Novel prodrug of doxorubicin modified by stearoylspermine encapsulated into PEG-chitosan stabilized liposomes

  • chair:

    Deygen, I.M. / Seidl, C. / Kölmel, D. K. / Bednarek, C. / Heissler, S. / Kudryashova, E.V. / Bräse, S. / Schepers, U. (2016) 

  • place:

    Langmuir, 2016, 32, 10861-10869, DOI: 10.1021/acs.langmuir.6b01023 

  • Date: September 2016


Here, we report a new modification of doxorubicin based on an amphiphilic stearoylspermine anchor, enabling loading into liposomal membranes. Doxorubicin is coupled to stearoylspermine via an acid-labile hydrazone linker in order to ensure the release of the drug in the acidic interstitium of tumors.

By ATR-FTIR spectroscopy (attenuated total reflectance Fourier transformed infrared spectroscopy), the mechanism of interaction of doxorubicin with the anionic liposomal membrane was studied: incorporation of stearoyl chains leads to an increase in local microfluidity and the amino groups of spermine interact with the phosphate groups of lipids.

To stabilize liposomes against aggregation, we have applied the copolymer PEG-chitosan as a coating: complex formation leads to charge neutralization and the liposomes grow in size. According to MTT tests and confocal microscopy for cell lines A459 and Caco-2, PEG-chitosan coated liposomes are as effective as neutral liposomes but much more stable.