Tissue targeting prodrugs

Tissue targeting may also be directed at tumors through the use of monoclonal antibodies, as briefly mentioned earlier. Finally, brain targeting can also be attempted with the prodrug approach, as exemplified by estradiol by use of a redox-based chemical delivery system (174). 

Appropriately designed prodrugs, for example, phosphonoamidates (Lee et al. 2005), may allow acyclic nucleoside phosphonates such as tenofovir to be specifically targeted at tissues, that is, lymphatic tissue, where the virus (i.e., HIV) replicates. This principle has been recently extended to another nucleotide analogue, GS-9148 (Cmiar et al. 2008) and its phosphonoamidate prodrug, GS-9131 (Ray et al. 2008). 

The discovery of monoclonal antibodies and combining them with polymeric prodrugs is the newest approach to overcome the lack of selectivity for disposition in target tissue (23). Recently the selectivity of antibody-targeted polymeric anthracycline antibiotics to T lymphocytes was accomplished (25). In addition decreased immunogenicity of proteinaceous conjugates with IgG and human transferrin has been reported (26). 

Bai, J. P. F., pGlu-L-Dopa-Pro a tripeptider prodrug targeting the intestinal peptide transporter for absorption and tissue enzymes for conversation, Pharm. Res. 1995, 12, 1101-1104. 

Enzyme-Mediated, Tissue-Selective Targeting of Peptide Prodrugs... 

As indicated in Chapter 15, the development of genomics and proteomics will undoubtedly provide further information of the differential experessions of enzymes in diseased and normal tissues. This will allow the future development of prodrug-based chemical delivery systems to target specific cell types through the use of the upregulated enzymes in diseased tissues to release the active drag. 

Considering the reductive condition in the anaerobic environment in the center of tumor tissue, Damen et al. designed and prepared 2 -carbonate and 3 -A -carbamate prodrugs of paclitaxel that release the parental drug targeting hypoxic tumor tissue. Two of 11 prodrugs are selected for additional investigation. " ... 

---