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With the objective of developing a localized gentamicin sulfate (GS) delivery system with a controlled release kinetics for the prevention/management of osteomyelitis, composite electrospun fibers composed of poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) blends and GS loaded mesoporous silica nanoparticles (npSiGS) were prepared (PLA/PLGA: 1:3, 1:1, 3:1 w/w). GS was loaded into silica nanoparticles by adsorption, using a concentrated GS solution, and npSiGS were dispersed in the polymer solutions and immobilized in the polymeric matrix by occlusion, during fibers formations. For comparison, non-composite fibers with the same blend compositions containing GS simply dispersed in the polymeric phase were also produced. GS loaded nanoparticles were characterized by nitrogen adsorption/desorption isotherms and GS loading was quantified by thermogravimetric analysis. The morphology of the electrospun fibers, assessed by SEM, revealed that npSiGS were embedded along the composite fibers, some in the form of small aggregates. In vitro release studies showed that composite fibers exhibited lower initial burst releases and slower release kinetics, dependent on blend composition. Composite fibers with PLGA as the major component (25PLA-npSiGS) had the fastest release kinetics, while fibers with equal amounts of both polymers (50PLA-npSiGS) or with PLGA as the minor component (75PLA-npSiGS) had slower release kinetics, with constant GS release rates after the first day. These results suggest that PLA/PLGA blend composition can be manipulated to obtain composite fibers with a controlled and tailored GS release for at least three weeks. Finally, the antibacterial effect against Staphylococcus aureus of all produced fibers containing GS was confirmed by a disk diffusion method. [ABSTRACT FROM AUTHOR]

Abstract This work investigates the immobilization of the antibiotic gentamicin sulfate (GS) in electrospun fiber mats composed of poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL) and the copolymer poly(lactic-co-glycolic acid) (PLGA). Since GS is highly water soluble but weakly soluble in the organic solvents commonly used in the electrospinning process, two methods of immobilization were investigated: by suspension electrospinning, in which GS particles were directly dispersed in the polymeric organic solutions, and by emulsion electrospinning, in which GS was solubilized in an aqueous phase that was then dispersed in the organic polymeric solution containing the surfactant SPAN80. Fibers with distinct diameters and morphologies were obtained for the different methods and compositions. Contrary to the fibers prepared by suspension electrospinning, emulsion electrospinning based fibers exhibited an excellent wettability, allegedly due to the effect of the surfactant SPAN80. Despite the differences between both methods the produced mats presented similar GS release profiles, with a considerable burst release in the first 8 h followed by a gradual release of the remaining drug during the next 4–6 days. Finally, all GS loaded fiber mats proved to have an antibacterial effect against the bacterial strain Staphylococcus aureus. Graphical abstract Unlabelled Image Highlights • GS was immobilized in PCL, PLA, PLGA or PLGA/PLA electrospun fibers by two methods. • Mats prepared by emulsion electrospinning displayed and excellent wettability. • Emulsion and suspension prepared fiber mats presented similar GS release profiles. • PLGA emulsion electrospinning mat had the most sustainable release profile. • All mats show antibacterial activity against Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

This work presents a framework for evaluating hybrid nanoflowers using Burkholderia cepacia lipase. It was expanded on previous findings by testing lipase hybrid nanoflowers (hNF-lipase) formation over a wide range of pH values (5–9) and buffer concentrations (10–100 mM). The free enzyme activity was compared with that of hNF-lipase. The analysis, performed by molecular docking, described the effect of lipase interaction with copper ions. The morphological characterization of hNF-lipase was performed using scanning electron microscopy. Fourier Transform Infrared Spectroscopy performed the physical–chemical characterization. The results show that all hNF-lipase activity presented values higher than that of the free enzyme. Activity is higher at pH 7.4 and has the highest buffer concentration of 100 mM. Molecular docking analysis has been used to understand the effect of enzyme protonation on hNF-lipase formation and identify the main the main binding sites of the enzyme with copper ions. The hNF-lipase nanostructures show the shape of flowers in their micrographs from pH 6 to 8. The spectra of the nanoflowers present peaks typical of the amide regions I and II, current in lipase, and areas with P–O vibrations, confirming the presence of the phosphate group. Therefore, hNF-lipase is an efficient biocatalyst with increased catalytic activity, good nanostructure formation, and improved stability. [ABSTRACT FROM AUTHOR]

Abstract: It is shown that the relationship between the alkyl chain length of 3-alkyl-3′,4′,5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n =1, 4, 6, 10 carbons and their capacity to counter oxidative damage varies markedly with the nature of the biological system. In Cu2+-induced lipid peroxidation of low-density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are probably located in the outer layer of LDL and parallel the reference flavonoid antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed with F4H and F6H present at concentration in the micromolar range. However, F10H the most hydrophobic FnH is even more effective than Q against both haemolysis and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In oxidation of RBC by H2O2, at least 50 times more F6H and F10H than by t-BuOOH are required to only partly inhibit haemolysis and MDA production. The F1H, F4H and Q are found rather inactive under these conditions. At concentrations in the micromolar range, a marked protection against the cytotoxic effects of the t-BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the four FnH species under study may be considered as potent antioxidants which manifest complementary anti-oxidative actions in biological systems of markedly different complexity. [Copyright &y& Elsevier]

Photodynamic therapy (PDT) of skin tumors or pre-cancerous lesions and of age-related macular degeneration combines the administration of porphyrins or porphyrin precursors and illumination with red light at the diseased sites. Photosensitizers absorbing light beyond 630 nm where tissues have the highest transmittance produce singlet oxygen, a highly reactive activated oxygen species and a major cytotoxin. The PDT of age-related macular degeneration is performed with red laser light after i.v. injection of verteporfin (Visudyne®) a hydrophobic porphyrin carried by serum lipoproteins whose endocytosis leads to accumulation of the porphyrin in endothelial cells of choroidal neo-vessels. In the PDT of skin cancers, local synthesis of the photosensitizer occurs after topical application of the natural protoporphyrin IX precursor δ-aminolevulinic acid (or its ester forms) on the lesions. In all the cases, the photosensitizers should be rapidly excreted to avoid a long lasting skin photosensitivity. [ABSTRACT FROM AUTHOR]

In the minor fraction of HDL3 containing α-tocopherol (αTocOH), selective one-electron oxidation of Trp and Tyr residues of apolipoproteins A-I and A-II by •Br2- radical-anions produces the corresponding semioxidized species, TyrO• and •Trp. Repair of TyrO• by endogenous αTocOH generates the α-tocopheroxyl radical (αTocO•). Fast spectroscopic studies show that two populations representing 80% of αTocO• initially formed are repaired over several seconds with rate constants of 3.0 × 106 and 1.5 × 105 M-1 s-1 by quercetin bound to human serum albumin (HSA) at physiologically relevant concentration. Formation of HSA-bound quercetin radicals (•Qb) is observed. In the major fraction of HDL3 particles lacking αTocOH, TyrO• and •Trp are repaired by free and HSA-bound quercetin. In LDL particles which all contain αTocOH, αTocO• radicals are formed in the millisecond time scale by repair of TyrO• radicals produced in apolipoprotein B. Then, 75% of initial TocO are repaired over seconds by HSA-bound quercetin (rate constant: 2.0 × 106 M-1 s-1). HSA-bound quercetin can also repair •Trp radicals. In O2-saturated solutions, the fraction of αTocO• radicals (more than 50%) not repaired by superoxide radical-anions can be repaired by HSA-bound quercetin with formation of •Qb but to a much lesser extent in LDL than in HDL. [ABSTRACT FROM AUTHOR]

It has been recently shown that the inhibition of apolipoprotein A-I (apoAI) reverse cholesterol transport activity during oxidation of HDL by myeloperoxidase may involve myeloperoxidase electron transfer pathways other than those leading to tyrosine chlorination. To better understand how such mechanisms might be initiated, the role of semioxidized Tyr and Trp residues in loss of apoAI and apolipoprotein A-II (apoAII) integrity has been assessed using selective Trp and Tyr one-electron oxidation by ̇Br2- radical-anions in HDL3 as well as in unbound apoAI and apoAII. Behavior of these radicals in apolipoprotein B of LDL has also been assessed. Formation of semioxidized Tyr in HDL3 is followed by partial repair during several milliseconds via reaction with endogenous α-tocopherol to form the α-tocopheroxyl radical. Subsequently, 2% of α-tocopheroxyl radical is repaired by HDL3 carotenoids. With LDL, a faster repair of semioxidized Tyr by α-tocopherol is observed, but carotenoid repair of α-tocopheroxyl radical is not. Only a small fraction of HDL3 particles contains α-tocopherol and carotenoids, which explains limited repair of semioxidized Tyr by α-tocopherol. All LDL particles normally contain multiple a-tocopherol and carotenoid molecules, and the lack of repair of α-tocopheroxyl radical by carotenoids probably results from hindered mobility of carotenoids in the lipid core. Western blots of v-irradiated HDL3 comparable to those reported for apoAI myeloperoxidase oxidation show that the incomplete repair of semioxidized Tyr and Trp induces apoAI and apoAII permanent damage including formation of a heterodimer of one apoAI with a monomeric apoAII at about 36 kDa. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) by porphyrins and related tetrapyrrole derivatives is an emerging new treatment modality of tumors of lung, eosophagus and skin and of age-related macular degeneration. Phase III clinical trials for other applications such as re-stenosis after angioplasty are also underway. Under systemic conditions, the transport of porphyrin photosensitizers by serum low density lipoproteins and their specific delivery to tumor cells and vasculature is a determinant of treatment effectiveness. However, this effectiveness can be improved by increasing the selectivity of the photosensitizer uptake by tumors and by using photosensitizers absorbing light in the 660–800 nm range where tissues have the highest transmittance. Another treatment showing great promise is the PDT of skin cancers after topical application of the protoporphyrin IX precursor delta-aminolevulinic acid (or its ester forms). In all the cases, the photosensitizers should be rapidly excreted to avoid a long lasting skin photosensitivity. [ABSTRACT FROM AUTHOR]

Four polyhydroxylated 2-styrylchromones, structurally related to flavones and cinnamic acid, have been studied. An SC derivative with OH groups only at positions 3′ and 4′ on the styryl moiety and another SC bearing an additional OH group at position 5 on the benzopyrone ring were more potent inhibitors of the Cu2+-induced peroxidation of LDL than the flavonoid quercetin. Fluorescence and absorption spectroscopies suggested that one LDL particle may bind 40 SC molecules. A pulse radiolysis study in pH 7 buffered micellar solutions of neutral TX100 and positively charged CTAB demonstrated that one-electron oxidation by ⋅Br2-, ⋅O2- and tryptophan radicals (⋅Trp) depends strongly on the micellar microenvironment. All SCs were readily oxidized by ⋅O2- in CTAB micelles (rate constants: 6–18×106 M-1 s-1). In TX100 micelles only the SC derivative with OH groups in position 3′ and 4′ reacted with ⋅O2- (rate constant: 1.1×106 M-1 s-1). In CTAB, electron transfer to ⋅Trp radicals was observed for all SCs with rate constants ≥3.2×107 M-1 s-1. In TX100 micelles, this reaction occurred solely with the derivative bearing OH groups only at positions 3′ and 4′. [Copyright &y& Elsevier]

Selective oxidative damage to apolipoprotein B in LDL can be effected radiolytically by •Br[sub 2][sup -] radicals. Twenty-seven Trp residues constitute major primary sites of oxidation, but two-thirds of oxidized Trps (•Trp) that are formed are repaired by intramolecular electron transfer from Tyr residues with formation of phenoxyl radicals (TyrO•). Analysis of •Trp and TyrO• transient absorbance changes suggests that other apolipoprotein B residues, probably Cys, are oxidized. LDL-bound quercetin can efficiently repair this damage. Absorption studies show that a LDL particle has the capacity to bind ∼10 quercetin molecules through interaction with apolipoprotein B. The repair occurs by intramolecular electron transfer characterized by a rate constant of 2 × 10³ s[sup -1]. In contrast, rutin, a related flavonoid which does not bind to LDL, cannot repair oxidized apolipoprotein B. Urate is a hydrophilic plasma antioxidant which displays synergistic antioxidant properties with flavonoids. Urate radicals produced by •Br[sub 2][sup -] can also be repaired by LDLbound quercetin. This repair occurs with a reaction rate constant of 6.8 × 10[sup 7] M[sup -1] s[sup -1]. Comparison with previous studies conducted with human serum albumin-bound quercetin suggests that quercetin analogues tailored to be carded preferentially by lipoproteins might be more powerful plasma antioxidants than natural quercetin carded by serum albumin. [ABSTRACT FROM AUTHOR]

Neutral tryptophan (•Trp) and tyrosine (TyrO•) radicals are repaired by certain flavonoids in buffer, in micelles and in human serum albumin (HSA) with corresponding formation of semioxidized flavonoid radicals. In deaerated buffer, •Trp but not TyrO• radicals react with catechin. In micelles, quercetin and rutin repair both •Trp and TyrO• radicals. In addition to amino acid reactivity, microenvironmental factors and nature of the flavonoids govern this repair. Electron transfer efficiencies from quercetin to negatively charged •Trp radicals are 100% in the micellar pseudophases of positively charged cetyltrimethylammonium bromide, (CTAB), and neutral Triton X100 (TX100), but 55% in negatively charged sodium dodecyl sulfate (SDS). In oxygen-saturated CTAB micelles, quercetin also reacts with the superoxide radical anion. When bound to domain IIA of HSA, quercetin repairs, by intra- or intermolecular encounter, less than 20% of oxidative damage to HSA. Quercetin can also repair freely circulating oxidized molecules with repair efficiencies falling to 7% for oxidized Trp, Tyr and α-MSH and to less than 2% for urate radical. This limited effectiveness is attributed both to the inaccessibility of bound quercetin and rutin toward radicals of circulating molecules and to the diffusion-controlled recombination of these radicals. [Copyright &y& Elsevier]

Neutral tryptophan (•Trp) and tyrosine (TyrO•) radicals are repaired by certain flavonoids in buffer, in micelles and in human serum albumin (HSA) with corresponding formation of semioxidized flavonoid radicals. In deaerated buffer, •Trp but not TyrO• radicals react with catechin. In micelles, quercetin and rutin repair both •Trp and TyrO• radicals. In addition to amino acid reactivity, microenvironmental factors and nature of the flavonoids govern this repair. Electron transfer efficiencies from quercetin to negatively charged •Trp radicals are 100% in the micellar pseudophases of positively charged cetyltrimethylammonium bromide, (CTAB), and neutral Triton X100 (TX100), but 55% in negatively charged sodium dodecyl sulfate (SDS). In oxygen-saturated CTAB micelles, quercetin also reacts with the superoxide radical anion. When bound to domain IIA of HSA, quercetin repairs, by intra- or intermolecular encounter, less than 20% of oxidative damage to HSA. Quercetin can also repair freely circulating oxidized molecules with repair efficiencies falling to 7% for oxidized •Trp, Tyr and α-MSH and to less than 2% for urate radical. This limited effectiveness is attributed both to the inaccessibility of bound quercetin and rutin toward radicals of circulating molecules and to the diffusion-controlled recombination of these radicals. [Copyright &y& Elsevier]

The article describes a case of papulonodular mucinosis (PNM) as an unusual presenting feature of systemic lupus erythematosus (SLE) in a 37-year-old White man presented with a one-month history of multiple asymptomatic papule on the face, trunk and arms. Topics discussed include the clinical characteristics of cutaneous mucinosis, details of the findings of the patient's histologic, immunofluorescence and urine examinations, and the symptoms of patients with PNE and SLE.