Novel Prodrug of Doxorubicin Modified by Stearoylspermine Encapsulated into PEG-Chitosan-Stabilized Liposomes
| Autor: | Stefan Bräse, Stefan Heissler, Elena V. Kudryashova, Christin Bednarek, Dominik K. Kölmel, Ute Schepers, I.M. Deygen, Carmen Seidl |
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| Předmět: |
0301 basic medicine
Liposome Chromatography Chemistry 02 engineering and technology Surfaces and Interfaces Prodrug 021001 nanoscience & nanotechnology Condensed Matter Physics Chitosan 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Membrane Amphiphile PEG ratio Electrochemistry Biophysics medicine General Materials Science Doxorubicin 0210 nano-technology Linker Spectroscopy medicine.drug |
| Zdroj: | CIÊNCIAVITAE ResearcherID |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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