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Nanogel Networks

One potential problem with the use of self-assembled complexes for drug and gene delivery is the possible insufficient stability of the complex within the body, particularly, when cell barriers, such as the intestinal barrier following oral administration, need to be crossed. To increase the stability of the complex, the polycation chains can be cross-linked with each other, forming a network in which the drug molecules are trapped.

One such type of system, termed NanoGel has recently been proposed. NanoGel represent small hydrogel particles that were synthesized by cross-linking of polyethyleneimine with double end activated PEO using an emulsification/solvent evaporation technique. Oligonucleotide molecules can be easily immobilized in these systems by simple mixing with NanoGel particle suspensions. The oligonucleotide loaded NanoGel particle are small (80 nm) and are stable in aqueous dispersion, revealing no aggregation over an extended period of time and readily enter cells. Moreover, it has been demonstrated that antisense oligonucleotides incorporated in NanoGel are able to reach targets within the cell and efficiently suppress gene expression in a sequence-specific fashion. Additionally, modification of loaded NanoGel particles with transferrin increased both the uptake of oligonucleotides as well as the effects of the oligonucleotides in cells. Further, loaded NanoGel particles were able to cross intestinal cell monolayers with high efficiency and without degradation that would have resulted in premature release of oligonucleotides from the NanoGel. As a result of this work, it appears likely that one useful application of the NanoGel carriers may be in oral administration of antisense oligonucleotides.