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

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          Abstract

          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 (mPEG-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 mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. 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.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier
          1875-5364
          20 June 2018
          : 16
          : 6
          : 471-480
          Affiliations
          1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
          2Children's Hospital of Nanjing Medical University, Nanjing 210008, China
          3Department of Professional Institute, China Pharmaceutical University, Nanjing 210009, China
          Author notes
          *Corresponding author: Shen Yan, Tel.: 86-25-83271305. E-mail: shenyan19820801@ 123456126.com

          ΔThese authors contribute equally to this work.

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(18)30081-5
          10.1016/S1875-5364(18)30081-5
          Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: Ministry of Science and Technology of China
          Award ID: 2014ZX09507001006
          Funded by: National Natural Science Foundation of China
          Award ID: 81501579
          Funded by: Natural Science Foundation of Jiangsu Province
          Award ID: BK20150702
          Funded by: Science and Technology Development Fund of Nanjing Medical University
          Award ID: 2016NJMU105
          This work was 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), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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