Dendrimer cisplatin

Use of dendrimers such as PAMAM, PPI and poly(ether hydro q lamine) (PEHAM) in drug deliveiy is mostly focused on cancer treatment. Dendrimers encapsulate anticancer drugs such as cisplatin and doxorubicin and agents for boron neutron capture therapy and photodynamic therapy. Cisplatin encapsulated dendrimers are reported to increase the bioavailability and selectivity of the drug on a solid tumor model which was provided by injection of B16F10 cells to C57 mice. ... 

Malik, Duncan, Tomalia, and Esfand [29] reported the use of a variety of amine and acid-containing polymers that chelated platinum forming cisplatin derivatives. They also reported the synthesis of similar dendritic-antineoplastic drugs using vanadocene dichloride. The structure from the poly(propyleneimine) dendrimers contains units are shown in (5) and (6). 

Dendritic polymers may also have application in the delivery of anticancer agents. Dendrimers have been shown to selectively deliver a high payload of traditional chemotherapeutic agents, such as cisplatin, to a tumor [305]. Blood vessels in tumors have a higher permeability and poorer lymphatic drainage than vessels in normal tissue. This enhanced permeability and retention effects (EPR effect) allows selective delivery of a dmg to a tumor, and has been demonstrated with nondendritic polymer-antitumor agent conjugates [306,307]. 

Duncan and co-workers also created one of the first covalently linked DDS based on a dendrimer scaffold [52]. Carboxylated (COOH) PAMAM dendrimers were used to attach cisplatin, a common chemotherapeutic in clinical use. The covalent attachment of the drug increases the specific solubility of cisplatin ten-fold, and enables a loading of approximately 25% to be achieved for the PAMAM dendrimer. However, dendrimer clusters form as a consequence of the multiple COOH groups on the dendrimer scaffold and intermolecular reactions involving cisplatin. In vitro evaluation has shown that the covalent conjugation to the dendrimer results in a lower toxicity, and in vivo experiments have shown that the blood clearance rate is lower, with higher intra-tumoral concentrations of platinum than those achieved with the free drug. 

Malik et al. (1999) conjugated cisplatin, a potent anticancer drug, to PAMAM dendrimers and observed increased solubility, decreased systemic toxicity, and EPR effect to target tumors when administered intravenously. Targeting methotrexate to epithelial cancers using PAMAM-folic acid system also showed increased antitumor activity (Kukowska-Latallo et al. 2005) compared to free drug after intravenous administration. 

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