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Rationale: Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH., Methods: The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO., Results: In simulated-use extraction, calibration curves were evaluated in the range of 1-100 and 5-500 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5-50 and 2-200 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 μg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO., Conclusions: This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use., (© 2024 John Wiley & Sons Ltd.)

A "one-step" strategy has been demonstrated for the tunable synthesis of multifunctional aliphatic polycarbonates (APCs) with ethylene oxide (EO), ethylene carbonate (EC), and cyclohexene oxide (CHO) side groups by the copolymerization of 4-vinyl-1-cyclohexene diepoxide with carbon dioxide under an aminotriphenolate iron/PPNBz (PPN = bis(triphenylphosphine)-iminium, Bz = benzoate) binary catalyst. By adjusting the PPNBz-to-iron complex ratio and incorporating auxiliary solvents, the content of functional side groups can be tuned within the ranges of 53-75% for EO, 18-47% for EC, and <1-7% for CHO. The yield and molecular weight distribution of the resulting multifunctional APCs are affected by the viscosity of the polymerization system. The use of tetrahydrofuran as an auxiliary solvent enables the preparation of narrow-distribution polycarbonates at high conversion. This work presents a novel perspective for the preparation of tailorable multifunctional APCs.

Biodegradable shape memory polymers provide unique regenerative medicine approaches in minimally invasive surgeries. Once heated, thermally responsive shape memory polymer devices can be compressed, programmed to fit within a small profile, delivered in the cold programmed state, and expanded when heated to body temperature. We have previously developed a biodegradable shape memory elastomer (SME), poly(glycerol dodecanedioate) (PGD), with transition temperatures near 37°C exhibiting nonlinear elastic properties like numerous soft tissues. Using SMEs in the clinic requires disinfection and sterilization methods that conserve physiochemical, thermomechanical, and shape recovery properties. We evaluated disinfection protocols using 70% ethanol and UV254 nm for research applications and ethylene oxide (EtO) gas sterilization for clinical applications. Samples disinfected with ethanol for 0.5 and 1 min showed no changes in physiochemical material properties, but after 15 min showed slower recovery rates than controls (p < .05). EtO sterilization at 54.4°C decreased transition temperatures and shape recovery rate compared to EtO sterilization at 37.8°C (p < .01) and controls (p < .05). Aging samples for 9 months in a vacuum desiccator significantly reduced shape recovery, and the recovery rate in EtO sterilized samples compared to controls (p < .001). Cytotoxicity testing (ISO-10993.5C:2012) revealed media extractions from EtO sterilized samples, sterilized at 37.8°C, and high-density polyethylene negative control samples exhibit lower cytotoxicity (IC50) than Ethanol 1 min, UV 2 h, and EtO 54.4°C. Cell viability of NIH3T3 fibroblasts on sterilized surfaces was equivalent on EtO 37.7°C, EtO 54.4°C and Ethanol sterilized substrates. Finally, chromogenic bacterial endotoxin testing showed endotoxin levels were below the FDA prescribed levels for devices contacting blood and lymphatic tissues for ethanol 1 min, UV 120 min, EtO 37.7°C, EtO 54.4°C. These findings outline various disinfection and sterilization processes for research and pre-clinical application and provide a pathway for developing custom sterilization cycles for the translation of biomedical devices utilizing PGD shape memory polymers., (© 2022 Wiley Periodicals LLC.)

Reactions of oxirane ring opening provide a powerful tool for regio- and stereoselective synthesis of polyfunctional and heterocyclic compounds, widely used in organic chemistry and drug design. Cyclooctane, alongside other medium-sized rings, is of interest as a novel molecular platform for the construction of target-oriented leads. Additionally, cyclooctane derivatives are well known to be prone to transannular reactions, which makes them a promising object in the search for novel approaches to polycyclic structures. In the present work, a series of cyclooctanediones was studied in Corey-Chaykovsky reactions, and novel spirocyclic bis(oxiranes) containing cyclooctane core, namely, 1,5-dioxadispiro[2.0.2.6]dodecane and 1,8-dioxadispiro[2.3.2.3]dodecane, were synthesized. Ring opening of the obtained bis(oxiranes) upon treatment with sodium azide was investigated, and it was found that the reaction path is determined by the reciprocal orientation of oxygen atoms in the oxirane moieties. Diastereomers of the bis(oxiranes) with cis -orientation underwent independent ring opening, supplying corresponding diazidodiols, while in the case of stereoisomers with trans -orientation, domino-like reactions occurred, including intramolecular nucleophilic attack and the formation of a novel three- or six-membered O-containing ring. Summarily, a straightforward approach to polyfunctional compounds containing cyclooctane or oxabicyclo[3.3.1]nonane cores, employing bis(oxiranes), was elaborated.

Ensuring the sterility of life science products plays a pivotal role in the healthcare sector. Gamma irradiation and ethylene oxide sterilization are two commonly applied methods for the sterilization of medical devices, packaging components and Active Pharmaceutical Ingredients (API) for medicinal products. Focussed studies on the effects of sterilization processes on APIs remain limited. In this research study, five APIs, frequently used in sterile ophthalmic preparations were subjected to both gamma irradiation and ethylene oxide under different process conditions. The following APIs of GMP quality were selected: dexamethasone, aciclovir, tetracycline hydrochloride, triamcinolone and methylprednisolone. Analyses were performed using High Performance Liquid Chromatography equipped with UV detection and the effect of sterilization conditions on the APIs was evaluated by the assay and related substances test prescribed by the European Pharmacopoeia (Ph. Eur.). It was concluded that exposure to ethylene oxide resulted in compliance with Ph. Eur. for all APIs. While dexamethasone and methylprednisolone did not meet the requirement for the Ph. Eur. after exposure to gamma irradiation, the other three APIs did meet the requirement under the specified irradiation conditions. Subsequent optimization of sterilization parameters positively influenced the compliance to the Ph. Eur. requirements., Competing Interests: Declaration of Competing Interest Sterigenics has no conflict of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The 'ethylene glycol ethers' (EGE) are a broad family of solvents and hydraulic fluids produced through the reaction of ethylene oxide and a monoalcohol. Certain EGE derived from methanol and ethanol are well known to cause toxicity to the testes and fetotoxicity and that this is caused by the common metabolites methoxy and ethoxyacetic acid, respectively. There have been numerous published claims that EGE fall into the category of 'endocrine disruptors' often without substantiated evidence. This review systematically evaluates all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors. The conclusion reached is that there is no significant evidence to show that EGE target any endocrine organs or perturb endocrine pathways and that any toxicity that is seen occurs by non-endocrine modes of action., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

Recyclable aqueous two-phase systems with thermo-responsive phase-forming materials have been employed to separate macromolecules; however, these systems have achieved very limited separation efficiency for small molecules, such as antibiotics. In this study, aqueous two-phase systems composed of the ethylene oxide/propylene oxide copolymer and water were developed to extract alkaline antibiotics from the fermentation broth. In the aqueous two-phase systems with an ethylene oxide ratio of 20 and propylene oxide ratio of 80, the partition coefficients of tylosin and spiramycin reached 16.87 and 20.39, respectively, while the extraction recoveries were 70.67 and 86.70%, respectively. Coupled with mechanism analysis, we demonstrated the feasibility of extracting alkaline antibiotics using this aqueous two-phase system, especially for 16-membered macrolide antibiotics. The molecular dynamic simulation was employed to visualize the process of dual-phase formation and the partition behavior of antibiotics in an aqueous two-phase system. The dynamic simulation revealed the binding energy between the antibiotic and ethylene oxide/propylene oxide copolymers, which provides a simple indicator for screening suitable antibiotics in aqueous two-phase systems. Our recyclable aqueous two-phase systems provide a robust approach for the extraction of 16-membered macrolide antibiotics with ease of operation and high recovery rates, which is appropriate for large-scale extraction in the fermentation industry., (© 2021 Wiley-VCH GmbH.)

This study evaluated the performance of a new O 3 /H 2 O 2 mixed gas sterilization instrument for killing microorganisms and inactivating bacterial endotoxin at low temperatures. Sterility assurance level was achieved by an over 6-log reduction of Geobacillus stearothermophilus ATCC 12980, and the decimal reduction value was 0.77 min in sterilization mode. A reduction of over 3 logs in Limulus amebocyte lysate coagulation activity of purified endotoxin from Escherichia coli was observed after treatment in endotoxin-inactivation mode. The same inactivation ability was observed when treating dried bacterial cells. Biomaterials made of polymer or metal did not exhibit cytotoxicity after gas exposure at O 3 concentrations below 200 ppm. As the results of human cell-based pyrogen testing, significant amounts of endotoxin that were over the limit for medical devices contacting cerebrospinal fluid (2.15 EU/device) were detected on scissors washed with a washer-disinfector and sterilized with ethylene oxide or autoclaving. In contrast, endotoxin decreased to 0.29 ± 0.05 EU/device after O 3 /H 2 O 2 mixed gas sterilization in endotoxin-inactivation mode. Compared to conventional gas sterilization methods, O 3 /H 2 O 2 mixed gas has high sterilization ability and a strong capacity to inactivate endotoxin. It is expected that this sterilization technology will improve the safety of reusable medical devices and utensils for regenerative medicine., (© 2021 Wiley Periodicals LLC.)

The synthesis of poly(ethylene oxide) (PEO) with amino end group, a key functionality for PEGylation, is a long-standing challenge. Multistep routes based on postmodification or covalent protection have been adopted to circumvent ethoxylation of the amino group by ethylene oxide (EO). Here, we report a noncovalent protection strategy for one-step synthesis of PEO amine. An amino (di)alcohol is mixed with a small amount of mild phosphazene base and excess triethylborane (Et 3 B) before addition of EO. The complexation of the amino group with Et 3 B guarantees that polymerization of EO occurs selectively from the hydroxyl group through the bicomponent metal-free catalysis. Simply by precipitation in diethyl ether, the protective Et 3 B as well as the catalyst can be removed to afford α-amino-ω-hydroxyl PEO with controlled molar mass, low dispersity, and complete end functionality. The effect of initiator structure and retention of Et 3 B on the storage (oxidative) stability of PEO amine is also revealed.

Based on the Diels-Alder reaction of vinylchromenes with electron-poor dienophiles, we developed a strategy for the synthesis of tetrahydrocannabinol derivatives. Substituted vinyl chromenes could be converted with several dienophiles to successfully isolate several complex molecules. These molecules already contain the cannabinoid-like base structure and further processing of one such derivative led to a precursor of Δ 9 -tetrahydrocannabinol. The most challenging step towards this precursor was an epoxidation step that was ultimately achieved via dimethyl dioxirane., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Electrospun hybrid nanofibers have been extensively regarded as drug carriers. This study tries to introduce a nano fibrous wound dressing as a new strategy for a topical drug-delivery system. The vancomycin (VCM)-loaded hybrid chitosan/poly ethylene oxide (CH/PEO) nanofibers were fabricated by the blend-electrospinning process. Morphological, mechanical, chemical, and biological properties of nanofibers were examined by SEM, FTIR, release profile study, tensile assay, Alamar Blue cytotoxicity evaluation, and antibacterial activity assay. In vivo wound healing activity of hybrid CH/PEO/VCM nanofibers was evaluated in full-thickness skin wounds of rats. The hybrid CH/PEO/VCM nanofibers were successfully fabricated in a nanometer. The CH/PEO/VCM 2.5% had higher Young's Modulus, better tensile strength, smaller fiber diameter with sustained-release profiles compared to CH/PEO/VCM 5%. All nanofibers did not show any significant cytotoxicity (P < 0.05) on the normal fibroblast cells. Also, VCM-load hybrid CH/PEO nanofibers successfully inhibited bacterial growth. The wound area in the rats treated with CH/PEO/VCM 2.5% was less than CH/PEO/VCM 5% treated group. According to histological evaluation, the CH/PEO/VCM 2.5% group showed the fastest wound healing than other treatment groups. Results of this study proposed that CH/PEO/VCM nanofibers could promote the wound healing process by reducing the side effects of VCM as a topical antimicrobial agent., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

In this work, we treated chitin with 2-(azidomethyl)oxirane and successfully involved the resultant azido chitin derivatives in the ultrasound-assisted Cu(I)-catalyzed azido-alkyne click (CuAAC) reaction with propargylic ester of N,N,N-trimethyl glycine. Thus, we obtained novel water-soluble triazole chitin derivatives. The triazole chitin derivatives and their nanoparticles are characterized by a high in vitro antibacterial activity, which is the same or even higher than that of commercial antibiotics ampicillin and gentamicin. The obtained derivatives are non-toxic. Moreover, the obtained water-soluble polymers are highly efficient green catalysts for the aldol reaction in green solvent water. The catalysts can be easily extracted from the reaction mixture by its precipitation with green solvent ethanol followed by centrifugation and they can be reused at least 10 times., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The objectives of this study were to investigate the effects of processing parameters (relative humidity (RH), temperature, and exposure time) on the ethylene oxide (EtO) microbial inactivation of Salmonella spp. and to evaluate Enterococcus faecium NRRL B2354 as a suitable surrogate for Salmonella inactivation on cumin seeds. Five grams of cumin seeds inoculated with either Salmonella or E. faecium were treated with EtO at different temperatures (46, 53, and 60 °C) and RH (30, 40, and 50%) levels for different exposure time to investigate the effects of process parameters on the microbial inactivation. The Weibull model fit the survival data of both bacteria with a shape parameter p < 1, which showed a tailing effect with concave shape indicating that the sensitive cells were inactivated first, and the sturdy ones survived at low RH treatment conditions. In general, the log reductions of both bacteria on cumin seeds increased with the increasing RH and temperature for EtO treatment. RH is a critical factor for successful EtO inactivation treatment. RH must be higher than 40% to implement a successful and efficient EtO decontamination of cumin seeds. E. faecium consistently showed lower log reductions than those of Salmonella under all EtO treatment conditions investigated in this study, demonstrating that E. faecium is a suitable surrogate for Salmonella. Twenty minutes of EtO treatment at 50% RH achieved ~5 log reductions of both bacteria at all three temperatures. A response surface model was developed to predict the log reductions of both bacteria under different treatment conditions and the contour plots representing log reductions were created. Inactivation is positively correlated to temperature and RH. Therefore, a higher temperature is required to achieve the desired log reduction at lower RH and vice versa. The developed response surface model is a valuable tool for the spice industry in identifying the possible combinations of EtO process parameters (temperature, RH, and exposure time) required to achieve a desired microbial reduction of Salmonella for ensuring microbial food safety of spices., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Zhang et al.)

Diabetes can impair osteoblastic functions and negatively interfere with osteointegration at the bone/implant interface. Previously, we prepared a nanosized calcium silicate (CS) incorporated-polyetheretherketone (PK) biocomposite (CS/PK) and found that the CS/PK composite exhibited enhanced osteoblast functions in vitro and osteointegration in vivo, but its bioperformance under diabetic conditions remained elusive. In this study, MC3T3-E1 cells incubated on CS/PK and PK samples were subjected to diabetic serum (DS) and normal serum (NS); cell attachment, morphology, spreading, proliferation, and osteogenic differentiation were compared to assess in vitro osteoblastic functions on the surfaces of different materials. An in vivo test was performed on diabetic rabbits implanted with CS/PK or PK implants into the cranial bone defect to assess the osteointegration ability of the implants. In vitro results showed that diabetes inhibited osteoblastic functions evidenced by impaired morphology and spreading, and decreased attachment, proliferation, and osteogenic differentiation compared with the findings under normal conditions. Notably, CS/PK ameliorated osteoblastic disfunction under diabetic conditions in vitro. In vivo results from micro-CT and histologic examinations revealed that rabbits with CS/PK implants exhibited improved osteointegration at the bone/implant interface under diabetic conditions compared with PK. Therefore, the CS/PK composite improved the impaired osteointegration induced by diabetes and is a promising orthopedic or craniofacial implant material that may obtain good clinical performance in diabetic patients.

Wearing face masks is highly recommended to prevent SARS-CoV-2 transmission in health care workers and for the general public. The demand for high quality face masks has seen an upsurge in the recent times, leading to exploration of alternative economic and easily available options, without compromising on the quality. Particle removal from air in terms of capture efficiency of the filter media or the face mask is a crucial parameter for testing and quality assurance. Short-term reusability of the face masks is also an important aspect as the demand for masks will potentially outstrip the supply in future. Sterilization Wraps, which are used to wrap sterile surgical instruments, have shown a promising performance in terms of removal of particles from air. In this study, we evaluate the particle filtration characteristics of face masks made of 2 different metric weights [45 and 60 gram per square metre (GSM)] respectively, using locally available Sterilization Wraps. The aerosol filtration characteristics were also studied after sterilisation by different techniques such as heat with 50% humidity (thermal treatment), ethylene oxide (ETO), steam and radiation dose of 30kGy. We found that 60 GSM face mask had particle capture efficiency of 94% for total particles greater than 0.3 microns and this capture efficiency was maintained even after sterilisation with ETO and thermal treatment. The cost of producing these masks was 30 US cents/mask at our institute. Our study suggests that sterilization wrap material made of non-woven polypropylene spunbond-meltblown-spunbond (SMS) fibres could be an appropriate readily available inexpensive material for making face masks or N95 respirators., Competing Interests: Dr S. G:Institutional financial interests for conducted research - Roche, Sanofi, Johnson & Johnson, Amgen, Celltrion, Oncosten, Novartis, Intas, Eisai, Biocon, and Astrazeneca. Nonremunerated activities – Advisory board: Roche, Sanofi, Dr. Reddy’s Laboratories, Biocon, Pfizer, Oncosten, Core Diagnostics, Astrazeneca. All other Authors:none We further state that these competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Gelatin methacryloyl (GelMA) hydrogel scaffolds and GelMA-based bioinks are widely used in tissue engineering and bioprinting due to their ability to support cellular functions and new tissue development. Unfortunately, while terminal sterilization of the GelMA is a critical step for translational tissue engineering applications, it can potentially cause thermal or chemical modifications of GelMA. Thus, understanding the effect of terminal sterilization on GelMA properties is an important, though often overlooked, aspect of material design for translational tissue engineering applications. To this end, we characterized the effects of FDA-approved terminal sterilization methods (autoclaving, ethylene oxide treatment, and gamma (γ)-irradiation) on GelMA prepolymer (bioink) and GelMA hydrogels in terms of the relevant properties for biomedical applications, including mechanical strength, biodegradation rate, cell culture in 2D and 3D, and printability. Autoclaving and ethylene oxide treatment of the GelMA decreased the stiffness of the hydrogel, but the treatments did not modify the biodegradation rate of the hydrogel; meanwhile, γ-irradiation increased the stiffness, reduced the pore size and significantly slowed the biodegradation rate. None of the terminal sterilization methods changed the 2D fibroblast or endothelial cell adhesion and spreading. However, ethylene oxide treatment significantly lowered the fibroblast viability in 3D cell culture. Strikingly, γ-irradiation led to significantly reduced ability of the GelMA prepolymer to undergo sol-gel transition. Furthermore, printability studies showed that the bioinks prepared from γ-irradiated GelMA had significantly reduced printability as compared to the GelMA bioinks prepared from autoclaved or ethylene oxide treated GelMA. These results reveal that the choice of the terminal sterilization method can strongly influence important properties of GelMA bioink and hydrogel. Overall, this study provides further insight into GelMA-based material design with consideration of the effect of terminal sterilization.

Long-chain epoxides and specifically alkyl glycidyl ethers represent a class of highly hydrophobic monomers for anionic ring-opening polymerization (AROP), resulting in apolar aliphatic polyethers. In contrast, poly(ethylene glycol) is known for its high solubility in water. The combination of hydrophobic and hydrophilic monomers in block and statistical copolymerization reactions enables the synthesis of amphiphilic polyethers for a wide range of purposes, utilizing micellar interactions in aqueous solutions, e.g., viscosity enhancement of aqueous solutions, formation of supramolecular hydrogels, or for polymeric surfactants. Controlled polymerization of these highly hydrophobic long-chain epoxide monomers via different synthesis strategies, AROP, monomer-activated anionic ring-opening polymerization, catalytic polymerization, or via postmodification, enables precise control of the hydrophilic/lipophilic balance. This renders amphiphilic polymers highly interesting candidates for specialized applications, e.g., as co-surfactants in microemulsion systems. Amphiphilic polyethers based on propylene oxide and ethylene oxide, such as poloxamers are already utilized in many established applications due to the high biocompatibility of the polyether backbone. Long alkyl chain epoxides add an interesting perspective to this area and permit structural tailoring. This review gives an overview of the recent developments regarding the synthesis of amphiphilic polyethers bearing long alkyl chains and their applications., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A simple method for the synthesis of functionalized 2H-pyrans via a catalytic reaction of an oxirane, an alkyne, and a malonate has been developed in which a 6-exo-dig cyclization pathway is observed. In this transformation, the attack of in situ generated copper acetylides on oxiranes formed homopropargylic alcohol intermediates which further transferred to 2H-pyrans with the help of malonates.

The objective of the current study is to design and delivery of targeted PEG-PCL nanopolymersomes encapsulated with Gadolinium based Quantum Dots (QDs) and Doxorubicin (DOX) as magnetic resonance-florescence imaging and anti-cancer agent. Diagnostic and therapeutic efficiency of the prepared theranostic formulation was evaluated in vitro and in vivo. Hydrophobic QDs based on indium-copper-gadolinium-zinc sulfide were synthesized and characterized extensively. Hydrophobic QDs and hydrophilic DOX were loaded in PEG-PCL polymersomes through double emulsion method. Drug release pattern was studied in both citrate (pH 5.4) and phosphate (pH 7.4) buffer during 10 days. Both fluorescence and magnetic properties of bare QDs and prepared formulations were studied entirely. AS1411 DNA aptamer was covalently attached to the surface of polymersomal formulation in order to prepare targeted drug delivery system. Cellular cytotoxicity and cellular uptake analysis were performed in both nucleolin positive (MCF7 and 4T1) and nucleolin negative (CHO) cell lines. After in vitro evaluations, anti-tumor efficiency and diagnostic capability of the formulation was investigated in 4T1 tumor baring mice. Scanning emission electron microscopy (SEM) confirmed spherical shape and around 100 nm size of prepared formulations. Transmission electron microscopy (HRTEM) showed crystal shape of QDs with size of 2-3 nm. Drug release study obtained controlled release of encapsulated DOX and stability of formulation in physiologic condition. MTT and flow cytometry results demonstrated that AS1411 aptamer could enhance both toxicity and cellular uptake in nucleolin overexpressing cell lines (P < 0.05). Moreover, aptamer targeted formulation could increase survival rate and tumor inhibitory growth effect in 4T1 tumor baring mice (P < 0.05). Our results verify that aptamer targeted polymersomes loaded with non-toxic QDs as a diagnostic agent and DOX as an anti-cancer drug, could provide a theranostic platform with the purpose of optimization of treatment process and minimization of systemic side effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, lipase from Thermomyces lanuginosus (TLL) was immobilized onto the parent and organic groups modified SBA-15, and the enzymatic properties of the obtained immobilized TLL samples were investigated. 1) Activity of SBA-15-TLL at 2862.78 ± 293.24 U/g was obtained. 2) Most of the organic groups modification favored a great improvement in activity, and higher activity over 12000 U/g was observed for N-phenylaminomethyl and phenyl group modification. 3) Most of the supported TLL showed better thermostability in air while poor in phosphate buffer, with over 80% vers less than 20% of their initial activity retained after 4 h incubation at 70℃. 4) The n-dodecyl, phenyl and N-phenylaminomethyl group functionalization decreased the sensitivity of immobilized TLL in extreme pH values. 5) The n-octyl and 2-(propoxymethyl)oxirane group modification confered the supported TLL good reusability, and over 60% of their initial activity was retained after five successive cycles of reuse.

Medical devices are an important and growing aspect of healthcare provision and are increasing in complexity to meet established and emerging patient needs. Terminal sterilization plays a vital role in the provision of safe medical devices. While terminal sterilization technologies for medical devices include multiple radiation options, ethylene oxide remains the predominant nonthermal gaseous option, sterilizing c. 50% of all manufactured devices. Vaporized hydrogen peroxide (abbreviated VH2O2 by the International Organization for Standardization) is currently deployed for clinical sterilization applications, where its performance characteristics appear aligned to requirements, constituting a viable alternative low-temperature process for terminal processing of medical devices. However, VH2O2 has operational limitations that create technical challenges for industrial-scale adoption. This timely review provides a succinct overview of VH2O2 in gaseous sterilization and addresses its applicability for terminal sterilization of medical devices. It also describes underappreciated factors such as the occurrence of nonlinear microbial inactivation kinetic plots that may dictate a need to develop a new standard approach to validate VH2O2 for terminal sterilization of medical devices., (© 2019 The Society for Applied Microbiology.)

Formulating a hydrophobic drug that is water-soluble is a pharmaceutical challenge. One way is to incorporate the drug in an amphiphilic micelle composed from an aggregation of block copolymers. Design of a good nano-micelle requires many trial-and-error attempts. In this article, we developed a computational model based on a coarse-grained molecular dynamic (MD) simulation and correlated outputs with previous studies. A good correlation shows that this model reliably simulates poly-lactic acid-poly-ethylene glycol (PLA-PEG) and poly-caprolactone (PCL)-PEG aggregation in water with and without the presence of doxorubicin. Communicated by Ramaswamy H. Sarma.

Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed K i  = 8.30 ± 0.94 µM and K i ' = 9.54 ± 0.38 µM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) K i  = 8.23 ± 0.93 µM and K i ' = 13.07 ± 0.46 µM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The anionic ring opening polymerizations of ethylene oxide (EO) and propylene oxide (PO) are performed by using 1,3,5-triethanol hexahydro-1,3,5-triazine (TrAz) as a "sacrificial" trifunctional initiator. Well-defined three-arm star polymers are obtained with a narrow molecular weight distribution (M w /M n < 1.1). Molecular weights range from 3-15 kg mol -1 . Since these star polymers possess an acid-labile hexahydro-triazine core, acidic hydrolysis leads to cleavage of the arms. This gives access to well-defined α-amino-ω-hydroxyl heterobifunctional poly(ethylene glycol) (PEG) and poly(propylene oxide) (PPO) in the molecular weight range of 1-5 kg mol -1 and low dispersity M w /M n < 1.1. The α,ω-heterobifunctional polyethers are valuable structures for bioconjugation. Furthermore, an acid-labile triazine star polymer is directly used as a polyol component for the synthesis of a polyurethane network, which is stable under ambient conditions but degrades rapidly under acidic conditions., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hydroxy-containing cyclic ethers react with thermally generated benzynes to produce aryl ethers. Diverse reactivity was observed. Cleavage of the cyclic ether was involved in most of the pathways. The transformations are rationalized via initial formation of oxonium ion-containing 1,3-zwitterions arising from preferential nucleophilic attack on the benzyne by the ether oxygen. Pinacol-like rearrangements, including ring expansion, to yield aldehydes or ketones and oxirane fragmentations to generate aryl enol ethers were main competing events.

Reliable and scalable sterilisation of hydrogels is critical to the clinical translation of many biofabrication approaches, such as extrusion-based 3D bioprinting of cell-laden bio-inks. However sterilisation methods can be destructive, and may have detrimental effects on the naturally-derived hydrogels that constitute much of the bio-ink palette. Determining effective sterilisation methods requires detailed analysis of the effects of sterilisation on relevant properties such as viscosity, printability and cytocompatibility. Yet there have been no studies specifically exploring the effects of sterilisation on bio-inks to date. In this work, we explored the effects of various sterilisation techniques on four of the most widely used bio-ink components: gelatin, gelatin methacryloyl, hyaluronic acid, and hyaluronic acid methacrylate. Autoclaving was the most destructive sterilisation method, producing large reductions in viscosity and in mechanical properties following crosslinking. Filter sterilisation caused some reduction in rheological properties of GelMA due to removal of higher molecular weight components, but did not affect photocrosslinking. Ethylene oxide (EtO) was the least destructive sterilisation method in terms of rheological properties for all materials, had no detrimental effect on the photocrosslinkable methacrylate/methacrylamide groups, and so was chosen for more detailed examination. In biological analyses, we found that EtO treatment successfully eradicated a bacterial challenge of E. coli, caused no decrease in viability of human mesenchyman stem cells (hMSCs), and had no effect on their rate of proliferation. Finally, we found that EtO-treated hydrogels supported encapsulated hMSCs to differentiate towards the chondrogenic lineage, and to produce new cartilage matrix. Our results bring to light various effects that sterilisation can have on bio-inks, as well as highlighting EtO sterilisation as a method which minimises degradation of properties, while still promoting biological function.

Long and rigid objects formed by self-assembly in water are useful as templates or for their rheological or biological properties. They are usually obtained by combining hydrogen bonding and strong hydrophobic interactions brought by an alkyl or alkylene chain. A simple access to well-defined rod-like assemblies in water is reported based on a penta-urea sticker directly connected to poly(ethylene oxide) side chains. These assemblies are characterized by an average length of several hundreds of nanometers and a monodisperse radius (4.5 nm) resulting from a reduced lateral aggregation of the stickers., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Materials from prefilled syringe systems-such as silicone oil, tungsten, glass, and rubber-may enhance therapeutic protein aggregation and particle formation. Also, the sterilization method used for syringes may impact aggregation and chemical degradation of biologics during storage. Syringes are generally sterilized by radiation, ethylene oxide gas (EO), or steam. Among the sterilization methods, EO has the potential to cause chemical degradation by the formation of adducts with susceptible amino acid residues in the protein. In this study, EO- and steam-sterilized syringes were compared to determine the influence of residual EO on human serum albumin (HSA) degradation. Although the amount of residual EO in the EO-sterilized syringes was less than 220 μg/syringe, well below the International Organization for Standardization limit, EO adduction to cysteine (Cys) and methionine (Met) in HSA was observed by liquid chromatography and mass spectrometry analysis. The EO adduct ratio of HSA stored for 2 weeks in EO-sterilized syringes was about 45%. In contrast, no chemical degradation was observed in HSA formulation stored in steam-sterilized syringes. Because of the propensity of EO to readily form adducts with proteins, an alternative to EO sterilization should be used for prefilled syringes that will be used for therapeutic protein products., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

A dimer of quercetin prepared through a Mannich reaction protects pyridinium bisretinoid A2E from photooxidation at 430 nm in aqueous medium at pH 7.4. In the presence of light and O 2 , A2E is quickly attacked by 1 O 2 produced in situ (by excited A2E) to give nonaoxirane and other oxygenated compounds which can be involved in diseases of the macula. Peroxyl radicals might have only a marginal role on the photooxidation of A2E. The dimer is actually a potent quencher of 1 O 2 with a rate constant k Q of 8.5 × 10 8  M -1  s -1 in methanol at room temperature. On the other hand, its antioxidant abilities against ROO · radicals are quite limited since k ROO·  = 7.3 × 10 5  M -1  s -1 (in buffer solution at pH 7.4), the value being essentially identical to that of quercetin. The quenching of 1 O 2 by the dimer is therefore the main reason for the A2E protection and prevention of age-related macular degeneration., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The study describes the detailed examination of the effect of ethylene oxide sterilization on electrospun scaffolds constructed from biodegradable polyesters. Different fibrous layers fabricated from polycaprolactone (PCL) and a copolymer consisting of polylactide and polycaprolactone (PLCL) were investigated for the determination of their mechanical properties, degradation rates and interaction with fibroblasts. It was discovered that the sterilization procedure influenced the mechanical properties of the electrospun PLCL copolymer scaffold to the greatest extent. No effect of ethylene oxide sterilization on degradation behavior was observed. However, a delayed fibroblast proliferation rate was noticed with concern to the ethylene oxide sterilized samples compared to the ethanol sterilization of the materials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Over the past decade, the implementation of the novel nanomaterials in the field of nanotechnology for the biomedical applications is essential for the comfort factors such as non-toxicity and biocompatibility in the human biological systems. In this context, a novel synthesis was worked out through bacterial species (citrobacter braakii) in the biofabrication of bioactive gold nanoparticles (Au NPs) for the wound healing management. The biosynthesized Au NPs were further modified and improved its compatibility with polyethylene glycol (PEG) and polycaprolactone (PCL) for formed as Au-PEG/PCL nanocomposites to extent the activity in wound healing application. The combination of bioactive nanoparticles with biocompatible polymeric substances has been upsurges the activity of nanoparticles due to the strong interaction of polymers. The biofabricated Au NPs and its nanocomposites were characterized using UV-Vis, FT-IR, XRD, DLS and TEM studies. Further, the prepared materials were tested in a wound healing model of rat with the wound of 22 mm size. The found results are demonstrated that the improved materials are highly active in growth of keratinocytes proliferation and simultaneously reduce scar formation. After 15 days observations, the wound were almost completely healed by the developed Au- PEG/PCL nanocomposites material which was confirmed by Masson's Trichrome staining histological images and antibacterial efficacy was displayed by the CLSM images. Notably, polymeric Au-PEG/PCL nanocomposites showed no inflammation on the wounded portion and internal implantation on rats thus evidencing it as a safe and biologically very active wound healing agent., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Develop a hydrophobic, degradation-resistant dental restorative based on an Oxirane-Acrylate IPN System (OASys) with low shrinkage-stress to substantially extend clinical lifetime., Methods: Unfilled OASys blends were prepared using dipenta-erythritol-hexaacrylate (DPHA) and p-cycloaliphatic-diepoxide (EP5000). Varying proportions of camphorquinone/iodonium photoinitiator, with a co-reactant oligomeric-diol, served as the experimental curing system. The effects of oxirane-acrylate ratio on the degree-of-cure (Durometer-D hardness), hydrophobicity (contact angle), mechanical properties (3-point bending), near-infrared FTIR degree-of-conversion (DoC), polymerization shrinkage, and shrinkage stress were determined. 70:30 BisGMA:TEGDMA resin served as control., Results: Oxirane tended to decrease hardness and increase hydrophobicity. 0:100, 25:75, 50:50 EP5000:DPHA are harder after 24h than control. 75:25 and 100:0 EP5000:DPHA increased in hardness over 24h, but were softer than control. All groups increased in contact angle over 24h. After 24h, 50:50, 75:25 and 0:100 EP5000:DPHA were more hydrophobic (∼75-84°) than the control (∼65°). Acrylate DoC was ∼60% across all experimental groups. Initial oxirane conversion varied from ∼42% in 100:0 EP5000:DPHA to ∼82% 75:25 EP5000:DPHA. However, oxirane DoC increased for 100:0 EP5000:DPHA to ∼73° over 24h, demonstrating dark cure. Moduli and ultimate transverse strengths of OASys groups were higher than for 0:100 EP5000:DPHA, with 50:50 EP5000:DPHA having higher modulus than other experimental groups. However, the control had higher modulus and UTS than all experimental groups. Volumetric shrinkage averaged 7% for experimental groups, but stress decreased dramatically with increasing oxirane content., Significance: Hydrophobic, low shrinkage-stress OASys resins are promising for development of composites that improve longevity and reduce the cost of dental care., (Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

NMR data for natural products containing the epoxy moiety have been revisited and reanalyzed with the help of a recently developed parametric/DFT hybrid computational method, DU8+. More than 20 structures needed revision, which points to challenges in NMR solution structure assignment for molecules possessing this structural feature. Among the revised structures are achicretin 2, acremine P, aromaticane I, artanomalide B, botryosphaerihydrofuran, chloroklotzchin, crithmifolide, crotodichogamoin A, emervaridone C, 9α,15-epoxyafricanane, fischambiguine B, grandilobalide B, guaianolide A, guatterfriesols A and B, juncenolide G, roscotane D, secoafricane 7, taccalonolides AJ and AF, and related compounds.

Ethylene oxide (EO) gas is commonly used to sterilize medical devices. Bioavailable residual EO, however, presents a significant toxicity risk to patients. Residual EO is assessed using international standards describing extraction conditions for different medical device applications. We examine a series of polymers and explore different extraction conditions to determine residual EO. Materials were sterilized with EO and exhaustively extracted in water, in one of three organic solvents, or in air using thermal desorption. The EO exhaustively extracted varies significantly and is dictated by two factors: the EO that permeates the material during sterilization; and the effectiveness of the extraction protocol in flushing residual EO from the material. Extracted EO is maximized by a close matches between Hildebrand solubility parameters δ polymer , δ EO , and δ solvent . There remain complexities to resolve, however, because maximized EO uptake and detection are accompanied by great variability. These observations may inform protocols for material selection, sterilization, and EO extraction. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2455-2463, 2018., (© 2017 Wiley Periodicals, Inc.)

Hydrophobically modified ethylene oxide urethane (HEUR) rheology modifiers are polymers used widely in waterborne coatings and other consumer products. The incorporation of hydrophobic end-groups significantly affects the thickening performance of HEURs. Therefore, understanding the degree of incorporation of hydrophobic end-groups on the polymer chain can help gain important insights on the structure/property relationship for HEUR rheology modifiers. A comprehensive two-dimensional liquid chromatography (2D-LC) method was developed for separating polymeric HEUR rheology modifiers based on the number of hydrophobic end-groups incorporated on the polymer chain. Our 2D-LC method uses a size exclusion chromatography (SEC) separation in the first dimension ( 1 D) using an ultra-high performance Advance Polymer Chromatography (APC) column and a gradient reversed-phase liquid chromatography (RPLC) separation in the second dimension ( 2 D). A low flow rate was used in the first dimension SEC separation to minimize the strong organic eluent transferred to the second dimension LC column. A small inner diameter (ID) LC column was used for the second dimension to reduce the total solvent consumption for routine analysis of process samples. The 1 D flow rate, 2 D transfer volume and gradient profile were all optimized to avoid polymer breakthrough and to achieve optimal separation of the polymer chains based on end-groups. Three types of polymer chains with 0, 1, and 2 terminal hydrophobes were successfully separated using this method. The total run time was further reduced by implementing flow programing in the first dimension separation. The 2D-LC method was applied to study how the polymerization process recipes affected hydrophobe incorporation and how the hydrophobe incorporation correlated with thickening efficiency. The method was also used to separate HEUR rheology modifier with branched polymer architecture., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The optimal design of amorphous solid dispersion formulations requires the use of excipients to maintain supersaturation and improve physical stability to ensure shelf-life stability and better absorption during intestinal transit, respectively. Blends of excipients (surfactants and polymers) are often used within pharmaceutical products to improve the oral delivery of Biopharmaceutical Classification System class II drugs. Therefore, in this study, a dissolution enhancer, poloxamer 407 (P407), was investigated to determine its effect on the dissolution properties and on the amorphous nature of the active pharmaceutical ingredient contained in the formulation. Phase solubility studies of indomethacin (INM) in aqueous solutions of P407 and poly(vinylpyrrolidone-vinyl acetate copolymer) showed an increase in the kinetic solubility of INM compared with the pure drug at 37°C with a K a value of 0.041 μg/mL. The solid dispersions showed a higher dissolution rate when compared to pure and amorphous drugs when performed in pH buffer 1.2 with a kinetic solubility of 21 μg/mL. The stability data showed that the amorphous drug in solid solutions with poly(vinylpyrrolidone-vinyl acetate copolymer) and P407 remained amorphous, and the %P407 loading had no effect on the amorphous stability of INM. This study concluded that the amorphous solid dispersion contributed to the increased solubility of INM., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease and Notch pathway plays a pivotal role in synoviocytes involved in progression of RA., Methods: Herein, we have designed a self-assembled polymeric micelles based on polycaprolactone-polyethylene glycol (PCL-PEG) and polyethylenimine-polyethylene glycol (PEI-PEG) was prepared and loaded with methotrexate and Notch-1 siRNA for the effective treatment of rheumatoid arthritis., Results: The MTX/siRNA-loaded polymeric micelles (siM-PM) showed appreciable cellular uptake in Raw264.7 cells which were activated with LPS and did not exhibit any toxicity to Raw264.7 and HUVEC cells. The AUC of siM-PM was 4-fold higher compared to that of free MTX while t1/2 was 6 fold for siM-PM compared to that of free drug indicating the superior pharmacokinetic parameters. Importantly, siM-PM significantly reduced the paw thickness and slowed the disease progression remarkably, indicating that siM-PM is very effective in recovering the edema in arthritic animals. Importantly, 2-fold decrease in arthritic score was observed in siM-PM treated group at the end of day 24. The data clearly reveals anti-inflammatory effect of combinational nanoparticle due to the sequence specific downregulation of Notch-1 expression in the RA clinical models., Conclusions: Overall, nanomedicine-based delivery of MTX and siRNA could overcome the side effects of small molecules and could improve the therapeutic effect of siRNA in rheumatoid arthritis.

Objective: This study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant solutions., Significance: (1) Rationale for surfactant selection is provided; (2) the large data set can be used for validation of the drug solubility parameters used in oral absorption models., Methods: Equilibrium solubility of two hydrophobic drugs and one model hydrophobic steroid in micellar solutions of 19 surfactants was measured by HPLC. The drug solubilization locus in the micelles was assessed by UV spectrometry., Results: Danazol is solubilized much more efficiently than fenofibrate by ionic surfactants due to ion-dipole interactions between the charged surfactant head groups and the polar steroid backbone. Drug solubilization increases linearly with the increase of hydrophobic chain length for all studied surfactant types. Addition of 1-3 ethylene oxide (EO) units in the head group of dodecyl sulfate surfactants reduces significantly the solubilization of both studied drugs and decreases linearly the solubilization locus polarity of fenofibrate. The locus of fenofibrate solubilization is in the hydrophobic core of nonionic surfactant micelles and in the palisade layer of ionic surfactant micelles., Conclusions: Highest drug solubility can be obtained by using surfactants molecules with long chain length coupled with hydrophilic head group that provides additional drug-surfactant interactions (i.e. ion-dipole) in the micelles.

A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Acrylonitrile (AN) is widely used in the manufacture of resins, plastics, and polymers, where workers are exposed to it during its production, transportation, and application. After intake a portion of AN is converted to cyanoethylene oxide (CEO) by cytochrome P450 2E1. Both AN and CEO represent possible chemical carcinogens leading to DNA damage mainly in the form of the major 7-(2-oxoethyl)deoxyguanosine adduct. A kinetic model for its formation was devised and a corresponding second-order rate constant obtained from the experimental data on the reaction with CEO. A series of ab initio, density functional theory, and semiempirical calculations of activation free energies was then performed on the alkylation of nucleic bases with both CEO and AN. The combination of Hartree-Fock level of theory with the flexible 6-311++G(d,p) basis set and Langevin dipoles implicit solvation model gave the best agreement with the experimental activation barrier. It also predicted relative reactivities of all four nucleobases that are in agreement with the experimentally reported adduct yields. Moreover, this combination predicted higher reactivity of CEO than AN with all four nucleobases corroborating the experimental hypothesis that S N 2 substitution of CEO rather than direct Michael addition of AN is responsible for the genotoxic properties of AN. In a broader context this paper points to the applicability of quantum chemical methods to the studies of carcinogenesis.

Half of the female population over age 50 years will experience pelvic organ prolapse. We suggest a new approach based on tissue engineering principles to functionally reconstruct the anatomical structures of the pelvic floor. The aim of this study is to investigate the mechanical performance and effect on collagen and elastin production of a degradable mesh releasing basic fibroblast growth factor (bFGF). Implantation of biodegradable mesh with or without bFGF in their core has been conducted in 40 rats in an abdominal wall defect model. Samples were explanted after 4, 8, and 24 weeks, and tested for mechanical properties and the composition of connective tissue. The study showed an increase in mRNA expression for collagen-I (p = 0.0060) and collagen-III (p = 0.0086) in the 4 weeks group with bFGF. The difference was equalized at 8 and 24 weeks. No difference was found at any time for protein amount for collagen-I, collagen-III, and fibronectin. The amount of collagen decreased from 4 to 24 weeks but the fraction of collagen increased. The maximal load of the newly formed tissue showed no effect of bFGF at any time. Exclusively, histology showed a limited ingrowth of collagen fibers after 4 weeks with bFGF but signs of elastin fibers were seen at 24 weeks. The investigation showed that a biodegradable mesh promotes tissue formation with a promising strength. The mesh with bFGF did not represent any advantage on either long or short term in comparison to the mesh without bFGF. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 680-688, 2018., (© 2017 Wiley Periodicals, Inc.)

Aims and Background: The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801)., Materials and Methods: SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR., Results: The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously., Conclusion: Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Protein corona formed on nanomaterial surfaces play an important role in the bioavailability and cellular uptake of nanomaterials. Modification of surfaces with oligoethylene glycols (OEG) are a common way to improve the resistivity of nanomaterials to protein adsorption. Short-chain ethylene oxide (EO) oligomers have been shown to improve the protein resistance of planar Au surfaces. We describe the application of these EO oligomers for improved protein resistance of 30 nm spherical gold nanoparticles (AuNPs). Functionalized AuNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. Capillary electrophoresis (CE) was used for separation and quantitation of AuNPs and AuNP-protein mixtures. Specifically, nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) was employed for the determination of equilibrium and rate constants for binding between citrate-stabilized AuNPs and two model proteins, lysozyme and fibrinogen. Semi-quantitative CE analysis was carried out for mixtures of EO-functionalized AuNPs and proteins, and results demonstrated a 2.5-fold to 10-fold increase in protein binding resistance to lysozyme depending on the AuNP surface functionalization and a 15-fold increase in protein binding resistance to fibrinogen for both EO oligomers examined in this study. Graphical abstract Using capillary electrophoresis, the addition of short-chained oligo(ethylene oxide) ligands to gold nanoparticles was shown to improve protein binding resistance up to 15-fold.

Sterilization is the certain and absolute decontamination of microorganisms totally from all manner of alive and active species. Sterilization devices used in the sterilization processes are between laboratory and external patient application devices of biomedical device technology, and they are designed to remove equipments from germs. The application potential of hetarilazo indole based azo dyes in the biomedical sterilization are known and azo dyes come into prominence in this class because of simplicity of their synthesis and procurement of low-cost raw materials. In this work, the application potential of a novel synthesized azo dye, (E)-N-phenyl-4-(thiazole-2-yldiazenyl)aniline was investigated as an indicator in the biomedical sterilization performing the electrochemical and spectroscopic characterizations. The application of indicator was tested by ethylene oxide, hydrogen peroxide and peracetic acid sterilization techniques introducing into various sterilization rolls., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C 15 acetogenin medium-ring ethers. Here, we described the isolation of three new C 15 acetogenins ( 3 - 5 ), and one truncated derivative ( 6 ) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives ( 3 - 4 ). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J -based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated., Competing Interests: The authors declare no conflict of interest.

Block copolymers composed of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) have been widely used in cell membrane stabilization and permeabilization. To explore the mechanism of interaction between PPO-PEO block copolymers and lipid membranes, we have investigated how polymer structure influences the polymer-lipid bilayer association by varying the overall molecular weight, the hydrophobic and hydrophilic block lengths, and the end-group structure systematically, using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) unilamellar liposomes as model membranes. Pulsed-field-gradient NMR (PFG-NMR) was employed to probe polymer diffusion in the absence and presence of liposomes. The echo decay curves of free polymers in the absence of liposomes are single exponentials, indicative of simple translational diffusion, while in the presence of liposomes, the decays are biexponential, with the slower decay corresponding to polymers bound to liposomes. The binding percentage of polymer to the liposome was quantified by fitting the echo decay curves to a biexponential model. The NMR experiments show that increasing the total molecular weight and hydrophobicity of the polymer can significantly enhance the polymer-lipid bilayer association, as the binding percentage and liposome surface coverage both increase. We hypothesize that the hydrophobic PPO block inserts into the lipid bilayer due to the fact that little molecular exchange between bound and free polymers occurs on the time scale of the diffusion experiments. Additionally, as polymer concentration increases, the liposome surface coverage increases and approaches a limit. These results demonstrate that PFG-NMR is a simple yet powerful method to quantify interactions between polymers and lipid bilayers.

Capsaicin was extracted from capsicum oleoresin using an aqueous two-phase system (ATPS) composed of an ethylene oxide-propylene oxide (EOPO) copolymer, salt and ethanol. Capsaicin was concentrated in the top polymer-rich phase. To determine the optimal conditions, the partitioning of capsaicin in the ATPS was investigated, considering a single-factor experiment including the salt concentration, polymer concentration, buffer pH, ethanol concentration, sample loading and extraction duration. Response surface methodology was applied to investigate the effects of the polymer concentration, buffer pH and sample loading on capsaicin partitioning. A capsaicin yield of 95.5% was obtained using the optimal extraction system, which consisted of 16.3% UCON 50-HB-5100/10% K 2 HPO 4 /1% ethanol, a buffer pH of 4.35 and 0.24g of capsicum oleoresin. Capsaicin was purified from the capsaicinoid extract using a two-step macroporous adsorption resin (MAR) method. After purification using non-polar MAR ADS-17, the recovery and purity of capsaicin were 83.7% and 50.3%, respectively. After purification using weakly polar MAR AB-8, the recovery and purity of capsaicin were 88.0% and 85.1%, respectively., (Copyright © 2017. Published by Elsevier B.V.)

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) in tumor cells and tumor associated dendritic cells (DCs) plays a major role in the progression of cancer. JSI-124 (cucurbitacin I) is a potent inhibitor of STAT3; however, its poor solubility and nonspecificity limit its effectiveness in cancer immunotherapy. In order to achieve a nanocarrier for solubilization and passive targeting of JSI-124 to tumor cells and tumor associated DCs, the drug was chemically conjugated to pendent COOH groups of self-associating poly(ethylene oxide)-block-poly(α-carboxylate-ε-caprolactone) (PEO-b-PCCL). Developed PEO-b-P(CL-JSI-124) conjugates self-assembled to polymeric micelles of 40 nm size range with negligible drug release under physiological mimicking conditions. The conjugation of JSI-124 to PEO-b-PCCL was confirmed by 1 H NMR, thin layer chromatography (TLC), and HPLC with a conjugation of 8.9% w/w of the polymer. As expected, JSI-124 nanoconjugates showed lower potency in p-STAT3 inhibition and direct anticancer activity in B16-F10 melanoma cells. Interestingly, JSI-124 nanoconjugates were more powerful than free drug in reducing the level of p-STAT3 in tumor exposed bone marrow derived dendritic cells (BMDCs). The JSI-124 nanoconjugates were also significantly more active than free drug in reversing the immunosuppressive effect of B16-F10 tumor and led to significantly better phenotypical and functional stimulation of tumor exposed immature BMDCs in the presence of immune adjuvants like LPS and CpG. Our findings points to great promise for PEO-b-P(CL-JSI-124) micelles for modulation of immunosuppressive microenvironment in melanoma tumors, implicating application of this strategy in cancer immunotherapy.