PEGylation of biodegradable dextran nanogels for siRNA delivery

Abstract

In this paper we report on various ways to PEGylate dextran nanogels. PEGylation could be a valuable asset for the application of dextran nanogels in vivo as this will probably result in an improved pharmacokinetic profile of these carriers. We have shown that covalent coupling of PEG to nanogels is possible and that this approach is most suited compared to other methods of PEGylation.We hope that our manuscript will be of interest to your readership,

Interactions of siRNA loaded dextran nanogel with blood cells

“…The nanogels were loaded by adding increasing amounts of Dicer substrate 25/27-mer siRNA (DsiRNA) targeting EGFP (IDT, Leuven Belgium) to the initially positively charged nanogels. Increasing the siRNA/nanogel ratio resulted in neutral or negatively charged nanogels as described earlier [22,23] (Figure 1). The nanogels were consecutively PEGylated by adding 0, 0.25, 0.5, 1, 2.5 and 5 mg NHS-PEG/mg nanogels N-hydroxysuccinimidyl activated methoxypolyethylene glycol 5000 propionic acid (NHS-PEG, Sigma, Belgium) for 30 min [23].…”

“…Cationic dextran nanogels were prepared from dextran methacrylate (dex-MA), [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAEMA) and 2-aminoethyl methacrylate hydrochloride (AEMA) using inverse mini-emulsion photopolymerization as described earlier [22,23].…”

“…Dextran nanogels have been proposed earlier as a nanocarrier system and have already been shown to successfully deliver siRNA in vitro [22,23]. To further explore the potential of dextran nanogels for the intravenous delivery of siRNA, the first aim of this study is to evaluate to which extent siRNA loaded dextran nanogels are hemocompatible using several advanced methods that recently became available.…”

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…Additionally, cationic nanogels for therapeutics were prepared in an inverse miniemulsion photopolymerization method from dextran and [(2-(methacryloyloxy)ethyl)trimethylammonium chloride] with 2-aminoethyl methacrylate hydrochloride. These nanogels were loaded with a negatively charged conjugate of AlexaFluor 488-labeled 25/27-mer siRNA [324]. Then, neutral nanogels were consecutively PEGylated by using NHS (N-hydroxysuccinimide) activated methoxyPEG5000 propionic acid and such hemocompatible dextran nanogels were used in the intravenous delivery [324][325][326].…”

“…These nanogels were loaded with a negatively charged conjugate of AlexaFluor 488-labeled 25/27-mer siRNA [324]. Then, neutral nanogels were consecutively PEGylated by using NHS (N-hydroxysuccinimide) activated methoxyPEG5000 propionic acid and such hemocompatible dextran nanogels were used in the intravenous delivery [324][325][326]. Furthermore, the efficient delivery of deoxyribonucleic acid plasmid DNA (pDNA) to the nucleous of cells becomes easier especially in the presence of chromatin targeting peptides, which enhance the nuclear inclusion and a probability that DNA can be passed on during subsequent cell divisions in gene therapy.…”