Surfactant-Free Synthesis of Biodegradable, Biocompatible, and Stimuli-Responsive Cationic Nanogel Particles

Abstract

Nanogels have attracted much attention lately because of their many potential applications, including as nanocarriers for drug and gene delivery. Most nanogels reported previously, however, are not biodegradable, and their synthesis often requires the use of surfactants. Herein we report a surfactant-free method for the preparation of biodegradable, biocompatible, and stimuli-responsive cationic nanogels. The nanogels were synthesized by simply coaservating linear polymer precursors in mixed solvents followed by in situ cross-linking with homobifunctional cross-linkers. The versatility of this approach has been demonstrated by employing two different polymers and various cross-linkers to prepare nanogel particles with diameters ranging from 170 to 220 nm. Specifically, disulfide-containing tetralysine (TetK)- and oligoethylenimine (OEI)-based prepolymers were prepared and the subsequent nanogels were formed by covalently cross-linking the polymer coacervate phase. Nanogel particles are responsive to pH changes, increasing in size and zeta-potential with concomitant lowering of solution pH. Furthermore, as revealed by AFM imaging, nanogel particles were degradable in the presence of glutathione at concentrations similar to those in intracellular environment (10 mM). Both the nanogel and the polymer precursors were determined to exhibit minimal cytotoxicity against fibroblast 3T3 cells by flow cytometric analyses and fluorescent imaging. This study demonstrates a new surfactant-free method for preparing biodegradable, biocompatible, and stimuli-responsive nanogels as potential nanocarriers for the delivery of drugs and genes.

Templateless Synthesis of Polyacrylamide-Based Nanogels via RAFT Dispersion Polymerization

“…[1][2][3][4][5] Their distinct properties including permeable structure, high water content, excellent stability, and multiple functionality have attracted broad interest across multidisciplinary areas of nanotechnology and biotechnology. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Recently, several sophisticated strategies have been developed to address the challenges for use of nanogels as clinical multifunctional biomaterials. [21][22][23] From a synthetic point of view, nanogels have been prepared either by cross-linking of functionalized responsive ones cannot be used for nanogel synthesis, thus limiting the choice of constituent polymers for nanogels.…”

“…Nanogels with diameters of less than 200 nm are physically or chemically cross‐linked polymeric particles swollen with a high water content . Their distinct properties including permeable structure, high water content, excellent stability, and multiple functionality have attracted broad interest across multidisciplinary areas of nanotechnology and biotechnology . Recently, several sophisticated strategies have been developed to address the challenges for use of nanogels as clinical multifunctional biomaterials …”

Recent progress of polymeric nanogels for gene delivery

“…Variations in the chemical design enable them to respond to a variety of environmental factors, such as temperature, pH, ionic strength, reduction, and light. [30]…”

A green and facile method for the preparation of a pH-responsive alginate nanogel for subcellular delivery of doxorubicin

“…Their versatility is demonstrated in stimulus-responsive drug release, such as delivery of peptide drugs, 1 enzyme immobilization, 2 nasal vaccines, 3 siRNA or DNA delivery. Hydrophobic association, 9 electrostatic interactions [10][11][12] and hydrogen bonding 11,13 have been employed to form nanogels of this kind. 8 Complementary to the process of chemical crosslinking, physically crosslinked nanogels are very intriguing in terms of the reversible nature.…”