Polyamidoamine polymers were prepared by hydrogen-transfer polyaddition of 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid sodium salt to yield PAA-1, polyaddition of amino-β-cyclodextrin and 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid to give PAA-2 and polyaddition of the same amino-β-cyclodextrin and 2-methylpiperazine to 1,4-bis(acryloyl)piperazine to produce PAA-3. These polymers were reacted with cisplatin to give products containing between 8–70 wt.-% platinum. The amount of platinum released from the conjugates during incubation at pH 5.5 and pH 7.4 varied between 0–20%/72 h. PAA-3-Pt showed pH-dependent platinum release. The PAA-platinates were generally less toxic towards lung tumour cell lines in vitro. The IC50 for cisplatin being 2–5 μg/mL and for the PAA-platinates 1–130 μg/mL, this was only to be expected due to their very different cellular pharmacokinetics. In vivo experiments showed that the PAA-1-Pt and PAA-2-Pt were equi-active compared with cisplatin against an i.p. L1210 leukaemia model, confirming their ability to liberate biologically active platinum species. Whereas PAA-1-Pt was significantly less toxic than cisplatin, PAA-2-Pt did show toxicity on repeated dosing, suggesting further investigations are needed to establish the biocompatibility of PAAs containing pendant β-cyclodextrin. PAA-1-Pt is suitable for further in vivo preclinical study in a range of solid tumour models.

Synthesis, characterisation and antitumour activity of platinum(II) complexes of novel functionalised poly(amido amine)s / P. Ferruti, E. Ranucci, F. Trotta, E. Gianasi, E.G. Evagorou, M. Wilson, G. Wasil, R. Duncan. - In: MACROMOLECULAR CHEMISTRY AND PHYSICS. - ISSN 1022-1352. - 200:7(1999), pp. 1644-1654.

Synthesis, characterisation and antitumour activity of platinum(II) complexes of novel functionalised poly(amido amine)s

E. Ranucci
Secondo
;
1999

Abstract

Polyamidoamine polymers were prepared by hydrogen-transfer polyaddition of 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid sodium salt to yield PAA-1, polyaddition of amino-β-cyclodextrin and 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid to give PAA-2 and polyaddition of the same amino-β-cyclodextrin and 2-methylpiperazine to 1,4-bis(acryloyl)piperazine to produce PAA-3. These polymers were reacted with cisplatin to give products containing between 8–70 wt.-% platinum. The amount of platinum released from the conjugates during incubation at pH 5.5 and pH 7.4 varied between 0–20%/72 h. PAA-3-Pt showed pH-dependent platinum release. The PAA-platinates were generally less toxic towards lung tumour cell lines in vitro. The IC50 for cisplatin being 2–5 μg/mL and for the PAA-platinates 1–130 μg/mL, this was only to be expected due to their very different cellular pharmacokinetics. In vivo experiments showed that the PAA-1-Pt and PAA-2-Pt were equi-active compared with cisplatin against an i.p. L1210 leukaemia model, confirming their ability to liberate biologically active platinum species. Whereas PAA-1-Pt was significantly less toxic than cisplatin, PAA-2-Pt did show toxicity on repeated dosing, suggesting further investigations are needed to establish the biocompatibility of PAAs containing pendant β-cyclodextrin. PAA-1-Pt is suitable for further in vivo preclinical study in a range of solid tumour models.
Settore CHIM/04 - Chimica Industriale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/188452
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