title: Hydrogel containing L-valine residues as a platform for cisplatin chemotherapy.
abstract: Two acrylic hydrogels, of low cross-linking content and carrying the L-valine residues, were synthesized and studied as a platform to load and release the chemotherapeutic agent cisplatin. The platinum(II)-complex species showed a well-defined stoichiometric ratio in which two carboxylate groups of the collapsing gel coordinate a metal center; this was confirmed by FT-IR spectra. When loaded in water, a zero-order release rate of platinum(II)-species was shown in the physiologic solution (PBS, pH 7.40) for more than one week. Moreover, the amount of platinum(II)-species released from the hydrogel may be improved either by the cross-linking degree and by the temperature. Any increase of the cross-links results in a decreased slope of the straightline Pt(II)/gel (mg/g) versus time, whereas the increasing temperature results in a greater amount of platinum(II)-species in solution. The chemical- and swelling-controlled release are the main mechanisms supervising the whole release process. On the other hand, the loading of cisplatin and temsirolimus in DMF showed a characteristic two phase releasing pattern; the initial burst effect was always followed by the zero-order release rate for a week. In this case only a swelling-controlled mechanism was mainly invoked. The cytotoxic activity towards Me665/2/21 human melanoma cell line, afforded by the cisplatin-loaded hydrogel, was close and in some cases higher compared to the native cisplatin at the same concentration; an interesting synergy in term of cytotoxicity was observed when a combined treatment of temsirolimus and cisplatin was used, although temsirolimus exerted only a moderate inhibition of cell proliferation.
authors.affiliation: Department of Pharmaceutical and Applied Chemistry, University of Siena, Via Aldo Moro 2, I-53100 Siena, Italy. casolaro@unisi.it
authors.forename: Mario
authors.initials: M
authors.lastname: Casolaro
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Bello
authors.forename: Del Bello
authors.initials: del B
authors.lastname: Barbara
authors.forename: Emilia
authors.initials: E
authors.lastname: Maellaro
authors.forename: Maellaro
authors.initials: M
authors.lastname: Emilia
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D020123:Sirolimus / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013696:Temperature; D014633:Valine / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C401859:temsirolimus; D014633:Valine; D002945:Cisplatin; D020123:Sirolimus