Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis
| Autor: | Carsten Werner, Yvonne Körner, Ben Newland, Petra B. Welzel, Christian Michael Taplan, Andrea Brancale, F. Philipp Seib, Dagmar Pette, Giusy Tornillo, Carmine Varricchio, Dimitri Eigel, Franziska Hoppe, Heike Newland |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
RM Polymers and Plastics Cell Survival media_common.quotation_subject Static Electricity Breast Neoplasms Mice SCID 02 engineering and technology Molecular Dynamics Simulation Pharmacology 010402 general chemistry 01 natural sciences Metastasis Mice Mice Inbred NOD In vivo Materials Chemistry medicine Animals Humans Doxorubicin Neoplasm Metastasis media_common Drug Carriers Antibiotics Antineoplastic Heparin Chemistry Organic Chemistry 021001 nanoscience & nanotechnology medicine.disease Xenograft Model Antitumor Assays Controlled release Tumor Burden 0104 chemical sciences Drug Liberation Drug delivery MCF-7 Cells Systemic administration Female 0210 nano-technology Cryogels medicine.drug |
| ISSN: | 0144-8617 |
| Popis: | Developing drug delivery systems that release anticancer drugs in a controlled and sustained manner remains challenging. We hypothesized that highly sulfated heparin-based microcarriers would allow electrostatic drug binding and controlled release. In silico modelling showed that the anticancer drug doxorubicin has affinity for the heparin component of the microcarriers. Experimental results showed that the strong electrostatic interaction was reversible, allowing both doxorubicin loading and a subsequent slow release over 42 days without an initial burst release. The drug-loaded microcarriers were able to reduce cancer cell viability in vitro in both hormone-dependent and highly aggressive triple-negative human breast cancer cells. Focal drug treatment, of an in vivo orthotopic triple-negative breast cancer model significantly decreased tumor burden and reduced cancer metastasis, whereas systemic administration of an equivalent drug dose was ineffective. This study proves that heparin-based microcarriers can be used as drug delivery platforms, for focal delivery and sustained long-term drug release. |
| Databáze: | OpenAIRE |
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