ABSTRACT
Polymer-based drug delivery systems (DDS) have attracted signicant attention in biomedicine, pharmaceutics, and bio-nanotechnology. In particular, polymer-based DDS with controllable release of therapeutics and cell targeting have the potential to treat numerous diseases, including cancers, with a reduction in the side effects of the drugs. Several types of polymer-based DDS have been explored and nanogels are among the most promising DDS.1-4 Nanogels are hydrogel networks that are conned to submicron-size. In other words, nanogels are dened as nanosized networks of
54.1 Introduction ........................................................................................................................ 1271 54.1.1Brief Overview of Nanogels ................................................................................... 1271
54.2Preparation of Nanogels ..................................................................................................... 1272 54.2.1Preparation of Nanogels from Polymer Precursors ................................................ 1272
54.2.1.1Disulde-Based Cross-Linking .............................................................. 1272 54.2.1.2 Amine-Based Cross-Linking ................................................................. 1275 54.2.1.3Click Chemistry-Based Cross-Linking .................................................. 1279 54.2.1.4Imine Bonds-Induced Cross-Linking..................................................... 1283 54.2.1.5Photo-Induced Cross-Linking ................................................................ 1284 54.2.1.6Physical Cross-Linking .......................................................................... 1287
54.2.2 Preparation of Nanogels via Monomer Polymerization ......................................... 1287 54.2.2.1Heterogeneous Free Radical Polymerization ......................................... 1288 54.2.2.2Precipitation Polymerization.................................................................. 1288 54.2.2.3Inverse (Mini) Emulsion Polymerization ............................................... 1288 54.2.2.4Inverse Microemulsion Polymerization ................................................. 1289 54.2.2.5 Heterogeneous Controlled/Living Radical Polymerization ................... 1290 54.2.2.6Atom-Transfer Radical Polymerization .................................................. 1290 54.2.2.7Reversible Addition-Fragmentation Chain Transfer ............................. 1292 54.2.2.8Nanogels via Direct RAFT Polymerization ........................................... 1292 54.2.2.9Nanogel Synthesis by RAFT Polymerization in Water .......................... 1293 54.2.2.10 Nanogels Synthesis by Inverse RAFT Miniemulsion ............................ 1295
54.3Applications of Nanogels .................................................................................................... 1295 54.4Release Mechanisms from Nanogels .................................................................................. 1297 54.5 Conclusion.......................................................................................................................... 1298 Acknowledgments ........................................................................................................................ 1299 References .................................................................................................................................... 1299
chemically or physically cross-linked polymers composed of hydrophilic or amphiphilic chains.5 Like hydrogels, nanogels are three-dimensional biocompatible materials with high water content. For drug delivery applications, key features including high water content/swellability, biocompatibility, and adjustable chemical/mechanical properties are particularly attractive. The large surface area provides space for functionalization and bioconjugation. In addition, they have a tunable size from submicrons to tens of nanometers, and their size3,6 can be tuned to an optimal diameter for increased blood circulation time in vivo after IV administration. A smaller diameter (<200 nm) enables better cellular uptake and reduced NP uptake by mononuclear phagocyte system.7,8 Finally, the interior network allows for the encapsulation of therapeutics.
