In vitro and in vivo characteristics of core–shell type nanogel particles: Optimization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated nanogels

Abstract

The biocompatibility and body distribution of PEGylated polyamine nanogels composed of chemically cross-linked poly(2-N,N-(diethylamino)ethyl methacrylate) (PEAMA) gel cores surrounded by poly(ethylene glycol) (PEG) chains were investigated to evaluate their feasibility as drug nanocarriers for systemic administration. PEGylated nanogels with different cross-linking densities (1, 2, and 5mol.%) were prepared to evaluate their biocompatibilities by in vitro cytotoxicity assay, hemolysis assay, and in vivo acute toxicity assay. The toxic effect of the PEGylated nanogels derived from polyamine gel cores was significantly reduced when the cross-linking density was increased, and those with a cross-linking density of 5mol.% showed a remarkably high median lethal dose (LD(50)) value >200mgkg(-1),despite the abundance of amino groups in the core. One hour after intravenous injection the PEGylated nanogels were found to have been eliminated from the systemic circulation, and less than 1% of the injected dose (ID) remained in the bloodstream. To improve the blood circulation time by increasing the surface PEG density of the PEGylated nanogels post-PEGylation of the PEGylated nanogels (via the Menschutkin reaction between tertiary amines of the PEAMA gel core and bromobenzyl-terminated short PEG) was carried out. A biodistribution study of these post-PEGylated nanogels revealed that the blood circulation time of the nanogels was definitely prolonged as the PEG content was increased. Therefore, the precise design of PEGylated nanogels with increased cross-linking densities in their polyamine gel cores and increased surface PEG densities seems promising for systemic applications.

Optical cell separation from three-dimensional environment in photodegradable hydrogels for pure culture techniques

“…WST assay was performed according to the manufacture's instruction and previous report37. Briefly, RGK and RGM cells were inoculated in a 96-well plate at the total cell density of 1 × 10 4 cells/well [mixing ratio of RGK and RGM was 1:1 (n/n)].…”

Long circulating micelles of an amphiphilic random copolymer bearing cell outer membrane phosphorylcholine zwitterions

“…By providing a hydration layer and steric barrier surrounding the polymeric core, PEG coating can reduce non-specific binding of serum proteins to the particles, thereby reducing their clearance by MPS cells [9]. The stealth properties can be achieved and optimized by grafting a high density of PEG with MW ranging from 2k to 10k [3,[10][11][12][13]. Although PEGylation has been extensively studied on a variety of nanoparticle systems to increase surface hydrophilicity and improve circulation half-life by decreasing interactions with blood proteins and MPS cells [14][15][16][17], detailed investigations also recognize its disadvantages [18][19][20][21][22].…”

Novel biocompatible nanoreactor for silica/gold hybrid nanoparticles preparation

“…Coordination of the amino lone-pair of the PEAMA chain effectively stabilizes the Au nanoparticles in the nanogel. The PEGylated nanogel shows high stability against extremely dilute and high salt conditions, excellent biocompatibility, negligible toxicity, and prolonged blood circulation [25]. The nanogel also shows significant volume phase transitions (swelling/deswelling) in response to pH changes [23,26].…”