Cisplatin/Hydrogel Complex In Cancer Therapy

被引:46
作者
Casolaro, Mario [1 ]
Cini, Renzo [1 ]
Del Bello, Barbara [2 ]
Ferrali, Marco [2 ]
Maellaro, Emilia [2 ]
机构
[1] Univ Siena, Dipartimento Sci & Tecnol Chim & Biosistemi, I-53100 Siena, Italy
[2] Univ Siena, Dipartimento Fisiopatol, I-53100 Siena, Italy
关键词
L-HISTIDINE RESIDUES; PROTONATION THERMODYNAMICS; INDUCED APOPTOSIS; CELL-DEATH; POLYMERS; HYDROGELS; ACID; MICROSPHERES; PLATINUM; DELIVERY;
D O I
10.1021/bm8014939
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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) (N) 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.
引用
收藏
页码:944 / 949
页数:6
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