Cisplatin/hydrogel complex in cancer therapy.
Hydrogels containing alpha-amino acid residues (L-phenylalanine, L-histidine) were used to complex the chemotherapeutic agent cisplatin. The release of the drug in phosphate buffer solution showed an initial burst effect, followed by a near zero-order release phase over the seven days of reported period. Unlike the nonreleasing pattern of the hydrogel poly(N-acryloyl-L-phenylalanine-co-N-isopropylacrylamide) (CP2), the homopolymer poly(N-acryloyl-L-phenylalanine) (P9) hydrogel showed a released amount of cisplatin loaded from a water/DMSO mixture that was three times greater than that loaded from simple water. The hydrogel P9 formed with cisplatinum(II) complex species of well-defined stoichiometry; the drug species was released by a chemically controlled process. The Pt(II)/L (L is the monomeric unit of the polymer) stoichiometric molar ratio of 0.5, corresponding to two close carboxylate groups per Pt(II), was found by the viscometric data on the soluble polymer analogue. The platinum species released from cisplatin-loaded (from water) hydrogel retained its cytotoxic activity toward Me665/2/21 human melanoma cell line, in the same manner shown by the native cisplatin. On the contrary, the platinum species released from cisplatin-loaded (from water/DMSO) hydrogel was devoid of any cytotoxic effect.
Casolaro
Mario
M
Dipartimento di Scienze e Tecnologie Chimiche e dei Biosistemi, Medicina Sperimentale e Sanita Pubblica, Universita degli Studi di Siena, Via Aldo Moro 2, I-53100 Siena, Italy. casolaro@unisi.it
Cini
Renzo
R
Del Bello
Barbara
B
Ferrali
Marco
M
Maellaro
Emilia
E
D000178:Acrylamides / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006639:Histidine; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010649:Phenylalanine; D011108:Polymers / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry
D000178:Acrylamides; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D014867:Water; D010649:Phenylalanine; D006639:Histidine; C067295:N-isopropylacrylamide; D002945:Cisplatin; D004121:Dimethyl Sulfoxide