Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis

Ben Newland, Carmine Varricchio, Yvonne Körner, Franziska Hoppe, Christian Taplan, Heike Newland, Dimitri Eigel, Giusy Tornillo, Dagmar Pette, Andrea Brancale, Petra B. Welzel, F. Philipp Seib, Carsten Werner

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Article number116504
JournalCarbohydrate Polymers
Volume245
Early online date3 Jun 2020
DOIs
Publication statusE-pub ahead of print - 3 Jun 2020

Keywords

  • Alexa Fluor™ 647 CID: 102227060
  • cancer
  • Dimethyl sulfoxide (DMSO) CID: 679
  • Doxorubicin
  • Doxorubicin, hydrochloride salt CID: 443939
  • Heparin
  • local drug delivery system
  • N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) CID: 15908
  • N-Hydroxysulfosuccinimide (NHS) sodium salt CID: 133909
  • Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (Synperonic® PEP105) SID: 24888568
  • Sodium heparin CID: 22833565
  • sulfated microcarrier
  • Toluene (≥99.5%) CID: 1140

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  • Cite this

    Newland, B., Varricchio, C., Körner, Y., Hoppe, F., Taplan, C., Newland, H., Eigel, D., Tornillo, G., Pette, D., Brancale, A., Welzel, P. B., Seib, F. P., & Werner, C. (2020). Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis. Carbohydrate Polymers, 245, [116504]. https://doi.org/10.1016/j.carbpol.2020.116504