Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (9): 1-9.doi: 10.6040/j.issn.1671-7554.0.2023.0137

• Preclinical Medicine •     Next Articles

Development and characterization of π-π stacked and chemical crosslinked polymeric micelles

LYU Xiaolin1,2,3, WU Yingli1,2,3, YANG Yu1,2,3, GONG Xujin1,2,3, LIU Yanna1,2,3, YAO Qingqiang1,2,3,4   

  1. 1. School of Pharmaceutical Sciences &
    Institute of Materia Medica, Shandong First Medical University &
    Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China;
    2. NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Jinan 250117, Shandong, China;
    3. Key Lab for Rare &
    Uncommon Diseases of Shandong Province, Jinan 250117, Shandong, China;
    4. Jining Medical University, Jining 272067, Shandong, China
  • Received:2023-02-14 Published:2023-10-10

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Abstract: Objective To improve the stability of micelles in blood circulation and the retention of drugs in micelles by synthesizing amphiphilic block copolymer PEG-b-P(TMC-COOH)-b-P(CL-Bz). Methods PEG-b-P(TMC-Bz)block was firstly synthesized by carbonate monomers(TMC-Bz)containing benzyl side chains. Then, PEG-b-P(TMC-Bz)-b-P(CL-Bz)containing benzyl side chains was synthesized using hydroxyl end groups of PEG-b-P(TMC-Bz)as initiator. Finally, the benzyl group in P(TMC-Bz)was removed under Pd/C to obtain PEG-b-P(TMC-COOH)-b-P(CL-Bz). The synthesized monomers and polymers were characterized by nuclear magnetic resonance hydrogen spectroscopy(1H NMR)and gel permeation chromatography(GPC). In addition, the empty and drug-loaded crosslinked micelles prepared by the resulting polymer were characterized by dynamic light scattering(DLS), and the effects of crosslinking reaction time and the amount of crosslinking agent on crosslinking degree were explored by GPC. Results PEG-b-P(TMC-COOH)-b-P(CL-Bz)polymer was successfully synthesized. The crosslinked polymer micelles prepared had a small and uniform particle size(about 80 nm), and the loading efficiency of paclitaxel in the micelles reached more than 90%. The crosslinking reaction based on the activated carboxyl group in the polymer and the amino group in the crosslinker cystamine dihydrochloride ended within 12 h, and the degree of crosslinking increased with the increase of the amount of crosslinker. Conclusion The PEG-b-P(TMC-COOH)-b-P(CL-Bz)polymeric micelles as a drug delivery system were successfully developed, which can realize the interaction of π-π stacking and chemical crosslinking.

Key words: Polymer synthesis, Ring-opening polymerization, Chemical crosslinking, π-π stack, Polymeric micelles

CLC Number: 

  • R94
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