Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (6): 21-28.doi: 10.6040/j.issn.1671-7554.0.2017.875

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Cooperative pH-sensitivity polyion complex micelles for co-delivery of doxorubicin and paclitaxel

ZHU Yixin, FAN Xiaohui, CHEN Yan, LI Lingbing   

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To achieve co-delivery of paclitaxel(PTX)and doxorubicin(DOX)by pH-sensitive polyion complex micelles, and to evaluate its effects in vitro and in vivo. Methods Amphiphilic polyelectrolyte/prodrug micelles were constructed via synergistic electrostatic interactions between slightly positively charged pluronic F127-chitosan copolymer(F127-CS)and negatively charged cis-aconityl-doxorubicin(CA-DOX)prodrug. Mixed micelles were prepared using pluronic P105(P105)and F127-CS/CA-DOX, and poorly water-soluble anticancer drug PTX was incorporated into mixed micelles to realize the co-delivery of DOX and PTX. The particle size of micelles was measured and the critical micelle concentration(CMC)was observed by the pyrene fluorescence probe method. Finally, the characteristics of micelles such as in vitro drug release, in vitro cell uptake and in vivo pharmacodynamics studies were evaluated. Results The pH-sensitive micelles were prepared successfully. The average particle diameter of the micelles was 179.3 nm and the CMC was 0.039 mg/mL. DOX and PTX release from polymeric micelles followed a pH-dependent manner. The results of cell uptake studies exhibited that both DOX and PTX could be delivered into cells by P105/F127-CS/CA-DOX mixed micelles effectively. The in vivo pharmacodynamics studies of drug-loaded P105/F127-CS/CA-DOX micelles showed that the co-delivery micelles had a strong inhibitory effect on tumors with a lower toxicity. Conclusion The co-delivery micelles are pH-sensitive and have a strong inhibitory effect on cancer with a lower toxicity on normal tissues; it is potential for co-delivery of PTX and DOX.

Key words: Paclitaxel, Doxorubicin, Polyion complex micelles, Mixed micelles, Co-delivery, pH-sensitivity

CLC Number: 

  • R944.9
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