良好预测能力和实用性。DTX和GA联用对MGC-803，HGC-27细胞均具有协同作用，但不呈浓度依赖性。

Abstract

Objective:

The formulation of co-loaded docetaxel(DTX) and gambogic acid(GA) albumin nanoparticles(DTX-GA-BSA NPs) was optimized by central composite design-response surface methodology to prepare DTX-GA-BSA NPs

and its quality was evaluated. The optimal synergistic ratio of DTX and GA was screened by coefficient of drug interaction(CDI).

Method:

Nab™ method was used to prepare DTX-GA-BSA NPs with bovine serum albumin(BSA) as the carrier material. Design-Expert 8.0.6 software was used to design the experiment and process the data

overall desirability(OD) of particle size and polydispersity index(PDI)

encapsulation rate were taken as indexes. The particle size and Zeta potential of the nanoparticles were measured. Individual and synergistic inhibitory effects of DTX and GA on the proliferation of MGC-803 and HGC-27 cells were determined by methyl thiazolyl tetrazolium(MTT) assay

respectively.

Result:

The optimum prescription of DTX-GA-BSA NPs was as follows: BSA concentration of 5 g·L

-1

water-oil phase volume ratio of 1∶17

drug-loading ratio(mass ration of drug to carrier) of 1∶10.The average particle size of DTX-GA-BSA NPs was 135.8 nm and PDI was 0.09

Zeta potential was -21.4 mV. The deviation between the predicted value and the observed value of the model was small

the model had good predictability. For MGC-803 cell

when the concentrations of DTX and GA were 0.004

0.12 μmol·L

-1

respectively(mass ratio of DTX to GA was 1∶23)

the CDI value was the smallest and the synergistic proliferation inhibition was the most significant. For HGC-27 cell

when the concentrations of DTX and GA were 0.004

1 μmol·L

-1

respectively(mass ratio of DTX to GA was 1∶195)

the synergistic proliferation inhibition was the most significant.

Conclusion:

The optimized formulation of DTX-GA-BSA NPs is stable and reliable. The established mathematical model has good predictive ability and practicability. DTX combined with GA has synergistic effect on MGC-803 and HGC-27 cells without concentration dependence.

关键词

Keywords

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