to change the biodistribution in the rest of the body in rabbits. Pharmacokinetics and pharmacodynamics Dendrimers have the potential to completely change the pharmacokinetic and pharmacodynamic (PK/PD) profiles of a drug. As carriers, the PK/PD is no longer determined by the drug itself but by the dendrimer’s localization, drug release, and dendrimer excretion. ADME properties are very highly tunable by varying dendrimer size, structure, and surface characteristics. While G9 dendrimers biodistribute very heavily to the liver and spleen, G6 dendrimers tend to biodistribute more broadly. As molecular weight increases, urinary clearance and plasma clearance decrease while terminal half-life increases. Routes of delivery To increase patient compliance with prescribed treatment, delivery of drugs orally is often preferred to other routes of drug administration. However oral bioavailability of many drugs tends to be very low. Dendrimers can be used to increase the solubility and stability of orally-administered drugs and increase drug penetration through the intestinal membrane. The bioavailability of PAMAM dendrimers conjugated to a chemotherapeutic has been studied in mice; it was found that around 9% of dendrimer administered orally was found intact in circulation and that minimal dendrimer degradation occurred in the gut. Intravenous dendrimer delivery shows promise as gene vectors to deliver genes to various organs in the body, and even tumors. One study found that through intravenous injection, a combination of PPI dendrimers and gene complexes resulted in gene expression in the liver, and another study showed that a similar injection regressed the growth of tumors in observed animals. The primary obstacle to transdermal drug delivery is the epidermis. Hydrophobic drugs have a very difficult time penetrating the skin layer, as they partition heavily into skin oils. Recently, PAMAM dendrimers have been used as delivery vehicles for NSAIDS to increase hydrophilicity, allowing greater drug penetration. These modifications act as polymeric transdermal enhancers allowing drugs to more easily penetrate the skin barrier. Dendrimers may also act as new ophthalmic vehicles for drug delivery, which are different from the polymers currently used for this purpose. A study by Vanndamme and Bobeck used PAMAM dendrimers as ophthalmic delivery vehicles in rabbits for two model drugs and measured the ocular residence time of this delivery to be comparable and in some cases greater than current bioadhesive polymers used in ocular delivery. This result indicates that administered drugs were more active and had increased bioavailability when delivered via dendrimers than their free-drug counterparts. Additionally,