Targeting of Drugs (NATO Science Series A:, 47)

Successful drug use in biology and medicine is often prejudiced by the failure of drugs that are otherwise active in vitro to act as efficiently in vivo. This is because in the living animal drugs must, as a rule, bypass or traverse organs, membranes, cells and molecules that stand between the site of administration and the site of action. In practice, however, drugs can be toxic to normal tissues, have limited or no access to the target and be prematurely excreted or inactivated. There is now growing optimism that such problems may be resolved by the use of carrier systems that will not only protect the non-target environment from the drugs they carry but also deliver them to where they are needed or facilitate their release there. Carrier systems presently under investigation include antibodies, glycoproteins, cells, reconstituted viruses and liposomes. Recent advances in the chemistry of cell receptor and receptor-recognising molecules, llnmunology, and natural and artificial membranes have revealed a multitude of ways in which such carrier systems can be modified or improved upon.

Gene therapy, developed as an alternative to the use of therapeutic proteins, can be hampered by nuclease degradation of the plasmid DNA, its inability to access target cells or when within cells, to enter the nucleus and transfect these efficiently. This book deals with recent developments in circumventing the problems of direct plasmid administration by the use of viral or non-viral vectors. Representatives from both camps discuss the challenges and opportunities of the two approaches and present current progress with a variety of constructs. These include viruses such as retroviruses, lentiviruses, poxviruses, alphavirus, herpevirus and parvovirus. Non-viral constructs are represented by polycations, polymers, cationic liposomes and nanoparticles.