Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. STATEMENT OF SIGNIFICANCE: Biodegradable and biocompatible polymer-based biomaterials are recognized as potential future bioactive nanomedicines. To advance the development of such biomaterials, we developed polymerization platforms utilizing tailored chain transfer agents allowing the straightforward synthesis of hydrolytically degradable polymer biomaterials with tuned biodegradability from hours to several days. The platform allows for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterial serving as drug carriers or theranostics. The therapeutic potential was validated by preparation of polymer biomaterials containing pirarubicin, anticancer drug, bound via pH sensitive bond and by showing prolonged blood circulation and increased antitumor activity while keeping the drug side effects low. This work paves the way for future development of biodegradable polymer biomaterials with advanced properties in drug delivery.
Brominated flame retardants (BFRs) have been routinely used as additives in a number of consumer products for several decades in order to reduce the risk of fire accidents. Concerns about the massive use of these substances have increased due to their possible toxicity, endocrine disrupting properties and occurrence in almost all the environmental compartments, including humans and wildlife organisms. Several conventional BFRs (e.g. polybrominated diphenylethers (PBDE)) have been included in the list of Persistent Organic Pollutants and their use has been restricted because of their established toxicity and environmental persistence. Over the past few years, these compounds have been replaced with "new" BFRs (NBFRs). Despite the fact that NBFRs are different chemical molecules than traditional BFRs, most of physical-chemical properties (e.g. aromatic moiety, halogen substitution, lipophilic character) are common to both groups; therefore, their fate in the environment is potentially similar to the banned BFRs. Therefore, this article has been compiled to summarize the published scientific data regarding the biodegradability of the most widely used NBFRs, a key factor in their potential persistency in the environment, and their ecotoxicological effects on humans and test organisms. The data reviewed here document that the mechanisms through NBFRs exibit their ecotoxicity and the processes leading to their biotransformation in the environment are still poorly understood. Thus emphasis is placed on the need for further research in these areas is therefore emphasized, in order to avoid the massive use of further potentially harmful and recalcitrant substances of anthropogenic origin.
- MeSH
- Biodegradation, Environmental MeSH
- Hydrocarbons, Brominated metabolism toxicity MeSH
- Risk Assessment MeSH
- Humans MeSH
- Environmental Monitoring MeSH
- Flame Retardants metabolism toxicity MeSH
- Environmental Exposure * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The aim of our research was to assess the ecotoxicity and biodegradability of leachates originating from two parts of a municipal landfill before and after biological treatment in the existing treatment plant. Biotests represent important tools for adequate environmental characterization of landfill leachates and could be helpful in reliable assessment and monitoring of the treatment plant efficiency. For ecotoxicity testing of landfill leachate before and after biological treatment, different organisms were chosen: the bacteria Vibrio fischeri, a mixed culture of activated sludge, duckweed Lemna minor, white mustard Sinapis alba, brine shrimp Artemia salina, and water flea Daphnia magna. For assessment of biodegradability, the method for determination of oxygen demand in a closed respirometer was used. The investigated leachates were heavily polluted, and in some cases, effluent limits were exceeded even after treatment. Results indicated that toxicity tests and physico-chemical parameters determined before and after treatment equivalently assess the efficiency of the existing treatment plant. However, the investigated leachates showed higher toxicity to Daphnia magna and especially to Lemna minor in contrast to Vibrio fischeri and Artemia salina (neither was sensitive to any of the leachates). No leachates were readily biodegradable. Experiments confirmed that the battery of toxicity tests should be applied for more comprehensive assessment of landfill leachate treatment and for reliable assessment of the treated leachate's subsequent environmental impact. It was confirmed that treated leachate, in spite of its better physico-chemical characteristics, still represents a potential environmental risk and thus should not be released into the environment.
- MeSH
- Biodegradation, Environmental MeSH
- Bioreactors MeSH
- Water Pollutants, Chemical chemistry metabolism toxicity MeSH
- Biological Oxygen Demand Analysis MeSH
- Sewage MeSH
- Environmental Restoration and Remediation methods MeSH
- Toxicity Tests MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Biodegradation, Environmental MeSH
- European Union MeSH
- Research Support as Topic MeSH
- Environmental Pollutants economics standards MeSH
- Surface-Active Agents economics MeSH
- Legislation as Topic economics standards utilization MeSH
- Publication type
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
Cost-effective pretreatment of the highly concentrated and biorefractory coking wastewater to improve biodegradability is of significant importance, while green electrochemical technologies without external chemicals addition are charming but still challenging due to its high energy consumption. In this work, a novel multi-stages flow through peroxi-coagulation (PC) was for the first time developed with graphite felt cathode modified by graphene, showing an excellent performance in removal of 71.5% COD, 72.3% phenol and 59.4% NH3-N and significant biodegradability enhancement with a low energy consumption as 1.2 kWh/m3. Compared with conventional flow PC, this process was more cost-effective due to more intensive .OH production and higher utilization of generated active species. Through UV spectrophotometry and GC-MS analysis, the improvement of biodegradability was attributed to the reduction of both low and high molecular weight compounds content in the coking wastewater. Comparing to the electro-Fenton, electrocoagulation and ozonation process, the proposed PC process was highly cost-effective, providing a promising and new alternative for pretreatment of coking wastewater.
This paper presents the results of lab-scale experiments on low temperature thermal pre-treatment (less than 100 °C) prior to anaerobic digestion of sewage sludge. Two heating ways, microwave heating (MH) and conventional heating (CH), and two types of sludge, primary and waste activated sludge, were compared under the same experimental conditions. The degree of solubilisation produced by MH and CH up to 72, 82 and 93 °C was firstly estimated. For both types of heating, increase in soluble chemical oxygen demand (COD) caused by the pre-treatment was about 14% on waste activated sludge and only 3% on primary sludge. The final temperature of 72 °C resulted as the most cost-effective in terms of additional soluble COD per unit of energy required. Subsequently, five series of biochemical methane potential mesophilic assays were run in 120 mL serum bottles on sludge samples pre-treated at 72 °C. When compared with control reaction vessels, no significant differences were noticed in net methane production of pre-treated primary sludge, whereas a relevant increase occurred regarding the pre-treated waste activated sludge. It was also observed that the trend of methane content in biogas during the batch tests can be described by a second order polynomial.
Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N-(2-hydroxypropyl)methacrylamide copolymers onto a 2,2-bis(hydroxymethyl)propionic acid (bisMPA)-based polyester dendritic core of various structures. The hydrodynamic diameter of the star copolymer biomaterials can be tuned from 13 to 31 nm and could be adjusted to a given purpose by proper selection of the bisMPA dendritic core type and generation and by considering the sL copolymer molecular weight and polymer-to-core molar ratio. The hydrolytic degradation was proved for both the star copolymers containing either dendron or dendrimer core, showing the spontaneous hydrolysis in duration of few weeks. Finally, it was shown that the therapy with the biodegradable star conjugate with attached doxorubicin strongly suppresses the tumour growth in mice and is fully curative in most of the treated animals at dose corresponding approximately to one fourth of maximum tolerated dose (MTD) value. Both new biodegradable systems show superior efficacy and tumour accumulation over the first generation of star copolymers containing non-degradable PAMAM core.
- MeSH
- Acrylamides MeSH
- Biocompatible Materials * MeSH
- Doxorubicin MeSH
- Pharmaceutical Preparations * MeSH
- Drug Delivery Systems MeSH
- Methacrylates MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Drug Carriers MeSH
- Polymers MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
