Dextran-based therapeutic nanoparticles for hepatic drug delivery

Author:

Foerster Friedrich12,Bamberger Denise3,Schupp Jonathan4,Weilbächer Martin4,Kaps Leonard1,Strobl Stephanie1,Radi Lydia3,Diken Mustafa5,Strand Dennis2,Tuettenberg Andrea4,Wich Peter R3,Schuppan Detlef16

Affiliation:

1. Institute of Translational Immunology & Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany

2. Department of Medicine I, University Medical Center, Mainz, Germany

3. Institute of Pharmacy & Biochemistry, Johannes Gutenberg-University Mainz, Staudingerweg 5, Mainz, Germany

4. Department of Dermatology, University Medical Center, Mainz, Germany

5. TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University Mainz gGmbH, Freiligrathstraße 12, 55131 Mainz, Germany

6. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Abstract

Aim: Evaluation of dextran-based nanoparticles (DNP) as a drug delivery system to target myeloid cells of the liver. Materials & methods: DNP were synthesized and optionally PEGylated. Their toxicity and cellular uptake were studied in vitro. Empty and siRNA-carrying DNP were tested in vivo with regard to biodistribution and cellular uptake. Results: In vitro, DNP were taken up by cells of the myeloid lineage without compromising their viability. In vivo, empty and siRNA-carrying DNP distributed to the liver where a single treatment addressed approximately 70% of macrophages and dendritic cells. Serum parameters indicated no in vivo toxicity. Conclusion: DNP are multifunctional liver-specific drug carriers which lack toxic side effects and may be utilized in clinical applications targeting liver macrophages.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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