Cisplatin/Hydrogel Complex In Cancer Therapy

Abstract

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.

Multiple Stimuli-Responsive Hydrogels for Metal-Based Drug Therapy

“…The addition of a cisplatin solution to a swollen hydrogel in the ionized state always improved a timely deswelling phenomenon that was ascribed to the reaction of the platinum(II)-species undergoing a slowly complexation with the functional groups of the polymer [19]. The stoichiometric ratio 2:1 of the ligand:Pt(II)-metal center was shown either with the free and with the cross-linked polymers by viscometric and swelling measurements, respectively [24,26]. The swollen hydrogel in deionized water regularly decreased its EDS value upon the stepwise addition of a stock cisplatin solution.…”

“…When in the dry form, the Pt(II)-polymer material showed yellowish particles of tightly compact form. The interaction between the COO − groups of the closer monomer units and the aminated Pt(II)-species was supported by FT-IR spectra [24,26]. In all cases, the spectra of the hydrogels in the neutral, ionized, and Pt(II)-complexed forms were compared.…”

“…The presence of a shrunk region may suggest to tailor-made and perform tunable dual-stimuli responsive materials of great potential applications. In the present investigation we limited our approach to suitable platforms that are useful in the controlled release of cisplatin and/or lithium ion for cancer and/or bipolar disorder therapies [24,26,33,34].…”

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review

“…172 A stock solution of cisplatin was added stepwise to each polymer solution. The acrylic hydrogels P9 and CP2, which contain a carboxyl group, were obtained by free radical polymerization of the monomers N-acryloyll-phenylalanine and N-isopropylacrylamide (NIPAAm), and they were cross-linked with N,N'-ethylene-bis-acrylamide.…”

Polymer–metal complex nanoparticles-containing cisplatin and amphiphilic block copolymer for anticancer drug delivery

“…Therefore, many efforts have been devoted to develop a DDS aimed at increasing the blood circulation period and accumulation in solid tumors. [6][7][8] The association of cisplatin with long-circulating nano-sized carriers like polymer conjugates, liposomes, micelles and dendrimers alters drug pharmacokinetics and results in increased drug accumulation in tumors, based on the 'enhanced permeability and retention' (EPR) effect. The EPR effect is a result of leaky capillaries adjacent to solid tumors and a lack of a lymphatic system for the drainage of drugs back to the systemic circulation.…”