Cisplatin water solubility

Cis-DiCHLORODiAMMiNEPLATiNUM (II) (cisplatin, CDDP) has been widely used for clinical cancer therapy in spite of its severe renal toxicity [1] and low water-solubility. 

Cisplatin (dx-Diamminedichloroplatinum) is a divalent water-soluble platinum containing complex. It reacts directly with DNA, resulting in both intra-and inter-strand cross-links. It also causes DNA breaks and it inhibits DNA replication and RNA transcription. A mechanism for the occurrence of resistance appears to be an increased of the levels of DNA-excision repair enzymes. Cisplatin is used in combination therapies with other anticancer drugs in the treatment of testicular and ovarian cancers and it has also shown high activity against cancers of the bladder, head, neck and endometrium. It is administered intravenously by rapid injection or by continuous infusion. It is for more that 90% bound to... 

The B block may consist of a water-soluble polymer, for example, poly(aspartic acid) P(Asp), that is rendered hydrophobic by the chemical conjugation of a hydrophobic drug (Yokoyama et al., 1992, 1993, 1996 Nakanishi et al., 2001), or is formed through the association of two oppositely changed polyions (polyion complex micelles) (Hatada etal., 1995,1998 Kataoka etal., 1996). Drugs used to couple the B block include cyclophosphamide, doxorubicin, cisplatin, pyrene, and iodine derivative of benzoic acid (Kwon and Kataoka, 1995 Trubetskoy et al., 1997 Yu etal., 1998). 

Cisplatin contains two nitrogen ligands, and as expected these can be replaced by polymeric amine units. When tetrachloroplatinum is stoi-chiometrically reacted with PEI it forms a water-insoluble eomplex, but if block copolymers are employed (such as PEO-PEI) then a water-soluble platinum-loaded micellar construct was obtained which showed greater cytotoxicity than cisplatin. 

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