pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers.

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.

Oxidative degradation and mineralization of bentazone from water.

Bentazone degradation efficiency and mineralization in water solutions using chlorine dioxide treatment were evaluated. Double distilled water and a river water sample spiked with bentazone were studied and compared after chlorine dioxide treatment. Degradation efficiency was determined using high-performance liquid chromatography (HPLC). Daphnia magna toxicity testing and total organic carbon (TOC) analysis were used to ascertain the toxicity of the degraded solutions and mineralization degree. Bentazone degradation products were identified using gas chromatography with a triple quadrupole mass detector (GC-MS-MS). A simple mechanistic scheme for oxidative degradation of bentazone was proposed based on the degradation products that were identified. Decrease in D. magna mortality, high degradation efficiency and partial bentazone mineralization were achieved by waters containing bentazone degradation products, which indicate the formation of less toxic compounds than the parent bentazone and effective removal of bentazone from the waters. Bentazone degraded into four main degradation products. Humic acid from Sava River water influenced bentazone degradation, resulting in a lower degradation efficiency in this matrix (about 10% lower than in distilled water). Chlorine dioxide treatment of water to degrade bentazone is efficient and offers a novel approach in the development of new technology for removal of this herbicide from contaminated water.

Examination of degradation and ecotoxicology of pethoxamid and metazachlor after chlorine dioxide treatment.

Chlorine dioxide has been reported as very efficiently removing pesticides and other organic compounds from water matrixes. Due to pesticide toxicity and potential toxicity of their degradation products, it is important to monitor these compounds as environmental pollutants in ground and surface waters. Evaluating the effects of chlorine dioxide treatment is necessary, and toxicity studies are used to ascertain the severity of effects of intermediates due to incomplete degradation of the parent compounds. In this paper, for the first time, chlorine dioxide is applied and evaluated for the removal of chloroacetamide herbicides (pethoxamid and metazachlor) from waters (deionized water and Sava River water). The degradation degree of herbicides was measured by high-performance liquid chromatography, the main degradation products were identified using gas chromatography with a triple quadrupole mass detector, and the degree of mineralization was monitored by total organic carbon analysis. Four and two degradation products were identified after pethoxamid and metazachlor degradation, respectively. Total organic carbon analysis showed mineralization occurred, but it was incomplete. The mineralization and the characteristics of the degradation products obtained were tested using Daphnia magna and showed lower toxicity than the parent herbicides. The advantage of the applied treatment was a very high degradation percentage for pethoxamid removal from deionized water and Sava River water (100% and 97%, respectively), with higher mineralization efficiency (65%) than metazachlor. Slightly lower degradation efficiency in the Sava River water was due to chlorine dioxide oxidizing the herbicides and dissolved organic matter simultaneously.

Evaluation of azamethiphos and dimethoate degradation using chlorine dioxide during water treatment.

Chlorine dioxide (ClO2) degradation of the organophosphorus pesticides azamethiphos (AZA) and dimethoate (DM) (10 mg/L) in deionized water and in Sava River water was investigated for the first time. Pesticide degradation was studied in terms of ClO2 level (5 and 10 mg/L), degradation duration (0.5, 1, 2, 3, 6, and 24 h), pH (3.00, 7.00, and 9.00), and under light/dark conditions in deionized water. Degradation was monitored using high-performance liquid chromatography. Gas chromatography coupled with triple quadrupole mass detector was used to identify degradation products of pesticides. Total organic carbon was measured to determine the extent of mineralization after pesticide degradation. Real river water was used under recommended conditions to study the influence of organic matter on pesticide degradation. High degradation efficiency (88-100% for AZA and 85-98% for DM) was achieved in deionized water under various conditions, proving the flexibility of ClO2 degradation for the examined organophosphorus pesticides. In Sava River water, however, extended treatment duration achieved lower degradation efficiency, so ClO2 oxidized both the pesticides and dissolved organic matter in parallel. After degradation, AZA produced four identified products (6-chlorooxazolo[4,5-b]pyridin-2(3H)-one; O,O,S-trimethyl phosphorothioate; 6-chloro-3-(hydroxymethyl)oxazolo[4,5-b]pyridin-2(3H)-one; O,O-dimethyl S-hydrogen phosphorothioate) and DM produced three (O,O-dimethyl S-(2-(methylamino)-2-oxoethyl) phosphorothioate; e.g., omethoate; S-(2-(methylamino)-2-oxoethyl) O,O-dihydrogen phosphorothioate; O,O,S-trimethyl phosphorodithioate). Simple pesticide degradation mechanisms were deduced. Daphnia magna toxicity tests showed degradation products were less toxic than parent compounds. These results contribute to our understanding of the multiple influences that organophosphorus pesticides and their degradation products have on environmental ecosystems and to improving pesticide removal processes from water.

Poly(urethane-dimethylsiloxane) copolymers displaying a range of soft segment contents, noncytotoxic chemistry, and nonadherent properties toward endothelial cells.

Polyurethane copolymers based on α,ω-dihydroxypropyl poly(dimethylsiloxane) (PDMS) with a range of soft segment contents were prepared by two-stage polymerization, and their microstructures, thermal, thermomechanical, and surface properties, as well as in vitro hemo- and cytocompatibility were evaluated. All utilized characterization methods confirmed the existence of moderately microphase separated structures with the appearance of some microphase mixing between segments as the PDMS (i.e., soft segment) content increased. Copolymers showed higher crystallinity, storage moduli, surface roughness, and surface free energy, but less hydrophobicity with decreasing PDMS content. Biocompatibility of copolymers was evaluated using an endothelial EA.hy926 cell line by direct contact, an extraction method and after pretreatment of copolymers with multicomponent protein mixture, as well as by a competitive protein adsorption assay. Copolymers showed no toxic effect to endothelial cells and all copolymers, except that with the lowest PDMS content, exhibited resistance to endothelial cell adhesion, suggesting their unsuitability for long-term biomedical devices which particularly require re-endothelialization. All copolymers exhibited excellent resistance to fibrinogen adsorption and adsorbed more albumin than fibrinogen in the competitive adsorption assay, suggesting their good hemocompatibility. The noncytotoxic chemistry of these synthesized materials, combined with their nonadherent properties which are inhospitable to cell attachment and growth, underlie the need for further investigations to clarify their potential for use in short-term biomedical devices.

Structure and properties of thermoplastic polyurethanes based on poly(dimethylsiloxane): assessment of biocompatibility.

Properties and biocompatibility of a series of thermoplastic poly(urethane-siloxane)s (TPUSs) based on α,ω-dihydroxy ethoxy propyl poly(dimethylsiloxane) (PDMS) for potential biomedical application were studied. Thin films of TPUSs with a different PDMS soft segment content were characterized by (1) H NMR, quantitative (13) C NMR, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), contact angle, and water absorption measurements. Different techniques (FTIR, AFM, and DMA) showed that decrease of PDMS content promotes microphase separation in TPUSs. Samples with a higher PDMS content have more hydrophobic surface and better waterproof performances, but lower degree of crystallinity. Biocompatibility of TPUSs was examined after attachment of endothelial cells to the untreated copolymer surface or surface pretreated with multicomponent protein mixture, and by using competitive protein adsorption assay. TPUSs did not exhibit any cytotoxicity toward endothelial cells, as measured by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assays. The untreated and proteins preadsorbed TPUS samples favored endothelial cells adhesion and growth, indicating good biocompatibility. All TPUSs adsorbed more albumin than fibrinogen in competitive protein adsorption experiment, which is feature regarded as beneficial for biocompatibility. The results indicate that TPUSs have good surface, thermo-mechanical, and biocompatible properties, which can be tailored for biomedical application requirements by adequate selection of the soft/hard segments ratio of the copolymers.

In vitro biocompatibility evaluation of novel urethane-siloxane co-polymers based on poly(ϵ-caprolactone)-block-poly(dimethylsiloxane)-block-poly(ϵ-caprolactone).

Novel polyurethane co-polymers (TPUs), based on poly(ϵ-caprolactone)-block-poly(dimethylsiloxane)-block-poly(ϵ-caprolactone) (PCL-PDMS-PCL) as soft segment and 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as hard segment, were synthesized and evaluated for biomedical applications. The content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%. The influence of the content and length of the HS on the thermal, surface, mechanical properties and biocompatibility was investigated. The structure, composition and HS length were examined using (1)H- and quantitative (13)C-NMR spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments participated. It was found that an increase in the average HS length (from 1.2 to 14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the hard segments, storage moduli, hydrophilicity and degree of microphase separation of the co-polymers. Depending on the HS content, a gradual variation in surface properties of co-polymers was revealed by FT-IR, AFM and static water contact angle measurements. The in vitro biocompatibility of co-polymers was evaluated using the endothelial EA.hy926 cell line and protein adsorption on the polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen from multicomponent protein mixture, which may indicate biocompatibility. The polyurethane films with high HS content and/or high roughness coefficient exhibit good surface properties and biocompatible behavior, which was confirmed by non-toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic chemistry of the co-polymers makes them good candidates for further development as biomedical implants.