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Pharmaceuticsに論文が掲載されました。(アルブミンダイマー・ドキソルビシン複合体による膵臓がん進展抑制効果:徳島大学との共同研究)

2021/08/30
Pharmaceutics. 2021 Aug 5;13(8):1209. doi:10.3390/pharmaceutics13081209.

The therapeutic effect of human serum albumin dimer-doxorubicin Complex against human pancreatic tumors

Kinoshita R, Ishima Y, Chuang VTG, Watanabe H, Shimizu T, Ando H, Okuhira K, Otagiri M, Ishida T, Maruyama T.

Abstract:
Human serum albumin (HSA) is a versatile drug carrier with active tumor targeting capacity for an antitumor drug delivery system. Nanoparticle albumin-bound (nab)-technology, such as nab-paclitaxel (Abraxane®), has attracted significant interest in drug delivery research. Recently, we demonstrated that HSA dimer (HSA-d) possesses a higher tumor distribution than HSA monomer (HSA-m). Therefore, HSA-d is more suitable as a drug carrier for antitumor therapy and can improve nab technology. This study investigated the efficacy of HSA-d-doxorubicin (HSA-d-DOX) as next-generation nab technology for tumor treatment. DOX conjugated to HSA-d via a tunable pH-sensitive linker for the controlled release of DOX. Lyophilization did not affect the particle size of HSA-d-DOX or the release of DOX. HSA-d-DOX showed significantly higher cytotoxicity than HSA-m-DOX in vitro. In the SUIzo Tumor-2 (SUIT2) human pancreatic tumor subcutaneous inoculation model, HSA-d-DOX could significantly inhibit tumor growth without causing serious side effects, as compared to the HSA binding DOX prodrug, which utilized endogenous HSA as a nano-drug delivery system (DDS) carrier. These results indicate that HSA-d could function as a natural solubilizer of insoluble drugs and an active targeting carrier in intractable tumors with low vascular permeability, such as pancreatic tumors. In conclusion, HSA-d can be an effective drug carrier for the antitumor drug delivery system against human pancreatic tumors

Keywords:
antitumor; dimerization; doxorubicin; enhanced permeability and retention effect; human serum albumin.