How New Drugs are Developed: Drug Delivery
- Pp. 177-187 (11)Robert E. Smith
Medicinal chemists try to find ways to induce drugs to the target cell and organ, and not to the rest of the body, and to activate the drug only at the target organ, to make it effective. This can be done with liposomes, synthetic polymers, dendrimers and nanotechnology. Liposomes prepared from polyethylene glycol (PEG) are used to deliver the anticancer agent doxorubicin. Another way to deliver drugs to their specific target is through antibody-drug conjugates and fusion proteins, in which one part (such as the antibody) binds specifically to the target and the other part is released and presents the desired therapeutic effect. An example of this is the drug called trastuzumab emtansine, commonly referred to as T-DM1. There are also recombinant immunotoxins, in which a fusion protein is made that contains a bacterial toxin and a fragment which targets the specific cancer cells being treated. An example is anti- Tac(Fv)-PE38 or LMB-2, which contains a toxin fragment of Pseudomonas endotoxin and a monoclonal antibody against the cell surface protein, CD25, in cancer cells. Radionuclides can also be conjugated to antibodies, such as <sup>131</sup>I-tositumomab (Bexxar) and <sup>90</sup>Y-ibritumomab tiuxetan (Zevalin), which target the CD20 protein on cancer cells, for the treatment of non-Hodgkin’s lymphoma. Another example that is in development is targeted delivery of small inhibitory RNAs (siRNAs). Fusion proteins consisting of single-chain fragmented antibodies and positively charged peptides can deliver siRNAs into specific target cells.