How much are microplastics harmful to the health of amphibians? A study with pristine polyethylene microplastics and Physalaemus cuvieri.

Microplastics (MPs) are critical emerging pollutants found in the environment worldwide; however, its toxicity in aquatic in amphibians, is poorly known. Thus, the aim of the present study is to assess the toxicological potential of polyethylene microplastics (PE MPs) in Physalaemus cuvieri tadpoles. According to the results, tadpoles' exposure to MP PE at concentration 60 mg/L for 7 days led to mutagenic effects, which were evidenced by the increased number of abnormalities observed in nuclear erythrocytes. The small size of erythrocytes and their nuclei area, perimeter, width, length, and radius, as well as the lower nucleus/cytoplasm ratio observed in tadpoles exposed to PE MPs confirmed its cytotoxicity. External morphological changes observed in the animal models included reduced ratio between total length and mouth-cloaca distance, caudal length, ocular area, mouth area, among others. PE MPs increased the number of melanophores in the skin and pigmentation rate in the assessed areas. Finally, PE MPs were found in gills, gastrointestinal tract, liver, muscle tissues of the tail and in the blood, a fact that confirmed MP accumulation by tadpoles. Therefore, the present study pioneering evidenced how MPs can affect the health of amphibians.

Degradation of polyethylene microplastics in seawater: Insights into the environmental degradation of polymers.

Microplastic contamination of aquatic environments has become an increasingly alarming problem. These, defined as particles <5 mm, are mostly formed due to the cracking and embrittlement of larger plastic particles. Recent reports show that the increasing presence of microplastics in the environment could have significant deleterious consequences over the health of marine organisms, but also across the food chain. Herein, we have studied the effects of artificial seawater on polyethylene (PE)-based beads by exposing them up to eight weeks to saltwater in stirred batch reactors in the dark and examined the structural and morphological changes these endured. Electron microscopy observations showed that artificial seawater induces severe microcracking of the pellets' surfaces. Additionally, Fourier transform infrared spectroscopy (FTIR) analyses evidenced the formation of oxidized groups whenever these particles were exposed to water and an increase in organic matter content of the waters in which the pellets were kept was evidenced by Raman spectroscopy. There were also noticeable consequences in the thermal stability of the polyethylene pellets, as determined by thermogravimetric studies (TGA). Furthermore, the parallel exposure of polyethylene pellets to UV radiation yielded less pronounced effects, thus underscoring its lower preponderance in the degradation of this material. These results highlight the importance of determining the mechanisms of degradation of microplastics in marine settings and what the implications may be for the environment. Overall, the herein presented results show that a relatively short period of time of accelerated exposure can yield quantifiable chemical and physical impacts on the structural and morphological characteristics of PE pellets.

Fabrication of poly (butadiene-block-ethylene oxide) based amphiphilic polymersomes: An approach for improved oral pharmacokinetics of Sorafenib.

Sorafenib (SFN), a hydrophobic anticancer drug, has several limitations predominantly poor aqueous solubility and hepatic first-pass effect, limiting its oral delivery that results into several other complications. Present study aims to develop Sorafenib loaded polymersomes using poly butadiene block poly ethylene oxide (PB-b-PEO), an amphiphilic co-block polymer. Prior to drug loading, critical aggregate concentration (CAC) of polymer was calculated for stable formulation synthesis. The developed SFN loaded PB-b-PEO polymersomes (SFN-PB-b-PEO, test formulation) characterized by DLS and cryo-TEM showed particle size 282 nm, polydispersity (PDI) of less than 0.29 and membrane thickness of about 20 nm. SFN-PB-b-PEO polymersomes demonstrated encapsulation efficiency of 71% and showed sustained drug release up to 144 h. Formulation remained stable for 3 months in suspension form. In vitro cytotoxicity against HepG2 cells showed 1.7 folds improved toxicity compared to SFN suspension. In addition, oral administration of SFN-PB-b-PEO polymersomes in BALB/c mice showed increased Cmax and AUC0-96 by 1.7 and 2.77-fold respectively (p < 0.05) compared to those of SFN suspension (reference formulation). Findings suggest that the SFN-PB-b-PEO polymersomes can be a potential candidate for oral delivery of SFN.

Chemical stabilization of polymers: Implications for dermal exposure to additives.

Technical benefits of additives in polymers stand in marked contrast to their associated health risks. Here, a multi-analyte method based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) was developed to quantify polymer additives in complex matrices such as low-density polyethylene (LDPE) and isolated human skin layers after dermal exposure ex vivo. That way both technical aspects and dermal exposure were investigated. The effects of polymer additivation on the material were studied using the example of LDPE. To this end, a tailor-made polymer was applied in aging studies that had been furnished with two different mixtures of phenol- and diarylamine-based antioxidants, plasticizers and processing aids. Upon accelerated thermo-oxidative aging of the material, the formation of LDPE degradation products was monitored with attenuated total reflectance-Fourier transformed infrared (ATR-FTIR) spectroscopy. Compared to pure LDPE, a protective effect of added antioxidants could be observed on the integrity of the polymer. Further, thermo-oxidative degradation of the additives and its kinetics were investigated using LDPE or squalane as matrix. The half-lives of additives in both matrices revealed significant differences between the tested additives as well as between LDPE and squalane. For instance, 2-tert-butyl-6-[(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl]-4-methylphenol (Antioxidant 2246) showed a half-life 12 times lower when incorporated in LDPE as compared to squalane. As a model for dermal exposure of consumers, human skin was brought into contact with the tailor-made LDPE containing additives ex vivo in static Franz diffusion cells. The skin was then analyzed for additives and decomposition products. This study proved 10 polymer additives of diverse pysicochemical properties and functionalities to migrate out of the polymer and eventually overcome the intact human skin barrier during contact. Moreover, their individual distribution within distinct skin layers was demonstrated. This is exemplified by the penetration of the procarcinogenic antioxidant N-phenylnaphthalen-2-amine (Neozon D) into the viable epidermis and the permeation through the skin of the neurotoxic plasticizer N-butylbenzenesulfonamide (NBBS). In addition, the analyses of additive degradation products in the isolated skin layers revealed the presence of 2-tert-butyl-4-methylphenol in all layers after contact to a polymer with substances of origin like Antioxidant 2246. Thus, attention needs to be paid to absorption of polymer additives together with their degradation products when it comes to dermal exposure assessment.

Pharmacokinetics of Polymersomes Composed of Poly(Butadiene-Ethylene Oxide); Healthy versus Tumor-Bearing Mice.

Vesicles composed of block copolymers (i.e., polymersomes) are one of the most versatile nano-carriers for medical purposes due to their tuneable physicochemical properties and the possibility to encapsulate simultaneously hydrophobic and hydrophilic substances, allowing, for instance, the combination of therapy and imaging. In cancer treatment, these vesicles need to remain long enough in the blood stream to be sufficiently taken up by tumors. Here, we have investigated the biodistribution and the pharmacokinetics of polymersomes, composed of poly(butadiene-b-ethylene oxide) having dimensions around 80 nm. The polymersomes have been radiolabeled with ¹¹¹In via the so-called active loading method achieving a loading efficiency of 92.9 ± 0.9% with radionuclide retention in mouse serum of more than 95% at 24 h. The optimized ¹¹¹In containing polymersomes have been intravenously administered in healthy and tumor bearing mice for pharmacokinetic determination using microSPECT (Single Photon Emission Computed Tomography). In healthy mice these polymersomes have been found to exhibit relatively long blood circulation (> 6 h), low liver uptake (6 ± 1.5%ID/g, 48 h p.i.) and elevated spleen uptake (188 ± 30%ID/g). The blood circulation in tumor bearing mice is dramatically reduced (< 1.5 h) most likely due to elevated splenic filtration, clearly indicating the importance of in vivo studies in diseased mice. Finally, the polymersomes have been injected subcutaneously in tumor bearing mice revealing retention of 77% in the mice, primarily accumulated at the site of injection, up to 48 hours after administration.

Experimental degradation of polymer shopping bags (standard and degradable plastic, and biodegradable) in the gastrointestinal fluids of sea turtles.

The persistence of marine debris such as discarded polymer bags has become globally an increasing hazard to marine life. To date, over 177 marine species have been recorded to ingest man-made polymers that cause life-threatening complications such as gut impaction and perforation. This study set out to test the decay characteristics of three common types of shopping bag polymers in sea turtle gastrointestinal fluids (GIF): standard and degradable plastic, and biodegradable. Fluids were obtained from the stomachs, small intestines and large intestines of a freshly dead Green turtle (Chelonia mydas) and a Loggerhead turtle (Caretta caretta). Controls were carried out with salt and freshwater. The degradation rate was measured over 49 days, based on mass loss. Degradation rates of the standard and the degradable plastic bags after 49 days across all treatments and controls were negligible. The biodegradable bags showed mass losses between 3 and 9%. This was a much slower rate than reported by the manufacturers in an industrial composting situation (100% in 49 days). The GIF of the herbivorous Green turtle showed an increased capacity to break down the biodegradable polymer relative to the carnivorous Loggerhead, but at a much lower rate than digestion of natural vegetative matter. While the breakdown rate of biodegradable polymers in the intestinal fluids of sea turtles is greater than standard and degradable plastics, it is proposed that this is not rapid enough to prevent morbidity. Further study is recommended to investigate the speed at which biodegradable polymers decompose outside of industrial composting situations, and their durability in marine and freshwater systems.

Relationship between gastrointestinal transit time and anesthetic fasting protocols in the captive chimpanzee, Pan troglodytes.

BACKGROUND: Lengthy social separation and prolonged fasting time contribute to increased risks associated with anesthesia in captive primates. This study is an initial attempt to identify a safe pre-anesthetic fasting procedure by identifying gastric emptying time (GET) and gastrointestinal transit time (GTT) of captive chimpanzees, Pan troglodytes. METHODS: Seven adult chimpanzees at the North Carolina Zoo immobilized for annual physical examinations were fed barium-impregnated polyethylene spheres to measure GET. Eleven animals were individually fed a color dye marker and fecal passage was observed to determine GTT. RESULTS: Gastric emptying time (GET) was approximated to be >3 hours but <16 hours. The mean GTT was 16.5 hours. CONCLUSIONS: This study indicates that a fasting time of 3 hours would allow for complete gastric emptying and could potentially replace the current overnight fast (≥16 hour) to help minimize complications associated with pre-anesthetic fasting in captive primates.

Stability and release of antiviral drugs from ethylene vinyl acetate (EVA) copolymer.

The use of polymer based drug delivery systems in dentistry is a relatively new area of research with the exception of the inhibition of secondary caries by the release of fluoride ions from polyalkenoate cements and their predecessors silicate cements. The present study was to test on orally biocompatible material, ethylene vinyl acetate copolymer (EVA), for release of antiviral drugs at oral therapeutic levels over extended periods of time. We also determined their stability during film casting and release. Materials studied include gancyclovir (GCY), acyclovir (ACY), dichloromethane (DCM), and ethylene vinyl acetate (EVA). The square films (3 x 3 x 0.1 cm) were prepared from the dry sheet obtained by solvent evaporation of polymer casting solutions. These solutions were made of EVA and the drug (40:1) in 70 ml of dichloromethane at 38 degrees C. Then drug release characteristics from the drug loaded films were examined at 37 degrees C for a minimum of 14 days in 10 ml medium (ddwater) replaced daily. Kinetics of drug release were followed by spectral measurements using previously determined lambda(max) values (GCY = 250 nm; ACY = 253 nm). A minimum of three samples was tested and reproducible results were obtained. Drug stability (ACY) during film casting and its release was determined using 1H NMR spectrometer (Bruker DRX-500 and 400). Rate of drug release was determined from the part of the curve (rate vs. time) after the onset of the "burst." Although GCY has a larger molecular weight (255) than ACY (225), GCY exhibited about three times higher rate of release than ACY. This difference in rate values may be explained due to its relatively greater solubility in EVA, facilitating faster diffusion of the molecules through the channels present in EVA. This is consistent with the observation that the rate at which drug molecules diffuse through the channels of the polymer, can be increased by decreasing the molecular weight. In the case of ACY, the molecules may be undergoing molecular associations, perhaps dimerization or trimerization in addition to its lower solubility in EVA. The diffusion of ACY tends to be slower under these circumstances compared to GCY resulting in lower rate value than in the case of GCY. Biological studies revealed that ACY exhibited a remarkable decrease in a number of viral organisms present in virus infected cell culture system using real-time polymerase chain reaction (RT-PCR). NMR analysis indicates that the chemical structure of the drug remains stable during film casting process and release.

Fluid absorption study in ultra-high molecular weight polyethylene (UHMWPE) sterilized and unsterilized acetabular cups.

The weight gain due to fluid absorption was measured in gamma-sterilized, ethylene oxide (ETO) gas-sterilized, and unsterilized ultra-high molecular weight (UHMW) polyethylene acetabular cups. After about 2 months the total average fluid absorption gain of the polyethylene cups was: 1.76 +/- 0.45 mg (average +/- standard deviation) for the unsterilized polyethylene cups, 2.81 +/- 0.95 mg for the gamma-sterilized polyethylene cups and 1.51 +/- 0.34 for the ETO gas-sterilized polyethylene cups. There was little difference in fluid absorption between the sterilized and unsterilized specimens. In particular, the gamma-sterilized acetabular cups absorbed more than the ETO gas-sterilized and the unsterilized cups. However, the weight gain was higher in serum compared with that in water.

PCL-b-PEO micelles as a delivery vehicle for FK506: assessment of a functional recovery of crushed peripheral nerve.

The aim of this work was to test in vivo a new block copolymer-based delivery system containing lipophilic drug FK506, known as Tacrolimus. Tacrolimus is currently used in clinics as an immunosupressant agent, and more recently it has been shown that it can exert neurotrophic effects. We prepared, characterized, and assessed polycaprolactone-b-polyethylenoxyde (PCL-b-PEO) micelles containing FK506 in vitro and in vivo. By using well-established animal model of peripheral nerve injury (crushed sciatic nerve), we show that the rate of functional recovery of injured nerve is significantly enhanced in rats treated with micellar FK506. These findings support the notion that PCL-b-PEO is a suitable polymer material for FK506 and suggest its wider applicability as a delivery vehicle for other biologically active, poorly soluble therapeutic agents.