Potential tuberculostatic agents: Micelle-forming copolymer poly(ethylene glycol)-poly(aspartic acid) prodrug with isoniazid

With the objective of obtaining slow-acting isoniazid derivatives, of potential use as chemoprophylactics or chemotherapeutics in tuberculosis, the micelle-forming copolymer of poly(ethylene glycol)-poly(aspartic acid) prodrug with isoniazid was synthesized. The derivative obtained was found to be active in Mycobacterium Il(tuberculosis culture, with a minimal inhibitory concentration (MIC) 5.6 times lower than that of the tuberculostatic drug.

Potential tuberculostatic agent: Micelle-forming pyrazinamide prodrug

Pyrazinamide was condensed with the poly(ethylene glycol)-poly(aspartic acid) copolymer (PEG-PASP), a micelle-forming derivative was obtained that was characterized in terms of its critical micelle concentration (CMC) and micelle diameter. The CMC was found by observing the solubility of Sudan III in Poly(ethylene glycol)-poly(pyrazinamidomethyl aspartate) copolymer (PEG-PASP-PZA) solutions. The mean diameter of PEG-PASP-PZA micelles, obtained by analyzing the dynamic light-scattering data, was 78.2 nm. The PEG-PASP-PZA derivative, when assayed for anti-Mycobacterium activity, exhibited stronger activity than the simple drug.

Preparação e caracterização estrutural de aerogéis de sílica com diferentes concentrações de F127

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Preparation of polymeric micelles for use as carriers of tuberculostatic drugs

Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger antimycobacterial activity than the original drugs.Conclusion: the results demonstrate that polymeric micelles can be used as efficient carriers for drugs, which alone, exhibit undesired pharmacokinetics, poor solubility, and low stability. The synthesized micelle-forming tuberculostatic prodrugs opens a perspective of alternative prodrugs that prolong action and decrease the toxicity of the tuberculostatic drugs of choice.

Vesicle-micelle transition in mixtures of dioctadecyldimethylammonium chloride and bromide with nonionic and zwitterionic surfactants

We have investigated the effect of mixing spontaneously formed dispersions of the cationic vesicle-forming dioctadecyldimethylammonium chloride and bromide (DODAX, with X being anions Cl- (C) or Br- (B)) with solutions of the micelle-forming nonionic ethylene oxide surfactants penta-, hepta-, and octaethyleneglycol mono-n-dodecyl ether, C12En (n = 5, 7, and 8), and the zwitterionic 3-(N-hexadecyl-N,N-dimethylammonio)propane sulfonate (HPS). We used for this purpose differential scanning calorimetry (DSC), turbidity, and steady-state fluorescence spectroscopy to investigate the vesicle-micelle (V-M) transition yielded by adding C12En and HPS to 1.0 mM vesicle dispersions of DODAC and DODAB. The addition of these surfactants lowers the gel-to-liquid crystalline phase transition temperature (T-m) of DODAC and DODAB, and the transition becomes less cooperative, that is, the thermogram transition peak shifts to lower temperature and broadens to disappear when the V-M transition is complete, the vesicle bilayer becomes less organized, and the T., decreases, in agreement with measurements of the fluorescence quantum yield of trans-diphenylpolyene (t-DPO) fluorescence molecules incorporated in the vesicle bilayer. Turbidity data indicate that the V-M transition comes about in three stages: first surfactants are solubilized into the vesicle bilayer; after saturation, the vesicles are ruptured, and, finally, the vesicles are completely solubilized and only mixed micelles are formed. The critical points of bilayer saturation and vesicle solubilization were obtained from the turbidity and fluorescence curves, and are reported in this communication. The solubility of DODAX is stronger for C12En than it is for HPS, meaning that C12En solubilizes DODAX more efficiently than does HPS. The surfactant solubilization depends slightly on the counterion, and varies according to the sequence C12E5 > C12E7 > C12E8 > HPS.

Thermotropic phase behavior in aqueous mixtures of dioctadecyldimethylammonium bromide and alkyltrimethylammonium bromide surfactant series studied by differential scanning calorimetry

The effect of the micelle-forming surfactant series alkyltrimethylammonium bromide (C(n)TAB, n = 12, 14, 16 and 18) on the thermotropic phase behavior of dioctadecyldimethylammonium bromide (DODAB) vesicles in water was investigated by differential scanning calorimetry at constant 5.0 mM total surfactant concentration and varying individual surfactant concentrations. The pre-, post- and main transition temperatures (T-s, T-p and T-m), melting enthalpy (Delta H) and peak width of the main transition (Delta T-1/2) are reported as a function of the surfactant molar fraction. No clear dependence of these parameters on the C(n)TAB chain length was found. At 5 mM, neat DODAB in water exhibits two transition temperatures, T-s = 32.1 and T-m = 42.7 degrees C, as obtained from the DSC upscans, but not a clear T-p. For every n, except n = 12, T-s vanishes as CnTAB concentration increases and approaches CMC. T-m behaves differently for different n, the longer C(14)TAB and C(16)TAB decrease, while C(18)TAB increases T-m with increasing concentration. The data indicate that changes in T-m, T-s, T-p and Delta H of the transition are related not only to the extent of C(n)TAB affinity to DODAB but also to the surfactant chain length. Accordingly, C18TAB yields a more compact bilayer, thus increasing T-m, while C(14)TAB and C(1G)TAB yield a less organized bilayer and reduce T-m. C(12)TAB does not much affect T-s and T-m, although it yields T-p approximate to 51.6 degrees C. (C) 2008 Elsevier B.V. All rights reserved.

Dioctadecyldimethylammonium bromide vesicles prepared by the surfactant removal method

Dioctadecyldimethylammonium bromide (DODAB) is a double chain vesicle-forming cationic surfactant, whereas octa-ethyleneglycol mono-n-dodecyl ether (C12E8) is a single chain micelle-forming nonionic surfactant. At room temperature (ca. 22 degrees C) C12E8 molecules self-assemble in water as micelles while DODAB is insoluble. A mixture of DODAB and C12E8, however, can be soluble in water at room temperature depending on the relative amount of the compounds. We report the formation of small unilamellar vesicles (SUVs) by dialyzing at room temperature a mixture of 1.0 mM DODAB with 10 mM C12E8 in water. Extended bilayers are formed as well in equilibrium with vesicles. Such structures are viewed by a cryogenic transmission electron microscopy (cryo-TEM) image. (c) 2006 Elsevier B.V. All rights reserved.

Transição vesícula-micela em mistura aquosa de sais dialquilados de amônio quaternário com Pluronic® F127

Pós-graduação em Biofísica Molecular - IBILCE

Effect of an acrylic resin combined with an antimicrobial polymer on biofilm formation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lubricating coating prepared by PIIID on a forming tool

In this work, the performance of a-C: H films produced by the hybrid Plasma Immersion Ion Implantation and Deposition technique as lubricating layers for a steel forming tool has been investigated. Hardened steel (AISI M2, 64 HRC) plates coated with a commercial TiN layer were used as substrates and the films were deposited in a vacuum chamber fitted with two parallel-plate electrodes. The discharges were generated in atmospheres composed of 91% C2H2 and 9% Ar by the application of radiofrequency power (13.56 MHz, 100 W) to the upper electrode while the lower one, also used as the sample holder, was biased with high voltage negative pulses (3.6 kV, 30 mu s, 300 Hz). A deposition time of 840 s was used. The effects of the gas pressure, p, on thickness, molecular structure, wettability, surface morphology and topography, hardness and friction coefficient of the films lwere investigated. Film thickness increased from 0.3 to 0.5 mu m when p was increased from 2.7 to 16.5 Pa. Generally, the films were slightly hydrophilic, with contact angles of around 84 degrees, and the deposition decreased the roughness of the steel. A polymer-like structure was detected in high pressure depositions and an amorphous carbon structure derived from the low pressure procedures. Hardness decreased from 8.2 to 7.0 GPa with increasing p. Improvement in tribological performance was indicated by the fall in the friction coefficient from 0.5 to 0.2 as the deposition pressure was reduced. Operating at the latter value (of mu) would lead to a significant reduction in wear and hence to significant economy in diverse industrial applications.

Polymer treatment by plasma immersion ion implantation of nitrogen for formation of diamond-like carbon film

Nitrogen ions were implanted by plasma immersion in Kapton, Mylar and polypropylene, with the objective of forming a diamond-like carbon layer on these polymers. The Raman spectrum of the implanted polypropylene showed typical Diamond-Like Carbon (DLC) graphite (G) and disorder (D) peaks, with an sp 3/sp2 hybridization ratio of approximately 0.4 to 0.6. The XPS analysis of the three implanted polymers also showed peaks of C-C and N-C bonds in the sp3 configuration, with hybridization ratios in the same range as the Raman result. The implanted polymers were exposed to oxygen plasma to test the resistance of the polymers to oxygen degradation. Mass loss rate results, however, showed that the DLC layer formed is not sufficiently robust for this application. Nevertheless, the layer formed can be suitable for other applications such as in gas barriers in beverage containers. Further study of implantation conditions may improve the quality of the DLC layer.

Hydrothermal synthesis and crystal structure of a copper(ii) coordination polymer with bridging dicarboxylate and diamine ligands

This work reports on the synthesis of a copper(II) coordination compound with 4,4-oxibis(benzoate) (obb) and trans-1,2- bis(4-pyridyl)ethene (bpe) ligands. The complex was characterized by single-crystal X-ray diffraction, which showed a 3D polymeric structure. Each copper center is surrounded by four oxygen atoms at the basal plane and one nitrogen atom and one copper atom at the axial positions, revealing a distorted octahedral geometry. Four carboxylic groups bridge two copper atoms, forming a cage-like structure, with the distance between the metallic centers being 2.656(1)Å. 2008 © The Japan Society for Analytical Chemistry.

Anti-erosive properties of solutions containing fluoride and different film-forming agents

Objectives: To evaluate the anti-erosive potential of solutions containing sodium fluoride (NaF, 225 ppm F) and different film-forming agents.Methods: In Phase 1, hydroxyapatite crystals were pre-treated with solutions containing NaF (F), linear sodium polyphosphate (LPP), sodium pyrophosphate tetrabasic (PP), sodium tripolyphosphate (STP), sodium caseinate (SC), bovine serum albumin (BSA), stannous chloride (Sn) and some combinations thereof. Deionized water was the control (C). The pH-stat method was used to evaluate hydroxyapatite dissolution. In Phase 2, the most effective solutions were tested in two independent experiments. Both consisted of an erosion-remineralization cycling model using enamel and dentine specimens with three solution treatments per day. In Phase 2a, the challenge was performed with 0.3% citric acid (pH = 3.8). In Phase 2b, 1% citric acid (pH = 2.4) was used. Hard tissue surface loss was determined profilometrically. Data were analyzed with two-way ANOVA and Tukey tests.Results: In Phase 1, F, LPP, Sn and some of their combinations caused the greatest reduction in hydroxyapatite dissolution. In Phase 2a, C showed the highest enamel loss, followed by LPP. There were no differences between all other groups. In Phase 2b: (F + LPP + Sn) < (F + LPP) = (F + Sn) < (F) = (LPP + Sn) < (LPP) < (Sn) < C. For dentine, in both experiments, only the fluoride-containing groups showed lower surface loss than C, except for LPP + Sn in 2a.Conclusions: F, Sn, LPP reduced enamel erosion, this effect was enhanced by their combination under highly erosive conditions. For dentine, the F-containing groups showed similar protective effect.Clinical significance: The addition of LPP and/or Sn can improve the fluoride solution protection against erosion of enamel but not of dentine. (C) 2015 Elsevier Ltd. All rights reserved.