title: Novel Prodrug of Doxorubicin Modified by Stearoylspermine Encapsulated into PEG-Chitosan-Stabilized Liposomes.
abstract: Here, we report a new modification of doxorubicin based on an amphiphilic stearoylspermine anchor, enabling loading into liposomal membranes. Doxorubicin is coupled with stearoylspermine through an acid-labile hydrazone linker to ensure the release of the drug in the acidic interstitium of tumors. Using ATR-FTIR spectroscopy (Attenuated Total Reflectance-Fourier Transform 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 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 are much more stable.
authors: Department of Chemical Enzymology, Lomonosov Moscow State University , Moscow 119991, Russia.
authors: Irina M
authors: IM
authors: Deygen
authors: Carmen
authors: C
authors: Seidl
authors: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.
authors: Dominik K
authors: DK
authors: Kölmel
authors: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.
authors: Christin
authors: C
authors: Bednarek
authors: Stefan
authors: S
authors: Heissler
authors: Department of Chemical Enzymology, Lomonosov Moscow State University , Moscow 119991, Russia.
authors: Elena V
authors: EV
authors: Kudryashova
authors: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany.
authors: Stefan
authors: S
authors: Bräse
authors: Ute
authors: U
authors: Schepers