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pH‐responsive micelles with lower immunogenicity for smart drug delivery

Research Project

Project/Area Number 23K19230
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0403:Biomedical engineering and related fields
Research InstitutionKawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine

Principal Investigator

Mohamed Aziz・Awaad・Aziz  公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (50978286)

Project Period (FY) 2023-08-31 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordspolycarboxybetaine / immunogenicity / anti-tumor / drug delivery systems / pH-responsive
Outline of Research at the Start

For effective tumor targeting and smart drug delivery, the pH-responsive PGLu(DET-Car)-based polymeric micelles will be used for tumor therapy. The obtained data from this protocol will introduce detailed information about smart nanocarriers used for anti-tumor drug delivery systems development.

Outline of Annual Research Achievements

Successfully were prepared a polyzwitterion termed as PGLu(DET-car) was prepared with a pH-responsive against tumorous pH and with lower immunogenicity compared with conventional polymers. The PGLu(DET-car) polymer showed lower induction of serum immunoglobulin (IgM, IgG) in vivo and cytokines (IL-2, IFN‐γ) induction in vitro compared with polyethylene glycol (PEG) polymer. Additionally, conjugation of PGLu(DET-car) into PEG polymer reduced the Anti-PEG IgM in the blood serum. The polymeric micelles prepared from the PGLu(DET-car) showed compatible affinity to reach deeper in the tumor site compared with those prepared from PEG. Furthermore, the PGLu(DET-car) micelles showed lower induction of IgM in the blood serum, as well as lower induction of IL-2, IFN‐γ cytokines in vitro.

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

We successfully prepared a pH-responsive PGLu(DET-car)-based micelle. Additionally, we evaluated the immunogenicity of the prepared micelle both in vitro and in vivo. The current data showed lower immunogenicity of PGLu(DET-car) polymer as well as PGLu(DET-car)-based micelle compared with conventional polymers.
Unfortunately, we found difficulty loading a drug in the prepared micelles. The drug-loaded micelle preparation still needs more characterization and evaluation. we found unstable micelle after loading with anti-cancer drugs. therefore, it will take some time to optimize he conditions of loading drugs in the prepared micelles.

Strategy for Future Research Activity

During the current year we will evaluate the in vivo biodistribution of PGLu(DET-car)-based micelle. Additionally, anti-cancer or anti-aging drugs loading into the prepared micelle will be optimized and evaluated using different animal models.

Report

(1 results)
  • 2023 Research-status Report
  • Research Products

    (1 results)

All 2023

All Presentation (1 results)

  • [Presentation] Changeable Net Charge on Gold Nanoparticles Facilitates Intratumor Accumulation, Retention and Penetration2023

    • Author(s)
      Aziz Awaad, Hiroyasu Takemoto, Muneaki Iizuka, Koichi Ogi, Yuki Mochida, Abdul-Hackam Ranneh, Masahiro Toyoda, Makoto Matsui, Takahiro Nomoto, Kotaro Hayashi, Keishiro Tomoda, Tomoyuki Ohtake, Yutaka Miura, and Nobuhiro Nishiyama
    • Organizer
      Third International Conference of the Faculty of Pharmacy, Ain Shams University (ICPASU 2023)
    • Related Report
      2023 Research-status Report

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Published: 2023-09-11   Modified: 2024-12-25  

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