PBAT is biodegradable but what about the toxicity of its biodegradation products?

CONTEXT: Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable plastic. It was introduced to the plastics market in 1998 and since then has been widely used around the world. The main idea of this research is to perform quantum chemical calculations to study the potential toxicity of PBAT and its degradation products. We analyzed the electron transfer capacity to determine its potential toxicity. We found that biodegradable products formed with benzene rings are as good electron acceptors as PBAT and OOH•. Our results indicate that the biodegradation products are potentially as toxic as PBAT. This might explain why biodegradation products alter the photosynthetic system of plants and inhibit their growth. From this and other previous investigations, we can think that biodegradable plastics could represent a potential environmental risk. METHODS: All DFT computations were performed using the Gaussian16 at M062x/6-311 + g(2d,p) level of theory without symmetry constraints. Electro-donating (ω-) and electro-accepting (ω +) powers were used as response functions.

Marine degradation and ecotoxicity of conventional, recycled and compostable plastic bags.

Plastic bags are currently a major component of marine litter, causing aesthetical nuisance, and undesirable effects on marine fauna that ingest them or are entangled. Plastic litter also rises concern on the ecotoxicological effects due to the potential toxicity of the chemical additives leached in aquatic environments. Conventional plastic bags are made of polyethylene, either from first use or recycled, but regulations restricting single-use plastics and limiting lightweight carrier bags (<50 µm thickness) have fostered the replacement of thin PE bags by compostable materials advertised as safer for the environment. In this study, we assess the degradation of commercially available plastic bags in marine conditions at two scales: aquariums (60 days) and outdoors flow-through mesocosm (120 days). Strength at break point and other tensile strength parameters were used as ecologically relevant endpoints to track mechanical degradation. Ecotoxicity has been assessed along the incubation period using the sensitive Paracentrotus lividus embryo test. Whereas PE bags did not substantially lose their mechanical properties within the 60 d aquarium exposures, compostable bags showed remarkable weight loss and tensile strength decay, some of them fragmenting in the aquarium after 3-4 weeks. Sediment pore water inoculum promoted a more rapid degradation of compostable bags, while nutrient addition pattern did not affect the degradation rate. Longer-term mesocosms exposures supported these findings, as well as pointed out the influence of the microbial processes on the degradation efficiency of compostable/bioplastic bags. Compostable materials, in contrast toPE, showed moderate toxicity on sea-urchin larvae, partially associated to degradation of these materials, but the environmental implications of these findings remain to be assessed. These methods proved to be useful to classify plastic materials, according to their degradability in marine conditions, in a remarkably shorter time than current standard tests and promote new materials safer for the marine fauna.

A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: A perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

A review on fate and ecotoxicity of biodegradable microplastics in aquatic system: Are biodegradable plastics truly safe for the environment?

Plastic products are extensively used worldwide, but inadequate management of plastic waste results in significant plastic pollution. Biodegradable plastic (BPs) offers an alternative to traditional plastics, however, not all BPs can fully degrade under natural conditions. Instead, they may deteriorate into biodegradable microplastic (BMPs) at a faster rate than conventional plastic, thereby posing an additional hazard to aquatic environments. This study provides a comprehensive overview of the fate of BPs in aquatic systems and their eco-toxicological effects on aquatic organisms such as algae, invertebrates, and fish. The findings highlight that BMPs have comparable or heightened effects compared to conventional microplastics (MPs) which physiochemical characteristic of the polymer itself or by the chemical leached from the polymeric matrix can affect aquatic organisms. While BPs is not a flawless solution to address plastic pollution, future research should prioritize investigating their production, environmental behavior, ecological impact, and whether BMPs inflict greater harm than conventional MPs.

Research advances on the toxicity of biodegradable plastics derived micro/nanoplastics in the environment: A review.

The detrimental effects of plastic and microplastic accumulation on ecosystems are widely recognized and indisputable. The emergence of biodegradable plastics (BPs) offers a practical solution to plastic pollution. Problematically, however, not all BPs can be fully degraded in the environment. On the contrary, the scientific community has demonstrated that BPs are more likely than conventional plastics (CPs) to degrade into micro/nanoplastics and release additives, which can have similar or even worse effects than microplastics. However, there is very limited information available on the environmental toxicity assessment of BMPs. The absence of a toxicity evaluation system and the uncertainty regarding combined toxicity with other pollutants also impede the environmental toxicity assessment of BMPs. Currently, research is focused on thoroughly exploring the toxic effects of biodegradable microplastics (BMPs). This paper reviews the pollution status of BMPs in the environment, the degradation behavior of BPs and the influencing factors. This paper comprehensively summarizes the ecotoxicological effects of BPs on ecosystems, considering animals, plants, and microorganisms in various environments such as water bodies, soil, and sediment. The focus is on distinguishing between BMPs and conventional microplastics (CMPs). In addition, the combined toxic effects of BMPs and other pollutants are also being investigated. The findings suggest that BMPs may have different or more severe impacts on ecosystems. The rougher and more intricate surface of BMPs increases the likelihood of causing mechanical damage to organisms and breaking down into smaller plastic particles, releasing additives that lead to a series of cascading negative effects on related organisms and ecosystems. In the case of knowledge gaps, future research is also proposed and anticipated to investigate the toxic effects of BMPs and their evaluation.

A toxicological perspective of plastic biodegradation by insect larvae.

Larvae of some insect species (Coleoptera and Lepidoptera) can consume and biodegrade synthetic polymers, including polyethylene, polystyrene, polyvinyl chloride, and polypropylene. Multiple chemical (polymer mass loss and shift of the molecular weight, alterations in chemical functionality, formation of biodegraded intermediates, CO2 production), physical (surface hydrophobicity, thermal analysis), and biological approaches (antibiotic treatment, gut dysbiosis, isolation of plastic microbial degraders) have provided evidence for polymer biodegradation in the larva digestive tract. However, the extent and rate of biodegradation largely depend on the physicochemical structure of the polymer as well as the presence of additives. Additionally, toxicology associated with plastic biodegradation has not been investigated. This knowledge gap is critical to understand the gut symbiont-host interaction in the biodegradation process, its viability in the long term, the effects of plastic additives and their metabolites, and the phenotypic traits linked to a plastic-rich diet might be transferred in successive generations. Likewise, plastic-eating larvae represent a unique case study for elucidating the mechanisms of toxic action by micro- and nanoplastics because of the high concentration of plastics these organisms may be intentionally exposed to. This perspective review graphically summarizes the current knowledge on plastic biodegradation by insect larvae and describes the physiological processes (digestive and immune systems) that may be disrupted by micro- and nanoplastics. It also provides an outlook to advance current knowledge on the toxicity assessment of plastic-rich diets and the environmental risks of plastic-containing by-products (e.g., insect manure used as fertilizer).

Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery.

Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.

Progress in Conductive Polyaniline-Based Nanocomposites for Biomedical Applications: A Review.

Inherently conducting polymers (ICPs) are a specific category of synthetic polymers with distinctive electro-optic properties, which involve conjugated chains with alternating single and double bonds. Polyaniline (PANI), as one of the most well-known ICPs, has outstanding potential applications in biomedicine because of its high electrical conductivity and biocompatibility caused by its hydrophilic nature, low-toxicity, good environmental stability, and nanostructured morphology. Some of the limitations in the use of PANI, such as its low processability and degradability, can be overcome by the preparation of its blends and nanocomposites with various (bio)polymers and nanomaterials, respectively. This review describes the state-of-the-art of biological activities and applications of conductive PANI-based nanocomposites in the biomedical fields, such as antimicrobial therapy, drug delivery, biosensors, nerve regeneration, and tissue engineering. The latest progresses in the biomedical applications of PANI-based nanocomposites are reviewed to provide a background for future research.

Polymer-tetrodotoxin conjugates to induce prolonged duration local anesthesia with minimal toxicity.

There is clinical and scientific interest in developing local anesthetics with prolonged durations of effect from single injections. The need for such is highlighted by the current opioid epidemic. Site 1 sodium channel blockers such as tetrodotoxin (TTX) are extremely potent, and can provide very long nerve blocks but the duration is limited by the associated systemic toxicity. Here we report a system where slow release of TTX conjugated to a biocompatible and biodegradable polymer, poly(triol dicarboxylic acid)-co-poly(ethylene glycol) (TDP), is achieved by hydrolysis of ester linkages. Nerve block by the released TTX is enhanced by administration in a carrier with chemical permeation enhancer (CPE) properties. TTX release can be adjusted by tuning the hydrophilicity of the TDP polymer backbone. In vivo, 1.0-80.0 µg of TTX released from these polymers produced a range of durations of nerve block, from several hours to 3 days, with minimal systemic or local toxicity.

Biodegradable N, O-carboxymethyl chitosan/oxidized regenerated cellulose composite gauze as a barrier for preventing postoperative adhesion.

Tissue adhesion is one of the most common complications after surgery (especially after abdominal surgery), causing notable influences after the damaged tissue has healed. A physical barrier placed between the wound site and the adjacent tissues is a convenient and highly effective technique to minimize or prevent abdominal adhesions. In this work, the N, O-carboxymethyl chitosan/oxidized regenerated cellulose (N, O-CS/ORC) composite gauze was prepared. The N, O-CS/ORC composite gauze is degradable; in addition, the gauze exhibits excellent antimicrobial functionality against S. aureus and E. coli bacteria. Moreover, the notable hemostatic efficacy of the N, O-CS/ORC composite gauze was confirmed in rabbit livers/ears as models. The results showed that the N, O-CS/ORC composite gauze is nontoxic toward normal cells and can restrain the adhesion of fibroblast cells, thereby indicating its potential use in preventing tissue adhesion. In addition, the rat models for abdominal defect-cecum abrasion were used to evaluate the efficacy of N, O-CS/ORC composite gauze in preventing tissue adhesions after surgery. The results indicated that the N, O-CS/ORC composite gauze can significantly prevent postsurgical peritoneal adhesions. Finally, the potential anti-adhesion mechanism of the N, O-CS/ORC composite gauze, which may attribute to the combination of barrier function and instinct activity of N, O-CS and ORC, was investigated.

Zwitterionic Cross-Linked Biodegradable Nanocapsules for Cancer Imaging.

Zwitterionic cross-linked biodegradable nanocapsules (NCs) were synthesized for cancer imaging. A polylactide (PLA)-based diblock copolymer with two blocks carrying acetylenyl and allyl groups respectively was synthesized by ring-opening polymerization (ROP). Azide-alkyne "click" reaction was conducted to conjugate sulfobetaine (SB) zwitterions and fluorescent dye Cy5.5 onto the acetylenyl-functionalized first block of the diblock copolymer. The resulting copolymer with a hydrophilic SB/Cy5.5-functionalized PLA block and a hydrophobic allyl-functionalized PLA block could stabilize miniemulsions because of its amphiphilic diblock structure. UV-induced thiol-ene "click" reaction between a dithiol cross-linker and the hydrophobic allyl-functionalized block of the copolymer at the peripheral region of nanoscopic oil nanodroplets in the miniemulsion generated cross-linked polymer NCs with zwitterionic outer shells. These NCs showed an average hydrodynamic diameter ( Dh) of 136 nm. They exhibited biodegradability, biocompatibility and high colloidal stability. In vitro study indicated that these NCs could be taken up by MIA PaCa-2 cancer cells. In vivo imaging study showed that, comparing to a small molecule dye, NCs had a longer circulation time, facilitating their accumulation at tumors for cancer imaging. Overall, this work demonstrates the applicability of zwitterionic biodegradable polymer-based materials in cancer diagnosis.

Biodegradability of polyethylene by bacteria and fungi from Dandora dumpsite Nairobi-Kenya.

This study aimed at isolating and identifying bacteria and fungi with the capacity to degrade low density polyethylene (LDPE). The level of biodegradation of LDPE sheets with bacterial and fungal inoculums from different sampling points of Dandora dumpsite was evaluated under laboratory conditions. Incubation of the LDPE sheets was done for sixteen weeks at 37°C and 28°C for bacteria and fungi respectively in a shaker incubator. Isolation of effective candidates for biodegradation was done based on the recorded biodegradation outcomes. The extent of biodegradation on the polyethylene sheets was assessed by various techniques including weight loss analysis, Fourier Transform Infrared Spectroscopy (FTIR) and GC-MS. Fourier Transform Infra-Red spectroscopy (FTIR) analysis revealed the appearance of new functional groups attributed to hydrocarbon degradation after incubation with the bacteria and fungi. Analysis of the 16S rDNA and 18S rDNA sequences for bacteria and fungi respectively showed that bacteria belonging to genera Pseudomonas, Bacillus, Brevibacillus, Cellulosimicrobium, Lysinibacillus and fungi of genus Aspergillus were implicated as polyethylene degraders. An overall analysis confirmed that fungi are generally better degraders of polyethylene than bacteria. The highest fungal degradation activity was a mean weight reduction of 36.4±5.53% attributed to Aspergillus oryzae strain A5, 1 (MG779508). The highest degradation activity for bacteria was a mean of 35.72± 4.01% and 20.28± 2.30% attributed to Bacillus cereus strain A5,a (MG645264) and Brevibacillus borstelensis strain B2,2 (MG645267) respectively. Genus Aspergillus, Bacillus and Brevibacillus were confirmed to be good candidates for Low Density Poly Ethene bio-degradation. This was further confirmed by the appearance of the aldehyde, ether and carboxyl functional groups after FTIR analysis of the polythene sheets and the appearance of a ketone which is also an intermediary product in the culture media. To improve this degrading capacity through assessment of optimum conditions for microbial activity and enzyme production will enable these findings to be applied commercially and on a larger scale.

Biodegradable, Hydrogen Peroxide, and Glutathione Dual Responsive Nanoparticles for Potential Programmable Paclitaxel Release.

Reactive oxygen species (ROS) and glutathione (GSH) dual responsive nanoparticulate drug delivery systems (nano-DDSs) hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemo drugs in cancer theranosis. Herein, hydrogen peroxide (H2O2) and GSH dual responsive thioketal nanoparticle (TKN) was rationally designed for paclitaxel (PTX) delivery. Compared to other stimuli-sensitive nano-DDSs, this dual responsive DDS is not only sensitive to biologically relevant H2O2 and GSH for on-demand drug release but also biodegradable into biocompatible byproducts after fulfilling its delivering task. Considering the heterogeneous redox potential gradient, the PTX loaded TKNs (PTX-TKNs) might first respond to the extracellular ROS and then to the intracellular GSH, achieving a programmable release of PTX at the tumor site. The selective toxicity of PTX-TKNs to tumor cells with high levels of ROS and GSH was verified both in vitro and in vivo.

Poly(amino acid)-polyester graft copolymer nanoparticles for the acid-mediated release of doxorubicin.

Biodegradable polymers have emerged as highly effective drug delivery vehicles. We combine N-carboxyanhydride and O-carboxyanhydride ring opening polymerisations to synthesise a poly(amino acid)-polyester graft copolymer capable of encapsulating, and subsequently releasing doxorubicin via acid-mediated hydrolysis. Consequently, the nanoparticles detailed are extremely promising vehicles for the controlled delivery of chemotherapeutic agents.

Selenium-Substituted Hydroxyapatite/Biodegradable Polymer/Pamidronate Combined Scaffold for the Therapy of Bone Tumour.

The present study evaluated a new concept of combined scaffolds as a promising bone replacement material for patients with a bone tumour or bone metastasis. The scaffolds were composed of hydroxyapatite doped with selenium ions and a biodegradable polymer (linear or branched), and contained an active substance-bisphosphonate. For this purpose, a series of biodegradable polyesters were synthesized through a ring-opening polymerization of ε-caprolactone or d,l-lactide in the presence of 2-hydroxyethyl methacrylate (HEMA) or hyperbranched 2,2-bis(hydroxymethyl)propionic acid polyester-16-hydroxyl (bis-MPA) initiators, substances often used in the synthesis of medical materials. The polymers were obtained with a high yield and a number-average molecular weight up to 45,300 (g/mol). The combined scaffolds were then manufactured by a direct compression of pre-synthesized hydroxyapatite doped with selenite or selenate ions, obtained polymer and pamidronate as a model drug. It was found that the kinetic release of the drug from the scaffolds tested in vitro under physiological conditions is strongly dependent on the physicochemical properties and average molecular weight of the polymers. Furthermore, there was good correlation with the hydrolytic biodegradation results of the scaffolds fabricated without drug. The preliminary findings suggest that the fabricated combined scaffolds could be effectively used for the sustained delivery of bioactive molecules at bone defect sites.

Biodegradable and pH-responsive nanoparticles designed for site-specific delivery in agriculture.

We report the synthesis and characterization of pH-responsive polysuccinimide-based nanoparticles. Polysuccinimide (PSI), a precursor to biodegradable poly(aspartic acid), was synthesized from the condensation of l-aspartic acid and subsequently functionalized with primary amines to form random amphiphilic copolymers. The copolymers formed stable nanoparticles in aqueous medium via nanoprecipitation and were subsequently loaded with a model hydrophobic molecule to demonstrate their potential as controlled-release delivery vehicles. It was found that above pH 7, the hydrophobic succinimidyl units of the PSI nanoparticles hydrolyzed to release encapsulated materials. The release rate significantly increased at elevated pH and decreased with an increasing degree of functionalization. Finally, plant toxicity studies showed that the polymer materials exhibit little to no toxic effects at biologically relevant concentrations.

Interspecies differences in reaction to a biodegradable subcutaneous tissue filler: severe inflammatory granulomatous reaction in the Sinclair minipig.

Soft tissue filler products have become very popular in recent years, with ever-increasing medical and aesthetic indications. While generally considered safe, the number of reported complications with tissue fillers is growing. Nevertheless, there is no specific animal model that is considered as the gold standard for assessing safety or efficacy of tissue fillers, and there are very little data on interspecies differences in reaction to these products. Here, we report on interspecies differences in reaction to a subcutaneous injectable co-polyester, composed of castor oil and citric acid. Comparison of the histopathological local tissue changes following 1-month postimplantation, indicated that in rats the reaction consisted of cavities, surrounded by relatively thin fibrotic enveloping capsule. In contrast, an unexpected severe inflammatory granulomatous reaction was noticed in Sinclair minipigs. To our knowledge, this is the first report on significant interspecies differences in sensitivity to tissue fillers. It emphasizes the importance of using the appropriate animal model for performing preclinical biocompatibility assays for biodegradable polymers, tissue fillers, and implanted medical devices in general. It also makes the Sinclair minipig subject for scrutiny as an animal model in future biocompatibility studies.