Dextran-based therapeutic nanoparticles for hepatic drug delivery

被引:27
作者
Foerster, Friedrich [1 ,2 ,3 ]
Bamberger, Denise [4 ]
Schupp, Jonathan [5 ]
Weilbaecher, Martin [5 ]
Kaps, Leonard [1 ,2 ]
Strobl, Stephanie [1 ,2 ]
Radi, Lydia [4 ]
Diken, Mustafa [6 ]
Strand, Dennis [3 ]
Tuettenberg, Andrea [5 ]
Wich, Peter R. [4 ]
Schuppan, Detlef [1 ,2 ,7 ]
机构
[1] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Translat Immunol, Langenbeckstr 1, D-55131 Mainz, Germany
[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Res Ctr Immunotherapy FZI, Langenbeckstr 1, D-55131 Mainz, Germany
[3] Univ Med Ctr, Dept Med 1, Mainz, Germany
[4] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Staudingerweg 5, Mainz, Germany
[5] Univ Med Ctr, Dept Dermatol, Mainz, Germany
[6] Johannes Gutenberg Univ Mainz gGmbH, Univ Med Ctr, TRON Translat Oncol, Freiligrathstr 2, D-55131 Mainz, Germany
[7] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02115 USA
关键词
biodegradable; dendritic cell; dextran; drug delivery; liver targeting; macrophage; nanoparticles; PEGylation; siRNA; PARTICLES; PEG;
D O I
10.2217/nnm-2016-0156
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:2663 / 2677
页数:15
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