Search

Multidrug-resistant bacteria represent a global health and economic burden that urgently calls for new technologies to combat bacterial antimicrobial resistance. Here, we developed novel nanocomposites (NCPs) based on chitosan that display different degrees of acetylation (DAs), and conjugated polymer cyano-substituted poly(p-phenylene vinylene) (CNPPV) as an alternative approach to inactivate Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Chitosan's structure was confirmed through FT-Raman spectroscopy. Bactericidal and photobactericidal activities of NCPs were tested under dark and blue-light irradiation conditions, respectively. Hydrodynamic size and aqueous stability were determined by DLS, zeta potential (ZP) and time-domain NMR. TEM micrographs of NCPs were obtained, and their capacity of generating reactive oxygen species (ROS) under blue illumination was also characterized. Meaningful variations on ZP and relaxation time T2 confirmed successful physical attachment of chitosan/CNPPV. All NCPs exhibited a similar and shrunken spherical shape according to TEM. A lower DA is responsible for driving higher bactericidal performance alongside the synergistic effect from CNPPV, lower nanosized distribution profile and higher positive charged surface. ROS production was proportionally found in NCPs with and without CNPPV by decreasing the DA, leading to a remarkable photobactericidal effect under blue-light irradiation. Overall, our findings indicate that chitosan/CNPPV NCPs may constitute a valuable asset for the development of innovative strategies for inactivation and/or photoinactivation of bacteria. Keywords: photoantimicrobial activity; blue-light irradiation; chitosan; CNPPV; nanocomposites; E. coli; S. aureus

Vulvovaginal candidiasis (VVC) represents a considerable health burden for women. Despite the availability of a significant array of antifungal drugs and topical products, the management of the infection is not always effective, and new approaches are needed. Here, we explored cationic N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan nanoparticles (NPs) as carriers of clotrimazole (CLT) for the topical treatment of VVC. CLT-NPs with approximately 280 nm in diameter were obtained by self-assembly in water and subsequent stabilization by ionic crosslinking with tripolyphosphate. The nanosystem featured pH-independent sustained drug release up to 24 h, which affected both in vitro anti-Candida activity and cytotoxicity. The CLT-loaded nanostructured platform yielded favorable selectivity index values for a panel of standard strains and clinical isolates of Candida spp. and female genital tract cell lines (HEC-1-A, Ca Ski and HeLa), as compared to the free drug. CLT-NPs also improved in vitro drug permeability across HEC-1-A and Ca Ski cell monolayers, thus suggesting that the nanocarrier may provide higher mucosal tissue levels of the active compound. Overall, data support that CLT-NPs may be a valuable asset for the topical treatment of VVC. Statement of significance Topical azoles such as clotrimazole (CLT) are first line antifungal drugs for the management of vulvovaginal candidiasis (VVC), but their action may be limited by issues such as toxicity and poor capacity to penetrate the genital mucosa. Herein, we report on the ability of a new cationic N-(2‑hydroxy)-propyl-3-trimethylammonium, O-dipalmitoyl chitosan derivative (DPCat35) to yield tripolyphosphate-reinforced micelle-like nanostructures that are suitable carriers for CLT. In particular, these nanosystems were able to improve the in vitro selectivity index of the drug and to provide enhanced epithelial drug permeability when tested in cell monolayer models. These data support that CLT-loaded DPCat35 nanoparticles feature favorable properties for the development of new nanomedicines for the topical management of VVC.

Wound repair is a complex process that calls for strategies to allow a rapid and effective regeneration of injured skin, which has stimulated the research of advanced wound dressings. Herein, highly porous membranes of N,O-carboxymethylchitosan (CMCh), and poly (vinyl alcohol) (PVA) were successfully prepared via a green and facile freeze-drying method of blend solutions containing CMCh/PVA at weight ratio 25/75. Membranes composed only by CMCh were also prepared and genipin was used for crosslinking. Different contents of TiO2 nanoparticles were incorporated to both type of membranes, which were characterized in terms of morphology, porosity (Φ), swelling capacity (S.C.), mechanical properties, susceptibility to lysozyme degradation and in vitro cytotoxicity toward human fibroblast (HDFn) and keratinocytes (HaCaT) cells. Larger apparent pores were observed in the surface of the genipin-crosslinked CMCh membrane, which resulted in higher porosity (Φ ≈ 76%) and swelling capacity (S.C. ≈ 1720%) as compared to CMCh/PVA membrane (Φ ≈ 68%; S.C. ≈ 1660%). The porosity of both types of membranes decreased upon the addition of TiO2 nanoparticles while swelling capacity increased. Due to their high porosity and swelling capacity, adequate mechanical properties, controlled degradability, and cytocompatibility, such carboxymethylchitosan-based membranes are potentially useful as wound dressings.

Since chitosan presents the ability to interact with a wide range of molecules, it has been one of the most popular natural polymers for the construction of layer-by-layer thin films. In this study, depth-profiling X-ray photoelectron spectroscopy (XPS) was employed to track the diffusion of sulfonated polystyrene (SPS) in carboxymethyl cellulose/chitosan (CMC/Chi) multilayers. Our findings suggest that the CMC/Chi film does not constitute an electrostatic barrier sufficient to block diffusion of SPS, and that diffusion can be controlled by adjusting the diffusion time and the molecular weight of the polymers that compose the CMC/Chi system. In addition to monitoring the diffusion, it was also possible to observe a process of preferential interaction between Chi and SPS. Thus, the nitrogen N 1s peak, due to functional groups found exclusively in chitosan chains, was the key factor to identifying the molecular interactions involving chitosan and the different polyanions. Accordingly, the presence of a strong polyanion such as SPS shifts the N 1s peak to a higher level of binding energy. Such results highlight that understanding the fundamentals of polymer interactions is a major step to fine-tuning the internal architecture of LbL structures for specific applications (e.g., drug release).

Langmuir monolayers are used to simulate the biological membrane environment, acting as a mimetic system of the outer or the inner membrane leaflet. Herein, we analyze the interaction of membrane models with a partially N-acetylated chitosan (Ch35%) possessing a quasi-ideal random pattern of acetylation, full water solubility up to pH ≈ 8.5 and unusually high weight average molecular weight. Lipid monolayers containing dipalmitoyl phosphatidyl choline (DPPC), dipalmitoyl phosphatidyl ethalonamine (DPPE), dipalmitoyl phosphatidyl glycerol (DPPG) or E. coli total lipid extract were spread onto subphases buffered at pH 4.5 or 7.4. The incorporation of Ch35% chitosan caused monolayer expansion and a general trend of decreasing monolayer rigidity with Ch35% concentration. Due to its relatively high content of N-acetylglucosamine (GlcNAc) units, Ch35% interactions with negatively charged monolayers and with E. coli extract were weaker than those involving zwitterionic monolayers or lipid rafts. While the smaller interaction with negatively charged lipids was unexpected, this finding can be attributed to the degree of acetylation (35%) which imparts a small number of charged groups for Ch35% to interact. Chitosan properties are therefore determinant for interactions with model cell membranes, which explains the variability in chitosan bactericide activity in the literature. This is the first study on the effects from chitosans on realistic models of bacterial membranes under physiological pH.

Immobilization of cells on surfaces can be strongly affected by several properties of a substrate, including surface properties, topography and charge density. Controlling the cell adhesion mechanism is a real challenge in biotechnological processes. Here, we assessed the influence of the average degree of deacetylation of chitosan ( DD ¯ ) and the polyelectrolyte solution pH on the physicochemical properties of multilayered hyaluronan/chitosan films and their ability to bind tumor cells. These functional coatings explore CD44-hyaluronate interactions to improve the capture of tumor cells (PC3 line). Film characterization was carried out using XPS, UV–Vis and scanning probe techniques such as Capacitance, KPFM and AFM-IR measurements. The increase in the solution pH from 3.0 to 5.0 was the major factor to control both the film structure and the cell capture, enhancing the number of cells adhered in a range of 1.5 to 3.5-fold. These results also suggest that limited HA availability induces cell-film adhesion, whereas more irregular and rougher surfaces inhibit this process. These findings indicate that surface chemistry and morphology are critical factors for the development of new biomaterials designed to capture cells selectively.

Chitosans with different average degrees of acetylation and weight molecular weight were analyzed by time-domain NMR relaxometry using the recently proposed pulse sequence named Rhim and Kessemeier - Radiofrequency Optimized Solid-Echo (RK-ROSE) to acquire 1H NMR signal of solid-state materials. The NMR signal decay was composed of faster (tenths of μs) and longer components, where the mobile-part fraction exhibited an effective relaxation transverse time assigned to methyl hydrogens from N-acetyl-d-glucosamine (GlcNAc) units. The higher intrinsic mobility of methyl groups was confirmed via DIPSHIFT experiments by probing the 1H-13C dipolar interaction. RK-ROSE data were modeled by using Partial Least Square (PLS) multivariate regression, which showed a high coefficient of determination (R2 > 0.93) between RK-ROSE signal profile and average degrees of acetylation and crystallinity index, thus indicating that time-domain NMR consists in a promising tool for structural and morphological characterization of chitosan.

Made available in DSpace on 2021-06-26T06:17:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Auxilio Financeiro a Projeto Educacional ou de Pesquisa Two samples of N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan (DPCat) with different av-erage degrees of quaternization named as DPCat35 (DQ = 35%) and DPCat80 (DQ = 80%), were successfully syn-thesized by reacting glycidyltrimethylammonium chloride (GTMAC) with O-palmitoyl chitosan (DPCh) derivative (DS = 12%). Such amphiphilic derivatives of chitosan were fully water-soluble at 1.0 < pH < 12.0 and showed significant electrostatic stability enhancement of a self-assembly micellar nanostructure (100 & ndash;320 nm) due to its positively-charged out-layer. In vitro mucoadhesive and cytotoxicity essays toward healthy fibroblast cells (Balb/C 3T3 clone A31 cell), human prostate cancer (DU145) and liver cancer (HepG2/ C3A) cell lines revealed that the biological properties of DPCat derivatives were strongly dependent on DQ. Ad-ditionally, DPCat35 had better interactions with the biological tissue and with mucin glycoproteins at pH 7.4 as well as exhibited potential to be used on the development of drug delivery systems for prostate and liver cancer treatment. (c) 2021 Elsevier B.V. All rights reserved. Sao Paulo State Univ, Inst Chem, Av Prof Francisco Degni 55,237, BR-14800900 Araraquara, SP, Brazil Univ Sao Paulo, Sao Carlos Inst Chem, Av Trabalhador Sao Carlense 400,780, BR-13566590 Sao Carlos, SP, Brazil Brazilian Corp Agr Res, Embrapa Instrumentat, Rua XV Novembro 1452, BR-13560970 Sao Carlos, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Rod Araraquara Jau Km 01 S-N, BR-14800903 Araraquara, SP, Brazil Sao Paulo State Univ, Inst Chem, Av Prof Francisco Degni 55,237, BR-14800900 Araraquara, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Rod Araraquara Jau Km 01 S-N, BR-14800903 Araraquara, SP, Brazil FAPESP: FAPESP 2016/20970-2 FAPESP: 2017/20973-4 FAPESP: 2019/13656-8 CNPq: CNPq 141353/2016-3 CNPq: 150964/2017-0 CNPq: 309568/2019-6 CAPES: 001 Auxilio Financeiro a Projeto Educacional ou de Pesquisa: AUXPE 139/2015

We report on layer-by-layer (LbL) films of chitosans (CHI) and hyaluronic acid (HA) whose properties could be controlled by employing chitosans with different degrees of deacetylation ( DD ¯ ≈ 85%; 65%; 40%) and high average molecular weight (ca. 106 g/mol). In spite of their high molecular weight, these chitosans are soluble within a wide pH range, including physiological pH. HA/CHI LbL films produced from polymer solutions at pH 4.5 were thinner, smoother, more hydrophilic than those prepared at pH 7.2. This is attributed to the more extended conformation adopted by chitosan due to its very high charge density at low pH, favoring a compact chain packing during the film formation and resulting in lower film thickness and roughness. The smoother HA/CHI LbL films obtained at pH 4.5 were effective against Escherichia coli, while the thicker, rougher LbL films fabricated at pH 7.2 could be used in the controlled released of Rose Bengal dye. In summary, the tuning of only two parameters, i.e. solution pH and DD ¯ of chitosans, provides access to a library of HA/CHI LbL films for tailored, diversified applications.

In this paper, chitosan was used as protective agent for dual temperature-/pH-sensitive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate)- based hydrogel nanoparticles (poly(NVCL-co-IA-co-EGDMA)) aiming avoid their undesirable colloidal destabilization at different conditions of body human tissues. Thus, poly(NVCL-co-IA-co-EGDMA) was embedded into chitosan and a new solid dispersion was prepared via spray-drying and ketoprofen was used as carrier. Two different sizes of hydrogel nanoparticles (120.6 nm and 185.9 nm) were evaluated and they exhibited a drug encapsulation efficiency of the 39.6% and 57.8%, respectively. The smaller nanoparticles showed to be faster for releasing of ketoprofen at pH 7.4 and 37 °C due to their larger surface area and higher swelling ability. Chitosan played a role of a secondary barrier for the ketoprofen diffusion, extending its release compared to hydrogel nanoparticles alone. Among two concentrations (40 wt% and 70 wt%) of hydrogel nanoparticles related to chitosan, the first one induced higher percentages of ketoprofen release: 74.2% against 64.6%. In addition, the interactions between chitosan matrix and poly(NVCL-co-IA-co-EGDMA) did not change the multi-responsive behavior of hydrogels, suggesting the chitosan was efficient for keeping integrity of nanoparticles hydrogels. Chitosan/poly(NVCL-co-IA-co-EGDMA) hybrid microparticles seems to be a promising new carrier for release of hydrophobic drugs, such as ketoprofen.

The chitin insoluble characteristics in aqueous media creates a barrier for biological applications. While the chitosan, the most used derivative from chitin, have been widely used for several applications, due to high solubility in slightly acidic aqueous solution. Reported herein is a new approach, consisting of ultrasound irradiation of beta-chitin, which can produce stable suspensions in water (pH= 7.0). With the aim of obtained the most stable beta-chitin suspensions, we played with beta-chitin concentration (0.4 g/L and 1.6 g/L), sonication time (ranged in the interval from 5 min. to 30 min.) and the irradiation amplitude (from 30 % to 50%). When beta-chitin is processed by ultrasound, in aqueous media, we observed the decrease of crystallinity (DRX) and the appearance of micro and nanofibers (MEV). Testing the stability of beta-chitin suspensions, was demonstrate that these suspensions can be stable since 5 min. until several days. Coupling the efficient process to produce stable suspensions in water with biodegradable and biocompatible characteristics of beta-chitin holds great considerable promise for advanced in biological applications.

Blend solutions of poly(e-caprolactone) (PCL) and N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride (QCh) were successfully electrospun. The weight ratio PCL/QCh ranged in the interval 95/5–70/30 while two QCh samples were used, namely QCh1 ( D Q ¯ = 47.3%; D P v ¯ = 2218) and QCh2 ( D Q ¯ = 71.1%; D P v ¯ = 1427). According to the characteristics of QCh derivative and to the QCh content on the resulting PCL/QCh nonwoven, the nanofibers displayed different average diameter (175 nm–415 nm), and the nonwovens exhibited variable porosity (57.0%–81.6%), swelling capacity (175%–425%) and water vapor transmission rate (1600 g m−2 24 h–2500 g m−2 24 h). The surface hydrophilicity of nonwovens increases with increasing QCh content, favoring fibroblast (HDFn) adhesion and spreading. Tensile tests revealed that the nonwovens present a good balance between elasticity and strength under both dry and hydrated state. Results indicate that the PCL/QCh electrospun nonwovens are new nanofibers-based biomaterials potentially useful as wound dressings.

Este artigo tem o objetivo de analisar o uso das fontes de informações ambientais em pequenas empresas. A abordagem de pesquisa utilizada foi a qualitativa, por meio de estudo de casos múltiplos, aplicados em pequenas empresas, nos setores metal mecânico e de base tecnológica. Como resultado, descobriu-se que as principais fontes externas de informações são os clientes, o departamento comercial e os empresários. A principal contribuição desta pesquisa é mostrar que não há diferenças significantes nas fontes de informação que os empresários, de ambos os setores, utilizam para obter informações sobre o ambiente externo.

We systematically investigated the effect of β-chitin (BCH) particle size on the preparation of nanocrystals/nanowhiskers (CWH) by acid hydrolysis. Regardless this variable, CWH aqueous suspension exhibited outstanding stability and the average degree of acetylation remained nearly constant after the acid treatment. In contrast, the morphology, dimensions, crystallinity, and molecular weight of CHW were significantly affect by the particle size. Although needle-like crystals have predominated, BCH particles sizes significantly affected the dimensions and asymmetry of CWH, as confirmed by the rheological and NMR relaxation (T2) behaviors. According to different SSNMR approaches, the acid hydrolysis meaningless affected the local chain conformation, while the spatial freedom of BCH intersheets, rated upon the mobility of methyl segments, was taken as evidence of higher permeability of acid into small particle sizes. Thus, this study demonstrated the importance of standardizing the surface/bulk proportions of β-chitin aiming to predict and control the CWH morphology and related properties.

Langmuir monolayers have been used as cell membrane models, where lipid composition is normally varied to mimic distinct types of membranes. For eukaryotic membranes, for instance, rather than using only zwitterionic phospholipids there is now a trend to employ mixtures to simulate the lipid rafts known to be relevant for various cellular processes. In this study, we demonstrate that effects from chitosans on Langmuir monolayers are considerably higher if lipid raft compositions (ternary mixtures of dipalmitoyl phosphatidyl choline (DPPC), sphingomyelin (SM) and cholesterol) are used. Significantly, measurable effects on the surface pressure isotherms start at 10-6 mg mL-1 for chitosans in lipid rafts, to be compared with 10-2 mg mL-1 for neat dipalmitoyl phosphatidylcholine (DPPC). This applies to both a commercial chitosan and chitosans soluble at physiological pH. Incorporation of these chitosans in the raft monolayers was confirmed in polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) experiments, where both the tail groups and headgroups were found to interact with chitosan. Since the effects on membrane models may be observed at such small concentrations for chitosans and probably other molecules, some studies may have to be revisited where neat phospholipids should be replaced by lipid raft compositions.

Made available in DSpace on 2020-12-12T01:47:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Core-sheath nanofibers were successfully prepared via coaxial electrospinning by using chitosan with well-defined structural characteristics as the shell layer and poly (vinyl alcohol) (PVA) containing tetracycline hydrochloride (TH) as the core layer. The effects of the average degree of deacetylation (DD‾) of chitosan and the post-electrospinning genipin crosslinking on physicochemical and biological properties of resulting nonwovens were evaluated. Defect-free and geometrically uniform nanofibers with diameters predominantly in the range of 100–300 nm were prepared, and transmission electron microscopy (TEM) revealed the core-sheath structures and its preservation after crosslinking. The mechanical properties, as well as the stability of nonwovens in aqueous medium, were greatly improved by genipin-crosslinking, which enabled a sustained release of TH over 14 days. Results also revealed that the release profile of TH in the presence of lysozyme was affected by the composition of the shell layer, as the TH release rate increases with decreasing of DD‾. Further in vitro antimicrobial activity demonstrated that the cross-linked nonwovens containing TH showed strong activity against bacterial strains associated with periodontal disease. Additionally, the nonwovens did not demonstrate cytotoxic toward fibroblast (HDFn) cells, hence showing their potential for applications as a novel drug delivery platform for periodontitis treatment. Nanotechnology National Laboratory for Agriculture (LNNA), Embrapa Instrumentação, 13560-970 São Carlos PPG-Biotec Center for Exact Sciences and Technology Federal University of São Carlos (UFSCar) Sao Carlos Institute of Physics/University of São Paulo, PO Box 369, 13560-970 São Carlos Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP) Sao Carlos Institute of Chemistry/University of São Paulo, Av. Trabalhador sao-carlense, 400, 13566-590 São Carlos Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP) FAPESP: 2013/07276-1 FAPESP: 2017/12174-4 FAPESP: 2017/20973-4 FAPESP: 2018/09088-1 FAPESP: 2018/23015-7

We propose a novel approach relied on high-resolution solid-state 13C NMR spectroscopy to quantify the crystallinity index of chitosans (Ch) prepared with variable average degrees of acetylation ( D A ¯ ) from 5% to 60 % and average weight molecular weight ( M ¯ w ) ranged in 0.15 × 106 g mol−1–1.2 × 106 g mol−1. The Dipolar Chemical Shift Correlation (DIPSHIFT) curve of the C(6)OH segment revealed increased mobility dynamic, which induced different distribution from trans-to-gauche conformations in relation to C(4). Indeed, 1H-13C Heteronuclear Correlation (2D HETCOR) showed that distinguished C4 chemical shifts correlates with the same aliphatic protons. The short-range ordering can be assigned to C4/C6 signals on 13C CPMAS and, for our case, the deconvolution procedure between disordered and ordered phases revealed increasing crystallinity with D A ¯ , as confirmed by SVD multivariate analysis. This work extended the knowledge regarding the use of 13C CPMAS technique to predict the crystallinity of chitosans without the use of amorphous standards.

A hybrid hydrogel combining collagen and chitosan (Ch) and human amniotic membranes (AM) were produced. To produce hybrid hydrogels, a fixed concentration of chitosan (2%) was used, adding AM as a ...

Miniaturized and inexpensive sensing platforms remains an important goal for the field-deployable monitoring of toxic gases. In this work, we report a disposable ethanol sensor based on nanochitin-composite containing chitin nanowhiskers/zinc oxide nanoparticles/polyaniline (ChitNW-ZnO/PANI) produced via solution casting method. The as-prepared material was fully characterized by transmission electron microscopy, atomic force microscopy, contact angle measurements, mechanical tests, thermogravimetric analysis and X-ray diffraction, confirming its successful preparation and revealing its morphology, microstructure and composition. Such nanocomposite showed enhanced ethanol sensing performance at room temperature, in which quantitative analysis was obtained in the range 20–100 ppm with a detection limit of 17 ppm (S/N = 3). We further validated that common potential interfering agents were not misidentified with ethanol. The development of such a unique nanochitin-based composite as a disposable sensor is a great step ahead in flexible and wearable electronics having potential applications in different fields such as biomedical and biotechnological engineering, security and internet of things (IoT).

N-acetyl-D-glucosamine (GlcNAc) is an important amino-monosaccharide with great potential for biotechnological applications. It has traditionally been produced by the chemical hydrolysis of chitin, despite certain industrial and environmental drawbacks, including acidic wastes, low yields and high costs. Therefore, enzymatic production has gained attention as a promising environmentally-friendly alternative to the chemical processes. In this study we demonstrate the GlcNAc bioproduction from colloidal α-chitin using an enzyme cocktail containing endochitinases and exochitinases (chitobiosidases and N-acetyl-glucosaminidases). The enzyme cocktail was extracted after fermentation in a bioreactor by Aeromonas caviae CHZ306, a chitinolytic marine bacterium with great potential for chitinase production. Hydrolysis parameters were studied in terms of temperature, pH, enzyme and substrate concentration, and reaction time, achieving over 90% GlcNAc yield within 6 h. The use of colloidal α-chitin as substrate showed a substantial improvement of GlcNAc yields, when compared with β-chitin and α-chitin polymorphs. Such result is directly related to a significant decrease in crystallinity and viscosity from natural α-chitin, providing the chitinase with greater accessibility to the depolymerized chains. This study provides valuable information on the GlcNAc bioproduction from chitin using an enzymatic approach, addressing the key points for its production, including the enzyme cocktail composition and the substrate structures.

An amphiphilic derivative of chitosan containing quaternary ammonium and myristoyl groups, herein named as ammonium myristoyl chitosan (DMCat), was synthesized by reacting glycidyltrimethylammonium chloride (GTMAC) and myristoyl chitosan (DMCh). The success of the modification was confirmed using Fourier-transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (NMR) spectroscopy. The average degrees of alkylation and quaternization ( D Q &macr, ) were determined by using 1H NMR and conductometric titration. The zeta potential of the micelles was higher than 28 mV while its average size and encapsulation efficiency ranged from 280 nm to 375 nm and 68% to 100%, respectively. The in vitro cytotoxicity of the unloaded and curcumin (CUR)-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cell lines. The results showed no cytotoxic effect from loaded and unloaded micelles as compared to free CUR. In the permeability test, it was observed that both types of micelles, i.e., DMCh and DMCat, improved CUR permeability. Additionally, higher permeability was verified for both systems in Caco-2/HT29-MTX:Raji B because of the mucoadhesive character of chitosan and its ability to open tight junctions. The results indicated that DMCat micelles, due to the physico-chemical, improved characteristics may be a promising carrier to encapsulate CUR aiming cancer therapy.

Methoxypoly(ethyleneglycol)-graft-chitosan (PEG-g-Ch) was prepared by grafting polyethyleneglycol into chitosans (Ch) exhibiting different average degree of deacetylation (60% DD ¯ DS ¯ ≈ 40%) and such derivatives exhibited full water solubility at 1.0 DD ¯ ≈ 76%; [η] ≈ 1201 mL g−1) showed a distinct rheological behavior as it formed a physically cross-linked hydrogel that exhibited a thermo-induced sol-gel transition at ≈38 °C.

International audience; The interactions between a polyelectrolyte and an oppositely charged surfactant allows obtaining complexes with specific properties. Such complexes between a quaternized chitosan, obtained from the reaction between chitosan and quaternary ammonium epoxides, and sodium 1-decanesulfonate were studied. Physico-chemical characteristics were obtained from conductimetric experiments as well as surface tension studies. A strong associative electrostatic interaction between the polysaccharide and the surfactant was shown from conductimetric experiments and a degree of association equal to 0.74 was determined. The complex presents better interfacial properties than surfactant and polysaccharide alone. The critical aggregation concentration is much smaller than the critical micellar concentration of the surfactant alone in solution. Moreover the viscoelastic moduli of the interfacial layer was increased in presence of the complex by comparing with surfactant alone. All these considerations allow using the surfactant-polysaccharide complex as a better emulsion stabilizer than either surfactant or polysaccharide alone.

This paper discusses the production of chitosan by applying high intensity ultrasound irradiation to alpha-chitin suspended in 40% aqueous sodium hydroxide. The average degree of acetylation (DA) of chitosan was determined by 1H NMR spectroscopy and titrimetry while its viscosity average molecular weight (Mv) was calculated from the intrinsic viscosity as determined by capillary viscometry. The results show that fully acid-soluble chitosans (DA 95%) by applying non-isothermal ultrasound-assisted N-deacetylation process to alpha-chitin suspension (44 mg/mL). It is also shown that such a process is more efficient than thermochemical N-deacetylation, even being carried out at a lower temperature due to the effects of high intensity ultrasound irradiation.

The effects of reaction time, concentration of aqueous sodium hydroxide and molar ratio iodomethane/chitosan on the yield of the reaction of chitosan with iodomethane in N-methyl-2-pyrrolidone (NMP) at 25.0 ± 0.1 °C, as well as on the characteristics of the resulting N,N,N-trimethylchitosan (TMCh), were evaluated by using full-factorial 23 design analysis and response surface methodology. This study also aimed to determine the reaction conditions allowing the production of water-soluble TMCh presenting a high average degree of quaternization and intrinsic viscosity at high reaction yield. 1H NMR spectroscopy was employed for structural characterization, including the determination of average degrees of acetylation (DA‾) and quaternization (DQ‾), while capillary viscometry was used to determine intrinsic viscosity [η]. The results show that when the extensive N-methylation is carried out for 24 h in NMP/15% NaOH (w/v) employing a lower excess of iodomethane (CH3I/Ch = 9), water-soluble highly substituted (DQ‾ = 46.0%) TMCh ([η] = 213.0 mL g−1) can be produced in high yield (81.8%). The highly significant mathematical models resulting from this study describe the dependence of the experimental responses on the reaction conditions and allow the characteristics and properties of the resulting TMCh to be defined by properly choosing the reaction conditions. © 2015 Society of Chemical Industry

This chapter proposes Chitosan, a natural polymer with excellent properties, as the ideal candidate for the hydrophilic part of polymeric micelles or nanoparticles (NPs). The generation of NPs includes natural or synthetic biocompatible and biodegradable polymers. The chapter focuses on NPs obtained from amphiphilic chitosan derivatives. It also focuses on chemical modifications of chitosan, highlighting those that allow the preparation of amphiphilic derivatives that are intended to encapsulate therapeutic agents for biomedical and biopharmaceutical applications. The chapter revises the literature on the regioselective synthesis of chitosan derivatives, focusing on the addition of hydrophobic groups to the chitosan chain through alkylation and acylation reactions, aiming to tailor the polymer solubility. As a viable and cost-effective strategy, amphiphilic derivatives with self-assembly properties has been widely used to prepare chitosan nanocarriers that have been investigated as vehicles for the drug delivery, such as proteins and peptides, anti-inflammatory drugs, and anticancer drugs.

Streams situated in areas of sugarcane cultivation receive high concentrations of metal ions from the adjacent areas, causing accumulation of metals in the aquatic sediment. Several adsorbents have been used to remove metal from water. Activated carbons clays and biopolymers are among the common adsorbents utilized. Chitosan beads, an alternative biopolymer that exhibits a high affinity for metal ions, are easy to prepare under laboratory conditions, have low overall cost and can be indicated for the removal of metals from aquatic sediments. This work studied, for the first time, the possible use of Chitosan beads in the adsorption of metals from sediments of streams located in areas adjacent to sugarcane cultivation. The sediments were collected from four streams historically impacted by sugarcane; one of them is located in a preserved area, used as the control site. The sediments were evaluated for adsorption of Cr, Cu, Zn, Mn and Mg. The results showed that the maximum adsorption of metals in chitosan beads (containing only 5.5% of chitosan) were obtained in Sao Joao Stream, such as: 0.65 mg kg−1 for Cr6+, 2.85 mg kg−1 for Cu2+, 2.5 mg kg−1 for Mg2+ and 0.85 mg kg−1 for Zn2+. For manganese, the maximum adsorption was 0.84 mg kg−1, obtained for the Agua Sumida Stream. The adsorption had high affinity for Cu, Zn and Cr and low affinity for Mg and Mn. Chitosan presented potential and viability for use in the remediation of the impacts of metals on aquatic sediment systems, with high adsorption and capacity to be applied “in loco”.

Made available in DSpace on 2018-12-11T17:35:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-08 European Regional Development Fund Fundação para a Ciência e a Tecnologia Ministério da Ciência, Tecnologia e Ensino Superior This work addresses the establishment and characterization of gellan gum:pectin (GG:P) biodegradable mucoadhesive beads intended for the colon-targeted delivery of resveratrol (RES). The impact of the polymer carrier system on the cytotoxicity and permeability of RES was evaluated. Beads of circular shape (circularity index of 0.81) with an average diameter of 914 μm, Span index of 0.29, and RES entrapment efficiency of 76% were developed. In vitro drug release demonstrated that beads were able to reduce release rates in gastric media and control release for up to 48 h at an intestinal pH of 6.8. Weibull's model correlated better with release data and b parameter (0.79) indicated that the release process was driven by a combination of Fickian diffusion and Case II transport, indicating that both diffusion and swelling/polymer chains relaxation are processes that contribute equally to control drug release rates. Beads and isolated polymers were observed to be safe for Caco-2 and HT29-MTX intestinal cell lines. RES encapsulation into the beads allowed for an expressive reduction of drug permeation in an in vitro triple intestinal model. This feature, associated with low RES release rates in acidic media, can favor targeted drug delivery from the beads in the colon, a promising behavior to improve the local activity of RES. Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP), Araraquara, Rodovia Araraquara-Jaú, Km 1 Instituto de Química de São Carlos Universidade de São Paulo (USP), Avenida Trabalhador São-Carlense, 400 I3S-Instituto de Investigação e Inovação em Saúde Universidade do Porto, Rua Alfredo Allen, 208 INEB-Instituto de Engenharia Biomédica Universidade do Porto, Rua Alfredo Allen, 208 CESPU-Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude, Rua Central de Gandra 1317 School of Pharmacy Queen's University Belfast Medical Biology Centre, 97 Lisburn Road Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP), Araraquara, Rodovia Araraquara-Jaú, Km 1 Fundação para a Ciência e a Tecnologia: NORTE-01-0145-FEDER-000012 Fundação para a Ciência e a Tecnologia: SFRH/BD/118721/2016

Chitosan-based thin films were assembled using the layer-by-layer technique, and the axial composition was accessed using X-ray photoelectron spectroscopy with depth profiling. Chitosan (CHI) samples possessing different degrees of acetylation ([Formula: see text]) and molecular weight ([Formula: see text]) produced via the ultrasound-assisted deacetylation reaction were used in this study along with two different polyanions, namely, sodium polystyrenesulfonate (PSS) and carboxymethylcellulose (CMC). When chitosan, a positively charged polymer in aqueous acid medium, was combined with a strong polyanion (PSS), the total positive charge of chitosan, directly related to its [Formula: see text], was the key factor affecting the film formation. However, for CMC/CHI films, the pH of the medium and [Formula: see text] of chitosan strongly affected the film structure and composition. Consequently, the structure and the axial composition of chitosan-based films can be finely adjusted by choosing the polyanion and defining the chitosan to be used according to its DA and [Formula: see text] for the desired application, as demonstrated by the antibacterial tests.

Made available in DSpace on 2018-12-11T17:14:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The demand for low cost and effective materials to remove contaminants such as residues of oil spills has encouraged studies on new biosorbents produced from wastes. Considering the overgeneration of fishing residues and the necessity to provide an alternative purpose for such materials, this study aimed to evaluate squid gladius and its derivatives (β-chitin and chitosan) as sorbents to remove marine diesel oil (MDO) from fresh and artificial seawater. It was also executed an attempted to improve their performances through a high-intensity ultrasound treatment (UT-gladius and UT-β-chitin). All sorbents removed MDO at both salinities. Contact surface area, salinity, and water retention seemed to play a key role in the outcomes. UT-β-chitin’s performance was significantly superior to β-chitin’s and chitosan’s in MDO removal at salinity 0, as well as at salinity 30, where gladius and UT-gladius also excelled. Ultrasound treatment improved the oil removal performance of UT-β-chitin by increasing its contact surface area. This is the first report on the efficiency of gladius and UT-β-chitin for such purpose, and brought up huge possibilities and new questions that can lead to the achievement of biosorbents of great efficiency. Instituto de Biociências do Campus do Litoral Paulista Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Praça Infante Dom Henrique s/n°, Bairro: Parque Bitarú Departamento de Físico Química Universidade de São Paulo Instituto de Química de São Carlos (IQ-USP), Avenida do Trabalhador Sancarlense, 400, Centro Instituto de Pesquisas Energéticas e Nucleares (IPEN), Avenida Lineu Prestes, 2242, Cidade Universitária Instituto de Biociências do Campus do Litoral Paulista Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Praça Infante Dom Henrique s/n°, Bairro: Parque Bitarú FAPESP: 2015/10362-2 CNPq: 459388/2014-2

Made available in DSpace on 2018-12-11T17:09:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-04-01 The aim of the present study was to investigate the potential application of 3,6-O,O’- dimyristoyl chitosan DMCh, an amphiphilic derivative of chitosan, for improving the oral bioavailability of paclitaxel (PTX), a water insoluble anticancer drug. The O-acylation of chitosan with myristoyl chloride was carried out by employing high (≈13.3) or low (2.0) molar excess of chitosan to result in samples DMCh07 and DMCh12, respectively. The successful O-acylation of chitosan was confirmed by FTIR and 1H NMR spectroscopy, the latter allowing also the determination of average degree of substitution (DS). The critical aggregation concentration (CAC) of samples DMCh07 (DS ≈ 6.8%) and DMCh12 (DS ≈ 12.0%) were 8.9 × 10−3 mg/mL and 13.2 × 103 mg/mL, respectively. It was observed by TEM that the DMCh micelles showed spherical shape while DLS measurements allowed the determination of their average size (287 nm–490 nm) and zeta potential (+32 mV to +44 mV). Such DMCh micelles were able to encapsulate paclitaxel with high drug encapsulation efficiency (EE), as confirmed by HPLC analyses. Studies on the cytotoxicity of DMCh07 micelles toward Caco-2 and HT29-MTX cells showed that, regardless the PTX loaded, DMCh07 micelles slightly decreased cellular viability at low micelles concentration (≤1 μg/mL) while at high concentration (>10 μg/mL) PTX-loaded DMCh07 micelles were less toxic toward Caco-2 cells when compared to free PTX. The PTX permeation across Caco-2 monoculture and Caco-2/HT29-MTX co-culture model confirmed the potential of DMCh micelles in improving the intestinal absorption of PTX. These results suggest that DMCh micelles may be a promising carrier to encapsulate PTX aiming cancer therapy. Institute of Chemistry of São Carlos University of São Paulo, Avenida Trabalhador São-Carlense Institute for Research and Innovation in Health (i3S) and Institute of Biomedical Engineering (INEB) University of Porto, Rua Alfredo Allen, 208 Graduate Program in Pharmaceutical Sciences Department of Drugs and Pharmaceuticals School of Pharmaceutical Sciences São Paulo State University - UNESP, Rodovia Araraquara-Jaú, Km 1 CESPU Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde Instituto Universitário de Ciências da Saúde Graduate Program in Pharmaceutical Sciences Department of Drugs and Pharmaceuticals School of Pharmaceutical Sciences São Paulo State University - UNESP, Rodovia Araraquara-Jaú, Km 1

One of the major challenges in establishing the mechanisms responsible for the chitosan action in biomedical applications lies in the determination of the molecular-level interactions with the cell membrane. In this study, we probed hydrophobic interactions and H-bonding in experiments with O,O'-diacetylchitosan (DACT) and O,O'-dipropionylchitosan (DPPCT) incorporated into monolayers of distinct phospholipids, the zwitterionic dipalmitoyl phosphatidyl choline (DPPC), and the negatively charged dipalmitoyl phosphatidyl glycerol (DPPG) and dimyristoyl phosphatidic acid (DMPA). The importance of hydrophobic interactions was confirmed with the larger effects observed for DACT and DPPCT than for parent chitosan (Chi), particularly for the more hydrophobic DPPCT. Such larger effects were noted in surface pressure isotherms and elasticity of the monolayers. Since H-bonding is hampered for the chitosan derivatives, which have part of their hydroxyl groups shielded by O-acylation, these effects indicate that H-bonding does not play an important role in the chitosan-membrane interactions. Using polarization-modulated infrared reflection absorption (PM-IRRAS) spectroscopy, we found that the chitosan derivatives were incorporated into the hydrophobic chain of the phospholipids, even at high surface pressures comparable to those in a real cell membrane. Taken together, these results indicate that the chitosan derivatives containing hydrophobic moieties would probably be more efficient than parent chitosan as antimicrobial agents, where interaction with the cell membrane is crucial.

We prepared self-assembled materials consisting of TiO2 nanoparticles, N,O-carboxymethylchitosan (NOCMCh), and poly(ethylene oxide) (PEO) by the layer-by-layer (LbL) technique, aiming to employ them as modified electrodes under high lithium ion electroinsertion rate. Electrostatic interaction between the components promoted growth of visually uniform TiO2/NOCMCh films with highly controlled thickness. We used NOCMCh to produce a polymeric mixture with PEO to incorporate the polyether into the self-assembled structure during the preparation of the LbL TiO2/NOCMCh/PEO films. Scanning electron microscopy (SEM) and contact angle measurements between the electrolytic solution and the thin films surface suggested that the polymers affected the mean size of the aggregates and the permeation of the electrolytic solution into the host matrix, leading to greater electrolytic connection between the TiO2 sites. Chronopotentiometric curves and the differential capacities recorded as a function of the potential under s...

The influence from the chitosan molecular weight on its interaction with cell membrane models has been studied. A low molecular weight chitosan (LMWChi) adsorbed from the subphase expanded the surface pressure-area and surface potential-area isotherms of dimyristoyl phosphatidic acid (DMPA) monolayers and decreased the compressional modulus. The expansion in the monolayers and the decrease in the compressional modulus were larger for LMWChi than for a high molecular weight chitosan (Chi). The polymeric nature is still essential for the interaction though, which was demonstrated by measuring negligible changes in the mechanical properties of the DMPA monolayer when the subphase contained glucosamine and acetyl-glucosamine. The results were rationalized in a model through which chitosan interacted with the membrane via electrostatic and hydrophobic interactions, with the smaller chains of LMWChi having less steric hindrance to be accommodated in the membrane. In summary, the activity based on membrane interactions depends on the distribution of molar mass, with lower molecular weight chitosan more likely to have stronger effects.

Made available in DSpace on 2018-12-11T17:30:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Herein, we developed honeycomb-like scaffolds by combining poly (D, L-lactic acid) (PDLLA) with a high amount of graphene/multi-walled carbon nanotube oxides (MWCNTO-GO, 50% w/w). From pristine multi-walled carbon nanotubes (MWCNT) powders, we produced MWCNTO-GO via oxygen plasma etching (OPE), which promoted their exfoliation and oxidation. Initially, we evaluated PDLLA and PDLLA/MWCNTO-GO scaffolds for tensile strength tests, cell adhesion and cell viability (with osteoblast-like MG-63 cells), alkaline phosphatase (ALP, a marker of osteoblast differentiation) activity and mineralized nodule formation. In vivo tests were carried out using PDLLA and PDLLA/MWCNTO-GO scaffolds as fillers for critical defects in the tibia of rats. MWCNTO-GO loading was responsible for decreasing the tensile strength and elongation-at-break of PDLLA scaffolds, although the high mechanical performance observed (~�600�MPa) assures their application in bone tissue regeneration. In vitro results showed that the scaffolds were not cytotoxic and allowed for osteoblast-like cell interactions and the formation of mineralized matrix nodules. Furthermore, MG-63 cells grown on PDLLA/MWCNTO-GO significantly enhanced osteoblast ALP activity compared to controls (cells alone), while the PDLLA group showed similar ALP activity when compared to controls and PDLLA/MWCNTO-GO. Most impressively, in vivo tests suggested that compared to PDLLA scaffolds, PDLLA/MWCNTO-GO had a superior influence on bone cell activity, promoting greater new bone formation. In summary, the results of this study highlighted that this novel scaffold (MWCNTO-GO, 50% w/w) is a promising alternative for bone tissue regeneration and, thus, should be further studied. Laboratory of Biomedical Nanotechnology University of Vale do Paraiba, Av. Shishima Hifumi 2911 Department of Bioscience and Oral Diagnosis Institute of Science and Technology State University of Sao Paulo (UNESP), Av. Engenheiro Francisco Jose Longo, 777 Laboratory of Biomedical Nanotechnology Biomedical Engineering Innovation Center Universidade Brasil, Rua Carolina Fonseca 235 Chemistry Institute of Sao Carlos University of Sao Paulo, Av. Trabalhador Sao-Carlense, 400 Department of Medicine Biomaterials Innovation Research Center Brigham and Women's Hospital Harvard Medical School Department of Chemical Engineering Northeastern University Department of Bioscience and Oral Diagnosis Institute of Science and Technology State University of Sao Paulo (UNESP), Av. Engenheiro Francisco Jose Longo, 777 FAPESP: 2011/17877-7 FAPESP: 2011/20345-7, 2015/09697-0 FAPESP: 2016/00575-1 CNPq: 474090/2013-2 CAPES: 88887.095044/2015-00

Made available in DSpace on 2018-12-11T17:29:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-02 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) In this paper, we show that chitosan may induce conformation changes in silk fibroin (SF) in layer-by-layer (LbL) films, which were used as matrix for immobilization of the enzyme phytase to detect phytic acid. Three chitosan (CH) samples possessing distinct molecular weights were used to build CH/SF LbL films, and a larger change in conformation from random coils to β-sheets for SF was observed for high molecular weight chitosan (CHH). The CHH/SF LbL films deposited onto interdigitated gold electrodes were coated with a layer of phytase, with which phytic acid could be detected down to 10−9 M using impedance spectroscopy as the principle of detection and treating the data with a multidimensional projection technique. This high sensitivity may be ascribed to the suitability of the CHH/SF matrix, thus indicating that the molecular-level interactions between chitosan and SF may be exploited in other biosensors and biodevices. São Carlos Institute of Physics University of São Paulo (USP), CP 369 Institute of Science and Technology at the Federal University of São Paulo (UNIFESP), 330 Talim Street São Carlos Institute of Chemistry University of São Paulo (USP), CP 780 Institute of Chemistry São Paulo State University (UNESP), CP 355 Institute of Chemistry São Paulo State University (UNESP), CP 355

The aim of this study was to evaluate the influence of cellulose and/or lignin on the properties of mats prepared from dissolution (for 48 h or 72 h, solvent: trifluoroacetic acid) of recycled poly (ethylene terephthalate) (PET). Briefly, the presence of cellulose led to a tendency of higher average fiber diameter and average pore area as well as lower average porosity compared to the neat mat (PETref, 242 ± 59 nm, 9.6 ± 1.1 104 nm2 and 19.0 ± 1.1%, respectively). The Tg values for electrospun PET combined with cellulose and/or lignin were higher than that of PETref (92.5 ± 0.1 °C), and the tensile strength increased with the cellulose and/or lignin loading. In addition, the presence of lignin (72 h of dissolution) led to a mat with an elongation at break of 149 ± 9% compared to 14 ± 2% for PETref. The results indicated that the properties of mats based on PET can be tuned by adding cellulose and/or lignin to solutions posteriorly electrospun as well as by varying the dissolution time.

Made available in DSpace on 2018-12-11T17:14:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fuel Cell Technologies Office Federación Española de Enfermedades Raras The aim of this work was to investigate the potential of a new 3,6-O,O’-dimyristoyl derivative amphiphilic chitosan (DMCh), in improving the solubility of camptothecin (CPT), a hydrophobic anticancer drug, and its potential oral delivery. FTIR, 1H NMR and solid-state 13C NMR spectroscopy were used to characterize DMCh and to determine its average degree of substitution (DS¯ = 6.8%). DMCh/CPT micelles size ranged from (281–357 nm), zeta potential (+32–50 mV) of encapsulation efficiency of 42–100%. The in vitro cell viability showed that DMCh/CPT micelles were able to reduce the toxicity of CPT. The in vitro permeability of CPT through Caco-2 and Caco-2/HT29-MTX intestinal models was increased up to ten fold when formulated into DMCh micelles, underlining the mucoadhesive properties of the nanocarrier. DMCh/CPT micelles are able to enhance CPT solubility and bioavailability while reduce its cytotoxicity, showing the great potential for intestinal delivery of hydrophobic drugs. São Carlos Institute of Chemistry University of Sao Paulo Avenida Trabalhador São-Carlense Institute for Research and Innovation in Health (i3S) and Institute of Biomedical Engineering (INEB) University of Porto, Rua Alfredo Allen, 208 Graduate Program in Pharmaceutical Sciences Department of Drugs and Pharmaceuticals School of Pharmaceutical Sciences São Paulo State University—UNESP, Rodovia Araraquara–Jaú, Km 1 Embrapa Instrumentação, Rua XV de Novembro 1452 IIFACTS—Institute for Research and Advanced Training in Health Sciences and Technologies, Rua Central de Gandra 1317 Graduate Program in Pharmaceutical Sciences Department of Drugs and Pharmaceuticals School of Pharmaceutical Sciences São Paulo State University—UNESP, Rodovia Araraquara–Jaú, Km 1

International audience; High intensity ultrasound irradiation was used to convert beta-chitin (BCHt) into chitosan (CHs). Typically, beta-chitin was suspended in 40% (w/w) aqueous sodium hydroxide at a ratio 1/10 (g mL(-1)) and then submitted to ultrasound-assisted deacetylation (USAD) during 50 min at 60 degrees C and a fixed irradiation surface intensity (52.6 W cm(-2)). Hydrogen nuclear magnetic resonance spectroscopy and capillary viscometry were used to determine the average degree of acetylation ((DA) over bar) and viscosity average degree of polymerization ((DPv) over bar), respectively, of the parent beta-chitin ((DA) over bar = 80.7%; (DPv) over bar = 6865) and USAD chitosans. A first USAD reaction resulted in chitosan CHs1 ((DA) over bar = 36.7%; (DPv) over bar = 5838). Chitosans CHs2 ((DA) over bar = 15.0%; (DPv) over bar = 5128) and CHs3 ((DA) over bar = 4.3%; (DPv) over bar = 4889) resulted after repeating the USAD procedure to CHs1 consecutively once and twice, respectively. Size-exclusion chromatography analyzes allowed the determination of the weight average molecular weight ((M-w) over bar) and dispersity (D) of CHs1 ((M-w) over bar = 1,260,000 g mol(-1); D =1.4), CHs2 ((M-w) over bar = 1,137,000 g mol(-1); D =1.4) and CHs3 ((M-w) over bar = 912,000 g mol(-1); D = 1.3). Such results revealed that, thanks to the action of high intensity ultrasound irradiation, the USAD process allowed the preparation of unusually high molecular weight, randomly deacetylated chitosan, an important breakthrough to the development of new high grade chitosan-based materials displaying superior mechanical properties.

International audience; The formation of chitosan hydrogels without any external cross-linking agent was successfully achieved by inducing the gelation of a viscous chitosan solution with aqueous NaOH or gaseous NH3. The hydrogels produced from high molecular weight (M-w approximate to 640 000 g mol(-1)) and extensively deacetylated chitosan (DA approximate to 2.8%) at polymer concentrations above similar to 2.0% exhibited improved mechanical properties due to the increase of the chain entanglements and intermolecular junctions. The results also show that the physicochemical and mechanical properties of chitosan hydrogels can be controlled by varying their polymer concentration and by controlling the gelation conditions, that is, by using different gelation routes. The biological evaluation of such hydrogels for regeneration of infarcted myocardium revealed that chitosan hydrogels prepared from 1.5% polymer solutions were perfectly incorporated onto the epicardial surface of the heart and presented partial degradation accompanied by mononuclear cell infiltration.

O objetivo do trabalho foi o de estudar o processo estratégico, testar algumas hipóteses acerca desse processo e propor modelos explicativos para a criação de estratégia em pequenas empresas de base tecnológica. A estratégia empresarial é uma área de significativa importância para os estudos administrativos, tendo em vista o impacto das decisões e ações estratégicas para o sucesso das empresas. Além disso, a teoria sobre estratégia está fortemente fundamentada em estudos realizados em empresas de grande porte, maduras, podendo, portanto, apresentar viés quando considerada a sua aplicação em empresas de pequeno porte e empresas em fase de desenvolvimento. Este estudo analisou os processos de criação de estratégias e propôs um conjunto de modelos representativos desses processos para pequenas empresas de base tecnológica criadas sem a formalização de planos de negócios, o que foi muito comum no início dos polos tecnológicos brasileiros na década de 80. Foi realizado um trabalho de campo cuja natureza foi a de pesquisa aplicada. O procedimento técnico utilizado foi o estudo multicasos, sendo investigadas cinco empresas de pequeno e uma de médio porte, conforme classificação pelo número de empregados, todas de base tecnológica e localizadas no Polo Tecnológico de São Carlos, em São Carlos, SP. O resultado da pesquisa evidenciou que as estratégias são criadas por etapas distintas, o que permitiu a construção de um conjunto de modelos representativos do processo de criação de estratégias, além de confirmar algumas hipóteses formuladas, podendo destacar que a ausência de formalização de planos de negócios não impediu o sucesso das empresas estudadas.

Ultrasound-assisted deacetylation (USAD) produces chitosan by treating beta-chitin suspended in 40% aqueous sodium hydroxide with high-intensity ultrasound irradiation. Chitosans resulting from the application of non-isothermal and isothermal USAD processes were characterized using NMR spectroscopy, X-ray diffraction, scanning electron microscopy, viscosity measurements and size-exclusion chromatography. The characteristics of the USAD-produced chitosan strongly depend on the processing temperature and ultrasound parameters, namely the irradiation amplitude and duration, with viscosity-average molecular weight in the range 100 000―750 000 g mol ―1 and average degree of acetylation in the range 6.0―25.0%. Moreover, appropriate adjustment of the USAD parameters allows the production of chitosan with high molecular weight (M w ≈ 10 6 g mol ―1 ) and low degree of acetylation (ca 7.0%) after a single-step short-time processing (30 min) carried out at low to moderate temperature (50―80 °C). The occurrence of cavitation, a phenomenon whose intensity depends on the irradiation amplitude and duration as well as on the processing temperature, is responsible for reducing the average size of the polysaccharide particles, favoring the accessibility of sodium hydroxide to the reactive sites and supporting a more efficient deacetylation of beta-chitin as compared to the thermochemical process.

A Desacetilação Assistida por Irradiação de Ultrassom de Alta Intensidade (DAIUS) foi aplicada à beta-quitina visando à produção de quitosana. As características das quitosanas obtidas dependem da amplitude da irradiação de ultrassom, da duração e da temperatura do tratamento. Assim, em função desses parâmetros, os graus médios de acetilação e as massas molares médias viscosimétricas dos produtos variam nos intervalos 5%

The development and application of a functionalized carbon nanotubes paste electrode (CNPE) modified with crosslinked chitosan for determination of Cu(II) in industrial wastewater, natural water and human urine samples by linear scan anodic stripping voltammetry (LSASV) are described. Different electrodes were constructed using chitosan and chitosan crosslinked with glutaraldehyde (CTS-GA) and epichlorohydrin (CTS-ECH). The best voltammetric response for Cu(II) was obtained with a paste composition of 65% (m/m) of functionalized carbon nanotubes, 15% (m/m) of CTS-ECH, and 20% (m/m) of mineral oil using a solution of 0.05 mol L−1 KNO3 with pH adjusted to 2.25 with HNO3, an accumulation potential of −0.3 V vs. Ag/AgCl (3.0 mol L−1 KCl) for 300 s and a scan rate of 100 mV s−1. Under these optimal experimental conditions, the voltammetric response was linearly dependent on the Cu(II) concentration in the range from 7.90 × 10−8 to 1.60 × 10−5 mol L−1 with a detection limit of 1.00 × 10−8 mol L−1. The samples analyses were evaluated using the proposed sensor and a good recovery of Cu(II) was obtained with results in the range from 98.0% to 104%. The analysis of industrial wastewater, natural water and human urine samples obtained using the proposed CNPE modified with CTS-ECH electrode and those obtained using a comparative method are in agreement at the 95% confidence level.

Background: Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions. Methods: Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system. Results: The severity score was lower in the KGF group than in the control group (11.5 vs 17, p = 0.005). The dissection time was lower in the KGF group (9.2 1.4 min vs 33.9 9.2 min, p = 0.004) and presented a significant correlation with the severity score (r = 0.83, p = 0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly lower in the KGF group than in the control group.Conclusion:The stimulation of pericardial cells with KGF reduced the intensityof postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.