Excipient Drug Conjugates

Whether chelation (as opposed to covalent bonding) of an active moiety to an excipient qualifies the entire construct as a new chemical entity (NCE) is a moot point. A case in point is polymer platinate. This compound consists of a polymer backbone, hydroxypropylmethacrylamide, linked to a polypeptide spacer. The peptide is in turn linked with an aminomalonate chelating group, which chelates the platinum compound (Fig. 2). 

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Receptor-mediated transporters are excipients that serve as substrates to exploit specific receptors present on cell membranes. Examples of various receptors that have been explored for permeation enhancement include bile acids (45), vitamin Bi2 (46), amino acids (47), and folic acid (48). Most of the work in receptor-mediated transporters is conducted via the use of prodrugs. For example, a prodrug of acyclovir conjugated to bile acids was seen to have higher permeability as compared to the original drug, because of receptor-mediated transport of the prodrug via bile acid transporters (49). 

One of the major obstacles to definitively examining the role of formulation components on enterocyte-based processes is the possible effect of excipient inclusion on other complicating factors. For example, the inclusion of lipids or surfactants in in vitro metabolic or transport screens runs the risk of affecting the thermodynamic activity of the drug in solution, thereby obscuring the role of metabolic and transport processes. Similarly, some surfactants and lipid-surfactant conjugates may cause transient increases in intestinal permeability as... 

Reisch, J., Topaloglu, Y., and Henkel, G., 1986b, Photostability of pharmacopeial drugs and excipients. II. Cross-conjugated corticoids of the European Pharmacopeia, Acta Pharm. Technol. 32, 115-121. 

Kast CE, Bemkop-Schnurch A (2002) Polymer-cysteamine conjugates new mucoadhesive excipients for drug delivery Int J Pharm 234 91-99... 

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