Dendrimers have unique molecular architectures and properties that make them attractive materials for the development of nanomedicines. Key properties such as defined architecture and a high ratio of multivalent surface moieties to molecular volume also make these nanoscaled materials highly interesting for the development of synthetic (non-viral) vectors for therapeutic nucleic acids. Rational development of such vectors requires the link to be made between dendrimer structure and the morphology and physicochemistry of the respective nucleic acid complexes and, furthermore, to the biological performance of these systems at the cellular and systemic level. The review focuses on the current understanding of the role of dendrimers in those aspects of synthetic vector development. Dendrimer-based transfection agents have become routine tools for many molecular and cell biologists but therapeutic delivery of nucleic acids remains a challenge.

New vehicles for the non-invasive delivery of agents are introduced. These carriers can transport pharmacological agents, including large polypeptides, through the permeability barriers, such as the intact skin. This capability depends on the self-regulating carrier deformability which exceeds that of the related but not optimized lipid aggregates by several orders of magnitude. Conventional lipid suspensions, such as standard liposomes or mixed lipid micelles, do not mediate a systemic biological effect upon epicutaneous applications. In contrast to this, the properly devised adaptable carriers, when administered on the intact skin, transport therapeutic amounts of biogenic molecules into the body. This process can be nearly as efficient as an injection needle, as seen from the results of experiments in mice and humans with the insulin-carrying vesicles. The carrier-mediated transcutaneous insulin delivery is unlikely to involve shunts, lesions or other types of skin damage. Rather than this, insulin is inferred to be transported into the body between the intact skin cells with a bio-efficiency of at least 50% of the s.c. dose action.

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As 95% of all prescriptions are for orally administered drugs, the issue of oral absorption is central to the development of pharmaceuticals. Oral absorption is limited by a high molecular weight (>500 Da), a high log P value (>2.0) and low gastrointestinal permeability. We have designed a triple action nanomedicine from a chitosan amphiphile: quaternary ammonium palmitoyl glycol chitosan (GCPQ), which significantly enhances the oral absorption of hydrophobic drugs (e.g., griseofulvin and cyclosporin A) and, to a lesser extent, the absorption of hydrophilic drugs (e.g., ranitidine). The griseofulvin and cyclosporin A C(max) was increased 6- and 5-fold respectively with this new nanomedicine. Hydrophobic drug absorption is facilitated by the nanomedicine: (a) increasing the dissolution rate of hydrophobic molecules, (b) adhering to and penetrating the mucus layer and thus enabling intimate contact between the drug and the gastrointestinal epithelium absorptive cells, and (c) enhancing the transcellular transport of hydrophobic compounds. Although the C(max) of ranitidine was enhanced by 80% with the nanomedicine, there was no appreciable opening of tight junctions by the polymer particles.