Measuring the intravitreal mobility of nanomedicines with single-particle tracking microscopy. (December 2013)

• Record Type: Journal Article
• Authors: Martens, Thomas F; Vercauteren, Dries; Forier, Katrien; Deschout, Hendrik; Remaut, Katrien; Paesen, Rik; Ameloot, Marcel; Engbersen, Johan FJ; Demeester, Jo; De Smedt, Stefaan C; Braeckmans, Kevin
• Is Part Of: Nanomedicine. Volume 8:Number 12(2013)
• Page Start: 1955
• Page End: 1968
• Publication Date: 2013-12
• Subjects: diffusion -- intravitreal injection -- nanomedicine -- nanoparticle -- ocular gene therapy -- polyplex -- single-particle tracking; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.12.202
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: To develop a robust assay to evaluate and compare the intravitreal mobility of nanoparticles in the intact vitreous body.Materials & methods: Excised bovine eyes were prepared to preserve the fragile structure of the vitreous humor, while permitting high-resolution fluorescence microscopy and single-particle tracking analysis of intravitreally injected nanoparticles. This assay was validated by analyzing polystyrene beads and further employed to evaluate gene nanomedicines composed of poly(amido amine)s and plasmid DNA.Results: The assay was able to distinguish immobilized cationic nanoparticles from mobile PEGylated nanoparticles. PEGylation of the polyplexes resulted in a drastic improvement of their mobility.Conclusion: An ex vivo eye model is presented for studying nanoparticle mobility in intact vitreous humor by single-particle tracking microscopy. These results give important guidelines for developing gene- and drug-delivery nanomedicines that are compatible with intravitreal administration. Original submitted 20 April 2012; Revised submitted 22 November 2012