Dysfunctional antioxidant capacity of high-density lipoprotein in rheumatoid arthritis.

BACKGROUND: High-density lipoprotein (HDL) presents atheroprotective functions not readily reflected by plasma HDL-cholesterol levels. The aim of this study was to investigate HDL antioxidant function in patients with rheumatoid arthritis (RA). METHODS: This pilot and cross-sectional study included 50 RA patients and 50 controls matched by age, gender, cardiovascular risk factors and drug therapy. The antioxidant capacity of HDL was assessed by the total radical-trapping antioxidative potential test (TRAP-assay) and the susceptibility of low-density lipoprotein (LDL) to oxidation by the Conjugated Dienes Assay (Dmax ). A carotid ultrasound was performed in all participants to detect subclinical atherosclerosis. RESULTS: High-density lipoprotein from RA patients showed lower antioxidant capacity than those from controls [oxidized-LDL%: 35.8 (27-42) vs. 24.4 (20-32), p < .001] when analysed with the TRAP-assay. In addition, the time to achieve 50% of maximal LDL oxidation (Lag-time) was shorter in RA-patients than in matched controls [57.2 (42-71) vs. 69.5 (55-75) minutes, (p = .003)]. RA patients showed a higher atherosclerotic burden than controls. The pro-oxidant pattern in RA was irrespective of the presence of carotid atherosclerosis. On the contrary, there was a positive correlation between inflammatory parameters (erythrocyte sedimentation rate, ultrasensitive C-reactive protein and fibrinogen) and the loss of HDL-anti-oxidant capacity measured by the TRAP-assay (rho = .211, p = .035; rho = .231, p = .021 and rho = .206, p = .041, respectively). Furthermore, the glucocorticoid dose at recruitment was negatively associated with the Lag-time in RA patients (rho = -.387, p = .026). CONCLUSION: Rheumatoid arthritis patients present reduced HDL antioxidant capacity and a lower resistance of LDL particles to oxidation, mainly related to the degree of inflammation.

Embryonic nutritional hyperglycemia decreases cell proliferation in the zebrafish retina.

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. While there is a major focus on the study of juvenile/adult DR, the effects of hyperglycemia during early retinal development are less well studied. Recent studies in embryonic zebrafish models of nutritional hyperglycemia (high-glucose exposure) have revealed that hyperglycemia leads to decreased cell numbers of mature retinal cell types, which has been related to a modest increase in apoptotic cell death and altered cell differentiation. However, how embryonic hyperglycemia impacts cell proliferation in developing retinas still remains unknown. Here, we exposed zebrafish embryos to 50 mM glucose from 10 h postfertilization (hpf) to 5 days postfertilization (dpf). First, we confirmed that hyperglycemia increases apoptotic death and decreases the rod and Müller glia population in the retina of 5-dpf zebrafish. Interestingly, the increase in cell death was mainly observed in the ciliary marginal zone (CMZ), where most of the proliferating cells are located. To analyze the impact of hyperglycemia in cell proliferation, mitotic activity was first quantified using pH3 immunolabeling, which revealed a significant decrease in mitotic cells in the retina (mainly in the CMZ) at 5 dpf. A significant decrease in cell proliferation in the outer nuclear and ganglion cell layers of the central retina in hyperglycemic animals was also detected using the proliferation marker PCNA. Overall, our results show that nutritional hyperglycemia decreases cellular proliferation in the developing retina, which could significantly contribute to the decline in the number of mature retinal cells.

Biomechanical characteristics of different methods of neo-chordal fixation to the papillary muscles.

BACKGROUND AND AIM OF THE STUDY: Several techniques have been described for neo-chordal fixation to the papillary muscles without any reported clinical differences. The objective of this study is to compare in vitro the biomechanical properties of four of these common techniques. METHODS: We studied the biomechanical properties of expanded polytetrafluoroethylene neo-chordal fixation using four techniques: nonknotted simple stitch, nonknotted figure-of-eight stitch, knotted pledgeted mattress stitch, and knotted pledgeted stitch using commercially available prefabricated loops. Neo-chordae were submitted to a total of 20 traction-relaxation cycles with incremental loads of 1, 2, and 4 N. We calculated the elongation, the force-strain curve, elasticity, and the maximum tolerated load before neo-chordal failure. RESULTS: The elongation of the neo-chordae was lowest in the simple stitch followed by the figure-of-eight, the pledgeted mattress, and he commercially prefabricated loops (p < .001). Conversely, the elastic modulus was highest in the simple stitch followed by the figure-of-eight, the pledgeted mattress, and the prefabricated loops (p < .001). The maximum tolerated load was similar with the simple stitch (28.87 N) and with the figure-of-eight stitch (31.39 N) but was significantly lower with the pledgeted mattress stitch (20.51 N) and with the prefabricated loops (7.78 N). CONCLUSION: In vitro, neo-chordal fixation by nonknotted simple or nonknotted figure-of-eight stitches resulted in less compliance as opposed to the use of knotted pledgeted stitches. Fixation technique seemed to influence neo-chordal biomechanical properties, however, it did not seem to affect the strength of the suture when subjected to loads within physiological ranges.

Restoring Endogenous Repair Mechanisms to Heal Chronic Wounds with a Multifunctional Wound Dressing.

Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.

Comparison between thermophysical and tribological properties of two engine lubricant additives: electrochemically exfoliated graphene and molybdenum disulfide nanoplatelets.

Recently graphene and other 2D materials were suggested as nano additives to enhance the performance of nanolubricants and reducing friction and wear-related failures in moving mechanical parts. Nevertheless, to our knowledge there are no previous studies on electrochemical exfoliated nanomaterials as lubricant additives. In this work, engine oil-based nanolubricants were developed via two-steps method using two different 2D nanomaterials: a carbon-based nano additive, graphene nanoplatelets (GNP) and a sulphide nanomaterial, molybdenum disulfide (MoS2) nanoplatelets (MSNP). The influence of these nano additives on the thermophysical properties of the nanolubricants, such as viscosity index, density and wettability, was investigated. The unique features of the electrochemical exfoliated GNP and MSNP allow the formulation of nanolubricant with unusual thermophysical properties. Both the viscosity and density of the nanolubricants decreased by increasing the nanoplatelets loading. The effect of the nano additives loading and temperature on the tribological properties of nanolubricants was investigated using two different test configurations: reciprocating ball-on-plate and rotational ball-on-three-pins. The tribological specimens were analysed by scanning electron microscopy (SEM) and 3D profiler in order to evaluate the wear. The results showed significant improvement in the antifriction and anti-wear properties, for the 2D-materials-based nanolubricants as compared with the engine oil, using different contact conditions. For the reciprocal friction tests, maximum friction and worn area reductions of 20% and 22% were achieved for the concentrations of 0.10 wt% and 0.20 wt% GNP, respectively. Besides, the best anti-wear performance was found for the nanolubricant containing 0.05 wt% MSNP in rotational configuration test, with reductions of 42% and 60% in the scar width and depth, respectively, with respect to the engine oil.

Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications.

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

Coating Lacticaseibacillus rhamnosus GG in Alginate Systems: an Emerging Strategy Towards Improved Viability in Orange Juice.

Fruit juices are successfully proposed as suitable probiotic vehicles, but researchers' efforts should be developed to avoid effects of bacteria overgrowing on sensory and nutritional cues of final products and to preserve viability of probiotic bacteria during storage. In the present study, encapsulation of Lacticaseibacillus rhamnosus GG strain in alginate systems was performed through ionotropic gelation technology. The alginate systems were optimized by using Box-Behnken Design to investigate the influence of three independent variables at three different levels: particle mean size and polydispersity index. The optimized probiotic-loaded alginate particles were added to orange juice samples. The viability of the probiotic strain, both as free and microencapsulated, was evaluated in orange juice stored at 5°C for 35 days. Morphology and size of probiotic-loaded alginate particles were found suitable for incorporation into juice. TEM analysis revealed that unloaded systems were clustered as nanoparticles (CL_NP), while the loaded sample appeared as a coated system (Coated_LGG). Microbiological evaluation revealed that the encapsulation assured the survival of Coated_LGG, with a reduction of less than 1-unit log in cellular density after 35 days of refrigerated storage in orange juice. Results indicated that the encapsulated bacteria did not affect the macroscopic properties neither the microbiological characteristic of orange juice; thus, it can be proposed as functional food.

Orodispersible Carbamazepine/Hydroxypropyl-ß-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients.

The development of orodispersible tablets (ODTs) for poorly soluble and poorly flowable drugs via direct compression is still a challenge. This work aimed to develop ODTs of poorly soluble drugs by combining cyclodextrins that form inclusion complexes to improve wetting and release properties, and directly compressible co-processed excipients able to promote rapid disintegration and solve the poor flowability typical of inclusion complexes. Carbamazepine (CBZ) and hydroxypropyl-ß-cyclodextrin (HPßCD) were used, respectively, as a model of a poorly soluble drug with poor flowability and as a solubilizing agent. Specifically, CBZ-an antiepileptic and anticonvulsant drug-may benefit from the studied formulation approach, since some patients have swallowing difficulties or fear of choking and are non-cooperative. Prosolv® ODT G2 and F-Melt® type C were the studied five-in-one co-processed excipients. The complex was prepared by kneading. Flow properties of all materials and main properties of the tablets were characterized. The obtained results showed that ODTs containing CBZ/HPßCD complex can be prepared by direct compression through the addition of co-processed excipients. The simultaneous use of co-processing and cyclodextrin technologies rendered ODTs with an in vitro disintegration time in accordance with the European Pharmacopoeia requirement and with a fast and complete drug dissolution. In conclusion, the combination of five-in-one co-processed excipients and hydrophilic cyclodextrins may help addressing the ODT formulation of poorly soluble drugs with poor flowability, by direct compression and with desired release properties.

Smart Drug Release from Medical Devices.

Medical devices are becoming key players on health monitoring and treatment. Advances in materials science and electronics have paved the way to the design of advanced wearable, insertable, and implantable medical devices suitable for the prevention and cure of diseases and the physical or functional replacement of damaged tissues or organs. However, intimate and prolonged contact of the medical devices with the human body increases the risks of adverse foreign-body reactions and biofilm formation. Drugs can be included in/on the medical device not only to minimize the risks but also to improve the therapeutic outcomes. Drug-eluting medical devices can deliver the drug in the place where it is needed using lower doses and avoiding systemic effects. Drug-device combination products that release the drug following preestablished rates have already demonstrated their clinical relevance. The aim of this mini-review is to bring attention to medical devices that can actively regulate drug release as a function of tiny changes in their environment, caused by the pathology itself, microorganisms adhesion or some external events. Thus, endowing medical devices with stimuli-responsiveness should allow for precise, on-demand, regulated release of the ancillary drugs to expand the therapeutic performance of the medical device and also should serve as a first step to offer personalized solutions to each patient. Main sections deal with smart drug-eluting medical devices that are sensitive to infection-related stimuli, natural healing processes, mechanical forces, electric fields, ultrasound, near-infrared radiation, or chemicals such as vitamin C.

Nanotheranostic Pluronic-Like Polymeric Micelles: Shedding Light into the Dark Shadows of Tumors.

Cancer is a leading cause of death worldwide. Despite the advances in prevention, detection, diagnosis, and treatment, many tumors relapse and become resistant to conventional treatments. Theranostics and real-time molecular imaging using nanoscale materials, such as polymeric micelles, are being widely explored as promising gold standard approaches in a personalized medicine perspective for cancer. Theranostics is intended for the three-in-one purpose of simultaneously diagnose, treat, and monitor tumor evolution. Compared to the conventional treatments, theranostic functional polymeric micelles have demonstrated great potential to improve and monitor the delivery of pharmacological agents following administration, which can enhance therapeutic efficacy and minimize off-target toxicity. This review provides an overview of the current state of the art related to the use of polymeric micelles as theranostic multicarriers targeting the cancer cells and tumor microenvironment. Some future directions toward the design of nanotheranostic platforms are also proposed. In particular, we focused our attention on Pluronics and Tetronics as they advantageously present sol-gel transition, which makes them smart nanosystems suitable for oral theranostic administration and sustained depots, increasing patient compliance.

Sensitivity and wound healing after hot-iron disbudding in goat kids.

Hot-iron disbudding in goat kids causes acute pain and tissue damage. However, the duration of healing and wound sensitivity is unknown. We assessed wound healing and pain sensitivity in 18 female dairy goat kids disbudded with a heated iron at 10 d of age (range: 5-15 d). Pressure algometry was carried out twice a week from d 1 after disbudding to determine the mechanical nociceptive threshold (MNT) in 4 locations on each bud (front, lateral, caudal, and middle). At the same time, digital and infrared images of the wounds were used to visually and thermally describe the healing process. Wounds were visually scored daily for the presence of 7 tissue types: attached necrotic tissue, detached necrotic tissue, burns outside the necrotic ring, exudate, granulation, crust, and epithelium. All data were taken until epithelium was present for 4 consecutive days. Necrotic tissue detached completely from the scalp 26 ± 5 d after the procedure (mean ± SD; range: 17-43 d), and wounds took 50 ± 8 d (35-63 d) to re-epithelialize. Wounds were more sensitive at all stages of the healing process compared with re-epithelialized tissue. The caudal and middle locations were the most- and least-sensitive test sites (1.24 ± 0.10 and 1.90 ± 0.10 N, respectively; mean ± SE). Goats became less responsive to stimulation as their wounds decreased in size. Sensitivity did not differ between left and right sides of the head. Maximum surface temperature of necrotic tissue, when present, tended to be higher than that of epithelium (38.8 ± 0.2 vs. 38.1 ± 0.2°C); temperature did not differ among other tissue types. Our results indicate that hot-iron disbudding wounds in goats take, on average 7, wk to re-epithelialize (35-63 d) and are painful throughout this time, raising additional welfare concerns about this procedure.

Iron and laterality effects on healing of cautery disbudding wounds in dairy calves.

Hot-iron disbudding, the process of cauterizing the horn buds of calves or goat kids at an early age to prevent horn growth, is routinely practiced in dairy production. The wounds take weeks to heal and are painful to touch throughout this time. Possible strategies to hasten the healing of disbudding wounds are not well understood, but the type of iron used may be an important factor to consider. When evaluating strategies to hasten healing, a within-subjects design may be preferable, but laterality effects might act as a potential source of variation and confounding in this type of experiment. Our objectives were to compare healing after disbudding with 2 commercially available irons, and to determine whether wounds healed differently on the left versus the right side of the head. Ten Holstein calves 4 to 10 d of age were disbudded using the Rhinehart X50A electric disbudder (Rhinehart Development Corp., Spencerville, IN) on one horn bud and the Portasol gas disbudder (Portasol USA, Elmira, OR) on the other; side (left vs. right) was balanced between treatments. We scored wounds daily for the presence of 6 tissue types: attached necrotic tissue, detached necrotic tissue, exudate, granulation, crust, and epithelium. Surface temperature and size of the wound were measured twice-weekly using thermal and digital photographs, respectively. The type of iron used did not affect latency to re-epithelialize, which took on average (mean ± standard deviation) 53 ± 3 d and 55 ± 3 d for Portasol and Rhinehart wounds, respectively (range: 40-70 d). However, compared with Portasol wounds, those from the Rhinehart had fewer days of granulation tissue and tended to have more days of detached necrotic tissue. The Portasol tip had a smaller total surface area than the Rhinehart, which may have resulted in a less severe burn, causing the necrotic tissue to fall off sooner. The left side tended to re-epithelialize faster than the right side (mean ± standard error: left 51 ± 3 d; right 57 ± 3 d) and have fewer days of crust. Left-sided wounds were also cooler and tended to be smaller than those on the right. To assess the external validity of these laterality effects in our primary experiment (experiment A), we analyzed wound healing data from 2 other disbudding studies, one on calves (experiment B) and one on goat kids (experiment C). We observed laterality effects in the opposite direction in Experiment B, but negligible effects in experiment C, indicating that the differences in laterality had low external validity; the biological meaning of this asymmetry is unclear. Nonetheless, if using a within-subjects design, asymmetries in wound healing should be considered to avoid confounding effects. In conclusion, wounds from both irons took 7 to 8 wk to heal, on average; other strategies to accelerate healing should be explored.

Sterile and Dual-Porous Aerogels Scaffolds Obtained through a Multistep Supercritical CO2-Based Approach.

Aerogels from natural polymers are endowed with attractive textural and biological properties for biomedical applications due to their high open mesoporosity, low density, and reduced toxicity. Nevertheless, the lack of macroporosity in the aerogel structure and of a sterilization method suitable for these materials restrict their use for regenerative medicine purposes and prompt the research on getting ready-to-implant dual (macro + meso)porous aerogels. In this work, zein, a family of proteins present in materials for tissue engineering, was evaluated as a sacrificial porogen to obtain macroporous starch aerogels. This approach was particularly advantageous since it could be integrated in the conventional aerogel processing method without extra leaching steps. Physicochemical, morphological, and mechanical characterization were performed to study the effect of porogen zein at various proportions (0:1, 1:2, and 1:1 zein:starch weight ratio) on the properties of the obtained starch-based aerogels. From a forward-looking perspective for its clinical application, a supercritical CO2 sterilization treatment was implemented for these aerogels. The sterilization efficacy and the influence of the treatment on the aerogel final properties were evaluated mainly in terms of absence of microbial growth, cytocompatibility, as well as physicochemical, structural, and mechanical modifications.

Mobility of Water and Polymer Species and Rheological Properties of Supramolecular Polypseudorotaxane Gels Suitable for Bone Regeneration.

The aim of this work was to prepare polypseudorotaxane-based supramolecular gels combining αCD with two temperature-responsive copolymers of different architecture (i.e., linear poloxamer P and X-shaped poloxamine T), at the lowest concentration as possible to form syringeable depots, and to shed light on the self-diffusion and spatial closeness of all components (including water) which in turn may determine the cooperative self-assembly phenomena and the performance of the gels at the macroscopic level. The exchange rate between bound water and bulk water was measured with a novel NMR experiment Water Diffusion Exchange-Diffusion Optimized Spectroscopy (WDE-DOSY). Polypseudorotaxane formation caused opposite effects on the mobility of αCD species (decreased) and internal water (increased) but did not affect PPO-water interaction. Consequently, designed ternary P/T/αCD supramolecular gels exhibited in situ gelling at body temperature could host large amounts of PLA/PLGA microspheres and behaved as porous 3D-scaffolds for mesenchymal stem cells (MSCs) supporting their osteogenic differentiation. Interestingly, the gels withstood freeze-drying and reconstitution with minor changes in inner structure and rheological properties. The gathered information may help to understand better the supramolecular gels and provide tools for the rational design of syringeable bone scaffolds that can simultaneously accommodate cells and drug microcarriers for efficient tissue regeneration.

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery.

Cyclosporine is an immunosuppressant agent approved for the treatment of dry eye disease and used off-label for other ocular pathologies. Its formulation and ocular bioavailability present a real challenge due to the large molecular weight (1.2 kDa), high lipophilicity, and low water solubility. The aim of the work was to develop an aqueous micellar formulation for an efficient cyclosporine delivery to the ocular tissues, using a water-soluble derivative of vitamin E (TPGS: d-α-tocopheryl polyethylene glycol 1000 succinate) and poloxamer 407 (Pluronic ®F127) as excipients. The mixed micelles were characterized in terms of particle size, zeta potential, rheology, and stability upon dilution and freeze-drying. Additionally, the enzymatic-triggered release of vitamin E and vitamin E succinate from TPGS was investigated in vitro in the presence of esterase. Compared to the commercially available ophthalmic formulation, the poloxamer 407:TPGS 1:1 molar ratio micellar formulation significantly improved cyclosporine solubility, which increased proportionally to surfactant concentration reaching 0.4% (w/v) for 20 mM surfactant total concentration. Cyclosporine-loaded mixed micelles efficiently retained the drug once diluted in simulated lachrymal fluid and, in the presence of a 20 mM surfactant concentration, were stable upon freeze-drying. The drug-loaded mixed micelles were applied ex vivo on porcine cornea and compared to Ikervis®. Drug accumulation in the cornea resulted proportional to drug concentration (6.4 ± 1.9, 17.6 ± 5.4, and 26.9 ± 7.4 µgdrug/gcornea, after 3 h for 1, 2.5, and 4 mg/mL cyclosporine concentration respectively). The formulation containing cyclosporine 4 mg/mL (20 mM surfactant) was also evaluated on the sclera, with a view to targeting the posterior segment. The results demonstrated the capability of mixed micelles to diffuse into the sclera and sustain cyclosporine delivery (28 ± 7, 38 ± 10, 57 ± 9, 145 ± 27 µg/cm2 cyclosporine accumulated after 3, 6, 24, and 48 h respectively). Reservoir effect experiments demonstrated that the drug accumulated in the sclera can be slowly released into the underlying tissues. Finally, all the formulations developed in this work successfully passed the HET-CAM assay for the evaluation of ocular irritability.

Electrospun Fibers of Cyclodextrins and Poly(cyclodextrins).

Cyclodextrins (CDs) can endow electrospun fibers with outstanding performance characteristics that rely on their ability to form inclusion complexes. The inclusion complexes can be blended with electrospinnable polymers or used themselves as main components of electrospun nanofibers. In general, the presence of CDs promotes drug release in aqueous media, but they may also play other roles such as protection of the drug against adverse agents during and after electrospinning, and retention of volatile fragrances or therapeutic agents to be slowly released to the environment. Moreover, fibers prepared with empty CDs appear particularly suitable for affinity separation. The interest for CD-containing nanofibers is exponentially increasing as the scope of applications is widening. The aim of this review is to provide an overview of the state-of-the-art on CD-containing electrospun mats. The information has been classified into three main sections: (i) fibers of mixtures of CDs and polymers, including polypseudorotaxanes and post-functionalization; (ii) fibers of polymer-free CDs; and (iii) fibers of CD-based polymers (namely, polycyclodextrins). Processing conditions and applications are analyzed, including possibilities of development of stimuli-responsive fibers.

One-step grafting of temperature-and pH-sensitive (N-vinylcaprolactam-co-4-vinylpyridine) onto silicone rubber for drug delivery.

A one-step method was implemented to graft N-vinylcaprolactam (NVCL) and 4-vinylpyridine (4VP) onto silicone rubber (SR) films using gamma radiation in order to endow the silicone surface with temperature- and pH-responsiveness, and give it the ability to host and release diclofenac in a controlled manner and thus prevent bacterial adhesion. The effects of radiation conditions (e.g., dose and monomers concentration) on the grafting percentage were evaluated, and the modified films were characterized by means of FTIR-ATR, Raman spectroscopy, calorimetry techniques (DSC and TGA) and contact angle measurements. The films responsiveness to stimuli was evaluated by recording the swelling degree of pristine and modified SR in buffer solutions (critical pH point) and as a function of changes in temperature (Upper Critical Solution Temperature, UCST). The graft copolymers of SR-g-(NVCL-co-4VP) showed good cytocompatibility against fibroblast cells for prolonged times, could host diclofenac and release it in a sustained manner for up to 24 h, and exhibited bacteriostatic activity when challenged against Escherichia coli.

Encapsulation of Antioxidant Gallate Derivatives in Biocompatible Poly(ε-caprolactone)-b-Pluronic-b-Poly(ε-caprolactone) Micelles.

Formulation of antioxidant agents is still a challenge that limits their application in the biomedical field. Pentablock copolymers obtained through modification of two common PEO-PPO-PEO copolymers (Pluronic F127 and F68) with poly(ε-carprolactone) (PCL) were evaluated regarding their capability to form nanocarriers suitable for gallic acid, methyl gallate, and ethyl gallate. Applying a dialysis method, PCL/F127/PCL and PCL/F68/PCL self-assembled into spherical micelles in 0.9% NaCl aqueous solution but notably differed in critical micellar concentration (CMC), micelle core hydrophobicity, and micelle size, as evidenced by pyrene fluorescence, transmission electron microscopy, and dynamic light scattering. Cytotoxicity studies showed that the copolymers were safe at concentrations well above the CMC. Transfer of gallic acid and derivatives from aqueous medium to the micelle phase was characterized in terms of distribution constant and free energy of transference, which were shown to be strongly dependent on the hydrophobicity of the gallate derivatives and the length of PCL in the pentablock copolymer. Antioxidant activity of gallates was challenged against DPPH previously loaded in PCL/F127/PCL and PCL/F68/PCL micelles. The more the hydrophobicity of the gallate derivative, the greater the capability to enter in the micelle and to consume free radicals. In vitro release studies of gallic acid, methyl gallate, and ethyl gallate from the pentablock copolymer micelles also evidenced the influence of the hydrophobicity of both the gallate derivative and the micelle core on release rate, recording a variety of release patterns. Overall, PCL/F127/PCL and PCL/F68/PCL appear as suitable nanocarriers of potent antioxidant agents in a wide range of polarities, which may be useful for diverse therapeutic applications.

Magnetic Surfactants and Polymers with Gadolinium Counterions for Protein Separations.

New magnetic surfactants, (cationic hexadecyltrimethlyammonium bromotrichlorogadolinate (CTAG), decyltrimethylammonium bromotrichlorogadolinate (DTAG), and a magnetic polymer (poly(3-acrylamidopropyl)trimethylammonium tetrachlorogadolinate (APTAG)) have been synthesized by the simple mixing of the corresponding surfactants and polymer with gadolinium metal ions. A magnetic anionic surfactant, gadolinium tri(1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate) (Gd(AOT)3), was synthesized via metathesis. Both routes enable facile preparation of magnetically responsive magnetic polymers and surfactants without the need to rely on nanocomposites or organic frameworks with polyradicals. Electrical conductivity, surface tensiometry, SQUID magnetometry, and small-angle neutron scattering (SANS) demonstrate surface activity and self-aggregation behavior of the magnetic surfactants similar to their magnetically inert parent analogues but with added magnetic properties. The binding of the magnetic surfactants to proteins enables efficient separations under low-strength (0.33 T) magnetic fields in a new, nanoparticle-free approach to magnetophoretic protein separations and extractions. Importantly, the toxicity of the magnetic surfactants and polymers is, in some cases, lower than that of their halide analogues.

Oxytetracycline recovery from aqueous media using computationally designed molecularly imprinted polymers.

Polymers for recovery/removal of the antimicrobial agent oxytetracycline (OTC) from aqueous media were developed with use of computational design and molecular imprinting. 2-Hydroxyethyl methacrylate, 2-acrylamide-2-methylpropane sulfonic acid (AMPS), and mixtures of the two were chosen according to their predicted affinity for OTC and evaluated as functional monomers in molecularly imprinted polymers and nonimprinted polymers. Two levels of AMPS were tested. After bulk polymerization, the polymers were crushed into particles (200-1000 µm). Pressurized liquid extraction was implemented for template removal with a low amount of methanol (less than 20 mL in each extraction) and a few extractions (12-18 for each polymer) in a short period (20 min per extraction). Particle size distribution, microporous structure, and capacity to rebind OTC from aqueous media were evaluated. Adsorption isotherms obtained from OTC solutions (30-110 mg L(-1)) revealed that the polymers prepared with AMPS had the highest affinity for OTC. The uptake capacity depended on the ionic strength as follows: purified water > saline solution (0.9 % NaCl) > seawater (3.5 % NaCl). Polymer particles containing AMPS as a functional monomer showed a remarkable ability to clean water contaminated with OTC. The usefulness of the stationary phase developed for molecularly imprinted solid-phase extraction was also demonstrated. Graphical Abstract Selection of functional monomers by molecular modeling renders polymer networks suitable for removal of pollutants from contaminated aqueous environments, under either dynamic or static conditions.