Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

pH-Compensation Effect of Lysine on the Acidic Degradation of Electrospun Poly( lactide-co-glycolide) Fibers in PBS

Electrospun aligned ultrafine fibers of poly( lactide-coglycolide)( PLGA) can be used to construct biomimetic scaffolds for engineering those structurally anisotropic and dense tissues( e. g.,tendon,ligament,etc.). But the acidic degradation products of the PLGA could result in p H decrease in the vicinity of the scaffolds,which may give rise to biocompatibility concerns. To address the noted problem, this study was designed to evaluate the p Hcompensation capacity of using Lysine( Lys) —a kind of basic amino acid on the acidic degradation products of PLGA. Ultrafine PLGA( 50∶ 50) fibers with 0,10%,20%,and 30% by weight of Lys loadings were prepared by a stable jet electrospinning( SJES)approach. The morphology,structure,and mechanical properties of the electrospun aligned fibrous mats of Lys-incorporated PLGA( 50∶50) were characterized by scanning electron microscope( SEM),Fourier transform infrared spectroscopy( FTIR),and tensile testing,respectively. Thereafter,the fibrous PLGA( 50 ∶50) scaffolds were subjected to degradation by being immersed in phosphate buffered saline( PBS,p H 6. 86) solution at 37 ℃ for 5weeks. Our results show that the formed Lys / PLGA composite ultrafine fibers have a well-aligned and uniform morphology with a fineness of ca. 1 #m in diameter. Introduction of Lys led to increased mechanical performance; that is,when the Lys loading is less than 30%,tensile strength and Young's modulus of the aligned Lys / PLGA fibers reached up to the impressive values of 84. 5 MPa and 2. 4 GPa,respectively. Degradation results show that the p H of the PLGA group fell to 5. 6 in 5 weeks while the p H of the Lys /PLGA groups with 10%,20%, and 30% of Lys loadings was maintained at 6. 3, 6. 5 and 6. 7, respectively. This work demonstrated that incorporation of Lys into electrospun PLGA fibers could be an effective approach in mediating the p H decrease caused by the acidic degradation products of the PLGA.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.

Preparation of poly(lactide-co-glycolide)microspheres and evaluation of pharmacokinetics and tissue distribution of BDMC-PLGA-MS in rats

The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 μm and the size distribution was narrow. The encapsulation efficiency(EE) and drug loading efficiency(DLE) of BDME loaded PLGA microspheres(BDMC-PLGA-MS) was 94.18% and 8.14%,respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGAMS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.

High-performance and robust high-temperature polymer electrolyte membranes with moderate microphase separation by implementation of terphenyl-based polymers

Acid loss and plasticization of phosphoric acid(PA)-doped high-temperature polymer electrolyte membranes(HT-PEMs)are critical limitations to their practical application in fuel cells.To overcome these barriers,poly(terphenyl piperidinium)s constructed from the m-and p-isomers of terphenyl were synthesized to regulate the microstructure of the membrane.Highly rigid p-terphenyl units prompt the formation of moderate PA aggregates,where the ion-pair interaction between piperidinium and biphosphate is reinforced,leading to a reduction in the plasticizing effect.As a result,there are trade-offs between the proton conductivity,mechanical strength,and PA retention of the membranes with varied m/p-isomer ratios.The designed PA-doped PTP-20m membrane exhibits superior ionic conductivity,good mechanical strength,and excellent PA retention over a wide range of temperature(80–160°C)as well as satisfactory resistance to harsh accelerated aging tests.As a result,the membrane presents a desirable combination of performance(1.462 W cm^(-2) under the H_(2)/O_(2)condition,which is 1.5 times higher than that of PBI-based membrane)and durability(300 h at 160°C and 0.2 A cm^(-2))in the fuel cell.The results of this study provide new insights that will guide molecular design from the perspective of microstructure to improve the performance and robustness of HT-PEMs.

Synthesis and Characterization of Poly(L-lactide-co-glycolide)

Poly （ l- lactide- co-glycolide ） （ PLGA ） with different compositions was prepared using stannous octaoate as catalyst by bulk ring-opening copolymerization of l-lactide and glycolide. The structure and properties of the PLGA copolymers were cbaracterized by means of attenuated total reflectance-Fourier transform infrared （ATR-FTIR）, ^1H NMR, differential scanning calorimeter （ DSC and X-ray diffraction （XRD） methods, The experimented results indicate that the synthetic conditions and the composition of copolymers have art obvious influence on the structure of PLGA copolymers, The degradation rate of eopolymers increased with the increasing of the glycolide component in the copolymers.

Synthesis and Physicochemical Characterization of Biodegradable Star-Shaped Poly Lactide-Co-Glycolide-<i>β</i>-Cyclodextrin Copolymer Nanoparticles Containing Albumin

The purposes of this research were to synthesize and characterize star-shaped poly lactide-co-glycolide-β-cyclo-dextrin (PLGA-β-CD) copolymer by reacting L-lactide, glycolide and β-cyclodextrin in the presence of stannous octoate as a catalyst. The structure of PLGA-β-CD copolymer was confirmed with 1H-NMR, 13C-NMR and FT-IR spectra. Albumin as a model peptide drug was encapsulated within nanoparticles made of PLGA-β-CD with a modified double emulsion method. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the nanoparticles have the mean diameter within the range of 80 - 210 nm. Also they were almost spherical in shape. Effects of the experimental parameters, such as copolymer composition, copolymer concentration, and reaction temperature, on particular size and encapsulation efficiency were investigated.

Effect of the implant composite of poly lactide-co-glycolide and bone mesenchymal stem cells modified by basic fibroblast growth factor on injured spinal cord in rats

Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and

Synthesis of the Biomimetic Polymer: Aliphatic Diamine and RGDS Modified Poly(d,l-lactic acid)

A novel poly（d, /-lactic acid） （PDLLA） based biomimetic polymer was synthesized by grafting maleic anhydride, butanediamine and arg-gly-asp-ser （RGDS） peptides onto the backbone of PDLLA, aiming to overcome the acidity and auto-accelerating degradation of PDLLA during degradation and to improve its biospecificity and biocompatibility. The synthetic copolymer was characterized by FTIR, ^13C NMR and amino acid analyzer （AAA）.

CLAY CATALYZED SYNTHESIS OF BIO-DEGRADABLE POLY(GLYCOLIC ACID)

Glycolic acid was polymerized under vacuum in the presence and absence of nano sized clay.The added clay catalyzed the condensation polymerization which can be confirmed by recording FTIR spectroscopy and intrinsic viscosity (Ⅳ)values.The relative intensity of C=O/CH is increased while increasing the amount of clay.DSC showed the appearance of multiple endotherms of poly(glycolic acid).TGA showed the percentage weight residue remain above 750℃for polymer-nano composite system was 21% and hence proved the fl...

Preparation and properties of short natural fiber reinforced poly(lactic acid) composites

The natural fiber/poly(lactic acid) (PLA) composites were prepared with ramie and jute short fiber as reinforcement and PLA as matrix. The mechanical and thermal properties of the composites were investigated. The results show that the properties of the composites are better than those of plain PLA. When the content of the fiber is 30%, the composites can get the best mechanical properties. The dynamic mechanical analysis results show that the storage moduli of the PLA/ramie and PLA/jute composites increase with respect to the plain PLA. The Vicat softening temperature of the composites is greatly higher than that of PLA. The results of thermogravimetric analysis show that adding fiber to the PLA matrix can improve the degradation temperature of PLA.

Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation

AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid(PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids(SFAs) or PUFAs as well as combined with lipopolysaccharide(LPS). The expression of NOD-like receptor protein 3(NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B(NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.RESULTS: high-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid(PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid(Dh A) had thepotential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a highfat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but Dh A decreased phosphorylated NF-κB p65 protein expression in hepatocytes.CONCLUSION:Hepatic NLRP 3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.

Preparation and phase change performance of Na_2HPO_4·12H_2O@poly(lactic acid) capsules for thermal energy storage

Micro-encapsulated phase-change materials(micro PCMs) with Na_2 HPO_4·12 H_2 O encapsulated in poly(lactic acid)(PLA) shell were prepared by a solvent evaporation–precipitation method that involves the use of a coaxial needle. The effects of PLA concentration, stirring speed, injection rate of core and shell solutions, and polyvinyl alcohol(PVA) concentration on phase change properties were investigated. The thermal properties of microP CMs were characterized by differential scanning calorimetry(DSC). The capsules prepared under the optimal conditions are about 2 mm in diameter and show a latent heat of up to 122.2 J·g^(-1).

Poly (Acrylamide-co-Acrylic Acid) Hydrogel Induced by Glow-Discharge Electrolysis Plasma and Its Adsorption Properties for Cationic Dyes

In this paper, poly （acrylamide-co-acrylic acid） （P（AM-co-AA）） hydrogel was pre- pared in an aqueous solution by using glow-discharge electrolysis plasma （GDEP） induced copoly- merization of acrylamide （AM） and acrylic acid （AA）, in which N,N＇-methylenebisacrylamide （MBA） was used as a crosslinker. A mechanism for the synthesis of P（AM-co-AA） hydrogel was proposed. To optimize the synthesis condition, the following parameters were examined in detail： the discharge voltage, discharge time, the content of the crosslinker, and the mass ratio of AM to AA. The results showed that the optimum pH range for cationic dyes removal was found to be 5.0-10.0. The P（AM-co-AA） hydrogel exhibits a very high adsorption potential and the ex- perimental adsorption capacities for Crystal violet （CV） and Methylene blue （MB） were 2974.3 mg/g and 2303.6 mg/g, respectively. The adsorption process follows a pseudo-second-order kinetic model. In addition, the adsorption mechanism of P（AM-co-AA） hydrogel for cationic dyes was also discussed.

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly（D,L-lactide-co-glycolic acid） has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly（D,L-lactide-co-glycolic acid） into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced ceils prus the poly（O,L-lactide-co-glycolic acid） scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly（D,L-lactide-co-glycolic acid） scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.

A novel artificial nerve graft for repairing longdistance sciatic nerve defects:a self-assembling peptide nanofiber scaffold-containing poly (lactic-co-glycolic acid) conduit

In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

Synergistic effect of MXene on the flame retardancy and thermal degradation of intumescent flame retardant biodegradable poly(lactic acid)composites

The effect of Ti3C2 MXene nanosheets on the intumescent flame retardant(IFR)poly(lactic acid)(PLA)composites was investigated among a series of PLA/IFR/MXene,which were prepared by melt blending 0-2.0 wt%MXene,10.0 wt%-12.0 wt%IFR and PLA together.The results of limiting oxygen index(LOI)and vertical burning(UL-94)discover that the combination of 0.5 wt%MXene and 11.5 wt%IFR synergistically improves the fire safety of PLA to reach UL-94 V-0 rating with LOI value of 33.0%.The PLA/IFR/MXene composites perform an obvious reduction in peak of heat release rate(HRR)in cone calorimeter tests(CCTs).Furthermore,the carbon residues after CCTs were characterized by scanning electron microscope(SEM),laser Raman spectroscopy(LRS),X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS).It is demonstrated that both the titanium composition of the MXene structure and the characteristics of the two-dimensional material enhance the PLA/IFR/MXene composite materials’ability to produce a dense barrier layer to resist burnout during thermal degradation.

Synthesis and Characterization of Chitosan-g-poly- (D, L-lactic acid) Copolymer

Biodegradable chitosan-g-poly (D, L-lactic acid) copolymers were prepared via two methods. (1) The lactide was grafted onto hydroxyl groups of chitosan by using macromolecular initiator sodium of trimethylsilyl-chitosan, (2) poly (D,L-lactic acid)(PLA) with low molecular weight can be linked to the amino group by coupling activated PLA to trimethylsilyl-chitosan. Two graft copolymers had hydrophilic-hydrophobic character and can be applied as carriers for drug delivery.

Effects of Processing Variables on the Morphology and Diameter of Electrospun Poly(amino acid ester)phosphazene Nanofibers

Poly[（alanino ethyl ester）0.67 （glycino ethyl ester）0.33 phosphazene] （PAGP） was synthesized, and morphology and diameter of the electrospun PAGP nanofibers were systematically evaluated by using a cool field emission scanning electron microscope （SEM） with changing the important processing variables such as applied voltage, polymeric concentration, and ambient temperature. The average diameter of PAGP nanofibers was inversely proportional to the applied voltage, but increased with the increase of solution concentration. Lower environmental temperature was unfavorable due to the nanofibers conglutination.

Dorsal root ganglion-derived Schwann cells combined with poly(lactic-co-glycolic acid)/chitosan conduits for the repair of sciatic nerve defects in rats

Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells （〉95%） using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly（lactic-co-glycolic acid）/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly（lactic-co-glycolic acid）/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.