The 2000s have been characterized by an unprecedented exploration into research and development of nanotechnology and nanomaterials. Despite a slow start, new regulatory initiatives are popping up like mushrooms internationally. Many of these initiatives have yet to materialize themselves or are soft law initiatives, and their impact on the development of more authoritative and prescriptive regulatory measures is most likely to be limited.
This is due to a number of transnational regulatory challenges that include: (1) whether to adapt existing legislation or develop a new regulatory framework, (2) whether nanomaterials should be considered as different from their bulk counterparts, (3) how to define nanotechnology and nanomaterials, and (4) how to deal with the profound limitations of risk assessment when it comes to nanomaterials.
In this opinion, I discuss these and related issues and conclude that the development of a new authoritative and prescriptive regulatory framework might be the only way to effectively address these challenges while ensuring a transparent and informed decision-making process.
Hansen SF. A global view of regulations affecting nanomaterials. Published online ahead of print June 8, 2010. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. Correspondence to Steffen F. Hansen, Department of Environmental Engineering, Technical University of Denmark at srh@env.dtu.dk.
Review: Bioresponsive Polymers for the Delivery of Therapeutic Nucleic Acids
Polymers present an interesting option for the delivery of genes and other therapeutic nucleic acids. In the delivery process, the polymeric carriers face many different delivery tasks and different physiological microenvironments. Polymers can be designed to respond to microenvironmental differences with changes in their physio-chemical properties, enabling them to perform individual delivery tasks.
Cleavage of covalent bonds, disassembly of noncovalent interactions, changes of protonation, conformation, or hydrophilicity/lipophilicity, can trigger such dynamic physicochemical adjustments. The polymeric carrier has to stably bind the therapeutic nucleic acid during the extracellular delivery phase and protect it against degradation in the bloodstream. At the intracellular site of action, the polyplex has to disassemble to an extent that the nucleic acid is functionally accessible. Polyplexes need to be shielded in the circulation and be inert against numerous possible biological interactions, but should actively interact with the target cell surface by electrostatic or ligand receptor interactions. Lipid-membrane destabilization at the cell membrane or nontarget sites is usually associated with undesired cytotoxicity, the analogous biophysical event, however, is required within an endocytic vesicle for polyplex transfer into the cytosol.
Strategies will be presented how bioresponsive polymers can be designed and incorporated into polyplexes. Examples include dynamic stabilization of the polymer/nucleic acid core and transient activation of properties required for crossing lipid-membrane barriers. Bioresponsive delivery domains at the polyplex surface required for shielding, deshielding, and cell targeting also contribute to better performance.
Edinger D, Wagner E. Bioresponsive polymers for the delivery of therapeutic nucleic acids. Published online ahead of print June 8, 2010. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. Correspondence to Ernst Wagner, Pharmaceutical Biotechnology, LMU University at ernst.wagner@cup.uni-muenchen.de.
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