Synthesis, Reductive Cleavage, and Cellular Interaction Studies of Biodegradable, Polyglycerol Nanogels

• Published in: Advanced functional materials 2010-12, Vol.20 (23), p.4133-4138
• Main Authors: Steinhilber, Dirk, Sisson, Adam L., Mangoldt, Dorothea, Welker, Pia, Licha, Kai, Haag, Rainer
• Format: Article
• Language: English
• Subjects: biomedical applications; hydrogels; polyglycerol nanoparticles; polymeric materials; Stimuli-responsive materials
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201000410

In this paper we describe disulfide containing, polyglycerol nanogels as a new class of biodegradable materials. These nanoparticles are prepared in inverse miniemulsion via an acid catalyzed ring‐opening polyaddition of disulfide containing polyols and polyepoxides. Varying conditions allow us to tune particle size and disulfide content within the polymer network; particles can be prepared with narrow polydispersities and diameters in the range from 25 to 350 nm. Particle degradation under reductive intracellular conditions is studied by various analytical techniques. Gel permeation chromatography indicates that final degradation products have relatively low molecular weights (≤ 5 kDa). In addition, studies in cell culture show these nanoscale materials to be highly biocompatible. Dye‐labelled nanogels are shown by optical microscopy techniques to readily internalize into cells by endocytotic mechanisms. This study highlights the great potential of these particles to function as sophisticated nanotransporters that deliver cargo to a certain tissue or cell target and then biodegrade into smaller fragments which would be cleared from the body by the kidney. (with ≈ 30 kDa molecular weight cut off) Biodegradable, functional nanoparticles based on size‐defined, disulfide‐linked polyglycerol nanogels are a new class of cellular delivery vehicles. Their preparation via miniemulsion polymerization is simple, versatile, and controllable to fine tune material properties. By various methods we reveal how these hydrophilic materials degrade into small fragments in reducing environments. We demonstrate that these materials show little toxicity and rapidly endocytose into cells.