Fabrication of Hinokitiol-modified podophyllotoxin nano-prodrugs having a high drug loading capacity

Abstract

Nano-prodrug is a nanomedicine developed by the reprecipitation method, which allows nanoparticles to be fabricated by only prodrug molecules without using any nanocarriers. In the present study, we synthesized a heterodimer, composed of hinokitiol and podophyllotoxin (PPT) linked via different linkers of carbon chain length as new prodrug compounds, and fabricated their nano-prodrugs. We found that the longer the carbon chain linker, the smaller the size of nanoparticles, and the lower their cytotoxicity. We concluded that heterodimeric prodrugs can be fabricated into nano-prodrugs without reducing their drug loading capacity, and might eventually serve as a promising template for the development of novel nanomedicine.

Keywords:

• Heterodimeric prodrug
• Hinokitiol
• nano-prodrugs
• podophyllotoxin (PPT)
• reprecipitation method

Acknowledgments

We would like to thank Dr. Hiroshi Yabu of IMRAM, Tohoku University, who established the in vitro experiment.

Additional information

Funding

This study was supported by JSPS Grants-in-Aid for Scientific Research (No. 19K15690 and No. 19H02785), the Cooperative Research Program of “Network Joint Research Center for Materials and Devices”, and the Research Program of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” in “Network Joint Research Center for Materials and Devices”.