Corrosion mitigation of N-(2-hydroxy-3-trimethyl ammonium)propyl chitosan chloride as inhibitor on mild steel.

PubMed

Sangeetha, Y; Meenakshi, S; SairamSundaram, C

2015-01-01

The biopolymer N-(2-hydroxy-3-trimethyl ammonium)propyl chitosan chloride (HTACC) was synthesised and its influence as a novel corrosion inhibitor on mild steel in 1M HCl was studied using gravimetric and electrochemical experiments. The compound obtained was characterised using FTIR and NMR studies. The inhibition efficiency increased with the increase in concentration and reached a maximum of 98.9% at 500 ppm concentration. Polarisation studies revealed that HTACC acts both as anodic and cathodic inhibitor. Electrochemical impedance studies confirmed that the inhibition is through adsorption on the metal surface. The extent of inhibition exhibits a negative trend with increase in temperature. Langmuir isotherm provides the best description on the adsorption nature of the inhibitor. SEM analysis indicated the presence of protective film formed by the inhibitor on the metal surface. Copyright © 2014 Elsevier B.V. All rights reserved.

One step effective removal of Congo Red in chitosan nanoparticles by encapsulation

NASA Astrophysics Data System (ADS)

Alver, Erol; Bulut, Mehmet; Metin, Ayşegül Ülkü; Çiftçi, Hakan

2017-01-01

Chitosan nanoparticles (CNPs) were prepared with ionotropic gelation between chitosan and tripolyphosphate for the removal of Congo Red. The production of chitosan nanoparticles and the dye removal process was carried out in one-step. The removal efficiency of Congo Red by encapsulation within chitosan from the aqueous solution and its storage stability are examined at different pH values. The influence of some parameters such as the initial dye concentration, pH value of the dye solution, electrolyte concentration, tripolyphosphate concentration, mixing time and speed on the encapsulation is examined. Congo Red removal efficiency and encapsulation capacity of chitosan nanoparticles were determined as above 98% and 5107 mg Congo Red/g chitosan, respectively.

Effect of insulin-coated trimethyl chitosan nanoparticles on IGF-1, IGF-2, and apoptosis in the hippocampus of diabetic male rats.

PubMed

Kalantarian, Giti; Ziamajidi, Nasrin; Mahjoub, Reza; Goodarzi, Mohammad Taghi; Saidijam, Massoud; Asl, Sara Soleimani; Abbasalipourkabir, Roghayeh

2018-06-06

Subcutaneous injection of insulin can lead to problems such as hypoglycemia and edema. The purpose of this research was to evaluate the effect of oral insulin-coated trimethyl chitosan nanoparticles on control of glycemic status, IGF-1 and IGF-2 levels, and apoptosis in the hippocampus of rats with diabetes mellitus. Insulin-coated trimethyl chitosan nanoparticles were prepared by the complex polyelectrolyte (PEC) method. Insulin loading content, loading efficiency, quantity and quality of particle size were evaluated. In vivo study was performed in different treatment groups of male Wistar rats with diabetes mellitus by insulin-coated trimethyl chitosan nanoparticles or subcutaneous injection of trade insulin. The duration of diabetes was eight weeks and the treatment was started after that time and continued for another two weeks. Body weight, fasting blood glucose (FBS), hippocampal apoptosis, and immunohistochemical (IHC) protein levels of IGF-1 and IGF-2 were assessed at the end of the experiments. The size and polydispersity indexes were 533 nanometers and 0.533, respectively. Insulin coated trimethyl chitosan nanoparticles showed high loading efficiency (97.67% ) and loading content (48.83% ). The spherical shape of nanoparticle was confirmed by transmission electron microscopic (TEM). The amine, amide, ether and aliphatic groups were evaluated using FT-IR spectrophotometer which represented the correctness of the insulin coated trimethyl chitosan nanoparticles. Although the apoptotic index was not changed either by insulin-coated nano-particles or commercial insulin in vivo results showed the efficacy of insulin-coated nanoparticles as well as commercial insulin in compensated weight loss, FBS and protein levels of IGF-1 and IGF-2. The present study showed the efficacy of insulin coated nanoparticle in oral route manner that can be tested in Phase I- III clinical trials. However, a behavioral study could reveal the efficacy of insulin-loaded nanoparticles

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

PubMed

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret

PubMed Central

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

2016-01-01

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs. PMID:27822034

Surface modification of protein enhances encapsulation in chitosan nanoparticles

NASA Astrophysics Data System (ADS)

Koyani, Rina D.; Andrade, Mariana; Quester, Katrin; Gaytán, Paul; Huerta-Saquero, Alejandro; Vazquez-Duhalt, Rafael

2018-04-01

Chitosan nanoparticles have a huge potential as nanocarriers for environmental and biomedical purposes. Protein encapsulation in nano-sized chitosan provides protection against inactivation, proteolysis, and other alterations due to environmental conditions, as well as the possibility to be targeted to specific tissues by ligand functionalization. In this work, we demonstrate that the chemical modification of the protein surface enhances the protein loading in chitosan nanocarriers. Encapsulation of green fluorescent protein and the cytochrome P450 was studied. The increase of electrostatic interactions between the free amino groups of chitosan and the increased number of free carboxylic groups in the protein surface enhance the protein loading, protein retention, and, thus, the enzymatic activity of chitosan nanoparticles. The chemical modification of protein surface with malonic acid moieties reduced drastically the protein isoelectric point increasing the protein interaction with the polycationic biomaterial and chitosan. The chemical modification of protein does not alter the morphology of chitosan nanoparticles that showed an average diameter of 18 nm, spheroidal in shape, and smooth surfaced. The strategy of chemical modification of protein surface, shown here, is a simple and efficient technique to enhance the protein loading in chitosan nanoparticles. This technique could be used for other nanoparticles based on polycationic or polyanionic materials. The increase of protein loading improves, doubtless, the performance of protein-loaded chitosan nanoparticles for biotechnological and biomedical applications.

Improvement of Stability and Antioxidant Activities by Using Phycocyanin - Chitosan Encapsulation Technique

NASA Astrophysics Data System (ADS)

Suzery, Meiny; Hadiyanto; Majid, Dian; Setyawan, Deny; Sutanto, Heri

2017-02-01

Encapsulation is a coating process to improve the stability of bioactive compounds. Phycocyanin with high antioxidant activity has been encapsulated with chitosan in microcapsules form. In this study aims to determine the best conditions in the encapsulation process using the extrusion method, characterization of the physicochemical properties of the microcapsules, antioxidant activity test using DPPH, in vitro release performance and evaluate the storage stability against temperature. The results of the encapsulation process is obtained: Na-TPP is better than Na-citrate as crosslinker and chitosan content 3% as a coating with ratio of chitosan to phycocyanin ratio 1: 1. Test of antioxidant activity also showed encapsulation with chitosan content 3% has the highest antioxidant activity. Morphological analysis microcapsules were found to have compact spherical shape with diameter range 900-1000 µm. In vitro release testing showed a quick release in an acidic environment (SGF) for 2 hours and slowly release under alkaline conditions (SIF) for 8 hours under mechanical stirring at 37°C. Phycocyanin much more stable against temperature during storage in microcapsules.

Silk sericin-alginate-chitosan microcapsules: hepatocytes encapsulation for enhanced cellular functions.

PubMed

Nayak, Sunita; Dey, Sanchareeka; Kundu, Subhas C

2014-04-01

The encapsulation based technology permits long-term delivery of desired therapeutic products in local regions of body without the need of immunosuppressant drugs. In this study microcapsules composed of sericin and alginate micro bead as inner core and with an outer chitosan shell are prepared. This work is proposed for live cell encapsulation for potential therapeutic applications. The sericin protein is obtained from cocoons of non-mulberry silkworm Antheraea mylitta. The sericin-alginate micro beads are prepared via ionotropic gelation under high applied voltage. The beads further coated with chitosan and crosslinked with genipin. The microcapsules developed are nearly spherical in shape with smooth surface morphology. Alamar blue assay and confocal microscopy indicate high cell viability and uniform encapsulated cell distribution within the sericin-alginate-chitosan microcapsules indicating that the microcapsules maintain favourable microenvironment for the cells. The functional analysis of encapsulated cells demonstrates that the glucose consumption, urea secretion rate and intracellular albumin content increased in the microcapsules. The study suggests that the developed sericin-alginate-chitosan microcapsule contributes towards the development of cell encapsulation model. It also offers to generate enriched population of metabolically and functionally active cells for the future therapeutics especially for hepatocytes transplantation in acute liver failure. Copyright © 2014 Elsevier B.V. All rights reserved.

N6-Trimethyl-lysine metabolism. Structural identification of the metabolite 3-hydroxy-N6-trimethyl-lysine

PubMed Central

Novak, Raymond F.; Swift, Terrence J.; Hoppel, Charles L.

1980-01-01

1H and 13C nuclear-magnetic-resonance spectroscopy and functional-group analysis were used to determine the molecular structure of an isolated metabolite (IIb) of trimethyl-lysine as 3-hydroxy-N6-trimethyl-lysine, an important intermediate in the conversion of trimethyl-lysine into trimethylammoniobutyrate and carnitine [Hoppel, Cox & Novak (1980) Biochem. J. 188, 509–519]. Functional-group analysis revealed the presence of a primary amine and reaction of metabolite (IIb) with periodate yielded 4-N-trimethylammoniobutyrate as a product, showing 2,3-substitution on the molecule and suggesting that the 3-substitution on the molecule may be an alcohol ([unk]CH–OH), amine ([unk]CH[unk]–NH2) or carbonyl ([unk]C=O) functional group. 1H integration ratios, 1H and 13C chemical-shift data and 1H and 13C signal multiplicities from the sample (IIb) were used to complete the identification of metabolite (IIb) as 3-hydroxy-N6-trimethyl-lysine. For example, the proton multiplet at δ 4.2p.p.m. and doublet at δ 4.1p.p.m., positions representative of amine or alcohol substitution on methylene carbon atoms, integration ratios of 1:1:2:9:4 and a positive ninhydrin test suggest 3-hydroxy-N6-trimethyl-lysine as the molecular structure for metabolite (IIb). 13C chemical-shift data obtained from the sample (IIb) and compared with several model compounds (trimethylammoniohexanoate, trimethyl-lysine and 3-hydroxylysine) resulted in generation of the spectrum of the metabolite and allowed independent identification of metabolite (IIb) as 3-hydroxy-N6-trimethyl-lysine. The 1H spectrum of erythro- and threo-3-hydroxylysine are presented for comparison, and the 1H and 13C n.m.r. spectra of the erythro-isomer support this analysis. PMID:6772169

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

PubMed

Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.

PubMed

Yin, Lichen; Ding, Jieying; He, Chunbai; Cui, Liming; Tang, Cui; Yin, Chunhua

2009-10-01

Trimethyl chitosan-cysteine conjugate (TMC-Cys) was synthesized in an attempt to combine the mucoadhesion and the permeation enhancing effects of TMC and thiolated polymers related to different mechanisms for oral absorption. TMC-Cys with various molecular weights (30, 200, and 500 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanoparticles with insulin through self-assembly, which demonstrated particle size of 100-200 nm, zeta potential of +12 to +18 mV, and high encapsulation efficiency. TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Compared to insulin solution and TMC NP, TMC-Cys NP induced increased insulin transport through rat intestine by 3.3-11.7 and 1.7-2.6 folds, promoted Caco-2 cell internalization by 7.5-12.7 and 1.7-3.0 folds, and augmented uptake in Peyer's patches by 14.7-20.9 and 1.7-5.0 folds, respectively. Such results were further confirmed by in vivo experiment with the optimal TMC-Cys NP. Biocompatibility assessment revealed lack of toxicity of TMC-Cys NP. Therefore, self-assembled nanoparticles between TMC-Cys and protein drugs could be an effective and safe oral delivery system.

Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

PubMed Central

Caetano, Liliana A.; Almeida, António J.; Gonçalves, Lídia M.D.

2016-01-01

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

Exploring advantages/disadvantages and improvements in overcoming gene delivery barriers of amino acid modified trimethylated chitosan.

PubMed

Zheng, Hao; Tang, Cui; Yin, Chunhua

2015-06-01

Present study aimed at exploring advantages/disadvantages of amino acid modified trimethylated chitosan in conquering multiple gene delivery obstacles and thus providing comprehensive understandings for improved transfection efficiency. Arginine, cysteine, and histidine modified trimethyl chitosan were synthesized and employed to self-assemble with plasmid DNA (pDNA) to form nanocomplexes, namely TRNC, TCNC, and THNC, respectively. They were assessed by structural stability, cellular uptake, endosomal escape, release behavior, nuclear localization, and in vitro and in vivo transfection efficiencies. Besides, sodium tripolyphosphate (TPP) was added into TRNC to compromise certain disadvantageous attributes for pDNA delivery. Optimal endosomal escape ability failed to bring in satisfactory transfection efficiency of THNC due to drawbacks in structural stability, cellular uptake, pDNA liberation, and nuclear distribution. TCNC evoked the most potent gene expression owing to multiple advantages including sufficient stability, preferable uptake, efficient pDNA release, and high nucleic accumulation. Undesirable stability and insufficient pDNA release adversely affected TRNC-mediated gene transfer. However, incorporation of TPP could improve such disadvantages and consequently resulted in enhanced transfection efficiencies. Coordination of multiple contributing effects to conquer all delivery obstacles was necessitated for improved transfection efficiency, which would provide insights into rational design of gene delivery vehicles.

Novel chitosan film embedded with liposome-encapsulated phage for biocontrol of Escherichia coli O157:H7 in beef.

PubMed

Cui, Haiying; Yuan, Lu; Lin, Lin

2017-12-01

In recent years, phages used for the reduction of pathogenic bacteria have fostered many attentions, but they are liable to lost bioactivity in food due to the presence of acidic compounds, enzymes and evaporite materials. To improve the stability of phages, a chitosan edible film containing liposome-encapsulated phage was engineered in the present study. The characteristics of liposome-encapsulated phage and the chitosan film containing liposome-encapsulated phage were investigated. The encapsulation efficiency of phages in liposome reached 57.66±0.12%. Besides, the desirable physical properties of chitosan film were obtained. The chitosan film embedded with liposome-encapsulated phage exhibited high antibacterial activity against Escherichia coli O157:H7, without the impact on the sensory properties of beef. Hence, chitosan film containing liposome-encapsulated phage could be a promising antibacterial packaging for beef preservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A step-by-step approach to study the influence of N-acetylation on the adjuvanticity of N,N,N-trimethyl chitosan (TMC) in an intranasal nanoparticulate influenza virus vaccine.

PubMed

Verheul, Rolf J; Hagenaars, Niels; van Es, Thomas; van Gaal, Ethlinn V B; de Jong, Pascal H J L F; Bruijns, Sven; Mastrobattista, Enrico; Slütter, Bram; Que, Ivo; Heldens, Jacco G M; van den Bosch, Han; Glansbeek, Harrie L; Hennink, Wim E; Jiskoot, Wim

2012-03-12

Recently we reported that reacetylation of N,N,N-trimethyl chitosan (TMC) reduced the adjuvant effect of TMC in mice after intranasal (i.n.) administration of whole inactivated influenza virus (WIV) vaccine. The aim of the present study was to elucidate the mechanism of this lack of adjuvanticity. Reacetylated TMC (TMC-RA, degree of acetylation 54%) was compared with TMC (degree of acetylation 17%) at six potentially critical steps in the induction of an immune response after i.n. administration in mice. TMC-RA was degraded in a nasal wash to a slightly larger extent than TMC. The local i.n. distribution and nasal clearance of WIV were similar for both TMC types. Fluorescently labeled WIV was taken up more efficiently by Calu-3 cells when formulated with TMC-RA compared to TMC and both TMCs significantly reduced transport of WIV over a Calu-3 monolayer. Murine bone-marrow derived dendritic cell activation was similar for plain WIV, and WIV formulated with TMC-RA or TMC. The inferior adjuvant effect in mice of TMC-RA over that of TMC might be caused by a slightly lower stability of TMC-RA-WIV in the nasal cavity, rather than by any of the other factors studied in this paper. Copyright © 2011 Elsevier B.V. All rights reserved.

Mesoscopic Modeling of the Encapsulation of Capsaicin by Lecithin/Chitosan Liposomal Nanoparticles.

PubMed

Terrón-Mejía, Ketzasmin A; Martínez-Benavidez, Evelin; Higuera-Ciapara, Inocencio; Virués, Claudia; Hernández, Javier; Domínguez, Zaira; Argüelles-Monal, Waldo; Goycoolea, Francisco M; López-Rendón, Roberto; Gama Goicochea, Armando

2018-06-12

The transport of hydrophobic drugs in the human body exhibits complications due to the low solubility of these compounds. With the purpose of enhancing the bioavailability and biodistribution of such drugs, recent studies have reported the use of amphiphilic molecules, such as phospholipids, for the synthesis of nanoparticles or nanocapsules. Given that phospholipids can self-assemble in liposomes or micellar structures, they are ideal candidates to function as vehicles of hydrophobic molecules. In this work, we report mesoscopic simulations of nanoliposomes, constituted by lecithin and coated with a shell of chitosan. The stability of such structures and the efficiency of the encapsulation of capsaicin, as well as the internal and superficial distribution of capsaicin and chitosan inside the nanoliposome, were analyzed. The characterization of the system was carried out through density maps and the potentials of mean force for the lecithin-capsaicin, lecithin-chitosan, and capsaicin-chitosan interactions. The results of these simulations show that chitosan is deposited on the surface of the nanoliposome, as has been reported in some experimental works. It was also observed that a nanoliposome of approximately 18 nm in diameter is stable during the simulation. The deposition behavior was found to be influenced by a pattern of N-acetylation of chitosan.

Optimization of preparation of NDV F Gene encapsulated in N-2-HACC-CMC nanoparticles

NASA Astrophysics Data System (ADS)

Li, S. S.; Zhang, Y.; Zhao, K.; Wang, X. H.

2018-01-01

In this study, the biodegradable materials N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) and N, O-carboxymethyl chitosan (CMC) are used as delivery carrier for the pVAX I -F(o)-C3d6. The optimal preparation condition is as follows: concentration of N-2-HACC is 1.0 mg/ml, concentration of CMC is 0.85 mg/ml, concentration of pVAX I -F(o)-C3d6 is 100 μg ml. The results show that the prepared N-2-HACC-CMC/pFDNA NPs have regular round shape, smooth surface and good dispersion, the particle size is 310 nm, Zeta potential is 50 mV, the entrapment efficiency is 92 %, the loading capacity is 51 % (n=3).

Anti-botulism single-shot vaccine using chitosan for protein encapsulation by simple coacervation.

PubMed

Sari, Roger S; de Almeida, Anna Christina; Cangussu, Alex S R; Jorge, Edson V; Mozzer, Otto D; Santos, Hércules Otacílio; Quintilio, Wagner; Brandi, Igor Viana; Andrade, Viviane Aguiar; Miguel, Angelo Samir M; Sobrinho Santos, Eliane M

2016-12-01

The aim of the present study was to compare the potency and safety of vaccines against Clostridium botulinum (C. botulinum) type C and D formulated with chitosan as controlled release matrix and vaccines formulated in conventional manner using aluminum hydroxide. Parameters were established for the development of chitosan microspheres, using simple coacervation to standardize the use of this polymer in protein encapsulation for vaccine formulation. To formulate a single shot vaccine inactivated antigens of C. botulinum type C and D were used with original toxin titles equal to 5.2 and 6.2 log LD50/ml, respectively. For each antigen a chitosan based solution of 50 mL was prepared. Control vaccines were formulated by mixing toxoid type C and D with aluminum hydroxide [25% Al(OH) 3 , pH 6.3]. The toxoid sterility, innocuity and potency of vaccines were evaluated as stipulated by MAPA-BRASIL according to ministerial directive no. 23. Encapsulation efficiency of BSA in chitosan was 32.5-40.37%, while that the encapsulation efficiency to toxoid type C was 41,03% (1.94 mg/mL) and of the toxoid type D was 32.30% (1.82 mg/mL). The single shot vaccine formulated using chitosan for protein encapsulation through simple coacervation showed potency and safety similar to conventional vaccine currently used in Brazilian livestock (10 and 2 IU/mL against C. botulinum type C and D, respectively). The present work suggests that our single shot vaccine would be a good option as a cattle vaccine against these C. botulinum type C and D. Copyright © 2016 Elsevier Ltd. All rights reserved.

Controlling chitosan-based encapsulation for protein and vaccine delivery

PubMed Central

Koppolu, Bhanu prasanth; Smith, Sean G.; Ravindranathan, Sruthi; Jayanthi, Srinivas; Kumar, Thallapuranam K.S.; Zaharoff, David A.

2014-01-01

Chitosan-based nano/microencapsulation is under increasing investigation for the delivery of drugs, biologics and vaccines. Despite widespread interest, the literature lacks a defined methodology to control chitosan particle size and drug/protein release kinetics. In this study, the effects of precipitation-coacervation formulation parameters on chitosan particle size, protein encapsulation efficiency and protein release were investigated. Chitosan particle sizes, which ranged from 300 nm to 3 μm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, was inversely related to the hydration strength of precipitant salts, protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. This study demonstrates that chitosan nano/microparticles with high protein loading efficiencies can be engineered with well-defined sizes and controllable release kinetics through manipulation of specific formulation parameters. PMID:24560459

Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

PubMed

Alibolandi, Mona; Taghdisi, Seyed Mohammad; Ramezani, Pouria; Hosseini Shamili, Fazileh; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

2017-03-15

In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

NASA Astrophysics Data System (ADS)

Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

2013-09-01

Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

Amidase encapsulated O-carboxymethyl chitosan nanoparticles for vaccine delivery.

PubMed

Smitha, K T; Sreelakshmi, M; Nisha, N; Jayakumar, R; Biswas, Raja

2014-02-01

This work reports the development of amidase encapsulated O-carboxymethyl chitosan nanoparticles (Ami-O-CMC NPs) of 300±50 nm size by ionic cross-linking method. The prepared Ami-O-CMC NPs had an encapsulation efficiency of 55.39%. Haemolysis assay and cytotoxicity studies proved the hemocompatibility and cytocompatibility of the prepared NPs. The sustained release of Ami from the NPs is expected to prolong its immunogenicity and in turn lead to development of better protective immunity against Staphylococcus aureus infections. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhanced adsorption of congo red from aqueous solutions by chitosan hydrogel beads impregnated with cetyl trimethyl ammonium bromide.

PubMed

Chatterjee, Sudipta; Lee, Dae S; Lee, Min W; Woo, Seung H

2009-06-01

The adsorption of congo red (CR) onto chitosan (CS) beads impregnated by a cationic surfactant (CTAB, cetyl trimethyl ammonium bromide) was investigated. Chitosan beads impregnated at a ratio of 1/20 of CTAB to CS (0.05% of CTAB and 1% of CS) increased the CR adsorption capacity by 2.2 times from 162.3 mg/g (0% CTAB) to 352.5 mg/g (0.05% CTAB). The CR adsorption decreased with an increase in pH of the CR solution from 4.0 to 9.0. The Sips isotherm model showed a good fit with the equilibrium experimental data and the values of the heterogeneity factor (n) indicated heterogeneous adsorption of CR onto CS/CTAB beads, as well as CS beads. The kinetic data showed better fit to the pseudo second-order rate model than to the pseudo first-order rate model. The impregnation of CS beads by cationic surfactants showed the highest adsorption capacities of CR compared to any other adsorbents and would be a good method to increase adsorption efficiency for the removal of anionic dyes in a wastewater treatment process.

Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

PubMed

Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

2017-03-15

As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from

40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL...-soya acyl derivs., chloride. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs...

40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL...-soya acyl derivs., chloride. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs...

40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL...-soya acyl derivs., chloride. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs...

40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.7270 1-propanaminium, 3-amino-, N,N,N-trimethyl-N...

40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.7270 1-propanaminium, 3-amino-, N,N,N-trimethyl-N...

Nanolayer encapsulation of insulin-chitosan complexes improves efficiency of oral insulin delivery

PubMed Central

Song, Lei; Zhi, Zheng-liang; Pickup, John C

2014-01-01

Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management. PMID:24833901

Encapsulation of ascorbyl palmitate in chitosan nanoparticles by oil-in-water emulsion and ionic gelation processes.

PubMed

Yoksan, Rangrong; Jirawutthiwongchai, Jatesuda; Arpo, Kridsada

2010-03-01

The encapsulation of ascorbyl palmitate (AP) in chitosan particles was carried out by droplet formation via an oil-in-water emulsion, followed by droplet solidification via ionic gelation using sodium triphosphate pentabasic (TPP) as a cross-linking agent. The success of AP encapsulation was confirmed by FT-IR, UV-vis spectrophotometry, TGA, and XRD techniques. The obtained AP-loaded chitosan particles were spherical in shape with an average diameter of 30-100nm as observed by SEM and TEM. Loading capacity (LC) and encapsulation efficiency (EE) of AP in the nanoparticles were about 8-20% and 39-77%, respectively, when the initial AP concentration was in the range of 25-150% (w/w) of chitosan. Augmentation of the initial AP concentration led to an increase of LC and a reduction of EE. The amount of AP released from the nanoparticles in ethanol and tris buffer (pH approximately 8.0) increased with increasing LC and decreasing TPP concentration.

Nanoparticles Prepared From N,N-Dimethyl-N-Octyl Chitosan as the Novel Approach for Oral Delivery of Insulin: Preparation, Statistical Optimization and In-vitro Characterization

PubMed Central

Shamsa, Elnaz Sadat; Mahjub, Reza; Mansoorpour, Maryam; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2018-01-01

In this study, N,N-Dimethyl-N-Octyl chitosan was synthesized. Nanoparticles containing insulin were prepared using PEC method and were statistically optimized using the Box-Behnken response surface methodology. The independent factors were considered to be the insulin concentration, concentration and pH of the polymer solution, while the dependent factors were characterized as the size, zeta potential, PdI and entrapment efficiency. The optimized nanoparticles were morphologically studied using SEM. The cytotoxicity of the nanoparticles on the Caco-2 cell culture was studied using the MTT cytotoxicity assay method, while the permeation of the insulin nanoparticles across the Caco-2 cell monolayer was also determined. The optimized nanoparticles posed appropriate physicochemical properties. The SEM morphological studies showed spherical to sub-spherical nanoparticles with no sign of aggregation. The in-vitro release study showed that 95.5 ± 1.40% of the loaded insulin was released in 400 min. The permeability studies revealed significant enhancement in the insulin permeability using nanoparticles prepared from octyl chitosan at 240 min (11.3 ± 0.78%). The obtained data revealed that insulin nanoparticles prepared from N,N-Dimethyl-N-Octyl chitosan can be considered as the good candidate for oral delivery of insulin compared to nanoparticles prepared from N,N,N-trimethyl chitosan.

Preparation and Efficacy of a Live Newcastle Disease Virus Vaccine Encapsulated in Chitosan Nanoparticles

PubMed Central

Gao, Ting-ting; Li, Wei; Zhao, Yan; Zhang, Feng-qiang; Wu, Jin; Cui, Xianlan; Wang, Yun-Feng

2012-01-01

Background Newcastle disease (ND) is a highly contagious viral disease of poultry caused by pathogenic strains of the Newcastle disease virus (NDV). Live NDV vaccines are administered by drinking water, eyedrops or coarse aerosol spray. To further enhance mucosal immune responses, chitosan nanoparticles were developed for the mucosal delivery of a live NDV vaccine. Methodology/Principal Findings A lentogenic live-virus vaccine (strain LaSota) against NDV encapsulated in chitosan nanoparticles were developed using an ionic crosslinking method. Chitosan nanoparticles containing the lentogenic live-virus vaccine against NDV (NDV-CS-NPs) were produced with good morphology, high stability, a mean diameter of 371.1 nm, an encapsulation rate of 77% and a zeta potential of +2.84 mV. The Western blotting analysis showed that NDV structural proteins were detected in NDV-CS-NPs. The virus release assay results of NDV-CS-NPs indicated that NDV was released from NDV-CS-NPs. Chickens immunized orally or intranasally with NDV-CS-NPs were fully protected whereas one out of five chickens immunized with the LaSota live NDV vaccine and three out of five chickens immunized with the inactivated NDV vaccine were dead after challenge with the highly virulent NDV strain F48E9. Conclusions/Significance NDV-CS-NPs induced better protection of immunized specific pathogen free chickens compared to the live NDV vaccine strain LaSota and the inactivated NDV vaccine. This study lays a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles. PMID:23285276

Encapsulation and release studies of strawberry polyphenols in biodegradable chitosan nanoformulation.

PubMed

Pulicharla, Rama; Marques, Caroline; Das, Ratul Kumar; Rouissi, Tarek; Brar, Satinder Kaur

2016-07-01

Polyphenols (negative groups) of strawberry extract interacts with positively protonated amino groups of chitosan which helps in maximum encapsulation. This approach can improve the bioavailability and sustained release of phytochemicals having lower bioavailability. The optimum mass ratio of chitosan-tripolyphosphate and polyphenols (PPs) loading was investigated to be 3:1 and 0.5mg/ml of strawberry extract, respectively. Prepared nanoformulation were characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy. The formed particles size ranged between 300 and 600nm and polydispersity index (PDI) of≈0.5. The optimized formulation showed encapsulation efficiency of 58.09% at 36.47% of polyphenols loading. Initial burst and continuous release of PPs was observed at pH 7.4 of in vitro release studies. PPs release profile at this pH was found to be non-Fickian analomous diffusion and the release was followed first order kinetics. And at pH 1.4, diffusion-controlled Fickian release of PPs was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

Chitosan/cashew gum nanogels for essential oil encapsulation.

PubMed

Abreu, Flávia O M S; Oliveira, Erick F; Paula, Haroldo C B; de Paula, Regina C M

2012-08-01

Nanogels based on chitosan and cashew gum were prepared and loaded with Lippia sidoides oil. Several parameters such as cashew gum concentration and relative oil content in the matrix had their influence on nanogel properties investigated. Nanogels were characterized regarding their morphologies, particle size distributions, zeta potential, Fourier transform infrared spectroscopy and essential oil contents. The release profile was investigated by UV/vis spectroscopy and its efficacy was determined through bioassays. Results showed that samples designed using relative ratios matrix:oil 10:2, gum:chitosan 1:1 and 5% gum concentration showed high loading (11.8%) and encapsulation efficiency (70%). Nanogels were found to exhibit average sizes in the range 335-558 nm. In vitro release profiles showed that nanoparticles presented slower and sustained release. Bioassays showed that larval mortality was related mainly to oil loading, with samples presenting more effective larvicide efficacies than the pure L. sidoides oil. Copyright © 2012 Elsevier Ltd. All rights reserved.

Formulation, characterization, and expression of a recombinant MOMP Chlamydia trachomatis DNA vaccine encapsulated in chitosan nanoparticles

PubMed Central

Cambridge, Chino D; Singh, Shree R; Waffo, Alain B; Fairley, Stacie J; Dennis, Vida A

2013-01-01

Chlamydia trachomatis is a bacterial sexually transmitted infection affecting millions of people worldwide. Previous vaccination attempts have employed the recombinant major outer membrane protein (MOMP) of C. trachomatis nonetheless, with limited success, perhaps, due to stability, degradation, and delivery issues. In this study we cloned C. trachomatis recombinant MOMP DNA (DMOMP) and encapsulated it in chitosan nanoparticles (DMCNP) using the complex coacervation technique. Physiochemical characterizations of DMCNP included transmission and scanning electron microcopy, Fourier transform infrared and ultraviolet-visible spectroscopy, and zeta potential. Encapsulated DMOMP was 167–250 nm, with a uniform spherical shape and homogenous morphology, and an encapsulation efficiency > 90%. A slow release pattern of encapsulated DMOMP, especially in acidic solution, was observed over 7 days. The zeta potential of DMCNP was ~8.80 mV, which indicated that it was highly stable. Toxicity studies of DMCNP (25–400 μg/mL) to Cos-7 cells using the MTT assay revealed minimal toxicity over 24–72 hours with >90% viable cells. Ultra-violet visible (UV-vis) spectra indicated encapsulated DMOMP protection by chitosan, whereas agarose gel electrophoresis verified its protection from enzymatic degradation. Expression of MOMP protein in DMCNP-transfected Cos-7 cells was demonstrated via Western blotting and immunofluorescence microscopy. Significantly, intramuscular injection of BALB/c mice with DMCNP confirmed the delivery of encapsulated DMOMP, and expression of the MOMP gene transcript in thigh muscles and spleens. Our data show that encapsulation of DMOMP in biodegradable chitosan nanoparticles imparts stability and protection from enzymatic digestion, and enhances delivery and expression of DMOMP in vitro and in mice. Further investigations of the nanoencapsulated DMCNP vaccine formulation against C. trachomatis in mice are warranted. PMID:23690681

Injectable and microporous scaffold of densely-packed, growth factor-encapsulating chitosan microgels.

PubMed

Riederer, Michael S; Requist, Brennan D; Payne, Karin A; Way, J Douglas; Krebs, Melissa D

2016-11-05

In this work, an emulsion crosslinking method was developed to produce chitosan-genipin microgels which acted as an injectable and microporous scaffold. Chitosan was characterized with respect to pH by light scattering and aqueous titration. Microgels were characterized with swelling, light scattering, and rheometry of densely-packed microgel solutions. The results suggest that as chitosan becomes increasingly deprotonated above the pKa, repulsive forces diminish and intermolecular attractions cause pH-responsive chain aggregation; leading to microgel-microgel aggregation as well. The microgels with the most chitosan and least cross-linker showed the highest yield stress and a storage modulus of 16kPa when condensed as a microgel paste at pH 7.4. Two oppositely-charged growth factors could be encapsulated into the microgels and endothelial cells were able to proliferate into the 3D microgel scaffold. This work motivates further research on the applications of the chitosan microgel scaffold as an injectable and microporous scaffold in regenerative medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Photo-crosslinked HAMA hydrogel with cordycepin encapsulated chitosan microspheres for osteoarthritis treatment.

PubMed

Xia, Chen; Chen, Pengfei; Mei, Sheng; Ning, Lei; Lei, Chenyang; Wang, Jiying; Zhang, Jianfeng; Ma, Jianjun; Fan, Shunwu

2017-01-10

Autophagy is a protective mechanism in normal cartilage. The present study aimed to investigate the synergistic therapeutic effect of promotion of chondrocyte autophagy via exposure to cordycepin encapsulated by chitosan microspheres (CM-cordycepin) and photo-crosslinked hyaluronic acid methacrylate (HAMA) hydrogel, with the goal of evaluating CM-cordycepin as a treatment for patients with osteoarthritis. First, we developed and evaluated the characteristics of HAMA hydrogels and chitosan microspheres. Next, we measured the effect of cordycepin on cartilage matrix degradation induced by IL1-β in chondrocytes and an ex vivo model. Cordycepin protects cartilage from degradation partly by activation of autophagy. Moreover, we surgically induced osteoarthritis in mice, which were injected intra-articularly with CM-cordycepin and HAMA. The combination of CM-cordycepin and HAMA hydrogel retarded the progression of surgically induced OA. Cordycepin ameliorated cartilage matrix degradation at least partially by inducing autophagy in vivo. Our results demonstrate that the combination of cordycepin encapsulated by CMs and photo-crosslinked HAMA hydrogel could be a promising strategy for treating patients with osteoarthritis.

Trimethyl chitosan-capped silver nanoparticles with positive surface charge: Their catalytic activity and antibacterial spectrum including multidrug-resistant strains of Acinetobacter baumannii.

PubMed

Chang, T Y; Chen, C C; Cheng, K M; Chin, C Y; Chen, Y H; Chen, X A; Sun, J R; Young, J J; Chiueh, T S

2017-07-01

We report a facile route for the green synthesis of trimethyl chitosan nitrate-capped silver nanoparticles (TMCN-AgNPs) with positive surface charge. In this synthesis, silver nitrate, glucose, and trimethyl chitosan nitrate (TMCN) were used as silver precursor, reducing agent, and stabilizer, respectively. The reaction was carried out in a stirred basic aqueous medium at room temperature without the use of energy-consuming or expensive equipment. We investigated the effects of the concentrations of NaOH, glucose, and TMCN on the particle size, zeta potential, and formation yield. The AgNPs were characterized by UV-vis spectroscopy, photon correlation spectroscopy, laser Doppler anemometry, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The catalytic activity of the TMCN-AgNPs was studied by the reduction of 4-nitrophenol using NaBH 4 as a reducing agent. We evaluated the antibacterial effects of the TMCN-AgNPs on Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the broth microdilution method. The results showed that both gram-positive and gram-negative bacteria were killed by the TMCN-AgNPs at very low concentration (<6.13μg/mL). Moreover, the TMCN-AgNPs also showed high antibacterial activity against clinically isolated multidrug-resistant A. baumannii strains, and the minimum inhibitory concentration (MIC) was ≤12.25μg/mL. Copyright © 2017 Elsevier B.V. All rights reserved.

Properties of Lactobacillus reuteri chitosan-calcium-alginate encapsulation under simulated gastrointestinal conditions.

PubMed

Huang, Hui-Ying; Tang, Yi-Ju; King, V An-Erl; Chou, Jen-Wei; Tsen, Jen-Horng

2015-03-01

The protective effects of encapsulation on the survival of Lactobacillus reuteri and the retention of the bacterium's probiotic properties under simulated gastrointestinal conditions were investigated. Viable counts and the remaining probiotic properties of calcium (Ca)-alginate encapsulated (A group), chitosan-Ca-alginate encapsulated (CA group), and unencapsulated, free L. reuteri (F group) were determined. Encapsulation improved the survival of L. reuteri subjected to simulated gastrointestinal conditions, with the greatest protective effect achieved in the CA group. The degree of cell membrane injury increased with increasing bile salt concentrations at constant pH, but the extent of injury was less in the encapsulated than in the free cells. Adherence rates were, in descending order: CA (0.524%)>A (0.360%)>F (0.275%). Lactobacillus reuteri cells retained their antagonistic activity toward Listeria monocytogenes even after incubation of the lactobacilli under simulated gastrointestinal conditions. Displacement of the pathogen by cells released from either of the encapsulation matrices was higher than that by free cells. The safety of L. reuteri was demonstrated in an in vitro invasion assay. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Efficacy of ferulic acid encapsulated chitosan nanoparticles against Candida albicans biofilm.

PubMed

Panwar, Richa; Pemmaraju, Suma C; Sharma, Asvene K; Pruthi, Vikas

2016-06-01

Candida albicans, an opportunistic fungal pathogen is a major causative agent of superficial to systemic life-threating biofilm infections on indwelling medical devices. These biofilms acts as double edge swords owing to their resistance towards antibiotics and immunological barriers. To overcome this threat ferulic acid encapsulated chitosan nanoparticles (FA-CSNPs) were formulated to assess its efficacy as an antibiofilm agent against C. albicans. These FA-CSNPs were synthesized using ionotropic gelation method and observed through field emission scanning electron microscopy (FESEM) and fluorescent microscopy. Assessment of successful encapsulation and stability of ferulic acid into chitosan nanoparticles was made using Fourier transform infrared spectrum (FTIR), (1)H NMR and thermal analyses. Synthesized FA-CSNPs, were found to be cytocompatible, when tested using Human Embryonic Kidney (HEK-293) cell lines. XTT assay revealed that FA-CSNPs reduced the cell metabolic activity of C. albicans upto 22.5% as compared to native ferulic acid (63%) and unloaded CSNPs (88%) after 24 h incubation. Disruption of C. albicans biofilm architecture was visualized by FESEM. Results highlighted the potential of FA-CSNPs to be used as an effective alternative to the conventional antifungal therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.

PubMed

Yang, Hae Kyung; Ham, Dong-Sik; Park, Heon-Seok; Rhee, Marie; You, Young Hye; Kim, Min Jung; Shin, Juyoung; Kim, On-You; Khang, Gilson; Hong, Tae Ho; Kim, Ji-Won; Lee, Seung-Hwan; Cho, Jae-Hyoung; Yoon, Kun-Ho

2016-02-01

Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules. Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants. The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P < 0.001) compared to that of alginate capsules up to 1 year after transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation. The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.

Geraniol encapsulated in chitosan/gum arabic nanoparticles: a promising system for pest management in sustainable agriculture.

PubMed

de Oliveira, Jhones Luiz; Campos, Estefania Vangelie Ramos; Pereira, Anderson E S; Nunes, Lucas E S; da Silva, Camila C L; Pasquoto, Tatiane; Lima, Renata; Smaniotto, Giovani; Polanczyk, Ricardo Antonio; Fraceto, Leonardo F

2018-05-07

The nanoencapsulation of botanical compounds (such as geraniol) is an important strategy that can be used to increase the stability and efficiency of these substances in integrated pest management. In this study, chitosan/gum arabic nanoparticles containing geraniol were prepared and characterized. In addition, evaluation was made of the biological activity of geraniol encapsulated in chitosan/gum arabic nanoparticles towards whitefly (Bemisia tabaci). The optimized formulation showed a high encapsulation efficiency (>90%) and remained stable for about 120 days. The formulation protected the geraniol against degradation by UV radiation, and the in vitro release was according to a diffusion mechanism that was influenced by temperature. An attraction effect was observed for Bemisia tabaci, indicating the potential of this type of system for use in pest management, especially in trap devices.

Cyclodextrin based ternary system of modafinil: Effect of trimethyl chitosan and polyvinylpyrrolidone as complexing agents.

PubMed

Patel, Parth; Agrawal, Y K; Sarvaiya, Jayrajsinh

2016-03-01

Modafinil is an approved drug for the treatment of narcolepsy and have a strong market presence in many countries. The drug is widely consumed for off-label uses and currently listed as a restricted drug. Modafinil has very low water solubility. To enhance the aqueous solubility of modafinil by the formation of a ternary complex with Hydroxypropyl-β-cyclodextrin and two hydrophilic polymers was the main objective of the present study. Pyrrolidone (PVP K30) and a water soluble chitosan derivative, trimethyl chitosan (TMC) were studied by solution state and solid state characterization methods for their discriminatory efficiency in solubility enhancement of modafinil. Phase solubility study depicted the highest complexation efficiency (2.22) of cyclodextrin derivative in the presence of TMC compared to the same in the presence of PVP K30 (0.08) and in the absence of any polymer (0.92). FT-IR analysis of binary and ternary complex expressed comparable contribution of both polymers in formation of inclusion complex. The thermal behaviour of binary and ternary complex, involving individual polymers disclosed the influence of TMC on polymorphism of the drug. DSC study revealed efficiency of TMC to prevent conversion of metastable polymorphic form to stable polymorphic form. Ternary complex, involving TMC enhanced water solubility of the drug 1.5 times more compared to the binary complex of the drug whereas PVP K30 reduced the Solubility. Copyright © 2015 Elsevier B.V. All rights reserved.

Live encapsulated Lactobacillus acidophilus cells in yogurt for therapeutic oral delivery: preparation and in vitro analysis of alginate-chitosan microcapsules.

PubMed

Urbanska, Aleksandra Malgorzata; Bhathena, Jasmine; Prakash, Satya

2007-09-01

Targeted delivery of live microencapsulated bacterial cells has strong potential for application in treating various diseases, including diarrhea, kidney failure, liver failure, and high cholesterol, among others. This study investigates the potential of microcapsules composed of two natural polymers, alginate and chitosan (AC), and the use of these artificial cells in yogurt for delivery of probiotic Lactobacillus acidophilus bacterial live cells. Results show that the integrity of AC microcapsules was preserved after 76 h of mechanical shaking in MRS broth and after 12 h and 24 h in simulated gastric and intestinal fluids. Using an in vitro computer-controlled simulated human gastrointestinal (GI) model, we found 8.37 log CFU/mL of viable bacterial cells were present after 120 min of gastric exposure and 7.96 log CFU/mL after 360 min of intestinal exposure. In addition, AC microcapsules composed of chitosan 10 and 100 at various concentrations were subjected to 4-week storage in 2% milk fat yogurt or 0.85% physiological solution. It was found that 9.37 log CFU/mL of cells encapsulated with chitosan 10 and 8.24 log CFU/mL of cells encapsulated with chitosan 100 were alive after 4 weeks. The AC capsule composed of 0.5% chitosan 10 provided the highest bacterial survival of 9.11 log CFU/mL after 4 weeks. Finally, an investigation of bacterial viability over 72 h in different pH buffers yielded highest survival of 6.34 log CFU/mL and 10.34 log CFU/mL at pH 8 for free and AC-encapsulated cells, respectively. We conclude from these findings that encapsulation allows delivery of a higher number of bacteria to desired targets in the GI tract and that microcapsules containing bacterial cells are good candidates for oral artificial cells for bacterial cell therapy.

Effect of chitosan, O-carboxymethyl chitosan, and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride on overweight and insulin resistance in a murine diet-induced obesity.

PubMed

Liu, Xiaofei; Zhi, Xiaona; Liu, Yunfei; Wu, Bo; Sun, Zhong; Shen, Jun

2012-04-04

Two water-soluble chitosan derivatives, O-carboxymethyl chitosan (O-CM-chitosan) and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride (N-CQ-chitosan), were prepared, and the therapeutic effects of chitosan, O-CM-chitosan, and N-CQ-chitosan on insulin resistance were simultaneously evaluated by rats fed on a high-fat diet. The parameters of high-fat diet-induced rats indicated that chitosan and its two derivatives not only have low cytotoxicity but can control overnutrition by fat and achieve insulin resistance therapy. However, the results in experiment in vivo showed that the therapeutic degree varied by the molecular weight and surface charge of chitosan, O-CM-chitosan, and N-CQ-chitosan. N-CQ-chitosan with a MW of 5 × 10(4) decreased body weight, the ratio of fat to body weight, triglyceride, fasting plasma glucose, fasting plasma insulin, free fatty acid, and leptin by 11, 17, 44, 46, 44, 87, and 64% and increased fecal lipid by 95%, respectively.

Thiolated trimethyl chitosan nanocomplexes as gene carriers with high in vitro and in vivo transfection efficiency.

PubMed

Zhao, Xin; Yin, Lichen; Ding, Jieying; Tang, Cui; Gu, Shaohua; Yin, Chunhua; Mao, Yumin

2010-05-21

Trimethyl chitosan-cysteine conjugate (TMC-Cys) was evaluated as non-viral gene carriers to combine the advantages of TMC and thiolated chitosan. TMC-Cys with various molecular weights (30, 100, and 200 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanocomplexes with plasmid encoding enhanced green fluorescence protein (pEGFP), which demonstrated preferable diameters of below 200 nm and zeta potentials of +15 to +20 mV. Cell binding and uptake of TMC-Cys/pEGFP nanocomplexes (TMC-Cys NC) were enhanced 2.4-3.0 and 1.4-3.0 folds, respectively, compared to TMC/pEGFP nanocomplexes (TMC NC). pEGFP could be easily released from TMC-Cys NC at the intracellular glutathione concentration, which promoted its nuclear transport and accumulation. Consequently, TMC-Cys NC showed a 1.4 to 3.2-fold increase in the transfection efficiency in HEK293 cells as compared to TMC NC and the optimal TMC-Cys(100,30) NC showed a 1.5-fold enhancement than Lipofectamine2000. Such results were further confirmed by in vivo transfection with a 2.3-fold and 4.1-fold higher transfection efficiency of TMC-Cys(100,30) NC than TMC(100,30) NC and Lipofectamine2000, respectively. Therefore, TMC-Cys/DNA nanocomplexes could be a promising gene delivery system with in vitro and in vivo superiority to Lipofectamine2000. Copyright 2010 Elsevier B.V. All rights reserved.

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations.

PubMed

Mahjub, Reza; Radmehr, Moojan; Dorkoosh, Farid Abedin; Ostad, Seyed Naser; Rafiee-Tehrani, Morteza

2014-12-01

The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan. Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined. Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24 h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared

Antidiabetic Activity from Gallic Acid Encapsulated Nanochitosan

NASA Astrophysics Data System (ADS)

Purbowatiningrum; Ngadiwiyana; Ismiyarto; Fachriyah, E.; Eviana, I.; Eldiana, O.; Amaliyah, N.; Sektianingrum, A. N.

2017-02-01

Diabetes mellitus (DM) has become a health problem in the world because it causes death. One of the phenolic compounds that have antidiabetic activity is gallic acid. However, the use of this compound still provides unsatisfactory results due to its degradation during the absorption process. The solution offered to solve the problem is by encapsulated it within chitosan nanoparticles that serve to protect the bioactive compound from degradation, increases of solubility and delivery of a bioactive compound to the target site by using freeze-drying technique. The result of chitosan nanoparticle’s Scanning Electron Microscopy (SEM) showed that chitosan nanoparticle’s size is uniform and it is smaller than chitosan. The value of encapsulation efficiency (EE) of gallic acid which encapsulated within chitosan nanoparticles is about 50.76%. Inhibition test result showed that gallic acid-chitosan nanoparticles at 50 ppm could inhibite α-glucosidase activity in 28.87% with 54.94 in IC50. So it can be concluded that gallic acid can be encapsulated in nanoparticles of chitosan and proved that it could inhibit α-glucosidase.

High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging.

PubMed

Xiao, Yunbin; Lin, Zuan Tao; Chen, Yanmei; Wang, He; Deng, Ya Li; Le, D Elizabeth; Bin, Jianguo; Li, Meiyu; Liao, Yulin; Liu, Yili; Jiang, Gangbiao; Bin, Jianping

2015-01-01

Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors.

High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging

PubMed Central

Xiao, Yunbin; Lin, Zuan Tao; Chen, Yanmei; Wang, He; Deng, Ya Li; Le, D Elizabeth; Bin, Jianguo; Li, Meiyu; Liao, Yulin; Liu, Yili; Jiang, Gangbiao; Bin, Jianping

2015-01-01

Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors. PMID:25709439

Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design.

PubMed

Abul Kalam, Mohd; Khan, Abdul Arif; Khan, Shahanavaj; Almalik, Abdulaziz; Alshamsan, Aws

2016-06-01

Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type. Copyright © 2016 Elsevier B.V. All rights reserved.

Encapsulation of rat bone marrow stromal cells using a poly-ion complex gel of chitosan and succinylated poly(Pro-Hyp-Gly).

PubMed

Kusumastuti, Yuni; Shibasaki, Yoshiaki; Hirohara, Shiho; Kobayashi, Mime; Terada, Kayo; Ando, Tsuyoshi; Tanihara, Masao

2017-03-01

Encapsulation of stem cells into a three-dimensional (3D) scaffold is necessary to achieve tissue regeneration. Prefabricated 3D scaffolds, such as fibres or porous sponges, have limitations regarding homogeneous cell distribution. Hydrogels that can encapsulate cells such as animal-derived collagen gels need adjustment of the pH and/or temperature upon cell mixing. In this report, we fabricated a poly-ion complex (PIC) hydrogel of chitosan and succinylated poly(Pro-Hyp-Gly) and assessed its effect on cell viability after encapsulation of rat bone marrow stromal cells. PIC hydrogels were obtained successfully with a concentration of each precursor as low as 3.0-3.8 mg/ml. The maximum gelation and swelling ratios were achieved with an equal molar ratio (1:1) of anionic and cationic groups. Using chitosan acetate as a cationic precursor produced a PIC hydrogel with both a significantly greater gelation ratio and a better swelling ratio than chitosan chloride. Ammonium succinylated poly(Pro-Hyp-Gly) as an anionic precursor gave similar gelation and swelling ratios to those of sodium succinylated poly(Pro-Hyp-Gly). Cell encapsulation was also achieved successfully by mixing rat bone marrow stromal cells with the PIC hydrogel simultaneously during its formation. The PIC hydrogel was maintained in the culture medium for 7 days at 37°C and the encapsulated cells survived and proliferated in it. Although it is necessary to improve its functionality, this PIC hydrogel has the potential to act as a 3D scaffold for cell encapsulation and tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Cytotoxicity and metal ions removal using antibacterial biodegradable hydrogels based on N-quaternized chitosan/poly(acrylic acid).

PubMed

Mohamed, Riham R; Elella, Mahmoud H Abu; Sabaa, Magdy W

2017-05-01

Physically crosslinked hydrogels resulted from interaction between N,N,N-trimethyl chitosan chloride (N-Quaternized Chitosan) (NQC) and poly(acrylic acid) (PAA) were synthesized in different weight ratios (3:1), (1:1) and (1:3) taking the following codes Q3P1, Q1P1 and Q1P3, respectively. Characterization of the mentioned hydrogels was done using several analysis tools including; FTIR, XRD, SEM, TGA, biodegradation in simulated body fluid (SBF) and cytotoxicity against HepG-2 liver cancer cells. FTIR results proved that the prepared hydrogels were formed via electrostatic and H-bonding interactions, while XRD patterns proved that the prepared hydrogels -irrespective to their ratios- were more crystalline than both matrices NQC and PAA. TGA results, on the other hand, revealed that Q1P3 hydrogel was the most thermally stable compared to the other two hydrogels (Q3P1 and Q1P1). Biodegradation tests in SBF proved that these hydrogels were more biodegradable than the native chitosan. Examination of the prepared hydrogels for their potency in heavy metal ions removal revealed that they adsorbed Fe (III) and Cd (II) ions more than chitosan, while they adsorbed Cr (III), Ni (II) and Cu (II) ions less than chitosan. Moreover, testing the prepared hydrogels as antibacterial agents towards several Gram positive and Gram negative bacteria revealed their higher antibacterial activity as compared with NQC when used alone. Evaluating the cytotoxic effect of these hydrogels on an in vitro human liver cancer cell model (HepG-2) showed their good cytotoxic activity towards HepG-2. Moreover, the inhibition rate increased with increasing the hydrogels concentration in the culture medium. Copyright © 2017 Elsevier B.V. All rights reserved.

Peptide-decorated chitosan derivatives enhance fibroblast adhesion and proliferation in wound healing.

PubMed

Patrulea, V; Hirt-Burri, N; Jeannerat, A; Applegate, L A; Ostafe, V; Jordan, O; Borchard, G

2016-05-20

RGD peptide sequences are known to regulate cellular activities by interacting with α5β1, αvβ5 and αvβ3 integrin, which contributes to the wound healing process. In this study, RGDC peptide was immobilized onto chitosan derivative 1,6-diaminohexane-O-carboxymethyl-N,N,N-trimethyl chitosan (DAH-CMTMC) to display RGDC-promoting adhesion for enhanced wound healing. The efficiency of N-methylation, O-carboxymethylation and spacer grafting was quantitatively and qualitatively analyzed by (1)H NMR and FTIR, yielding 0.38 degree of substitution for N-methylation and >0.85 for O-carboxymethylation. The glass transition temperatures for chitosan derivatives were also studied. Peptide immobilization was achieved through sulfhydryl groups using sulfosuccinimidyl (4-iodoacetyl)amino-benzoate (sulfo-SIAB method). RGDC immobilized peptide onto DAH-CMTMC was found to be about 15.3 μg/mg of chitosan derivative by amino acid analysis (AAA). The significant increase of human dermal fibroblast (HDF) viability in vitro over 7 days suggests that RGDC-functionalized chitosan may lead to enhanced wound healing (viability >140%). Moreover, bio-adhesion and proliferation assays confirmed that coatings of RGDC-functionalized chitosan derivatives exhibit in vitro wound healing properties by enhancing fibroblast proliferation and adhesion. These results showed that RGDC peptide-functionalized chitosan provides an optimal environment for fibroblast adhesion and proliferation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery.

PubMed

Farhadian, Asma; Dounighi, Naser Mohammadpour; Avadi, Mohammadreza

2015-01-01

Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 µg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

Effects of Environmental Stresses and in Vitro Digestion on the Release of Tocotrienols Encapsulated Within Chitosan-Alginate Microcapsules.

PubMed

Tan, Phui Yee; Tan, Tai Boon; Chang, Hon Weng; Tey, Beng Ti; Chan, Eng Seng; Lai, Oi Ming; Sham Baharin, Badlishah; Nehdi, Imededdine Arbi; Tan, Chin Ping

2017-12-06

Considering the health benefits of tocotrienols, continuous works have been done on the encapsulation and delivery of these compounds. In this study, we encapsulated tocotrienols in chitosan-alginate microcapsules and evaluated their release profile. Generally, these tocotrienols microcapsules (TM) displayed high thermal stability. When subjected to pH adjustments (pH 1-9), we observed that the release of tocotrienols was the highest (33.78 ± 0.18%) under basic conditions. The TM were also unstable against the effect of ionic strength, with a high release (70.73 ± 0.04%) of tocotrienols even at a low sodium chloride concentration (50 mM). As for the individual isomers, δ-tocotrienol was the most sensitive to pH and ionic strength. In contrast, β-/γ-tocotrienols were the most ionic-stable isomers but more responsive toward thermal treatment. Simulated gastrointestinal model showed that the chitosan-alginate-based TM could be used to retain tocotrienols in the gastric and subsequently release them in the intestines for possible absorption.

Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles.

PubMed

Pooja, Deep; Babu Bikkina, Dileep J; Kulhari, Hitesh; Nikhila, Nalla; Chinde, Srinivas; Raghavendra, Y M; Sreedhar, B; Tiwari, Ashok K

2014-08-01

Silibinin is reported to possess multiple biological activities. However, its hydrophobic nature limits its bioavailability compromising in vivo biological activities. Nanoparticles-based delivery of such molecules has emerged as new technique to resolve these issues. Bio-degradable, compatible and adhesive nature of chitosan has recently attracted its suitability as a carrier for biologically active molecules. This study presents fabrication and characterization of chitosan-tripolyphosphate based encapsulation of silibinin. Various preparations of silibinin encapsulated chitosan-tripolyphosphate nanoparticles were studied for particle size, morphology, zeta-potential, and encapsulation efficiencies. Preparations were also evaluated for cytotoxic activities in vitro. The optimized silibinin loaded chitosan nanoparticles were of 263.7±4.1nm in particle size with zeta potential 37.4±1.57mV. Nanoparticles showed high silibinin encapsulation efficiencies (82.94±1.82%). No chemical interactions between silibinin and chitosan were observed in FTIR analysis. Powder X-ray diffraction analysis revealed transformed physical state of silibinin after encapsulation. Surface morphology and thermal behaviour were determined using TEM and DSC analysis. Encapsulated silibinin displayed increased dissolution and better cytotoxicity against human prostate cancer cells (DU145) than silibinin alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Interaction of PLGA and trimethyl chitosan modified PLGA nanoparticles with mixed anionic/zwitterionic phospholipid bilayers studied using molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Novak, Brian; Astete, Carlos; Sabliov, Cristina; Moldovan, Dorel

2012-02-01

Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer. Nanoparticles of PLGA are commonly used for drug delivery applications. The interaction of the nanoparticles with the cell membrane may influence the rate of their uptake by cells. Both PLGA and cell membranes are negatively charged, so adding positively charged polymers such as trimethyl chitosan (TMC) which adheres to the PLGA particles improves their cellular uptake. The interaction of 3 nm PLGA and TMC-modified-PLGA nanoparticles with lipid bilayers composed of mixtures of phosphatidylcholine and phosphatidylserine lipids was studied using molecular dynamics simulations. The free energy profiles as function of nanoparticles position along the normal direction to the bilayers were calculated, the distribution of phosphatidylserine lipids as a function of distance of the particle from the bilayer was calculated, and the time scale for particle motion in the directions parallel to the bilayer surface was estimated.

Encapsulation of biological active phenolic compounds extracted from wine wastes in alginate-chitosan microbeads.

PubMed

Moschona, Alexandra; Liakopoulou-Kyriakides, Maria

2018-04-23

Grapes (Vitis vinifera) are produced in large amounts worldwide and mostly are used for winemaking. Their untreated wastes are rich in valuable secondary metabolites, such as phenolics. Thus, in this study, white and red wine wastes (Malagouzia and Syrah variety) were investigated for their added value phenolics, which were analysed by high performance liquid chromatography (HPLC) and electrospray ionisation-mass spectrometry (ESI/MS) and subsequently encapsulated in several polymers. Extracts from all wastes gave high amounts of total phenolics (13 ± 2.72-22 ± 2.69 mg g -1 ) and possessed high antioxidant activity (67-97%). In addition to their significant antibacterial activity against gram-negative and gram-positive bacteria, interesting results were also obtained from their anti-inflammatory and antiplatelet activity, in vitro. Encapsulation of the extracts was selective, leaving out most of sugars and other organic compounds when alginate-chitosan was used. Encapsulation efficiency recorded for all extracts ranged from 55% to 79%. Release studies were also performed in several solutions aiming in their commercial use in food and pharmaceutical industries.

Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

NASA Astrophysics Data System (ADS)

Islam, Nazrul; Ferro, Vito

2016-07-01

The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

Synthesis of N-oleyl O-sulfate chitosan from methyl oleate with O-sulfate chitosan as edible film material

NASA Astrophysics Data System (ADS)

Daniel; Sihaloho, O.; Saleh, C.; Magdaleni, A. R.

2018-04-01

The research on the synthesis of N-oleyl O-sulfate chitosan through sulfonation reaction on chitosan with ammonium sulfate and followed by amidation reaction using methyl oleate has been done. In this study, chitosan was chemically modified into N-oleyl O-sulfatechitosan as an edible film making material. N-oleyl O-sulfate chitosan was synthesized by reaction between methyl oleate and O-sulfate chitosan. Wherein the depleted chitosan of O-sulfate chitosan into O-sulfate chitosan was obtained by reaction of sulfonation between ammonium sulfate and chitosan aldimine. While chitosan aldimine was obtained through reaction between chitosan with acetaldehyde. The structure of N-oleyl O-sulfate chitosan was characterized by FT-IR analysis which showed vibration uptake of C-H sp3 group, S=O group, and carbonyl group C=O of the ester. The resulting of N-oleyl O-sulfate chitosan yielded a percentage of 93.52%. Hydrophilic-Lipophilic Balance (HLB) test results gave a value of 6.68. In the toxicity test results of N-oleyl O-sulfate chitosan obtained LC50 value of 3738.4732 ppm. In WVTR (Water Vapor Transmission Rate) test results for chitosan film was 407.625 gram/m2/24 hours and N-oleylO-sulfate chitosan film was 201.125 gram/m2/24 hours.

Fortification of dark chocolate with spray dried black mulberry (Morus nigra) waste extract encapsulated in chitosan-coated liposomes and bioaccessability studies.

PubMed

Gültekin-Özgüven, Mine; Karadağ, Ayşe; Duman, Şeyma; Özkal, Burak; Özçelik, Beraat

2016-06-15

Fine-disperse anionic liposomes containing black mulberry (Morus nigra) extract (BME) were prepared by high pressure homogenization at 25,000 psi. Primary liposomes were coated with cationic chitosan (0.4, w/v%) using the layer-by-layer depositing method and mixed with maltodextrin (MD) (20, w/v%) prior to spray drying. After that, spray dried liposomal powders containing BME were added to chocolates with alkalization degrees (pH 4.5, 6, 7.5) at conching temperatures of 40 °C, 60 °C, and 80 °C. The results showed that, compared to spray dried extract, chitosan coated liposomal powders provided better protection of anthocyanin content in both increased temperature and pH. In addition, encapsulation in liposomes enhanced in vitro bioaccessability of anthocyanins. Chocolate was fortified with encapsulated anthocyanins maximum 76.8% depending on conching temperature and pH. Copyright © 2016. Published by Elsevier Ltd.

Effects of pore forming agents of potassium bicarbonate and drug loading method against dissolution mechanisms of amoxicillin drugs encapsulated in hydrogel full-Ipn chitosan-poly(N-vinylcaprolactam) as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Aini, Nurul; Rahayu, Dyah Utami Cahyaning; Budianto, Emil

2018-04-01

The limitation of amoxicillin trihydrate in the treatment of H. pylori bacteria is relatively short retention time in the stomach. The FDDS (Floating Drug Delivery System) amoxicillin trihydrate into a chitosan-poly(N-vinylcaprolactam) full-Ipn hydrogel matrix using a pore-forming agent KHCO3 is expected to overcome these limitations. The pore-forming agent to be used is 15% KHCO3 compound. Chemical kinetics approach is performed to determine the dissolution mechanism of amoxicillin trihydrate from K-PNVCL hydrogel in vitro on gastric pH and characterization using SEM performed to confirm the dissolution mechanism. Hydrogels with the addition of pore-forming agents will be loading in situ loading and post loading. Fourier Transform Infra Red (FTIR) spectroscopy was used to characterize K-PNVCL and UV-Vis hydrogels used to calculate the efficiency of encapsulation and drug dissolution rate in K-PNVCL hydrogel. Hydrogel K-PNVCL / KHCO3 that encapsulated by in situ loading method resulted in an encapsulation efficiency of 93.5% and dissolution of 93.4%. While the Hydrogel K-PNVCL / KHCO3 which is drug encapsulation resulted in an encapsulation efficiency of 87.2% with dissolution of 81.5%. Chemical kinetics approach to in situ encapsulation of loading and post loading shows the dissolution mechanism occurring in the K-PNVCL / KHCO3 hydrogel matrix occurs by diffusion. Observation using optical microscope and SEM showed the mechanism of drug dissolution in Hydrogel K-PNVCL occurred by diffusion.

Potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies.

PubMed

Cheng, Yiyun; Li, Mingzhong; Xu, Tongwen

2008-08-01

Camptothecin (CPT), a plant alkaloid isolated from Camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. In the present study we investigated the potential of poly(amidoamine) (PAMAM) dendrimers as drug carriers of CPT through aqueous solubility studies. Results showed that the aqueous solubility of CPT was significantly increased by PAMAM dendrimers. The effect of PAMAM generation on CPT solubility was also evaluated. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of CPT.

Preparation and characterization of microparticles of β-cyclodextrin/glutathione and chitosan/glutathione obtained by spray-drying.

PubMed

Webber, Vanessa; de Siqueira Ferreira, Daniel; Barreto, Pedro Luis Manique; Weiss-Angeli, Valeria; Vanderlinde, Regina

2018-03-01

Reduced glutathione (GSH) is an efficient antioxidant on limitation of browning, of the loss of aromas and off-flavor formation in white wines. The encapsulation of GSH in a polymer system to be added in white wines may prolong its antioxidant action. The aim of this work was to prepare and characterize spray-dried microparticles using β-cyclodextrin (β-CD) or chitosan as polymers for encapsulation of GSH for its addition to wine to prevent oxidation. The microparticles obtained after the drying process were characterized regarding morphology, chemical interaction between GSH and polymers, thermal stability, microstructure, encapsulation efficiency and in vitro GSH release. SEM showed spherical microparticles, with wrinkled surfaces for β-CD/GSH and smooth surfaces for chitosan/GSH. A wide distribution of particle size was observed. In general, β-CD/GSH showed an average diameter smaller than the chitosan/GSH microparticles. FT-IR showed a possible interaction between GSH and both polymers. DSC and DRX showed that encapsulation process produced a marked decrease in GSH crystallinity. The encapsulation efficiency was 25.0% for chitosan/GSH and 62.4% for β-CD/GSH microparticles. The GSH release profiles from microparticles showed that β-CD can control the release behaviors of GSH better than chitosan in a model wine. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicates a trend the non-Fickian release of GSH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antidiabetic activity from cinnamaldydhe encapsulated by nanochitosan

NASA Astrophysics Data System (ADS)

Purbowatingrum; Ngadiwiyana; Fachriyah, E.; Ismiyarto; Ariestiani, B.; Khikmah

2018-04-01

Diabetes mellitus (DM) is a disease characterized by chronic hyperglycemia and metabolic disorders of carbohydrates, proteins, and fats due to reduced function of insulin. Treatment of diabetes can be done by insulin therapy or hypoglycemic drugs. Hypoglycemic drugs usually contain compounds that can inhibit the action of α-glucosidase enzymes that play a role in breaking carbohydrates into blood sugar. Cinnamaldehyde has α-glucosidase inhibit activity because it has a functional group of alkene that is conjugated with a benzene ring and a carbonyl group. However, the use of this compound still provides unsatisfactory results due to its degradation during the absorption process. The solution offered to solve the problem is by encapsulated it within chitosan nanoparticles that serve to protect the bioactive compound from degradation, increases of solubility and delivery of a bioactive compound to the target site by using freeze-drying technique. The value of encapsulation efficiency (EE) of cinnamaldyhde which encapsulated within chitosan nanoparticles is about 74%. Inhibition test result showed that cinnamaldehyde-chitosan nanoparticles at 100 ppm could inhibit α-glucosidase activity in 23.9% with 134,13 in IC50. So it can be concluded that cinnamaldehyde can be encapsulated in nanoparticles of chitosan and proved that it could inhibit α-glucosidase.

Effect of drug loading method against the dissolution mechanism of encapsulated amoxicillin trihidrate drug in matrix of semi-IPN chitosan-poly (N-vinyl pyrrolidone) hydrogel with pore forming agent CaCO3

NASA Astrophysics Data System (ADS)

Nurjannah, Yanah; Budianto, Emil

2018-04-01

Heliobacter pylori (H.pylori) is a type of bacteria that causes inflammation in the lining of the stomach. The treatment of the bacterial infection by using conventional medicine which is amoxicillin trihidrate has a very short retention time in the stomach which is about 1-1,5 hours. Floating drug delivery system is expected to have a long retention time in the stomach so the efficiency of drug can be achieved. In this study, has been synthesized matrix of semi-IPN chitosan-Poly(N-vinil pyrrolidone) hydrogel with a pore-forming agent of CaCO3 under optimum conditions. Amoxicillin is encapsulated in a matrix hydrogel to be applied as a floating drug delivery system by in situ loading and post loading methods. The encapsulation efficiency and dissolution of in situ loading and post loading hydrogels are performed in vitro on gastric pH. In situ loading hydrogel shows higer percentage of encapsulation efficiency and dissolution compared to post loading hydrogel. The encapsulation efficiency of in situ and post loading hydrogels were 92,1% and 89,4%, respectively. The aim of drug dissolution by mathematical equation model is to know kinetics and the mecanism of dissolution. The kinetics release of in situ hydrogel tends to follow first order kinetics, while the post loading hydrogel follow the Higuchi model. The dissolution mecanism of hydrogels is erosion.

Synthesis of camptothecin-loaded gold nanomaterials

NASA Astrophysics Data System (ADS)

Xing, Zhimin; Liu, Zhiguo; Zu, Yuangang; Fu, Yujie; Zhao, Chunjian; Zhao, Xiuhua; Meng, Ronghua; Tan, Shengnan

2010-04-01

Camptothecin-loaded gold nanomaterials have been synthesized by the sodium borohydride reduction method under a strong basic condition. The obtained gold nanomaterials have been characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM) and UV-vis absorption spectroscopy. The camptothecin-loaded gold colloidal solution was very stable and can be stored for more than two months at room temperature without obvious changes. The color of the colloidal solution can change from wine red to purple and blue during the acidifying process. It was revealed that the release of camptothecin and the aggregation of gold nanoparticles can be controlled by tuning the solution pH. The present study implied that the gold nanomaterials can be used as the potential carrier for CPT delivery.

A simple and convenient method to synthesize N-[(2-hydroxyl)-propyl-3-trimethylammonium] chitosan chloride in an ionic liquid.

PubMed

Yang, Xiaodeng; Zhang, Chuanguang; Qiao, Congde; Mu, Xueli; Li, Tianduo; Xu, Jinku; Shi, Lei; Zhang, Dongju

2015-10-05

N-[(2-Hydroxyl)-propyl-3-trimethyl ammonium] chitosan chloride (HTCC) was synthesized through nucleophilic substitution of 2,3-epoxypropyltrimethyl ammonium chloride (EPTAC) onto chitosan using ionic liquid of 1-allyl-3-methylimidazole chloride (AmimCl) as a homogeneous and green reaction media. The chemical structure of HTCC was confirmed by FTIR, (1)H NMR and (13)C NMR. The FTIR peak intensity of amino group at 1595 cm(-1) decreased and that of [Formula: see text] at 1475 cm(-1) increased with the increase of reaction time, confirming the substitution of EPTAC on CS. The degree of substitutions (DS) were calculated from the integral area of (1)H NMR, and the optimum reaction condition was obtained, namely, reaction time of 8h, temperature of 80°C and [Formula: see text] of 3/1. The degree of crystallinity and thermal properties of HTCC were characterized by XRD, TG, DSC, and DMA methods. Data from XRD, TG, DSC and DMA show that the degree of crystallinity, thermal stability, as well as glass transition temperature of HTCC decreased with the increase of DS. The reaction mechanism of chitosan with EPTAC in AmimCl was elucidated by performing density functional theory (DFT) calculations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physical and antimicrobial properties of starch-carboxy methyl cellulose film containing rosemary essential oils encapsulated in chitosan nanogel.

PubMed

Mohsenabadi, Nafiseh; Rajaei, Ahmad; Tabatabaei, Meisam; Mohsenifar, Afshin

2018-06-01

This study was set to prepare a new active film by using a biodegradable bio-based source, i.e., corn starch. To achieve that, benzoic acid (BA) and chitosan (CS) were covalently bound and CS-BA nanogel was then obtained using self-assembly method. Subsequently, rosemary essential oil (REO) was encapsulated in CS-BA nanogel. Finally, REO in both free and encapsulated forms were incorporated in starch-carboxy methyl cellulose (CMC) films and their physical, mechanical and antimicrobial properties were studied. The films incorporating CS-BA nanogel had a higher water vapor permeability compared with the films containing REO. Moreover, film containing 0.2% CS-BA nanogel had the highest transparency and tensile strength. The REO and nanogel alone had inhibitory effects against Staphylococcus aureus (S. aureus) and by encapsulation, the inhibitory effect of REO was increased. By encapsulating REO in nanogel, both immediately (REO) and gradual (Nanogel) antimicrobial effect against S. aureus in the starch-CMC suspensions were obtained. Copyright © 2018 Elsevier B.V. All rights reserved.

Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis.

PubMed

Cheng, Nai-Chen; Lin, Wei-Jhih; Ling, Thai-Yen; Young, Tai-Horng

2017-03-15

Adipose-derived stem cells (ASCs) secrete several angiogenic growth factors and can be applied to treat ischemic tissue. However, transplantation of dissociated ASCs has frequently resulted in rapid cell death. Therefore, we aimed to develop a thermosensitive chitosan/gelatin hydrogel that is capable of ASC sustained release for therapeutic angiogenesis. By blending gelatin in the chitosan thermosensitive hydrogel, we significantly enhanced the viability of the encapsulated ASCs. During in vitro culturing, the gradual degradation of gelatin led to sustained release of ASCs from the chitosan/gelatin hydrogel. In vitro wound healing assays revealed significantly faster cell migration by co-culturing fibroblasts with ASCs encapsulated in chitosan/gelatin hydrogel compared to pure chitosan hydrogels. Additionally, significantly higher concentrations of vascular endothelial growth factor were found in the supernatant of ASC-encapsulated chitosan/gelatin hydrogels. Co-culturing SVEC4-10 endothelial cells with ASC-encapsulated chitosan/gelatin hydrogels resulted in significantly more tube-like structures, indicating the hydrogel's potential in promoting angiogenesis. Chick embryo chorioallantoic membrane assay and mice wound healing model showed significantly higher capillary density after applying ASC-encapsulated chitosan/gelatin hydrogel. Relative to ASC alone or ASC-encapsulated chitosan hydrogel, more ASCs were also found in the wound tissue on post-wounding day 5 after applying ASC-encapsulated chitosan/gelatin hydrogel. Therefore, chitosan/gelatin thermosensitive hydrogels not only maintain ASC survival, they also enable sustained release of ASCs for therapeutic angiogenesis applications, thereby exhibiting great clinical potential in treating ischemic diseases. Adipose-derived stem cells (ASCs) exhibit great potential to treat ischemic diseases. However, poor delivery methods lead to low cellular survival or dispersal of cells from target sites. In this study, we

Chitosan-thioglycolic acid as a versatile antimicrobial agent.

PubMed

Geisberger, Georg; Gyenge, Emina Besic; Hinger, Doris; Käch, Andres; Maake, Caroline; Patzke, Greta R

2013-04-08

As functionalized chitosans hold great potential for the development of effective and broad-spectrum antibiotics, representative chitosan derivatives were tested for antimicrobial activity in neutral media: trimethyl chitosan (TMC), carboxy-methyl chitosan (CMC), and chitosan-thioglycolic acid (TGA; medium molecular weight: MMW-TGA; low molecular weight: LMW-TGA). Colony forming assays indicated that LMW-TGA displayed superior antimicrobial activity over the other derivatives tested: a 30 min incubation killed 100% Streptococcus sobrinus (Gram-positive bacteria) and reduced colony counts by 99.99% in Neisseria subflava (Gram-negative bacteria) and 99.97% in Candida albicans (fungi). To elucidate LMW-TGA effects at the cellular level, microscopic studies were performed. Use of fluorescein isothiocyanate (FITC)-labeled chitosan derivates in confocal microscopy showed that LMW-TGA attaches to microbial cell walls, while transmission electron microscopy indicated that this derivative severely affects cell wall integrity and intracellular ultrastructure in all species tested. We therefore propose LMW-TGA as a promising and effective broad-band antimicrobial compound.

Cinnamomum casia Extract Encapsulated Nanochitosan as Antihypercholesterol

NASA Astrophysics Data System (ADS)

Ngadiwiyana; Purbowatiningrum; Fachriyah, Enny; Ismiyarto

2017-02-01

Atherosclerosis vascular disease with clinical manifestations such as cardiovascular disease and stroke are the leading cause of death in Indonesia. One solution to these problems is a natural antihypercholesterol medicine by utilizing Cinnamomum casia extract. However, the use of natural extracts to lower blood cholesterol levels do not provide optimal results because it is possible that the active components of extract have been degraded/damaged during the absorption process. So that, we need to do the research to get a combination of chitosan nanoparticles-Cinnamomum casia. extract as a compound which has an antihypercholesterol activity through the in vitro study. Modification of natural extracts encapsulated nanochitosan be a freshness in this study, which were conducted using the method of inclusion. The combination of both has the dual function of protecting the natural extracts from degradation and deliver the natural extracts to the target site. Analysis of nanochitosan using the Particle Size Analyzer (PSA) shows the particle size of synthesis product that is equal to 64.9 nm. Encapsulation efficiency of Cinnamomum casia extract-Chitosan Nanoparticles known through UV-VIS spectrophotometry test and obtained the efficiency encapsulation percentage of 84.93%. Zeta Potential at 193,3 mv that chitosan appropriate for a delivery drug. Antihypercholesterol activity tested in vitro assay that showed the extract-nanoparticle chitosan in concentration 150 ppm gave the highest cholesterol decreasing level in the amount of 49.66% w/v. So it can be concluded that Cinnamomum casia extract can be encapsulated in nanoparticles of chitosan and proved that it has a cholesterol-lowering effect through the in vitro study.

Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin Delivery.

PubMed

Maciel, Vinicius B V; Yoshida, Cristiana M P; Pereira, Susana M S S; Goycoolea, Francisco M; Franco, Telma T

2017-10-12

A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was developed to encapsulate the hormone insulin. The aim of this work was to obtain small particles for oral insulin delivery without chemical crosslinkers based on natural and biodegradable polysaccharides. The nano- and microparticles were developed using chitosans (with different degrees of acetylation: 15.0% and 28.8%) and pectin solutions at various charge ratios (n⁺/n - given by the chitosan/pectin mass ratio) and total charge. Nano- and microparticles were characterized regarding particle size, zeta potential, production yield, encapsulation efficiency, stability in different media, transmission electron microscopy and cytotoxicity assays using Caco-2 cells. The insulin release was evaluated in vitro in simulated gastric and intestinal media. Small-sized particles (~240-~1900 nm) with a maximum production yield of ~34.0% were obtained. The highest encapsulation efficiency (~62.0%) of the system was observed at a charge ratio (n⁺/n - ) 5.00. The system was stable in various media, particularly in simulated gastric fluid (pH 1.2). Transmission electron microscopy (TEM) analysis showed spherical shape particles when insulin was added to the system. In simulated intestinal fluid (pH 6.8), controlled insulin release occurred over 2 h. In vitro tests indicated that the proposed system presents potential as a drug delivery for oral administration of bioactive peptides.

Development of carboxymethyl cellulose-chitosan hybrid micro- and macroparticles for encapsulation of probiotic bacteria.

PubMed

Singh, P; Medronho, B; Alves, L; da Silva, G J; Miguel, M G; Lindman, B

2017-11-01

Novel carboxymethyl cellulose-chitosan (CMC-Cht) hybrid micro- and macroparticles were successfully prepared in aqueous media either by drop-wise addition or via nozzle-spray methods. The systems were either physically or chemically crosslinked using genipin as the reticulation agent. The macroparticles (ca. 2mm) formed are found to be essentially of the core-shell type, while the microparticles (ca. 5μm) are apparently homogeneous. The crosslinked particles are robust, thermally resistant and less sensitive to pH changes. On the other hand, the physical systems are pH sensitive presenting a remarkable swelling at pH 7.4, while little swelling is observed at pH 2.4. Furthermore, model probiotic bacteria (Lactobacillus rhamnosus GG) was for the first time successfully encapsulated in the CMC-Cht based particles with acceptable viability count. Overall, the systems developed are highly promising for probiotic encapsulation and potential delivery in the intestinal tract with the purpose of modulating gut microbiota and improving human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and characterization of PEG-conjugated quaternized chitosan and its application as a gene vector.

PubMed

Zhang, Xi; Yao, Juan; Zhang, Lihong; Fang, Jianguo; Bian, Fengling

2014-03-15

Poly(ethylene glycol)-conjugated N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride (PHTAC) derivatives were prepared by incorporating PEG molecules onto quaternized chitosan backbone. The copolymers were characterized by FTIR, (1)H NMR and XRD. Agarose gel retardation assay indicated that PHTAC had good plasmid DNA (pDNA) binding capability and the particle sizes of PHTAC/pDNA complexes determined by DLS were about 200 nm. Cytotoxicity assays in HeLa and 293T cells showed that PHTAC had low cytotoxicity. In vitro luciferase assay showed that PHTAC with PEGylation degree of 9% (PHTAC-1) had good transfection efficiency about 5.3-fold higher than quaternized chitosan, which was comparable with PEI (25 kDa). These results suggest that PHTAC-1 is a promising candidate as an efficient nonviral gene vector. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis of an immunoconjugate of camptothecin.

PubMed

Walker, Michael A; Dubowchik, Gene M; Hofstead, Sandra J; Trail, Pamela A; Firestone, Raymond A

2002-01-21

The first immunoconjugate of camptothecin has been synthesized wherein the drug is attached to the tumor-recognizing antibody BR96 via a Cathepsin B cleavable linker. Endocytosis of the immunoconjugate upon binding to the tumor cell followed by enzymatic cleavage of the linker inside the endosome ensures tumor-specific release of the drug. In this way, it is hoped that the dose-limiting side effects associated with camptothecin can be eliminated while the antitumor activity is preserved.

Improved sugar co-utilisation by encapsulation of a recombinant Saccharomyces cerevisiae strain in alginate-chitosan capsules

PubMed Central

2014-01-01

Background Two major hurdles for successful production of second-generation bioethanol are the presence of inhibitory compounds in lignocellulosic media, and the fact that Saccharomyces cerevisiae cannot naturally utilise pentoses. There are recombinant yeast strains that address both of these issues, but co-utilisation of glucose and xylose is still an issue that needs to be resolved. A non-recombinant way to increase yeast tolerance to hydrolysates is by encapsulation of the yeast. This can be explained by concentration gradients occuring in the cell pellet inside the capsule. In the current study, we hypothesised that encapsulation might also lead to improved simultaneous utilisation of hexoses and pentoses because of such sugar concentration gradients. Results In silico simulations of encapsulated yeast showed that the presence of concentration gradients of inhibitors can explain the improved inhibitor tolerance of encapsulated yeast. Simulations also showed pronounced concentration gradients of sugars, which resulted in simultaneous xylose and glucose consumption and a steady state xylose consumption rate up to 220-fold higher than that found in suspension culture. To validate the results experimentally, a xylose-utilising S. cerevisiae strain, CEN.PK XXX, was constructed and encapsulated in semi-permeable alginate-chitosan liquid core gel capsules. In defined media, encapsulation not only increased the tolerance of the yeast to inhibitors, but also promoted simultaneous utilisation of glucose and xylose. Encapsulation of the yeast resulted in consumption of at least 50% more xylose compared with suspended cells over 96-hour fermentations in medium containing both sugars. The higher consumption of xylose led to final ethanol titres that were approximately 15% higher. In an inhibitory dilute acid spruce hydrolysate, freely suspended yeast cells consumed the sugars in a sequential manner after a long lag phase, whereas no lag phase was observed for the

Amphiphilic chitosan derivatives as carrier agents for rotenone

NASA Astrophysics Data System (ADS)

Kamari, Azlan; Aljafree, Nurul Farhana Ahmad

2017-08-01

In the present study, the feasibility of amphiphilic chitosan derivatives, namely oleoyl carboxymethyl chitosan (OCMCs), N,N-dimethylhexadecyl carboxymethyl chitosan (DCMCs) and deoxycholic acid carboxymethyl chitosan (DACMCs) as carrier agents for rotenone in water-insoluble pesticide formulations was investigated. Fourier Transform Infrared (FTIR) Spectrometer, CHN-O Elemental Analyser (CHN-O) and Transmission Electron Microscope (TEM) were used to characterise amphiphilic chitosan derivatives. The critical micelle concentration (CMC) of amphiphilic chitosan derivatives was determined using a Fluorescence Spectrometer. A High Performance Liquid Chromatography (HPLC) was used to determine the ability of OCMCs, DCMCs and DACMCs to load and release rotenone in an in vitro system. Based on TEM analysis, results have shown that amphiphilic chitosan derivatives formed self-assembly and exhibited spherical shape. The CMC values determined for OCMCs, DCMCs and DACMCs were 0.093, 0.098 and 0.468 mg/mL, respectively. The encapsulation efficiency (EE) values for the materials were more than 97.0%, meanwhile the loading capacity (LC) values were greater than 0.90%. OCMCs, DCMCs and DACMCs micelles exhibited an excellent ability to control the release of rotenone, of which 90.0% of rotenone was released within 40 to 52 h. In conclusion, OCMCs, DCMCs and DACMCs possess several key features to act as effective carrier agents for rotenone. Overall, amphiphilic chitosan derivatives produced in this study were successfully increased the solubility of rotenone by 49.0 times higher than free rotenone.

Preparation of inorganic/organic polymer hybrid microcapsules with high encapsulation efficiency by an electrospray technique.

PubMed

Yunoki, Ayumi; Tsuchiya, Eiko; Fukui, Yu; Fujii, Akihiro; Maruyama, Tatsuo

2014-08-13

Microcapsules composed of calcium phosphate and chitosan were prepared in a single step by electrospraying. An aqueous solution containing calcium chloride and chitosan was electrosprayed into a phosphate solution to form a calcium phosphate shell on the sprayed droplets. The resulting microcapsules were 350 μm in average diameter. Investigation using fluorescently labeled chitosan and XRD measurements revealed that the shells of the microcapsules were composed of calcium phosphate (mainly hydroxyapatite) and chitosan. Instead of chitosan, poly(diallyldimethylammonium chloride) and polyethylene glycol were also available for microcapsule production by electrospraying. Variations in the electrospraying conditions resulted in a variety of microcapsule shapes. Various types of substrates were successfully encapsulated in microcapsules with a high encapsulation efficiency (more than 80%). Finally, we succeeded in the encapsulation of living yeast cells in microcapsules, and observed their growth within these microcapsules.

Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

PubMed

Halevas, Eleftherios; Nday, Christiane M; Chatzigeorgiou, Evanthia; Varsamis, Vasileios; Eleftheriadou, Despoina; Jackson, Graham E; Litsardakis, Georgios; Lazari, Diamanto; Ypsilantis, Konstantinos; Salifoglou, Athanasios

2017-11-01

The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Encapsulated whey-native yeast Kluyveromyces marxianus as a feed additive for animal production.

PubMed

Díaz-Vergara, Ladislao; Pereyra, Carina Maricel; Montenegro, Mariana; Pena, Gabriela Alejandra; Aminahuel, Carla Ayelen; Cavaglieri, Lilia R

2017-05-01

Whey is the main byproduct of the cheese industry. While the composition is variable, it retains up to 55% of milk nutrients. The beneficial features of whey indicates a promising source of new potentially probiotic strains for the development of food additives destined for animal production. The aim of this study was to identify Kluyveromyces spp. isolated from whey, to study some probiotic properties and to select the best strain to be encapsulated using derivatised chitosan. Kluyveromyces marxianus strains (VM003, VM004 and VM005) were isolated from whey and identified by phenotypic and molecular techniques. These three yeast strains were able to survive under gastrointestinal conditions. Moreover, they exhibited weak auto-aggregation and co-aggregation with pathogenic bacteria (Salmonella sp., Serratia sp., Escherichia coli and Salmonella typhimurium). In general the K. marxianus strains had a strong antimicrobial activity against pathogenic bacteria. The potential probiotic K. marxianus VM004 strain was selected for derivatised-chitosan encapsulation. Material treated with native chitosan exhibited a strong antimicrobial activity of K. marxianus, showing a total growth inhibition at 10 min exposure. However, derivatised-chitosan encapsulation showed a reduced antimicrobial activity. This is the first study to show some probiotic properties of whey-native K. marxianus, in vitro. An encapsulation strategy was applied using derivatised chitosan.

Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin.

PubMed

Ridolfi, Daniela M; Marcato, Priscyla D; Justo, Giselle Z; Cordi, Lívia; Machado, Daisy; Durán, Nelson

2012-05-01

Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7±1.4 nm and -31.9±2.0 mV for SLN-TRE, and 284.8±15.0 nm and 55.9±3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesize and Characterization of Hydroxypropyl-N-octanealkyl Chitosan Ramification

NASA Astrophysics Data System (ADS)

Tan, Fu-neng

2018-03-01

A new type of amphiphilic ramification, hydroxypropyl-N-octanealkyl chitosan was prepared from chitosan via hydrophilic group and hydrophobic group were introduced. We could protect the amino group of chitosan via the reaction of chitosan and benzaldehyde could get Schiff base structure. Structures of the products were characterized with FT-IR, elemental analysis, themogrammetry (TG) analysis and X-ray diffraction. The degree of substitution of hydrophobic group was studied by elemental analysis. The result showed this chitosan ramification was soluble, biocompatible, biodegradable and nontoxic.

Chitosan nanoparticle based delivery systems for sustainable agriculture.

PubMed

Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

2015-01-01

Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of stiffness of chitosan-hyaluronic acid dialdehyde hydrogels on the viability and growth of encapsulated chondrocytes.

PubMed

V Thomas, Lynda; Vg, Rahul; D Nair, Prabha

2017-11-01

Substrate elasticity or stiffness can influence the phenotypic and functional characteristics of chondrocytes. This work aimed to study the effect of varying stiffness compositions of a two-component injectable hydrogel based on chitosan (CH) and oxidized hyaluronic acid (HDA) on the growth and functionality of encapsulated chondrocytes. Three different ratios of the gel were prepared (10:1,10:3 and 10:5 CH-HDA) and characterized. The stiffness of the gels was evaluated from the force displacement curves using force spectroscopy AFM analysis. Rabbit articular chondrocytes were harvested and the cells from Passage 2 to 4 were used for the encapsulation study. The viability and ECM production of encapsulated chondrocytes were assessed at 7day, 14day and 28day post culture. The results of the study show that as the ratio of hyaluronic acid dialdehyde component was increased, the stiffness of the gels increased from 130.78±19.83kPa to 181.47±19.77kPa which was also evidenced from the decrease in gelling time. Although there was an increase in the percentage of viable encapsulated cells which also maintained the spherical phenotype in the less stiff gels, decreased expression of ECM markers- Collagen type II and Glycosaminoglycans was observed compared to the stiffer gels. These findings indicate that gel stiffness strongly impacts the chondrocyte microenvironment both in maintenance of phenotypic integrity and ECM production. Copyright © 2017. Published by Elsevier B.V.

Thermogelling chitosan and collagen composite hydrogels initiated with β-glycerophosphate for bone tissue engineering

PubMed Central

Wang, Limin; Stegemann, Jan P.

2010-01-01

Chitosan and collagen type I are naturally-derived materials used as cell carriers because of their ability to mimic the extracellular environment and direct cell function. In this study beta-glycerophosphate (beta-GP), an osteogenic medium supplement and a weak base, was used to simultaneously initiate gelation of pure chitosan, pure collagen, and chitosan-collagen composite materials at physiological pH and temperature. Adult human bone marrow-derived stem cells (hBMSC) encapsulated in such hydrogels at chitosan/collagen ratios of 100/0, 65/35, 25/75, and 0/100 wt% exhibited high viability at day 1 after encapsulation, but DNA content dropped by about half over 12 days in pure chitosan materials while it increased two-fold in materials containing collagen. Collagen-containing materials compacted more strongly and were significantly stiffer than pure chitosan gels. In monolayer culture, exposure of hBMSC to beta-GP resulted in decreased cell metabolic activity that varied with concentration and exposure time, but washing effectively removed excess beta-GP from hydrogels. The presence of chitosan in materials resulted in higher expression of osterix and bone sialoprotein genes in medium with and without osteogenic supplements. Chitosan also increased alkaline phosphatase activity and calcium deposition in osteogenic medium. Chitosan-collagen composite materials have potential as matrices for cell encapsulation and delivery, or as in situ gel-forming materials for tissue repair. PMID:20170955

Preparation and anticoagulant activity of N-succinyl chitosan sulfates.

PubMed

Wang, Tan; Zhou, Yue; Xie, Weiguo; Chen, Lingyun; Zheng, Hua; Fan, Lihong

2012-12-01

In order to develop a promising substitute for heparin, N-succinyl chitosan (NSC) was chemically modified by sulfating agent N(SO(3)Na)(3), which were synthesized with sodium bisulfite and sodium nitrite in aqueous solution. The N-succinyl chitosan sulfates (NSCS) products were characterized by infrared spectroscopy (FT-IR) and (13)C NMR. The degree of substitution (DS) of NSCS depended on the ratio of sulfating agent to N-succinyl chitosan, reaction temperature, reaction time and pH of sulfation agent. N-succinyl chitosan sulfates with DS of 1.97 were obtained under optimal conditions. The in vitro coagulation assay of NSCS was determined by activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) assays. The results showed that NSCS obviously prolonged APTT. The anticoagulant activity strongly depended on DS, molecular weight (M(w)) and concentration of NSCS. The anticoagulant activity of NSCS promoted with the increase of DS and concentration, and NSCS exhibited the best anticoagulant activity with the M(w) of 1.37×10(4). Copyright © 2012. Published by Elsevier B.V.

Immunoadjuvant potential of cross-linked dextran microspheres mixed with chitosan nanospheres encapsulated with tetanus toxoid.

PubMed

Pirouzmand, Haniyeh; Khameneh, Bahman; Tafaghodi, Mohsen

2017-12-01

Nasal mucosa is a desirable route for mucosal vaccine delivery. Mucosal co-administration of chitosan nanoparticles with absorption enhancers such as cross-linked dextran microspheres (CDM, Sephadex ® ) is a promising antigen delivery system. In the current study, the chitosan nanospheres loaded with tetanus toxoid (CHT:TT NPs) was prepared and characterized. The immune responses against tetanus toxoid after nasal administration of CHT:TT NPs alone or mixed with CDM were also determined. Chitosan nanospheres were prepared by ionic gelation method. Particle size, releasing profile and antigen stability were evaluated by dynamic light scattering, diffusion chamber and SDS-PAGE methods, respectively. Rabbits were nasally immunized with different formulations loaded with 40 Lf TT. After three times immunizations with 2 weeks intervals, sera IgG titres and nasal lavage sIgA titres were determined. Mean size of CHT NPs and CHT:TT NPs were 205 ± 42 nm and 432 ± 85 nm, respectively. The release profile showed that 42.4 ± 10.5% of TT was released after 30 min and reached to a steady state after 1.5 h. Stability of encapsulated TT in nanospheres was confirmed by SDS-PAGE. The antibody titres showed that CHT:TT NPs-induced antibody titres were higher than TT solution. CHT NPs mixed with CDM induced the systemic IgG and nasal lavage sIgA titres higher than intranasal administration of TT solution (p < 0.001). As the results indicated, these CHT:TT NPs when co-administered with CDM were able to induce more immune responses and have the potential to be used in mucosal immunization.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer's disease.

PubMed

Meng, Qingqing; Wang, Aiping; Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang

2018-01-01

Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer's disease (AD). To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. HupA Lf-TMC NPs were prepared using the emulsion-solvent evaporation method and optimized using the Box-Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography-tandem mass spectrometry. Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus

Quaternary ammonium salt N-(dodecyloxycarboxymethyl)-N,N,N-trimethyl ammonium chloride induced alterations in Saccharomyces cerevisiae physiology.

PubMed

Oblak, Ewa; Piecuch, Agata; Maciaszczyk-Dziubinska, Ewa; Wawrzycka, Donata

2016-12-01

We investigated the influence of the quaternary ammonium salt (QAS) called IM (N-(dodecyloxycarboxymethyl)- N,N,N-trimethyl ammonium chloride) on yeast cells of the parental strain and the IM-resistant mutant (EO25 IMR) growth. The phenotype of this mutant was pleiotropic. The IMR mutant exhibited resistance to ethanol, osmotic shock and oxidative stress, as well as increased sensitivity to UV. Moreover, it was noted that mutant EO25 appears to have an increased resistance to clotrimazole, ketoconazole, fluconazole, nystatin and cycloheximide. It also tolerated growth in the presence of crystal violet, DTT and metals (selenium, tin, arsenic). It was shown that the presence of IM decreased ergosterol level in mutant plasma membrane and increased its unsaturation. These results indicate changes in the cell lipid composition. Western blot analysis showed the induction of Pma1 level by IM. RT-PCR revealed an increased PMA1 expression after IM treatment.

Formulation of chitosan-TPP-pDNA nanocapsules for gene therapy applications

NASA Astrophysics Data System (ADS)

Gaspar, V. M.; Sousa, F.; Queiroz, J. A.; Correia, I. J.

2011-01-01

The encapsulation of DNA inside nanoparticles meant for gene delivery applications is a challenging process where several parameters need to be modulated in order to design nanocapsules with specific tailored characteristics. The purpose of this study was to investigate and improve the formulation parameters of plasmid DNA (pDNA) loaded in chitosan nanocapsules using tripolyphosphate (TPP) as polyanionic crosslinker. Nanocapsule morphology and encapsulation efficiency were analyzed as a function of chitosan degree of deacetylation and chitosan-TPP ratio. The manipulation of these parameters influenced not only the particle size but also the encapsulation and release of pDNA. Consequently the transfection efficiency of the nanoparticulated systems was also enhanced with the optimization of the particle characteristics. Overall, the differently formulated nanoparticulated systems possess singular properties that can be employed according to the desired gene delivery application.

Cost-effective alternative to nano-encapsulation: Amorphous curcumin-chitosan nanoparticle complex exhibiting high payload and supersaturation generation.

PubMed

Nguyen, Minh Hiep; Yu, Hong; Kiew, Tie Yi; Hadinoto, Kunn

2015-10-01

While the wide-ranging therapeutic activities of curcumin have been well established, its successful delivery to realize its true therapeutic potentials faces a major challenge due to its low oral bioavailability. Even though nano-encapsulation has been widely demonstrated to be effective in enhancing the bioavailability of curcumin, it is not without drawbacks (i.e. low payload and costly preparation). Herein we present a cost-effective bioavailability enhancement strategy of curcumin in the form of amorphous curcumin-chitosan nanoparticle complex (or curcumin nanoplex in short) exhibiting a high payload (>80%). The curcumin nanoplex was prepared by a simple yet highly efficient drug-polysaccharide complexation method that required only mixing of the curcumin and chitosan solutions under ambient condition. The effects of (1) pH and (2) charge ratio of chitosan to curcumin on the (i) physical characteristics of the nanoplex (i.e. size, colloidal stability and payload), (ii) complexation efficiency, and (iii) production yield were investigated from which the optimal preparation condition was determined. The nanoplex formation was found to favor low acidic pH and charge ratio below unity. At the optimal condition (i.e. pH 4.4. and charge ratio=0.8), stable curcumin nanoplex (≈260nm) was prepared at >90% complexation efficiency and ≈50% production yield. The amorphous state stability, colloidal stability, and in vitro non-cytotoxicity of the nanoplex were successfully established. The curcumin nanoplex produced prolonged supersaturation (3h) in the presence of hydroxypropyl methylcellulose (HPMC) at five times of the saturation solubility of curcumin. In addition, curcumin released from the nanoplex exhibited improved chemical stability owed to the presence of chitosan. Both results (i.e. high supersaturation and improved chemical stability) bode well for the ability of the curcumin nanoplex to enhance the bioavailability of curcumin clinically. Copyright © 2015

Thermogelling chitosan and collagen composite hydrogels initiated with beta-glycerophosphate for bone tissue engineering.

PubMed

Wang, Limin; Stegemann, Jan P

2010-05-01

Chitosan and collagen type I are naturally derived materials used as cell carriers because of their ability to mimic the extracellular environment and direct cell function. In this study beta-glycerophosphate (beta-GP), an osteogenic medium supplement and a weak base, was used to simultaneously initiate gelation of pure chitosan, pure collagen, and chitosan-collagen composite materials at physiological pH and temperature. Adult human bone marrow-derived stem cells (hBMSC) encapsulated in such hydrogels at chitosan/collagen ratios of 100/0, 65/35, 25/75, and 0/100 wt% exhibited high viability at day 1 after encapsulation, but DNA content dropped by about half over 12 days in pure chitosan materials while it increased twofold in materials containing collagen. Collagen-containing materials compacted more strongly and were significantly stiffer than pure chitosan gels. In monolayer culture, exposure of hBMSC to beta-GP resulted in decreased cell metabolic activity that varied with concentration and exposure time, but washing effectively removed excess beta-GP from hydrogels. The presence of chitosan in materials resulted in higher expression of osterix and bone sialoprotein genes in medium with and without osteogenic supplements. Chitosan also increased alkaline phosphatase activity and calcium deposition in osteogenic medium. Chitosan-collagen composite materials have potential as matrices for cell encapsulation and delivery, or as in situ gel-forming materials for tissue repair. Copyright 2010 Elsevier Ltd. All rights reserved.

Camptothecin prodrug nanomicelle based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake.

PubMed

Gao, Ya; Xiao, Yi; Liu, Shiyuan; Yu, Jiahui

2018-02-01

A novel pH-sensitive polymeric prodrug of camptothecin (CPT) by polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu (CPT)-NCA) on boronate ester-linked poly (ethyleneglycol) (PEG) directly via the amine-initiated ring open polymerization (ROP) has been developed. The resulting amphiphilic prodrug (mPEG-BC-PGluCPT) could self-assemble into nanoparticles and encapsulate doxorubicin (Dox) simultaneously in aqueous solution for dual-drug delivery. The formation of polymeric prodrug micelles (mPEG-BC@PGluCPT) was confirmed by the measurements of critical aggregation concentration (CAC), particle size, and morphology observations. The mPEG-BC@PGluCPT micelles were colloidally stable in solutions for two weeks. Polymeric prodrug micelles mPEG-BC@PGluCPT and Dox-loaded micelles mPEG-BC@PGluCPT⋅Dox showed sustained drug release profiles over 48 h. As expected, drug release was accelerated by the decreasement of pH value from 7.4 to 6.0, which demonstrated pH-dependent manner of drug release. Additionally, it was found that cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles on HepG2 cells was higher than that on HL-7702 cells, especially in culture medium at pH 6.0. The enhanced cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles under acidic condition on HepG2 cells resulted in the higher cytotoxicity of mPEG-BC@PGluCPT⋅Dox micelles at acidic pH than that at pH 7.4.

Curcumin drug delivery by vanillin-chitosan coated with calcium ferrite hybrid nanoparticles as carrier.

PubMed

Kamaraj, Sriram; Palanisamy, Uma Maheswari; Kadhar Mohamed, Meera Sheriffa Begum; Gangasalam, Arthanareeswaran; Maria, Gover Antoniraj; Kandasamy, Ruckmani

2018-04-30

The aim of the present investigation is the development, optimization and characterization of curcumin-loaded hybrid nanoparticles of vanillin-chitosan coated with super paramagnetic calcium ferrite. The functionally modified vanillin-chitosan was prepared by the Schiff base reaction to enhance the hydrophobic drug encapsulation efficiency. Calcium ferrite (CFNP) nano particles were added to the vanillin modified chitosan to improve the biocompatibility. The vanillin-chitosan-CFNP, hybrid nanoparticle carrier was obtained by ionic gelation method. Characterizations of the hybrid materials were performed by XRD, FTIR, 1 H NMR, TGA, AFM and SEM techniques to ensure the modifications on the chitosan material. Taguchi method was applied to optimize the drug (curcumin) encapsulation efficiency by varying the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP (sodium tripolyphospate) to chitosan-vanillin ratios. The maximum encapsulation efficiency was obtained as 98.3% under the conditions of 0.1, 0.75 and 1.0 for the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP to chitosan-vanillin ratios, respectively. The curcumin release was performed at various pH, initial drug loading concentrations and magnetic fields. The drug release mechanism was predicted by fitting the experimental kinetic data with various drug release models. The drug release profiles showed the best fit with Higuchi model under the most of conditions. The drug release mechanism followed both non-Fickian diffusion and case II transport mechanism for chitosan, however the non-Fickian diffusion mechanism was followed for the vanillin modified chitosan. The biocompatibility of the hybrid material was tested using L929 fibroblast cells. The cytotoxicity test was performed against MCF-7 breast cancer cell line to check the anticancer property of the hybrid nano carrier with the curcumin drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2006-11-15

Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl beta cyclodextrin-insulin (HPbetaCD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HPbetaCD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HPbetaCD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immunosorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

Effects of pore forming agents on chitosan-graft-poly(N-vinylpyrrolidone) hydrogel properties for use as a matrix for floating drug delivery

NASA Astrophysics Data System (ADS)

Budianto, E.; Al-Shidqi, M. F.; Cahyana, A. H.

2017-07-01

Eradicating H. pylori-based infection by using conventional oral dosage form of amoxicillin trihydrate finds difficulties to overcome rapid gastric retention time. Encapsulating amoxicillin trihydrate in floating drug delivery system may solve the problem. In this research, the floating drug delivery system of amoxicillin trihydrate encapsulated in floating chitosan-graft-poly(N-vinyl pyrrolidone) hydrogels containing CaCO3 and NaHCO3 as pore forming agents has been successfully prepared. Pore forming agents used was varied with the ratio of 10 to 25% pore forming agents to total mass of the used materials. The hydrogel were characterizedusing FTIR spectrophotometer and stereo microscope. As pore forming agents compositions increased, the porosity (%) and floating properties increased but followed by decrease in drug entrapment efficiency. Most of the floating hydrogels possessed floating ability longer than 180 min and the highest porosity was found in hydrogel containing 25% NaHCO3. Hydrogel containing CaCO3 showed sustained drug release profile than hydrogel containing NaHCO3. However, the optimum formulation was achieved at composition of 10% NaHCO3 with 57% of drug entrapped within the hydrogel and 43% drug released. The results of these studies show that NaHCO3 is an effective pore forming agents for chitosan-graft-poly(N-vinyl pyrrolidone) hydrogel preparation as compare to CaCO3.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

PubMed Central

Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei

2018-01-01

Background Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD). Purpose To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods HupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry. Results Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse

Chitosan Enriched Three-Dimensional Matrix Reduces Inflammatory and Catabolic Mediators Production by Human Chondrocytes

PubMed Central

Oprenyeszk, Frederic; Sanchez, Christelle; Dubuc, Jean-Emile; Maquet, Véronique; Henrist, Catherine; Compère, Philippe; Henrotin, Yves

2015-01-01

This in vitro study investigated the metabolism of human osteoarthritic (OA) chondrocytes encapsulated in a spherical matrix enriched of chitosan. Human OA chondrocytes were encapsulated and cultured for 28 days either in chitosan-alginate beads or in alginate beads. The beads were formed by slowly passing dropwise either the chitosan 0.6%–alginate 1.2% or the alginate 1.2% solution through a syringe into a 102 mM CaCl2 solution. Beads were analyzed histologically after 28 days. Interleukin (IL)-6 and -8, prostaglandin (PG) E2, matrix metalloproteinases (MMPs), hyaluronan and aggrecan were quantified directly in the culture supernatant by specific ELISA and nitric oxide (NO) by using a colorimetric method based on the Griess reaction. Hematoxylin and eosin staining showed that chitosan was homogeneously distributed through the matrix and was in direct contact with chondrocytes. The production of IL-6, IL-8 and MMP-3 by chondrocytes significantly decreased in chitosan-alginate beads compared to alginate beads. PGE2 and NO decreased also significantly but only during the first three days of culture. Hyaluronan and aggrecan production tended to increase in chitosan-alginate beads after 28 days of culture. Chitosan-alginate beads reduced the production of inflammatory and catabolic mediators by OA chondrocytes and tended to stimulate the synthesis of cartilage matrix components. These particular effects indicate that chitosan-alginate beads are an interesting scaffold for chondrocytes encapsulation before transplantation to repair cartilage defects. PMID:26020773

Design, characterisation and application of alginate-based encapsulated pig liver esterase.

PubMed

Pauly, Jan; Gröger, Harald; Patel, Anant V

2018-06-05

Encapsulation of hydrolases in biopolymer-based hydrogels often suffers from low activities and encapsulation efficiencies along with high leaching and unsatisfactory recycling properties. Exemplified for the encapsulation of pig liver esterase the coating of alginate and chitosan beads have been studied by creating various biopolymer hydrogel beads. Enzyme activity and encapsulation efficiency were notably enhanced by chitosan coating of alginate beads while leaching remained nearly unchanged. This was caused by the enzymatic reaction acidifying the matrix, which increased enzyme retention through enhanced electrostatic enzyme-alginate interaction but decreased activity through enzyme deactivation. A practical and ready-to-use method for visualising pH in beads during reaction by co-encapsulation of a conventional pH indicator was also found. Our method proves that pH control inside the beads can only be realised by buffering. The resulting beads provided a specific activity of 0.267 μmol ∙ min -1 ∙ mg -1 , effectiveness factor 0.88, encapsulation efficiency of 88%, 5% leaching and good recycling properties. This work will contribute towards better understanding and application of encapsulated hydrolases for enzymatic syntheses. Copyright © 2018 Elsevier B.V. All rights reserved.

Formation of enriched black tea extract loaded chitosan nanoparticles via electrospraying

NASA Astrophysics Data System (ADS)

Hammond, Samuel James

Creating nanoparticles of beneficial nutraceuticals and pharmaceuticals has had a large surge of research due to the enhancement of absorption and bioavailability by decreasing their size. One of these ways is by electrohydrodynamic atomization, also known as electrospraying. In general, this novel process is done by forcing a liquid through a capillary nozzle and which is subjected to an electrical field. While there are different ways to create nanoparticles, the novel method of electrospraying can be beneficial over other types of nanoparticle formation. Reasons include high control over particle size and distribution by altering electrospray parameters (voltage, flow rate, distance, and time), higher encapsulation efficiency than other methods, and also it is a one step process without exposure to extreme conditions (Gomez-Estaca et. al. 2012, Jaworek and Sobcyzk 2008). The current study aimed to create a chitosan encapsulated theaflavin-2 enriched black tea extract (BTE) nanoparticles via electrospraying. The first step of this process was to create the smallest chitosan nanoparticles possible by altering the electrospray parameters and the chitosan-acetic acid solution parameters. The solution properties altered include chitosan molecular weight, acetic acid concentration, and chitosan concentration. Specifically, the electrospray parameters such as voltage, flow rate and distance from syringe to collector are the most important in determining particle size. After creating the smallest chitosan particles, the TF-2 enriched black tea extract was added to the chitosan-acetic acid solution to be electrosprayed. The particles were assessed with the following procedures: Atomic force microscopy (AFM) and scanning electron microscopy (SEM) for particle morphology and size, and loading efficiency with ultraviolet--visible spectrophotometer (UV-VIS). Chitosan-BTE nanoparticles were successfully created in a one step process. Diameter of the particles on average

Multilayer emulsions as a strategy for linseed oil and α-lipoic acid micro-encapsulation: study on preparation and in vitro characterization.

PubMed

Huang, Juan; Wang, Qiang; Li, Tong; Xia, Nan; Xia, Qiang

2018-07-01

Linseed oil and α-lipoic acid are bioactive ingredients, which play an important role in human nutrition and health. However, their application in functional foods is limited because of their instabilities and poor solubilities in hydrophilic matrices. Multilayer emulsions are particularly useful to protect encapsulated bioactive ingredients. The aim of this study was to fabricate multilayer emulsions by a high-pressure homogenization method to encapsulate linseed oil and α-lipoic acid simultaneously. Tween 20 and lecithin were used as surfactants to stabilize the oil droplets of primary emulsions. Multilayer emulsions were produced by using an electrostatic layer-by-layer deposition process of lecithin-chitosan membranes. Thermal treatment exhibited that chitosan encapsulation could improve the thermal stability of primary emulsions. During in vitro digestion, it was found that chitosan encapsulation had little effect on the lipolysis of linseed oil and bioaccessibility of α-lipoic acid. The oxidation stability of linseed oil in multilayer emulsions was improved effectively by chitosan encapsulation and α-lipoic acid. Chitosan encapsulation could inhibit the degradation of α-lipoic acid. A physical stability study indicated that multilayer emulsions had good centrifugal, dilution and storage stabilities. Multilayer emulsion is an effective delivery system to incorporate linseed oil and α-lipoic acid into functional foods and beverages. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin.

PubMed

Sadekar, S; Thiagarajan, G; Bartlett, K; Hubbard, D; Ray, A; McGill, L D; Ghandehari, H

2013-11-01

Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity. Poly(amido amine) or PAMAM dendrimers have shown promise as intestinal penetration enhancers, drug solubilizers and drug carriers for oral delivery in vitro and in situ. There have been very limited studies in vivo to evaluate PAMAM dendrimers for oral drug delivery. In this study, camptothecin (5 mg/kg) was formulated and co-delivered with cationic, amine-terminated PAMAM dendrimer generation 4.0 (G4.0) (100 and 300 mg/kg) and anionic, carboxylate-terminated PAMAM generation 3.5 (G3.5) (300 and 1000 mg/kg) in CD-1 mice. Camptothecin associated to a higher extent with G4.0 than G3.5 in the formulation, attributed to an electrostatic interaction on the surface of G4.0. Both PAMAM G4.0 and G3.5 increased camptothecin solubilization in simulated gastric fluid and caused a 2-3 fold increase in oral absorption of camptothecin when delivered at 2 h. PAMAM G4.0 and G3.5 did not increase mannitol transport suggesting that the oral absorption of camptothecin was not due to tight junction modulation. Histologic observations of the epithelial layer of small intestinal segments of the gastrointestinal tract (GIT) at 4 h post dosing supported no evidence of toxicity at the evaluated doses of PAMAM dendrimers. This study demonstrates that both cationic (G.4) and anionic (G3.5) PAMAM dendrimers were effective in enhancing the oral absorption of camptothecin. Results suggest that drug inclusion in PAMAM interior controlled solubilization in simulated gastric and intestinal fluids, and increased oral bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate.

PubMed

Gelfuso, Guilherme Martins; Gratieri, Taís; Simão, Patrícia Sper; de Freitas, Luís Alexandre Pedro; Lopez, Renata Fonseca Vianna

2011-01-01

Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (∼82%), a mean diameter of 3.0 µm and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.

Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine.

PubMed

Nair, Rahul; Kumar, Ashok C K; Priya, Vishnu K; Yadav, Chakrapani M; Raju, Prasanna Y

2012-06-13

The present work aims at preparing aqueous suspension of Solid lipid Nanoparticles containing Chitosan (CT) which is a biopolymer that exhibits a number of interesting properties which include controlled drug delivery. Carbamezapine (CBZ) is a lipophilic drug which shows it antiepileptic activity by inactivating sodium channels. The solid lipid Nanoparticles (SLN) of Chitosan-CBZ were prepared by using solvent injection method using ethanol as organic solvent. The prepared SLN formulations exhibited high encapsulation efficiency, high physical stability. The drug incorporated SLNs have demonstrated that the controlled release patterns of the drug for prolonged period. The prepared SLNs were characterized for surface morphology by SEM analysis, entrapment efficiency, zeta potential, FTIR, DSC and In-vitro diffusion studies. The hydrodynamic mean diameter and zeta potential were 168.7 ± 1.8 nm and -28.9 ± 2.0 mV for SLN-chitosan-CBZ respectively. Therefore chitosan-SLN can be good candidates to encapsulate CBZ and to increase its therapeutic efficacy in the treatment of Epilepsy.

Selective Cytotoxicity and Combined Effects of Camptothecin or Paclitaxel with Sodium-R-Alpha Lipoate on A549 Human Non-Small Cell Lung Cancer Cells

PubMed Central

Ibrahim, Sherif; Gao, Dayuan; Sinko, Patrick J.

2013-01-01

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the deadliest form of cancer in the US and worldwide. New therapies are highly sought after to improve outcome. The effect of sodium-R-alpha lipoate on camptothecin- and paclitaxel-induced cytotoxicity was evaluated on A549 NSCLC and BEAS-2B ‘normal’ lung epithelial cells. Combination indices (CI) and dose reduction indices (DRI) were investigated by studying the cytotoxicity of sodium-R-alpha lipoate (0–16 mM), camptothecin (0–25 nM) and paclitaxel (0–0.06 nM) alone and in combination. 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium-bromide (MTT) was used to assess cytotoxicity. The combinational cytotoxic effects of sodium-R-alpha lipoate with camptothecin or paclitaxel were analyzed using a simulation of dose effects (CompuSyn®3.01). The effects of sodium-R-alpha lipoate on camptothecin- and paclitaxel-induced cytotoxicity varied based on concentrations and treatment times. It was found that sodium-R-alpha lipoate wasn’t cytotoxic towards BEAS-2B cells at any of the concentrations tested. For A549 cells, CIs [(additive (CI=1); synergistic (CI<1); antagonistic (CI>1)] were lower and DRIs were higher for the camptothecin/sodium-R-alpha-lipoate combination (CI=~0.17–1.5; DRI=~2.2–22.6) than the paclitaxel/sodium-R-alpha-lipoate combination (CI=~0.8–9.9; DRI=~0.10–5.8) suggesting that the camptothecin regimen was synergistic and that the addition of sodium-R-alpha lipoate was important for reducing the camptothecin dose and potential for adverse effects. PMID:24063429

Controlled release of tyrosol and ferulic acid encapsulated in chitosan-gelatin films after electron beam irradiation

NASA Astrophysics Data System (ADS)

Benbettaïeb, Nasreddine; Assifaoui, Ali; Karbowiak, Thomas; Debeaufort, Frédéric; Chambin, Odile

2016-01-01

This work deals with the study of the release kinetics of antioxidants (ferulic acid and tyrosol) incorporated into chitosan-gelatin edible films after irradiation processes. The aim was to determine the influence of electron beam irradiation (at 60 kGy) on the retention of antioxidants in the film, their release in water (pH=7) at 25 °C, in relation with the barrier and mechanical properties of biopolymer films. The film preparation process coupled to the irradiation induced a loss of about 20% of tyrosol but did not affect the ferulic acid content. However, 27% of the ferulic acid remained entrapped in the biopolymer network during the release experiments whereas all tyrosol was released. Irradiation induced a reduction of the release rate for both compounds, revealing that cross-linking occurred during irradiation. This was confirmed by the mechanical properties enhancement which tensile strength value significantly increased and by the reduction of permeabilities. Although molecular weights, molar volume and molecular radius of the two compounds are very similar, the effective diffusivity of tyrosol was 40 times greater than that of ferulic acid. The much lower effective diffusion coefficient of ferulic acid as determined from the release kinetics was explained by the interactions settled between ferulic acid molecules and the gelatin-chitosan matrix. As expected, the electron beam irradiation allowed modulating the retention and then the release of antioxidants encapsulated.

Development of Cy5.5-Labeled Hydrophobically Modified Glycol Chitosan Nanoparticles for Protein Delivery

NASA Astrophysics Data System (ADS)

Chin, Amanda

Therapeutic proteins are often highly susceptible to enzymatic degradation, thus restricting their in vivo stability. To overcome this limitation, delivery systems designed to promote uptake and reduce degradation kinetics have undergone a rapid shift from macro-scale systems to nanomaterial based carriers. Many of these nanomaterials, however, elicit immune responses and may have cytotoxic effects both in vitro and in vivo. The naturally derived polysaccharide chitosan has emerged as a promising biodegradable material and has been utilized for many biomedical applications; nevertheless, its function is often constrained by poor solubility. Glycol chitosan, a derivative of chitosan, can be hydrophobically modified to impart amphiphilic properties that enable the self-assembly into nanoparticles in aqueous media at neutral pH. This nanoparticle system has shown initial success as a therapeutic agent in several model cell culture systems, but little is known about its stability against enzymatic degradation. Therefore, the goal of this research was to investigate the resistance of hydrophobically modified glycol chitosan against enzyme-catalyzed degradation using an in vivo simulated system containing lysozyme. To synthesize the nanoparticles, hydrophobic cholanic acid was first covalently conjugated to glycol chitosan using of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Conjugates were purified by dialysis, lyophilized, and ultra-sonicated to form nanoparticles. Fourier transform infrared (FT-IR) spectroscopy confirmed the binding of 5beta-cholanic acid to the glycol chitosan. Particle size and stability over time were determined with dynamic light scattering (DLS), and particle morphology was evaluated by transmission electron microscopy (TEM). The average diameter of the nanoparticles was approximately 200 nm, which remained stable at 4°C for up to 10 days. Additionally, a near infrared fluorescent (NIRF) dye

Immunological evaluation of chitosan nanoparticles loaded with tetanus toxoid.

PubMed

Ghalavand, M; Saadati, M; Ahmadi, A; Abbasi, E; Salimian, J

2018-01-01

The present study was aimed at comparing tetanus toxoid (TT)‑loaded-chitosan nanoparticles with aluminum hydroxide as a common vaccine adjuvant. Tetanus remains to be a major public health problem. Nanoparticles have been extensively used as immune adjuvants. Tetanus toxoid (TT) encapsulated in chitosan nanoparticles is considered to be a promising tetanus vaccine candidate. TT‑loaded chitosan nanoparticles were prepared by the ionic gelation method. The nanoparticles were studied by SEM for their size and morphology. In vivo study was conducted to evaluate the immunity response using mice divided into 4 groups and injected with encapsulated toxoid. The immune responses were then measured using indirect ELISA. The purity and integrity of antigen were confirmed by SDS-PAGE electrophoresis. The size of nanoparticles was estimated at 100 nm. As a result, the IgG antibody levels were 1.9, 1.76, and 0.87 in chitosan nanoparticles, aluminum hydroxide, and TT alone groups, respectively. Also, the immune responses were significantly higher in immunized groups compared to control groups vaccinated with free adjuvant vaccines (p < 0.05). The quality and efficacy of toxoid‑loaded chitosan nanoparticles were reasonable. It enhanced the immune responses as much as aluminum hydroxide adjuvant does and thus may be a good alternative candidate (Tab. 1, Fig. 3, Ref. 16).

Effect of biopolymer encapsulation on the digestibility of lipid and cholesterol oxidation products in beef during in vitro human digestion.

PubMed

Hur, Sun Jin; Lee, Seung Yuan; Lee, Seung-Jae

2015-01-01

In this study, beef patties were encapsulated with 3% chitosan, pectin, onion powder, or green tea powder and the beef patties were then passed through an in vitro human digestion model. The total lipid digestibility was lowest (p<0.05) in beef patties encapsulated with chitosan and pectin after digestion in the small intestine. Thiobarbituric acid reactive substance (TBARS) values were significantly lower (p<0.05) for beef patties encapsulated with chitosan and pectin, when compared with the control, after digestion in the small intestine. In contrast, the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical-scavenging activity was highest (p<0.05) in beef patties encapsulated with onion powder and green tea powder after digestion in the small intestine. The total cholesterol oxidation product (COP) content was significantly lower (p<0.05) in beef patties encapsulated with biopolymers than in the control after digestion in the small intestine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antimicrobial and Physicochemical Characterization of Biodegradable, Nitric Oxide-Releasing Nanocellulose-Chitosan Packaging Membranes.

PubMed

Sundaram, Jaya; Pant, Jitendra; Goudie, Marcus J; Mani, Sudhagar; Handa, Hitesh

2016-06-29

Biodegradable composite membranes with antimicrobial properties consisting of nanocellulose fibrils (CNFs), chitosan, and S-nitroso-N-acetyl-d-penicillamine (SNAP) were developed and tested for food packaging applications. As a nitric oxide donor, SNAP was encapsulated into completely dispersed chitosan in 100 mL of 0.1 N acetic acid and was thoroughly mixed with CNFs to produce a composite membrane. The fabricated membranes had a uniform dispersion of chitosan and SNAP within the CNFs, which was confirmed through scanning electron microscopy (SEM) micrographs and a chemiluminescence nitric oxide analyzer. The membranes prepared without SNAP showed lower water vapor permeability than that of the membranes with SNAP. The addition of SNAP resulted in a decrease in Young's modulus for both two- and three-layer membrane configurations. Antimicrobial property evaluation of SNAP-incorporated membranes showed an effective zone of inhibition against bacterial strains of Enterococcus faecalis, Staphylococcus aureus, and Listeria monocytogenes and demonstrated its potential applications for food packaging.

Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: ibuprofen.

PubMed

Hassani Najafabadi, Alireza; Abdouss, Majid; Faghihi, Shahab

2014-08-01

Current methods for preparation of PEGylated chitosan have limitations such as harsh de protecting step and several purification cycles. In the present study, a facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan under mild condition is introduced to improve water solubility of chitosan and control the release of poor water soluble drugs. The method consists of chitosan modification by grafting the C6 position of chitosan to mPEG which is confirmed by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance ((1)HNMR) analyses. The amine groups at the C2 position of chitosan are protected using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and (1)HNMR. The synthesized polymer is then employed to prepare nanoparticles which are characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for their size and morphology. The nanoparticles are used for encapsulation of ibuprofen followed by in vitro release investigation in gastrointestinal and simulated biological fluids. The chitosan nanoparticles are used as control. The PEGylated nanoparticles show a particle size of 80 nm with spherical morphology. The results clearly show that drug release from PEGylated chitosan nanoparticles is remarkably slower than chitosan. In addition, drug encapsulation and encapsulation efficiency in PEGylated nanoparticles are dependent on the amount of drug added to the formulation being significantly higher than chitosan nanoparticles. This study provides an efficient, novel, and facile method for preparing a nano carrier system for delivery of water insoluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine

PubMed Central

2012-01-01

The present work aims at preparing aqueous suspension of Solid lipid Nanoparticles containing Chitosan (CT) which is a biopolymer that exhibits a number of interesting properties which include controlled drug delivery. Carbamezapine (CBZ) is a lipophilic drug which shows it antiepileptic activity by inactivating sodium channels. The solid lipid Nanoparticles (SLN) of Chitosan-CBZ were prepared by using solvent injection method using ethanol as organic solvent. The prepared SLN formulations exhibited high encapsulation efficiency, high physical stability. The drug incorporated SLNs have demonstrated that the controlled release patterns of the drug for prolonged period. The prepared SLNs were characterized for surface morphology by SEM analysis, entrapment efficiency, zeta potential, FTIR, DSC and In-vitro diffusion studies. The hydrodynamic mean diameter and zeta potential were 168.7 ±1.8 nm and −28.9 ±2.0 mV for SLN-chitosan-CBZ respectively. Therefore chitosan-SLN can be good candidates to encapsulate CBZ and to increase its therapeutic efficacy in the treatment of Epilepsy. PMID:22695222

Preparation of astaxanthin-loaded DNA/chitosan nanoparticles for improved cellular uptake and antioxidation capability.

PubMed

Wang, Qian; Zhao, Yingyuan; Guan, Lei; Zhang, Yaping; Dang, Qifeng; Dong, Ping; Li, Jing; Liang, Xingguo

2017-07-15

DNA/chitosan co-assemblies were initially used as nanocarriers for efficient astaxanthin encapsulation and delivery. The obtained astaxanthin-loaded DNA/chitosan (ADC) colloidal system was transparent and homogenous, with astaxanthin content up to 65μg/ml. Compared to free astaxanthin, ADC nanoparticles with an astaxanthin concentration as low as 3.35nM still showed a more powerful cytoprotective effect on H 2 O 2 -induced oxidative cell damage, and improved cell viability from 49.9% to 61.9%. The ROS scavenging efficiency of ADC nanoparticles was as high as 54.3%, which was 2-fold higher than that of free astaxanthin. Besides this, ADC nanoparticles were easily engulfed by Caco-2 cells in a short time, indicating that the encapsulated astaxanthin could be absorbed through endocytosis by intestinal epithelial cells. The improved antioxidation capability and facilitated cellular uptake enabled the ADC nanoparticles to be good candidates for efficient delivery and absorption of astaxanthin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and characterization of N-benzoyl-O-acetyl-chitosan.

PubMed

Cai, Jinping; Dang, Qifeng; Liu, Chengsheng; Fan, Bing; Yan, Jingquan; Xu, Yanyan; Li, Jingjing

2015-01-01

A novel amphipathic chitosan derivative, N-benzoyl-O-acetyl-chitosan (BACS), was prepared by using the selective partial acylation of chitosan (CS), benzoyl chloride, and acetic acid under high-intensity ultrasound. The chemical structure and physical properties of BACS were characterized by FTIR, (1)H NMR, TGA, and XRD techniques. The degrees of substitution of benzoyl and acetyl for the chitosan derivatives were 0.26 and 1.15, respectively, which were calculated from the peak areas in NMR spectra by using the combined integral methods. The foaming properties of CS and BACS were determined and the results suggested BACS had better foam capacity and stability than those of chitosan. In addition, the antimicrobial activities of CS and BACS were also investigated against two species of bacteria (Escherichia coli and Staphylococcus aureus) and a fungus (Aspergillus niger), the results indicated that the antibacterial and antifungal activities of BACS were much stronger than those of the parent chitosan. These findings suggested that BACS was preferable for use as a food additive with a dual role of both foaming agent and food preservative. Copyright © 2015 Elsevier B.V. All rights reserved.

Chitosan-silane sol-gel hybrid thin films with controllable layer thickness and morphology.

PubMed

Spirk, Stefan; Findenig, Gerald; Doliska, Ales; Reichel, Victoria E; Swanson, Nicole L; Kargl, Rupert; Ribitsch, Volker; Stana-Kleinschek, Karin

2013-03-01

The preparation of thin films of chitosan-silane hybrid materials by combining sol-gel processing and spin coating is reported. A variety of silanes can be used as starting materials for the preparation of such thin films, namely tetraethoxysilane, tri-tert-butoxysilanol, trimethylethoxysilane, p-trifluoromethyltetra-fluorophenyltriethoxysilane, trivinylmethoxysilane, (methoxymethyl)trimethyl-silane, and hexamethoxydisilane. These silanes are subjected to a sol-gel process before they are added to acidic chitosan solutions. The chitosan:silane ratio is kept constant at 6:1 (w/w) and dilutions with ethanol are prepared and spin coated. Depending on the degree of dilution, film thickness can be controlled in a range between 5 and 70 nm. For the determination of additional surface properties, static water contact angle measurements and atomic force microscopy have been employed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Effects of Biopolymer Encapsulation on Total Lipids and Cholesterol in Egg Yolk during in Vitro Human Digestion

PubMed Central

Hur, Sun-Jin; Kim, Young-Chan; Choi, Inwook; Lee, Si-Kyung

2013-01-01

The purpose of this study was to examine the effect of biopolymer encapsulation on the digestion of total lipids and cholesterol in egg yolk using an in vitro human digestion model. Egg yolks were encapsulated with 1% cellulose, pectin, or chitosan. The samples were then passed through an in vitro human digestion model that simulated the composition of mouth saliva, stomach acid, and the intestinal juice of the small intestine by using a dialysis tubing system. The change in digestion of total lipids was monitored by confocal fluorescence microscopy. The digestion rate of total lipids and cholesterol in all egg yolk samples dramatically increased after in vitro human digestion. The digestion rate of total lipids and cholesterol in egg yolks encapsulated with chitosan or pectin was reduced compared to the digestion rate of total lipids and cholesterol in other egg yolk samples. Egg yolks encapsulated with pectin or chitosan had lower free fatty acid content, and lipid oxidation values than samples without biopolymer encapsulation. Moreover, the lipase activity decreased, after in vitro digestion, in egg yolks encapsulated with biopolymers. These results improve our understanding of the effects of digestion on total lipids and cholesterol in egg yolk within the gastrointestinal tract. PMID:23965957

trans-Bis(thio­cyanato-κN)tetra­kis­(3,4,5-trimethyl-1H-pyrazole-κN 2)nickel(II)–3,4,5-trimethyl-1H-pyrazole (1/1)

PubMed Central

Hossaini Sadr, Moayad; Engle, James T.; Ziegler, Christopher J.; Soltani, Behzad; Mousavi, Zahra

2011-01-01

In the title compound, [Ni(NCS)2(C6H10N2)4]·C6H10N2, the asymmetric unit comprises a NiII complex and a co-crystallised mol­ecule of 3,4,5-trimethyl-1H-pyrazole (PzMe3). The NiII atom is coordinated by four PzMe3 mol­ecules and two thio­cyanate anions to define a trans N4S2 distorted octa­hedral geometry. A number of intra­molecular N—H⋯N, N—H⋯S and C—H⋯N inter­actions contribute to the stability of the complex. The crystal structure is stabilized by inter­molecular N—H⋯S inter­actions, which link neighbouring mol­ecules into chains along the a axis. PMID:22219831

In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles.

PubMed

Esmaeili, Akbar; Asgari, Azadeh

2015-11-01

In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality. Copyright © 2015 Elsevier B.V. All rights reserved.

IGF-1 Release Kinetics from Chitosan Microparticles Fabricated Using Environmentally Benign Conditions

PubMed Central

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2014-01-01

The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated into microparticles to study release kinetics and bioactivity. In order to authenticate the harms of using organic solvents like hexane and acetone during microparticle preparation, IGF-1 encapsulated microparticles prepared by the emulsification and coacervation methods were compared. The microparticles fabricated by emulsification method have shown a significant decrease (p<0.05) in IGF-1 encapsulation efficiency, and cumulative release during the two-week period. The biocompatibility of chitosan microparticles and the bioactivity of the released IGF-1 were determined in vitro by live/dead viability assay. The mineralization data observed with Von Kossa assay, was supported by mRNA expression levels of osterix and runx2, which are transcription factors necessary for osteoblasts differentiation. Real time RT-PCR data showed an increased expression of runx 2 and a decreased expression of osterix over time, indicating differentiating osteoblasts. Chitosan microparticles prepared in optimum environmental conditions are a promising controlled delivery system for cells to attach, proliferate, differentiate and mineralize, thereby acting as a suitable bone repairing material. PMID:25063148

Semisynthesis, Cytotoxic Activity, and Oral Availability of New Lipophilic 9-Substituted Camptothecin Derivatives

PubMed Central

2013-01-01

Despite that 9-substituted camptothecins are promising candidates in cancer therapy, the limited accessibility to this position has reduced the studies of these derivatives to a few standard modifications. We report herein a novel semisynthetic route based on the Tscherniac–Einhorn reaction to synthesize new lipophilic camptothecin derivatives with amidomethyl and imidomethyl substitutions in position 9. Compounds were evaluated for their antiproliferative activity, topoisomerase I inhibition, and oral availability. Preliminary data demonstrated that bulky imidomethyl modification is an appropriate lipophilic substitution for an effective oral administration relative to topotecan. In addition, this general procedure paves the way for obtaining new camptothecin derivatives. PMID:24900725

Characteristics of eugenol loaded chitosan-tripolyphosphate particles as affected by initial content of eugenol and their in-vitro release characteristic

NASA Astrophysics Data System (ADS)

Cahyono, B.; A’yun, Qurrotu; Suzery, M.; Hadiyanto

2018-04-01

The aim of this research was to determine encapsulation efficiency, loading capacity and controlled release of eugenol loaded chitosan-tpp products which prepared by coaservation method. The characteristic of eugenol-loaded chitosan showed that %EE and % LC increased by increasing the initial eugenol content. The optimum of %EE (72.63%) and %LC (43.96%) were obtained at the ratio of chitosan to eugenol of 1:1.5. The FTIR spectrum showed the characteristic peaks of eugenol appearing on spectrum of eugenol encapsulated and blue-shift in the hydroxyl band from 3425.58 cm-1 in chitosan-tpp to 3417.86 cm-1 and 3394.72 cm-1 in eugenol loaded chitosan-tpp indicating that eugenol was successfully encapsulated. The surface morphologies of freeze-dried particles with the optimum %EE showed that more surface roughness and porosity than plain particles. Furthermore, the in vitro release of particles with minimum and optimum %EE were also investigated in acid (Simulated Gastric Fluid) and base (Simulated Intestinal Fluid) medium at ambient temperature.

Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric Nanoparticles: Towards Effective Delivery of Neuropeptides.

PubMed

Kaur, Sarabjit; Bhararia, Avani; Sharma, Krishna; Mittal, Sherry; Jain, Rahul; Wangoo, Nishima; Sharma, Rohit K

2016-05-01

Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.

T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues

NASA Astrophysics Data System (ADS)

Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

2016-05-01

Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the

Effect drug loading process on dissolution mechanism of encapsulated amoxicillin trihydrate in hydrogel semi-IPN chitosan methyl cellulose with pore forming agent KHCO3 as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Fithawati, Garnis; Budianto, Emil

2018-04-01

Common treatment for Helicobacter pylori by repeated oral consumption of amoxicillin trihydrate is not effective. Amoxicillin trihydrate has a very short residence time in stomach which leads into its ineffectiveness. Residence time of amoxicillin trihydrate can be improved by encapsulating amoxicillin trihydrate into a floating drug delivery system. In this study, amoxicillin trihydrate is encapsulated into hydrogel semi-IPN chitosan methyl cellulose matrix as a floating drug delivery system and then treated with 20% KHCO3 as pore forming agent. Drug loading process used are in-situ loading and post loading. In-situ loading process has higher efficiency percentage and dissolution percentage than post loading process. In-situ loading process resulted 100% efficiency with 92,70% dissolution percentage. Post loading process resulted 98,7% efficiency with 90,42% dissolution percentage. Mechanism of drug dissolution study by kinetics approach showed both in-situ loading process and post loading process are diffusion and degradation process (n=0,4913) and (n=0,4602) respectively. These results are supported by characterization data from optical microscope and scanning electron microscopy (SEM). Data from optical microscope showed both loading process resulted in coarser hydrogel surface. Characterization using SEM showed elongated pores in both loading process after dissolution test.

Lactosaminated- N-succinyl chitosan nanoparticles for hepatocyte-targeted delivery of acyclovir

NASA Astrophysics Data System (ADS)

Jain, Nivrati; Rajoriya, Vaibhav; Jain, Prateek Kumar; Jain, Ashish Kumar

2014-01-01

The present study discusses lactose-acyclovir- N-succinyl chitosan nanoparticles (Lac- N-Suc-CSNP) using lactose as an asialoglycoprotein receptor (ASGPR) ligand for hepatic parenchymatic cells targeting. For this purpose, N-succinyl chitosan nanoparticles ( N-Suc-CSNP) were prepared previously by ionotropic gelation method and lactose was conjugated to the free amino terminal group of chitosan. Lactose conjugation with N-Suc-CSNP was confirmed by FT-IR and zeta potential measurements. The Lac- N-Suc-CSNP obtained were characterized for their morphology, particle size, polydispersity index, and zeta potential. The Lac- N-Suc-CSNP showed spherical in shape with 220.3 ± 5.0 nm size range, +4.1 ± 0.2 mV zeta potential, 62.5 ± 1.2 % acyclovir entrapment efficiency and showed 27.3 ± 0.9 % cumulative acyclovir release up to 72 h. The acyclovir concentration from Lac- N-Suc-CSNP was found to be 19.9 ± 1.62 μg/g after 24 h administration revealed remarkably targeting potential to the hepatocytes and keep at a high level during the experiment. These results suggest that Lac- N-Suc-CSNP are potentially vector for hepatocytes targeting.

Effects of storage and yogurt matrix on the stability of tocotrienols encapsulated in chitosan-alginate microcapsules.

PubMed

Tan, Phui Yee; Tan, Tai Boon; Chang, Hon Weng; Tey, Beng Ti; Chan, Eng Seng; Lai, Oi Ming; Baharin, Badlishah Sham; Nehdi, Imededdine Arbi; Tan, Chin Ping

2018-02-15

Tocotrienol microcapsules (TM) were formed by firstly preparing Pickering emulsion containing tocotrienols, which was then gelled into microcapsules using alginate and chitosan. In this study, we examined the stability of TM during storage and when applied into a model food system, i.e. yogurt. During storage at 40°C, TM displayed remarkably lower tocotrienols loss (50.8%) as compared to non-encapsulated tocotrienols in bulk oil (87.5%). When the tocotrienols were incorporated into yogurt, the TM and bulk oil forms showed a loss of 23.5% and 81.0%, respectively. Generally, the tocotrienols were stable in the TM form and showed highest stability when these TM were added into yogurt. δ-Tocotrienol was the most stable isomer in both forms during storage and when incorporated into yogurt. The addition of TM into yogurt caused minimal changes in the yogurt's color and texture but slightly altered the yogurt's viscosity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunoadjuvant Chemotherapy of Visceral Leishmaniasis in Hamsters Using Amphotericin B-Encapsulated Nanoemulsion Template-Based Chitosan Nanocapsules

PubMed Central

Asthana, Shalini; Jaiswal, Anil K.; Gupta, Pramod K.; Pawar, Vivek K.; Dube, Anuradha

2013-01-01

The accessible treatment options for life-threatening neglected visceral leishmaniasis (VL) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. Here we formulated nanometric amphotericin B (AmB)-encapsulated chitosan nanocapsules (CNC-AmB) using a polymer deposition technique mediated by nanoemulsion template fabrication. CNC-AmB exhibited good steric stability in vitro, where the chitosan content was found to be efficient at preventing destabilization in the presence of protein and Ca2+. A toxicity study on the model cell line J774A and erythrocytes revealed that CNC-AmB was less toxic than commercialized AmB formulations such as Fungizone and AmBisome. The results of in vitro (macrophage-amastigote system; 50% inhibitory concentration [IC50], 0.19 ± 0.04 μg AmB/ml) and in vivo (Leishmania donovani-infected hamsters; 86.1% ± 2.08% parasite inhibition) experiments in conjunction with effective internalization by macrophages illustrated the efficacy of CNC-AmB at augmenting antileishmanial properties. Quantitative mRNA analysis by real-time PCR (RT-PCR) showed that the improved effect was synergized with the upregulation of tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and inducible nitric oxide synthase and with the downregulation of transforming growth factor β (TGF-β), IL-10, and IL-4. These research findings suggest that a cost-effective CNC-AmB immunoadjuvant chemotherapeutic delivery system could be a viable alternative to the current high-cost commercial lipid-based formulations. PMID:23357762

Sol-gel encapsulation of pullulanase in the presence of hybrid magnetic (Fe3O4-chitosan) nanoparticles improves thermal and operational stability.

PubMed

Long, Jie; Li, Xingfei; Zhan, Xiaobei; Xu, Xueming; Tian, Yaoqi; Xie, Zhengjun; Jin, Zhengyu

2017-06-01

Pullulanase was sol-gel encapsulated in the presence of magnetic chitosan/Fe 3 O 4 nanoparticles. The resulting immobilized pullulanase was characterized by scanning electron microscopy, vibrating sample magnetometry, Fourier transform infrared spectroscopy and thermogravimetric analysis. The results showed that the addition of pullulanase created a more regular surface on the sol-gel matrix and an enhanced magnetic response to an applied magnetic field. The maximal activity retention (83.9%) and specific activity (291.7 U/mg) of the immobilized pullulanase were observed under optimized conditions including an octyltriethoxysilane:tetraethoxysilane (OTES:TEOS) ratio of 1:2 and enzyme concentration of 0.484 mg/mL sol. The immobilized enzyme exhibited good thermal stability. When the temperature was above 60 °C, the immobilized pullulanase showed significantly higher activity than the free enzyme (p < 0.01); enzyme immobilized by simple sol-gel encapsulation and co-immobilized by crosslinking-encapsulation retained 52 and 69% of their initial activity after 5 h at 62 °C, respectively, compared to 11% for the free enzyme. Moreover, the stability of the pullulanase was improved by crosslinking-encapsulation, as the enzyme retained more than 85 and 81% of its original activity after 5 and 6 consecutive reuses, respectively, compared to 80 and 72% of its original activity for simple sol-gel encapsulated enzymes. This indicated the leakage of enzyme molecules through the pores of the gel was substantially abated by cross-linking. Such immobilized pullulanase provides high stability and ease of enzyme recovery, characteristics that are advantageous for applications in the food industry that involve continuous starch processing.

Phosphatidylcholine nanovesicles coated with chitosan or chondroitin sulfate as novel devices for bacteriocin delivery

NASA Astrophysics Data System (ADS)

da Silva, Indjara Mallmann; Boelter, Juliana Ferreira; da Silveira, Nádya Pesce; Brandelli, Adriano

2014-07-01

There is increased interest on the use of natural antimicrobial peptides in biomedicine and food preservation technologies. In this study, the antimicrobial activity of nisin encapsulated into nanovesicles containing polyanionic polysaccharides was investigated. Nisin was encapsulated in phosphatidylcholine (PC) liposomes containing chitosan or chondroitin sulfate by the thin-film hydration method and tested for antimicrobial activity against Listeria spp. The mean particle size of PC liposomes was 145 nm and varied to 210 and 134 nm with the incorporation of chitosan and chondroitin sulfate, respectively. Nisin-containing nanovesicles with and without incorporation of polysaccharides had a zeta potential values around -20 mV, showing mostly spherical structures when observed by transmission electron microscopy. Encapsulated nisin had similar efficiency as free nisin in inhibiting Listeria spp. isolated from bovine carcass, and greater efficiency in inhibiting Listeria monocytogenes. The formulation containing chitosan was more stable and more efficient in inhibiting L. monocytogenes when compared to the other nanovesicles tested. After 24 h, the viable cell counts were 2 log lower as compared with the other treatments and 7 log comparing to controls.

Encapsulation of mesenchymal stem cells in chitosan/β-glycerophosphate hydrogel for seeding on a novel calcium phosphate cement scaffold.

PubMed

Liu, Tao; Li, Jian; Shao, Zengwu; Ma, Kaige; Zhang, Zhicai; Wang, Baichuan; Zhang, Yannan

2018-06-01

Due to its moldability, biocompatibility, osteoconductivity and resorbability, calcium phosphate cement (CPC) is a highly promising scaffold material for orthopedic applications. However, pH changes and ionic activity during the CPC setting reaction may adversely affect cells seeded directly on CPC. Moreover, a lack of macropores in CPC limits ingrowth of new bone. The objectives of this study were to prepare macroporous CPC scaffolds via porogen leaching, using mannitol crystals as the porogen and to evaluate the in vitro proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) encapsulated in chitosan/β-glycerophosphate (C/GP) hydrogel prior to exposure to the novel CPC scaffold. MSCs were found to be adhered to the surfaces of CPC macropores via scanning electron microscopy. The viability and osteogenic differentiation of MSCs in C/GP hydrogel with or without exposure to CPC constructs containing mannitol crystals indicated that coating with C/GP hydrogel protected the cells during cement mixing and setting. In conclusion, novel, macroporous CPC scaffolds were prepared, and our data indicate that a hydrogel encapsulation-based strategy can be used to protect cells during scaffold formation. Thus, the MSC-laden CPC scaffolds show promise for the delivery of stem cells to promote bone regeneration. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

Ferritin glycosylated by chitosan as a novel EGCG nano-carrier: Structure, stability, and absorption analysis.

PubMed

Yang, Rui; Liu, Yuqian; Gao, Yunjing; Wang, Yongjin; Blanchard, Chris; Zhou, Zhongkai

2017-12-01

Ferritin is a shell-like carrier protein with an 8nm diameter cavity which endows a natural space to encapsulate food and drug components. In this work, phytoferritin was unprecedentedly glycosylated by chitosan to fabricate ferritin-chitosan Maillard reaction products (FCMPs) (grafting degree of 26.17%, 24h, 55°C). Results indicated that the amide I and II bands of ferritin were altered due to the chitosan grafting, whereas the ferritin spherical structure were retained. Simulated digestion analysis showed that the FCMPs were more resistant to pepsin and trypsin digestion as compared with ferritin alone. Furthermore, FCMPs were employed as carrier to encapsulate epigallocatechin gallate (EGCG) molecules with an encapsulation ratio of 12.87% (w/w), and the resulting FCMPs-EGCG complexes showed a slow release of EGCG in simulated gastrointestinal tract. Interestingly, different types of food components displayed different effects in EGCG release behavior from the FCMPs, wherein proanthocyanidin, milk and soy protein inhibited the EGCG release. In addition, the absorption of EGCG encapsulated in FCMPs in Caco-2 monolayer model was significantly improved as compared with free EGCG. This work provides a novel nano-vehicle for fabricating core-shell systems in food and drug delivery domain. Copyright © 2017 Elsevier B.V. All rights reserved.

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

PubMed Central

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2014-01-01

This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 μm containing ~100 ng of BMP-7. The release study profile indicates that nearly 98% of the BMP-7 coated on the microparticles was released in a period of 18 days while only 36% of the BMP-7 encapsulated in the microparticles was released in the same time period. Cell attachment study indicated that the BMP-7 coated microparticles have many cells adhered on the microparticles in comparison with microparticles without growth factors on day 10. DNA assay indicated a statistical significant increase (p<0.05) in the amount of DNA obtained from BMP-7 encapsulated and coated microparticles in comparison with microparticles without any growth factors. A real time RT-PCR experiment was performed to determine the expression of a few osteoblast specific genes - Dlx5, runx2, osterix, osteopontin, osteocalcin, and bone sialoprotein. The results thus suggest that chitosan microparticles obtained by coacervation method are biocompatible and helps in improving the encapsulation efficiency of BMP-7. Also BMP-7 incorporated in the microparticles is being released in a controlled fashion to support attachment, proliferation and differentiation of pre-osteoblasts, thus acting as a good scaffold for bone tissue regeneration. PMID:24497318

Gas-Phase Chemistry of Trimethyl Phosphite,

DTIC Science & Technology

keywords include: Flowing afterglow; Trimethyl phosphite ; Reaction mechanisms; Phosphorous ; and Nucleophilic displacement....The reactions of trimethyl phosphite were investigated with a series of nucleophiles. Products, branching ratios, and reaction rate constants are...of methoxide to form a new ion-dipole complex (CH3O-(CH3O)2PZ). If an additional acidic hydrogen is available on the nucleophile, the major products

40 CFR 180.1086 - 3,7,11-Trimethyl-1,6,10-dodecatriene-1-ol and 3,7,11-trimethyl-2,6,10-dodecatriene-3-ol...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false 3,7,11-Trimethyl-1,6,10-dodecatriene-1-ol and 3,7,11-trimethyl-2,6,10-dodecatriene-3-ol; exemption from the requirement of a tolerance. 180....1086 3,7,11-Trimethyl-1,6,10-dodecatriene-1-ol and 3,7,11-trimethyl-2,6,10-dodecatriene-3-ol; exemption...

Physical Stability Studies of Semi-Solid Formulations from Natural Compounds Loaded with Chitosan Microspheres

PubMed Central

Acosta, Niuris; Sánchez, Elisa; Calderón, Laura; Cordoba-Diaz, Manuel; Cordoba-Diaz, Damián; Dom, Senne; Heras, Ángeles

2015-01-01

A chitosan-based hydrophilic system containing an olive leaf extract was designed and its antioxidant capacity was evaluated. Encapsulation of olive leaf extract in chitosan microspheres was carried out by a spray-drying process. The particles obtained with this technique were found to be spherical and had a positive surface charge, which is an indicator of mucoadhesiveness. FTIR and X-ray diffraction results showed that there are not specific interactions of polyphenolic compounds in olive leaf extract with the chitosan matrix. Stability and release studies of chitosan microspheres loaded with olive leaf extract before and after the incorporation into a moisturizer base were performed. The resulting data showed that the developed formulations were stable up to three months. The encapsulation efficiency was around 44% and the release properties of polyphenols from the microspheres were found to be pH dependent. At pH 7.4, polyphenols release was complete after 6 h; whereas the amount of polyphenols released was 40% after the same time at pH 5.5. PMID:26389926

Chitin and Chitosan: Production and Application of Versatile Biomedical Nanomaterials

PubMed Central

Elieh-Ali-Komi, Daniel; Hamblin, Michael R

2016-01-01

Chitin is the most abundant aminopolysaccharide polymer occurring in nature, and is the building material that gives strength to the exoskeletons of crustaceans, insects, and the cell walls of fungi. Through enzymatic or chemical deacetylation, chitin can be converted to its most well-known derivative, chitosan. The main natural sources of chitin are shrimp and crab shells, which are an abundant byproduct of the food-processing industry, that provides large quantities of this biopolymer to be used in biomedical applications. In living chitin-synthesizing organisms, the synthesis and degradation of chitin require strict enzymatic control to maintain homeostasis. Chitin synthase, the pivotal enzyme in the chitin synthesis pathway, uses UDP-N-acetylglucosamine (UDPGlcNAc), produce the chitin polymer, whereas, chitinase enzymes degrade chitin. Bacteria are considered as the major mediators of chitin degradation in nature. Chitin and chitosan, owing to their unique biochemical properties such as biocompatibility, biodegradability, non-toxicity, ability to form films, etc, have found many promising biomedical applications. Nanotechnology has also increasingly applied chitin and chitosan-based materials in its most recent achievements. Chitin and chitosan have been widely employed to fabricate polymer scaffolds. Moreover, the use of chitosan to produce designed-nanocarriers and to enable microencapsulation techniques is under increasing investigation for the delivery of drugs, biologics and vaccines. Each application is likely to require uniquely designed chitosan-based nano/micro-particles with specific dimensions and cargo-release characteristics. The ability to reproducibly manufacture chitosan nano/microparticles that can encapsulate protein cargos with high loading efficiencies remains a challenge. Chitosan can be successfully used in solution, as hydrogels and/or nano/microparticles, and (with different degrees of deacetylation) an endless array of derivatives with

Tetra-butyl-ammonium tetra-kis-(trimethyl-silanolato-κO)ferrate(III).

PubMed

Hay, Michael; Staples, Richard; Lee, Andre

2012-09-01

In the title salt, (C(16)H(36)N)[Fe(C(3)H(9)OSi)(4)], the cation contains a central N atom bonded to four n-butyl alkyl groups in a tetra-hedral arrangement, while the anion contains a central Fe(III) atom tetra-hedrally coordinated by four trimethyl-silanolate ligands.

Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation.

PubMed

Shields, Kaitlyn M; Tooley, John G; Petkowski, Janusz J; Wilkey, Daniel W; Garbett, Nichola C; Merchant, Michael L; Cheng, Alan; Schaner Tooley, Christine E

2017-08-01

A subset of B-cell lymphoma patients have dominant mutations in the histone H3 lysine 27 (H3K27) methyltransferase EZH2, which change it from a monomethylase to a trimethylase. These mutations occur in aromatic resides surrounding the active site and increase growth and alter transcription. We study the N-terminal trimethylase NRMT1 and the N-terminal monomethylase NRMT2. They are 50% identical, but differ in key aromatic residues in their active site. Given how these residues affect EZH2 activity, we tested whether they are responsible for the distinct catalytic activities of NRMT1/2. Additionally, NRMT1 acts as a tumor suppressor in breast cancer cells. Its loss promotes oncogenic phenotypes but sensitizes cells to DNA damage. Mutations of NRMT1 naturally occur in human cancers, and we tested a select group for altered activity. While directed mutation of the aromatic residues had minimal catalytic effect, NRMT1 mutants N209I (endometrial cancer) and P211S (lung cancer) displayed decreased trimethylase and increased monomethylase/dimethylase activity. Both mutations are located in the peptide-binding channel and indicate a second structural region impacting enzyme specificity. The NRMT1 mutants demonstrated a slower rate of trimethylation and a requirement for higher substrate concentration. Expression of the mutants in wild type NRMT backgrounds showed no change in N-terminal methylation levels or growth rates, demonstrating they are not acting as dominant negatives. Expression of the mutants in cells lacking endogenous NRMT1 resulted in minimal accumulation of N-terminal trimethylation, indicating homozygosity could help drive oncogenesis or serve as a marker for sensitivity to DNA damaging chemotherapeutics or γ-irradiation. © 2017 The Protein Society.

Anti-listeria effects of chitosan-coated nisin-silica liposome on Cheddar cheese.

PubMed

Cui, H Y; Wu, J; Li, C Z; Lin, L

2016-11-01

Listeria monocytogenes poses an increasing challenge to cheese production. To minimize the risk of bacterial contamination, a chitosan-coated nisin-silica liposome was engineered for the present study. We investigated the characteristics of nisin-silica liposomes and the anti-listeria effects of a chitosan-coated nisin-silica liposome on Cheddar cheese. The encapsulation efficiency of nisin in a liposome was sharply increased after it was adsorbed on a silica particle surface. Chitosan-coated nisin-silica liposomes displayed sustained antibacterial activity against L. monocytogenes, without affecting the sensory properties of the cheese. Chitosan-coated nisin-silica liposomes could be a promising active antimicrobial for cheese preservation. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation.

PubMed

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2017-12-01

Therapeutic peptides are conventionally administered via subcutaneous injection. Chitosan-based nanoparticles are gaining increased attention for their ability to serve as a carrier for oral delivery of peptides and vaccination. They offered superior biocompatibiltiy, controlled drug release profile and facilitated gastrointestinal (GI) absorption. The encapsulated peptides can withstand enzymatic degradation and various pH. Chitosan-based nanoparticles can also be modified by ligand conjugation to the surface of nanoparticle for transcellular absorption and specific-targeted delivery of macromolecules to the tissue of interest. Current research suggests that chitosan-based nanoparticles can deliver therapeutic peptide for the treatment of several medical conditions such as diabetes, bacterial infection and cancer. This review summarises the role of chitosan in oral nanoparticle delivery and identifies the clinical application of peptide-loaded chitosan-based nanoparticles.

In vitro evaluation of encapsulated primary rat hepatocytes pre- and post-cryopreservation at -80°C and in liquid nitrogen.

PubMed

Durkut, Serap; Elçin, A Eser; Elçin, Y Murat

2015-02-01

Encapsulation techniques have the potential to protect hepatocytes from cryoinjury. In this study, we comparatively evaluated the viability and metabolic function of primary rat hepatocytes encapsulated in calcium alginate microbeads, in chitosan tripolyphosphate beads, and in three-layered alginate-chitosan-alginate (ACA) microcapsules, before and after cryopreservation at -80°C and in liquid nitrogen (LN2) for 1 and 3 months. Findings demonstrated that LN2 was atop of -80°C in regard to preservation of viability (> 90%) and hepatic functions. LN2-cryopreserved hepatocytes encapsulated in ACA microcapsules retained metabolic function post-thawing, with > 90% of the albumin, total protein and urea syntheses activities, and > 80% of oxidative function.

Synthesis, characterization, bioactivity and potential application of phenolic acid grafted chitosan: A review.

PubMed

Liu, Jun; Pu, Huimin; Liu, Shuang; Kan, Juan; Jin, Changhai

2017-10-15

In recent years, increasing attention has been paid to the grafting of phenolic acid onto chitosan in order to enhance the bioactivity and widen the application of chitosan. Here, we present a comprehensive overview on the recent advances of phenolic acid grafted chitosan (phenolic acid-g-chitosan) in many aspects, including the synthetic method, structural characterization, biological activity, physicochemical property and potential application. In general, four kinds of techniques including carbodiimide based coupling, enzyme catalyzed grafting, free radical mediated grafting and electrochemical methods are frequently used for the synthesis of phenolic acid-g-chitosan. The structural characterization of phenolic acid-g-chitosan can be determined by several instrumental methods. The physicochemical properties of chitosan are greatly altered after grafting. As compared with chitosan, phenolic acid-g-chitosan exhibits enhanced antioxidant, antimicrobial, antitumor, anti-allergic, anti-inflammatory, anti-diabetic and acetylcholinesterase inhibitory activities. Notably, phenolic acid-g-chitosan shows potential applications in many fields as coating agent, packing material, encapsulation agent and bioadsorbent. Copyright © 2017 Elsevier Ltd. All rights reserved.

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil.

PubMed

Bashir, Shahid; Teo, Yin Yin; Naeem, Sumaira; Ramesh, S; Ramesh, K

2017-01-01

There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug

pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid) hydrogels and in vitro release of 5-fluorouracil

PubMed Central

Bashir, Shahid; Teo, Yin Yin; Naeem, Sumaira; Ramesh, S.; Ramesh, K.

2017-01-01

There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug

Investigation of an elutable N-propylphosphonic acid chitosan derivative composition with a chitosan matrix prepared from carbonic acid solution.

PubMed

Mania, Szymon; Tylingo, Robert; Augustin, Ewa; Gucwa, Katarzyna; Szwacki, Jakub; Staroszczyk, Hanna

2018-01-01

Porous chitosan composites using CO 2 dissolution procedure and including water soluble N-propylphosphonic chitosan derivative (p-CHI) were obtained and characterized. In contrast to the control material, composites containing modified chitosan distinguished by a rapid moisture absorption and good adhesion to the skin. The FTIR analysis confirmed the presence of propylphosphonic group in the structure of the polymer. The porosity of the materials was in the range 55-77% and decreased with increasong amount of modified chitosan in materials. Solubility of composites was dependent on the content of p-CHI in scaffolds (40%, 25% and 15%) and reached values 11%, 9% and 6,5%, respectively. The values of other parameters like swelling degree (30g/g) good antioxidant and antimicrobial properties (almost 100% reduction of S.aureus, E.coli and C. albicans growth) and low in vitro cytotoxicity against fibroblasts were highly advantageous for possible biomedical applications of the composites. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and Characterization of Novel Cationic Chitosan Derivatives Bearing Quaternary Ammonium and Phosphonium Salts and Assessment of Their Antifungal Properties.

PubMed

Tan, Wenqiang; Li, Qing; Dong, Fang; Chen, Qiuhong; Guo, Zhanyong

2017-08-31

Chitosan is an abundant and renewable polysaccharide, its derivatives exhibit attractive bioactivities and the wide applications in various biomedical fields. In this paper, two novel cationic chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized via trimethylation, chloride acetylation, and quaternization with tricyclohexylphosphine and triphenylphosphine. The structures and properties of synthesized products in the reactions were characterized by FTIR spectroscopy, ¹H-NMR, 31 P-NMR, elemental and thermogravimetric analysis. The antifungal activities of chitosan derivatives against four kinds of phytopathogens, including Phomopsis asparagi , Watermelon fusarium , Colletotrichum lagenarium , and Fusarium oxysporum were tested using the radial growth assay in vitro. The results revealed that the synthesized cationic chitosan derivatives showed significantly improved antifungal efficiency compared to chitosan. It was reasonably suggested that quaternary phosphonium groups enabled the obviously stronger antifungal activity of the synthesized chitosans. Especially, the triphenylphosphonium-functionalized chitosan derivative inhibited the growth of Phomopsis asparagi most effectively, with inhibitory indices of about 80% at 0.5 mg/mL. Moreover, the data demonstrated that the substituted groups with stronger electron-withdrawing ability relatively possessed greater antifungal activity. The results suggest the possibility that cationic chitosan derivatives bearing quaternary phosphonium salts could be effectively employed as novel antifungal biomaterials for application in the field of agriculture.

Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels.

PubMed

Najafi-Soulari, Samira; Shekarchizadeh, Hajar; Kadivar, Mahdi

2016-11-01

Calcium alginate hydrogel beads were used to encapsulate lemon balm extract. Chitosan layer was used to investigate the effect of hydrogel coating. To determine the interactions of antioxidant compounds of extract with encapsulation materials and its stability, microstructure of hydrogel beads was thoroughly monitored using scanning electron microscopy and Fourier transform infrared (FTIR). Total polyphenols content and antiradical activity of lemon balm extract were also evaluated before and after encapsulation. Three significant parameters (lemon balm extract, sodium alginate, and calcium chloride concentrations) were optimized by response surface methodology to obtain maximum encapsulation efficiency. The FTIR spectra showed no interactions between extract and polymers as there were no new band in spectra of alginate hydrogel after encapsulation of active compounds of lemon balm extract. The antioxidant activity of lemon balm extract did not change after encapsulation. Therefore, it was found that alginate is a suitable material for encapsulation of natural antioxidants. Sodium alginate solution concentration, 1.84%, lemon balm extract concentration, 0.4%, and calcium chloride concentration, 0.2% was determined to be the optimum condition to reach maximum encapsulation efficiency.

Enhancement of antioxidant and antibacterial properties for tannin acid/chitosan/tripolyphosphate nanoparticles filled electrospinning films: Surface modification of sliver nanoparticles.

PubMed

Zhan, Fuchao; Sheng, Feng; Yan, Xiangxing; Zhu, Yingrui; Jin, Weiping; Li, Jing; Li, Bin

2017-11-01

The tannin acid/chitosan/tripolyphosphate nanoparticles were encapsulated in polyvinyl alcohol (PVA)/poly-acrylic acid (PAA) electrospinning films by electrostatic spinning technology. To optimize the prepared condition, properties and morphology of nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The optimized initial concentration of tannin, chitosan and tripolyphosphate solutions were 1, 1, 0.5mg/ml, respectively, with adding proportion for 5:5:1. The average diameter of tannin acid/chitosan/tripolyphosphate nanoparticles was ∼80nm. The electrospinning films showed an excellent water-resistant property with 0.5wt%N,N'-Methylenebisacrylamide (MBA). Due to the antioxidant and antibacterial of tannic acid, the films possessed these properties. The antioxidant and antibacterial of these fibers significantly improved after in situ formation of silver nanoparticles (AgNPs). Electrospun films were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Copyright © 2017 Elsevier B.V. All rights reserved.

Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity.

PubMed

Popat, Amirali; Karmakar, Surajit; Jambhrunkar, Siddharth; Xu, Chun; Yu, Chengzhong

2014-05-01

Curcumin (CUR), a naturally derived anti-cancer cocktail is arguably the most widely studied neutraceutical. Despite a lot of promises, it is yet to reach the market as an active anti-cancer formulation. In the present study, we have prepared highly soluble (3 mg/ml) CUR-γ-hydroxypropyl cyclodextrin (CUR-CD) hollow spheres. CUR-CD hollow spheres were prepared by a novel and scalable spray drying method. CUR-CD was then encapsulated into positively charged biodegradable chitosan (CUR-CD-CS) nanoparticles. The CUR-CD-CS nanoparticles were characterised by TEM, SEM, DLS, drug loading and in vitro release. We tested the efficacy of these CUR-CD-CS nanoparticles in SCC25 cell lines using MTT assay and investigated its cellular uptake mechanism. We also studied Oligo DNA loading in CUR-CD-CS nanoparticles and its delivery via confocal imaging and FACS analysis. Our results demonstrated that CUR-CD-CS nanoparticles showed superior in vitro release performance and higher cytotoxicity in SCC25 cell line amongst all tested formulations. The cytotoxicity results were corroborated by cell cycle analysis and apoptosis test, showing nearly 100% apoptotic cell death in the case of CUR-CD-CS nanoparticles. Compared to CS nanoparticles, CS-CD nanoformulation showed higher cellular delivery of Cy3-Oligo DNA which was tested quantitatively using flowcytometry analysis, indicating that CD not only enhanced CUR solubility but also boosted the cellular uptake. Our study shows that rationally designed bio-degradable natural biomaterials have great potential as next generation nano-carriers for hydrophobic drug delivery such as CUR with potential of dual drug-gene delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis, crystal structure and antitumor activities of water soluble protonated salt of 20(S)-camptothecin

NASA Astrophysics Data System (ADS)

Lu, Wen; Wang, Yong; Wang, Luna; Zhao, Fengyi; Yang, Shilong; Xi, Chengjie; Yang, Yu; Xu, Li; Chi, Xingwei

2018-03-01

A water soluble camptothecin protonated salt has been synthesized; single crystals were grown by slow evaporation solution growth technique at room temperature and characterized by single crystal X-ray diffraction, FT-IR and 1H NMR. The CPT was protonated as (CPT+H+) cations, the cationic protonation occurred on the N position at pyridine group, which fromed a cation-anion compound with perchlorate ion that determined by X-Ray diffraction. Its activities against Hela (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver) and HUVEC (umbilical vein, normal cell) were investigated. The toxicity of the protonated salt was slightly lower than camptothecin. IC50 values of 7.01 μM against HepG-2 cell, 8.61 μM against A549 cell, 17.82 μM against McF-7 cell, all of them are lower than the IC50 values of CPT against these cells except Hela cell.

Nanoparticles Based on Chitosan as Carriers for the Combined Herbicides Imazapic and Imazapyr

PubMed Central

Maruyama, Cintia Rodrigues; Guilger, Mariana; Pascoli, Mônica; Bileshy-José, Natalia; Abhilash, P.C.; Fraceto, Leonardo Fernandes; de Lima, Renata

2016-01-01

The use of lower concentrations and fewer applications of herbicides is one of the prime objectives of the sustainable agriculture as it decreases the toxicity to non-targeted organisms and the risk of wider environmental contamination. In the present work, nanoparticles were developed for encapsulation of the herbicides imazapic and imazapyr. Alginate/chitosan and chitosan/tripolyphosphate nanoparticles were manufactured, and their physicochemical stability was evaluated. Determinations were made of the encapsulation efficiency and release kinetics, and the toxicity of the nanoparticles was evaluated using cytotoxicity and genotoxicity assays. The effects of herbicides and herbicide-loaded nanoparticles on soil microorganisms were studied in detail using real-time polymerase chain reactions. The nanoparticles showed an average size of 400 nm and remained stable during 30 days of storage at ambient temperature. Satisfactory encapsulation efficiencies of between 50 and 70% were achieved for both types of particles. Cytotoxicity assays showed that the encapsulated herbicides were less toxic, compared to the free compounds, and genotoxicity was decreased. Analyses of soil microbiota revealed changes in the bacteria of the soils exposed to the different treatments. Our study proves that encapsulation of the herbicides improved their mode of action and reduced their toxicity, indicating their suitability for use in future practical applications. PMID:26813942

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

PubMed

Yadav, Monu; Parle, Milind; Sharma, Nidhi; Dhingra, Sameer; Raina, Neha; Jindal, Deepak Kumar

2017-11-01

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3 2 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP opt ) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP opt , with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

Chitosan-based nanocoatings for hypothermic storage of living cells.

PubMed

Bulwan, Maria; Antosiak-Iwańska, Magdalena; Godlewska, Ewa; Granicka, Ludomira; Zapotoczny, Szczepan; Nowakowska, Maria

2013-11-01

The formation of ultrathin chitosan-based nanocoating on HL-60 model cells and their protective function in hypothermic storage are presented. HL-60 cells are encapsulated in ultrathin shells by adsorbing cationic and anionic chitosan derivatives in a stepwise, layer-by-layer, procedure carried out in an aqueous medium under mild conditions. The chitosan-based films are also deposited on model lipid bilayer and the interactions are studied using ellipsometry and atomic force microscopy. The cells covered with the chitosan-based films and stored at 4 °C for 24 h express viability comparable to that of the control sample incubated at 37 °C, while the unprotected cells stored under the same conditions do not show viability. It is shown that the chitosan-based shell protects HL-60 cells against damaging effect of hypothermic storage. Such nanocoatings provide protection, mechanical stability, and support the cell membrane, while ensuring penetration of small molecules such as nutrients/gases what is essential for cell viability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An acid-free water-born quaternized chitosan/montmorillonite loaded into an innovative ultra-fine bead-free water-born nanocomposite nanofibrous scaffold; in vitro and in vivo approaches.

PubMed

Dastjerdi, Roya; Sharafi, Mahsa; Kabiri, Kourosh; Mivehi, Leila; Samadikuchaksaraei, Ali

2017-07-26

An acid-free water-born chitosan derivative/montmorillonite has been successfully synthesized. A natural-based biopolymer, N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride, was synthesized, and its structure confirmed by Fourier transform infrared microscopy and conductometric titration. It was applied to the cationic ion-exchange reaction of montmorillonite. Then, the synthesized materials were used to produce water-born composite scaffolds for tissue engineering applications and formed an ultra-fine bead-free multicomponent nanofibrous scaffold. The scaffold was subjected to in vitro and in vivo investigations. The effects of both acidic and neutral reaction media on the efficiency of the cationic ion-exchange reaction of montmorillonite were investigated. A mechanism has been suggested for the more efficient cationic ion-exchange reaction achieved in the absence of the acid. In in vitro studies, the modified montmorillonite showed synergistic biocompatibility and cell growth with enhanced bioactivity compared to unmodified clay and even chitosan and the chitosan derivative. Scanning electron microscopy showed ultra-fine bead-free nanocomposite nanofibers. Improved biocompatibility, cell attachment, and cell growth were observed for the nanofibrous scaffolds compared to the individual components. In vivo experiments showed complete restoration of a critical-sized full-thickness wound without infection in 21 d. The technique provides a guideline to achieve chitosan nanofibrous morphology for multifunctional biomedical applications.

Chitosan based metallic nanocomposite scaffolds as antimicrobial wound dressings.

PubMed

Mohandas, Annapoorna; Deepthi, S; Biswas, Raja; Jayakumar, R

2018-09-01

Chitosan based nanocomposite scaffolds have attracted wider applications in medicine, in the area of drug delivery, tissue engineering and wound healing. Chitosan matrix incorporated with nanometallic components has immense potential in the area of wound dressings due to its antimicrobial properties. This review focuses on the different combinations of Chitosan metal nanocomposites such as Chitosan/nAg, Chitosan/nAu, Chitosan/nCu, Chitosan/nZnO and Chitosan/nTiO 2 towards enhancement of healing or infection control with special reference to the antimicrobial mechanism of action and toxicity.

Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

PubMed

Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J

2018-01-01

Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p  < 0.05) reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared to

Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin.

PubMed

Aluani, Denitsa; Tzankova, Virginia; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Nikolova, Elena; Odzhakov, Feodor; Apostolov, Alexandar; Markova, Tzvetanka; Yoncheva, Krassimira

2017-10-01

The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe 2+ /AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

Mucosal delivery of liposome-chitosan nanoparticle complexes.

PubMed

Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

2009-01-01

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

Effect of complexation conditions on microcapsulation of Lactobacillus acidophilus in xanthan-chitosan polyelectrolyte complex gels.

PubMed

Chen, He; Song, Yajuan; Liu, Nina; Wan, Hongchang; Shu, Guowei; Liao, Na

2015-01-01

Lactobacillus acidophilus has become increasingly popular because of their beneficial effects on health of their host, and are called proboscis. In order to exert beneficial effects for probiotics, they must be able to tolerate the acidic conditions of the stomach environment and the bile in the small intestine. Microencapsulated form has received reasonable attention, since it can protect probiotic organisms against an unfavourable environment, and to allow their release in a viable and metabolically active state in the intestine. The aim of this study was to investigate some factores, such as chitosan solution pH and concentration, xanthan concentration, cell suspension-xanthan ratio, mixed bacteria glue liquid-chitosan ratio, which impacted the process of microencapsulation of L. acidophilus. In this study, L. acidophilus was immobilized with xanthan⁄chitosan gel using extrusion method. The viable counts and encapsulation yield of L. acidophilus encapsulated in different chitosan solution pH (4.5, 5, 5.5 and 6), in different chitosan concentration (0.5%, 0.7%, 0.9% and 1.1%), in different xanthan concentration (0.5%, 0.7%, 0.9% and 1.1%), in different cell suspension-xanthan ratios (1:5, 1:10, 1:15 and 1:20), in different mixed bacteria glue liquid-chitosan ratios (1:3, 1:4, 1:5 and 1:6), have been investigated by single factor experiment method. The optimum conditions of microencapsulated L. acidophilus have been observed. The optimum chitosan solution pH for L. acidophilus was 5.5; the optimum chitosan concentration was 0.9%; the optimum xanthan concentration was 0.7%; the optimum cell suspension-xanthan ratio was 1:10; the optimum mixed bacteria glue liquid-chitosan ratio was 1:3. These results will be helpful to further optimize the process of L. acidophilus microencapsulation, and provide reference for obtaining higher viable counts and entrapped yield of L. acidophilus microcapsules.

Carboxymethyl chitosan-poly(amidoamine) dendrimer core-shell nanoparticles for intracellular lysozyme delivery.

PubMed

Zhang, Xiaoyang; Zhao, Jun; Wen, Yan; Zhu, Chuanshun; Yang, Jun; Yao, Fanglian

2013-11-06

Intracellular delivery of native, active proteins is challenging due to the fragility of most proteins. Herein, a novel polymer/protein polyion complex (PIC) nanoparticle with core-shell structure was prepared. Carboxymethyl chitosan-grafted-terminal carboxyl group-poly(amidoamine) (CM-chitosan-PAMAM) dendrimers were synthesized by amidation and saponification reactions. (1)H NMR was used to characterize CM-chitosan-PAMAM dendrimers. The TEM images and results of lysozyme loading efficiency indicated that CM-chitosan-PAMAM dendrimers could self-assemble into core-shell nanoparticles, and lysozyme was efficiently encapsulated inside the core of CM-chitosan-PAMAM dendrimer nanoparticles. Activity of lysozyme was completely inhibited by CM-chitosan-PAMAM Dendrimers at physiological pH, whereas it was released into the medium and exhibited a significant enzymatic activity in an acidic intracellular environment. Moreover, the CM-chitosan-PAMAM dendrimer nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 3.16 mg/ml. The results indicated that these CM-chitosan-PAMAM dendrimers have excellent properties as highly potent and non-toxic intracellular protein carriers, which would create opportunities for novel applications in protein delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Encapsulation of a proteasome inhibitor with gold-polysaccharide nanocarriers

NASA Astrophysics Data System (ADS)

Coelho, Sílvia Castro; Rocha, Sandra; Sampaio, Paula; Pereira, Maria Carmo; Coelho, Manuel A. N.

2014-04-01

Organic-inorganic hybrid nanoparticles are potential effective systems for drug delivery in cancer therapy and diagnosis. Chitosan-gum arabic with entrapped gold nanoparticles were developed as a carrier for an anticancer drug bortezomib. The nanosystem was designed to enhance the proteasome inhibitor activity in pancreatic cell lines, S2-013 and hTERT-HPNE. The hydrodynamic diameter of chitosan-gum arabic-gold nanoparticles loaded with bortezomib is around 330 nm. Laser scanning confocal microscopy images show the uptake of the gold nanoparticle/bortezomib encapsulated in chitosan-gum arabic matrix and the fast internalization of these nano combinations into pancreatic cells. Cytotoxic assays assessed that positively charged nanosystems reduce the cell growth and cell proliferation of S2-013s, but the same effect was not observed in cytotoxic response in hTERT-HPNE cells. The outcomes of this study demonstrate the capacity of chitosan-gum arabic nanocarriers to deliver gold nanoparticles/anticancer drug and to increase the permeation and retention effect in S2-013 cells and minimize drug side effects in HPNE cells.

Preparation and drug release properties of chitosan/organomodified palygorskite microspheres.

PubMed

Wu, Jie; Ding, Shijie; Chen, Jing; Zhou, Suqin; Ding, Hongyan

2014-07-01

The novel composite microspheres, based on the hybridization of chitosan (CS) and organomodified palygorskite (OPAL), were prepared by emulsion cross-linking technique and applied as a drug carrier. Palygorskite, a kind of natural one-dimensional clay, was modified with hexadecyl betaine (BS-16) to improve the compatibility and affinity with chitosan matrix, and worked as a perfect micron-filler to enhance drug encapsulation and retard drug migration. The structure of the microspheres was characterized by fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. The swelling behavior of the microspheres and the effect of the amount of OPAL and BS-16 on the properties of the drug loading and releasing have been investigated. Compared to the pure chitosan microspheres (CM), the composite one with 20wt% OPAL modified by 20mmol/100g BS-16 possessed the higher encapsulation efficiency and the slower and continuous cumulative release for diclofenac sodium (DS) in phosphate buffer solution (pH 6.8). The study of drug release kinetics in vitro found that the drug release mechanism of the microspheres changed from the simple diffusion-control to diffusion and dissolution-control as the OPAL content in matrix increased from 0 to 20wt%. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation of microcapsules by complex coacervation of gum Arabic and chitosan.

PubMed

Butstraen, Chloé; Salaün, Fabien

2014-01-01

Gum Arabic-chitosan microcapsules containing a commercially available blend of triglycerides (Miglyol 812 N) as core phase were synthesized by complex coacervation. This study was conducted to clarify the influence of different parameters on the encapsulation process, i.e. during the emulsion formation steps and during the shell formation, using conductometry, zeta potential, surface and interface tension measurement and Fourier-transform infrared spectroscopy. By carefully analyzing the influencing factors including phase volume ratio, stirring rate and time, pH, reaction time, biopolymer ratio and crosslinking effect, the optimum synthetic conditions were found out. For the emulsion step, the optimum phase volume ratio chosen was 0.10 and an emulsion time of 15 min at 11,000 rpm was selected. The results also indicated that the optimum formation of these complexes appears at a pH value of 3.6 and a weight ratio of chitosan to gum Arabic mixtures of 0.25. Copyright © 2013 Elsevier Ltd. All rights reserved.

Electrospray-assisted encapsulation of caffeine in alginate microhydrogels.

PubMed

Nikoo, Alireza Mehregan; Kadkhodaee, Rassoul; Ghorani, Behrouz; Razzaq, Hussam; Tucker, Nick

2018-05-02

One of the major challenges with microencapsulation and delivery of low molecular weight bioactive compounds is their diffusional loss during storage and process conditions as well as under gastric conditions. In an attempt to slow down the release rate of core material, electrospray fabricated calcium alginate microhydrogels were coated with low molecular weight and high molecular weight chitosans. Caffeine as a hydrophilic model compound was used due to its several advantages on human behavior especially increasing consciousness. Mathematical modeling of the caffeine release by fitting the data with Korsmeyer-Peppas model showed that Fick's diffusion law could be the prevalent mechanism of the release. Electrostatic interaction between alginate and chitosan (particularly in the presence of 1% low molecular weight chitosan) provided an effective barrier against caffeine release and significantly reduced swelling of particles compared to control samples. The results of this study demonstrated that calcium alginate microhydrogels coated by chitosan could be used for encapsulation of low molecular compounds. However, more complementary research must be done in this field. In addition, electrospray, by producing monodisperse particles, would be as an alternative method for fabrication of microparticles based on natural polymers. Copyright © 2018. Published by Elsevier B.V.

Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells.

PubMed

Li, Pu-Wang; Wang, Guang; Yang, Zi-Ming; Duan, Wei; Peng, Zheng; Kong, Ling-Xue; Wang, Qing-Huang

2016-01-01

Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250 nm in diameter with smooth surface and were negatively charged with a zeta potential of - 17.4 mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs.

The use of cross-linked chitosan beads for nutrients (nitrate and orthophosphate) removal from a mixture of P-PO4, N-NO2 and N-NO3.

PubMed

Jóźwiak, Tomasz; Filipkowska, Urszula; Szymczyk, Paula; Kuczajowska-Zadrożna, Małgorzata; Mielcarek, Artur

2017-11-01

A hydrogel chitosan sorbent ionically cross-linked with sodium citrate and covalently cross-linked with epichlorohydrin was used to remove nutrients from an equimolar mixture of P-PO 4 , N-NO 2 and N-NO 3 . The scope of the study included, among other things, determination of the influence of pH on nutrient sorption effectiveness, nutrient sorption kinetics as well as determination of the maximum sorption capacity of cross-linked chitosan sorbents regarding P-PO 4 (H 2 PO 4 - , HPO 4 2- ), N-NO 2 (HNO 2 , NO 2 - ), and N-NO 3 (NO 3 - ). The effect of the type of the cross-linking agent on the affinity of the modified chitosan to each nutrient was studied as well. The kinetics of nutrient sorption on the tested chitosan sorbents was best described with the pseudo-second order model. The model of intramolecular diffusion showed that P-PO 4 , N-NO 2 and N-NO3 sorption on cross-linked hydrogel chitosan beads proceeded in two phases. The best sorbent of nutrients turned out to be chitosan cross-linked covalently with epichlorohydrin; with P-PO 4 , N-NO 2 and N-NO 3 sorption capacity reaching: 1.23, 0.94 and 0.76mmol/g, respectively (total of 2.92mmol/g). For comparison, the sorption capacity of chitosan cross-linked ionically with sodium citrate was: 0.43, 0.39 and 0.39mmol/g for P-PO 4 , N-NO 2 and N-NO 3 , respectively (total of 1.21mmol/g). Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity.

PubMed

Tzankova, Virginia; Aluani, Denitsa; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Odzhakov, Feodor; Apostolov, Alexandar; Yoncheva, Krassimira

2017-08-01

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10μg/ml) significantly attenuated the decrease in cell viability in H 2 О 2 -induced oxidative stress (0.1mM H 2 О 2 ) , thus showing an effective in vitro protection. In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol - induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18mg/kg b.w., 7days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Preparation of thermally stable microcapsules with a chitosan-silica hybrid.

PubMed

Kang, Hong-Yi; Chen, Hui-Huang

2014-09-01

Addition of microcapsules with a high dielectric constant and low specific heat capacity to a battered layer was designed to create a higher temperature in the crust than in the prefried fish nuggets to prevent the water vapor in the fish nuggets from migrating to the crust during microwave heating. Therefore, chitosan-silica hybrids and soybean oil were utilized to prepare the shell and core of the thermally stable microcapsules (MC(CS)), respectively. The MC(CS) were prepared by sol-gel coacervation from an oil-in-water emulsion. The sodium silicate was hydrolyzed and coacervated through polymerization for 24 h at pH 5. The zeta potential analysis indicated that chitosan with a positive charge and silica with a negative charge interacted through electrostatic attraction to form a hybrid shell. The volume mean particle size and encapsulation efficiency of the MC(CS) were 9.6 ± 0.2 μm and 75.6% ± 1.3%, respectively, when oil/chitosan = 0.2 and chitosan/silica = 0.5 (w/w). In addition to H-bonding and electrostatic attraction, Si-O-N bonds were formed between chitosan and silica. Dehydration of the bound water in the MC(CS) was observed in the range of 25 to 250 °C in the differential scanning calorimetry thermal analysis, with the lack of apparent thermal peaks indicating its high thermal stability. The decrease of force to cut the crust observed by texture analysis as well as the increase of hedonic score by consumer acceptance test revealed the addition of 1% MC(CS) significantly improved the crispness of the crust in the microwave-reheated nuggets. © 2014 Institute of Food Technologists®

Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering.

PubMed

Choi, Bogyu; Kim, Soyon; Lin, Brian; Wu, Benjamin M; Lee, Min

2014-11-26

Cartilaginous extracellular matrix (ECM) components such as type-II collagen (Col II) and chondroitin sulfate (CS) play a crucial role in chondrogenesis. However, direct clinical use of natural Col II or CS as scaffolds for cartilage tissue engineering is limited by their instability and rapid enzymatic degradation. Here, we investigate the incorporation of Col II and CS into injectable chitosan hydrogels designed to gel upon initiation by exposure to visible blue light (VBL) in the presence of riboflavin. Unmodified chitosan hydrogel supported proliferation and deposition of cartilaginous ECM by encapsulated chondrocytes and mesenchymal stem cells. The incorporation of native Col II or CS into chitosan hydrogels further increased chondrogenesis. The incorporation of Col II, in particular, was found to be responsible for the enhanced cellular condensation and chondrogenesis observed in modified hydrogels. This was mediated by integrin α10 binding to Col II, increasing cell-matrix adhesion. These findings demonstrate the potential of cartilage ECM-modified chitosan hydrogels as biomaterials to promote cartilage regeneration.

Hesperidinase encapsulation towards hesperitin production targeting improved bioavailability.

PubMed

Furtado, Andreia F M; Nunes, Mario A P; Ribeiro, Maria H L

2012-11-01

Hesperidin (hesperitin-7-O-rutinoside) and hesperitin (hesperitin-7-O-glucoside) show anti-inflammatory, antimicrobial, antioxidant, and anticarcinogenic effects and prevent bone loss. However, hesperidin has a low bioavailability compared to hesperitin due to the rutinoside moiety attached to the flavonoid. The removal of the rhamnose group to yield the corresponding flavonoid glucoside (hesperetin-7-glucoside) improved the bioavailability of the aglycone, hesperetin, in humans. In line with these assumptions, the aim of this work was the enzymatic production of hesperitin from hesperidin with hesperidinase. Despite the low hesperidin solubility in the reaction medium, the enzymatic bioconversion was carried with hesperidin soluble at lower concentrations (≤0.05 mg ml(-1)) and insoluble for high concentrations (>0.1-50 mg ml(-1)). A twofold increase in maximum reaction rates overtook the expected values, pointing to the enzyme ability to degrade insoluble hesperidin. To improve the bioprocess, hesperidinase was tested soluble and immobilized in calcium alginate (2%), k-carrageenan (2%), and chitosan (2%) beads. The immobilization was carried out by adsorption and encapsulation. Chitosan was cross-linked with glutaraldehyde (1% and 2%) and sodium sulfate (13.5% and 15%) in acetate buffer (0.02 M, pH 4.0). The relation between bioprocessing conditions and hesperidinase stability was studied. A residual activity of 193% was obtained with immobilized hesperidinase compared to the soluble form. A half-life of 770 min was attained with hesperidinase encapsulated in calcium alginate beads. The results presented in this work highlight the potential of hesperidinase encapsulation towards hesperitin production with insoluble substrate. To our knowledge, this work presents for the first time the potential of hesperidinase encapsulation on hydrogels for hesperitin production. This is an important achievement for pharmaceutical and nutraceutical applications of hesperitin

Effect of silibinin-loaded nano-niosomal coated with trimethyl chitosan on miRNAs expression in 2D and 3D models of T47D breast cancer cell line.

PubMed

Yazdi Rouholamini, Seyede Elmira; Moghassemi, Saeid; Maharat, Zahra; Hakamivala, Amirhossien; Kashanian, Susan; Omidfar, Kobra

2018-05-01

Silibinin is a natural flavonoid with a strong antioxidant property and weak cytotoxic activity. It has demonstrated anti-tumoural activity against many types of malignancies; however, due to its hydrophobic structure, it has poor water solubility, bioavailability and permeability across intestinal epithelial cells. To improve the effect of silibinin, we have vehiculated silibinin by a highly stable niosomal nanostructure based on a Span 60/cholesterol (CH)/N-trimethyl chitosan (TMC) system in order to study its potential application for the delivery of silibinin in T47D cultured under three-dimensional (3D) and two-dimensional (2D) conditions. To study the effect of nanodrug on miRNAs expression, we evaluated quantitative expression of miRNA-21 and miRNA-15a as well as miR-141 and miR-200c which act as oncogene and tumour suppressors by real-time PCR. Results demonstrated that the mechanism of nanodrug action as well as the response of tumour cells differed in 3D culture as compared to 2D. Delivery of silibinin-loaded niosomes coated with TMC was found to be more effective in inhibiting the growth of tumour cells and inducing apoptosis than free silibinin administration. In silibinin-treated cells, death occurred in a dose- and time- dependent manner by induction of apoptosis and alteration of the cell cycle. Real-time PCR analysis revealed a decrease in miR-21, miR-15a and miR-141while increase in miR-200c expression levels was observed in silibinin-treated cells relative to the levels in the untreated cells. The results show that nanodrug delivery was more effective than free silibinin administration in changing the level of miRNAs expression in cancer cells. Therefore, niosomal nanostructure with TMC could be a suitable vehicle for hydrophobic compounds, such as silibinin, by improving their action in cancer therapy.

Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma.

PubMed

Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

2017-09-01

Rationale of this study was framed to investigate the protective effect and anti-cancer property of nanoparticles based on chitosan isolated from squid, Sepioteuthis lessoniana, on hepatic cells in N-Nitrosodiethylamine-induced hepatocellular carcinoma in rats. The results conferred that the chitosan nanoparticle supplementation had a protective effect on liver cells by reducing the levels of marker enzymes and bilirubin and thus increasing the albumin levels. The level of reduced glutathione, ascorbic acid and α-tocopherol significantly increased in both post- and pre-treatment with chitosan nanoparticles. The levels of antioxidant enzymes were enhanced and lipid peroxidation products were diminished while treating nitrosodiethylamine-induced hepatocellular carcinoma with chitosan nanoparticles. Supplementation of chitosan nanoparticles had potent anti-hyperlipidemic property that was evidenced by monitoring the serum lipid levels and its components. Animals pre-treated with chitosan nanoparticles along with nitrosodiethylamine showed a significant reduction in the total cholesterol and triglycerides levels with increase in the levels of phospholipids and free fatty acids. Chitosan nanoparticles treated rats showed significant increment in high-density lipoprotein cholesterol and reduction in low-density lipoprotein and very low-density lipoprotein cholesterol when compared with levels in nitrosodiethylamine-induced hepatocellular carcinoma. Nitrosodiethylamine-induced carcinoma changes on circulation and hepatic antioxidant defense mechanism were regulated by chitosan nanoparticles, concluding that the chitosan nanoparticles have a potent protective effect on liver cells which might be due to its robust antioxidant and anti-lipidemic property. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of pore CaCO3 form agencies on dissolution mechanisms of amoxicillin drugs encapsulated in hydrogels full-IPN chitosan N-vinyl caprolactam

NASA Astrophysics Data System (ADS)

Budianto, Emil; Fauzia, Maghfira

2018-04-01

The administration of amoxicillin trihydrate in Helicobacter pylori infection is not effective enough because the conventional preparations used have a short retention time in the stomach. To overcome this problem, amoxicillin trihydrate was encapsulated into the floating drug delivery matrix-matrix. In this study, the full-ipn acetaldehyde crosslinked hydrogel (N-vinyl caprolactam) was synthesized with a 10% CaCO3 pore forming agent and then encapsulated on amoxicillin trihydrate and studied the mechanism of drug dissolution with its kinetic kinetics approach. The K-PNVCL Hydrogel produces optimal properties which are then loaded with amoxicillin trihydrate in situ and post loading. In this research, we have got the percentage of swelling, floating time, the efficiency of in situ and post loading 873%; 3.15 minutes; 99.8% and 99.4%. The dissolution test was performed on amoxicillin trihydrate which had been encapsulated K-PNVCL hydrogel in vitro at pH 1.2 resulting in 94.5% for in situ loading and 98.5% for post loading. Results of the kinetics of drug release for post loading and in situ loading methods tend to follow the Higuchi model kinetics. The drug release mechanism occurs by Fickian diffusion. Proof of drug release mechanism from K-PNVCL hydrogel matrix is further done by Scanning Electron Microscope (SEM) instrument.

Characterization of bioactive chitosan and sulfated chitosan from Doryteuthis singhalensis (Ortmann, 1891).

PubMed

Ramasamy, Pasiyappazham; Subhapradha, Namasivayam; Thinesh, Thangadurai; Selvin, Joseph; Selvan, Kanagaraj Muthamizh; Shanmugam, Vairamani; Shanmugam, Annaian

2017-06-01

Chitosan was extracted from the pen of squid Doryteuthis singhalensis and characterized using FT-IR, NMR, CHN, SEM and DSC analysis. Purified chitosan was sulfated with chlorosulfonic acid in N,N-dimethylformamide and the added sulfate group was confirmed with FT-IR analysis. The molecular weight and degree of deacetylation (DDA) of chitosan was found 226.6kDa and 83.76% respectively. Chitosan exhibited potent antioxidant activity evidenced by reducing power, chelating ability on ferrous ions and scavenging activity on DPPH, superoxide and hydroxyl radicals. The anticoagulant assay using activated partial thromboplastin time (APTT) and prothrombin time (PT) showed chitosan as a strong anticoagulant. The results of this study showed possibility of using D. singhalensis pen as a non-conventional source of natural antioxidants and anticoagulant which can be incorporated in functional food formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Biodegradable Chitosan Magnetic Nanoparticle Carriers for Sub-Cellular Targeting Delivery of Artesunate for Efficient Treatment of Breast Cancer

NASA Astrophysics Data System (ADS)

Subramanian, Natesan; Abimanyu, Sugumaran; Vinoth, Jeevanesan; Sekar, Ponnusamy Chandra

2010-12-01

Artesunate is a semi-synthetic derivative of artemisinin, the active principle extracted from Artemisia annua. It possesses good anti-proliferative activity and anti-angiogenic activity with very low toxicity to normal healthy cells. The drawback of most cancer drugs is their inability to accumulate selectively in the cancerous cells. So, large quantities of doses have to be administered to get the required therapeutic concentration in the target site and it resulted in many serious side effects due to the exposure of healthy cells to higher concentrations of cytotoxic drugs. The problem may be solved by selectively and quantitatively accumulating the drug at target site using magnetic nanoparticles guided by an externally applied magnetic field. A modest attempt has been made in this present study, the artesunate magnetic nanoparticle was successfully formulated using two forms of chitosan and evaluated for its in-vitro characteristics like surface morphology, particle size and distribution, zeta potential, magnetic susceptibility, encapsulation efficiency, loading capacity and in-vitro drug release. The synthesized magnetite size was 73 nm and the size of developed magnetic nanoparticles of artesunate was in the range of 90 to 575 nm. Acetic acid soluble chitosan at low concentration exhibit highest encapsulation efficiency and drug loading whereas increase in water soluble chitosan concentration increases the encapsulation efficiency and drug loading in formulations. The developed chitosan magnetic nanoparticles of artesunate shows better release characteristics and may be screened for its in-vivo breast cancer activity.

Effect of Chitosan on the Induction of DNA Damage Response by Selenium Compounds

USDA-ARS?s Scientific Manuscript database

Selenium (Se), a nutrient trace mineral, plays important roles in optimizing human health. Chitosan is an effective, natural-oriented material for synthesizing nanopolymers, with preferable properties such as biocompatibility, biodegradation and resistance to certain enzymes. In this study, encapsul...

Prosopis alba exudate gum as excipient for improving fish oil stability in alginate-chitosan beads.

PubMed

Vasile, Franco Emanuel; Romero, Ana María; Judis, María Alicia; Mazzobre, María Florencia

2016-01-01

The aim of the present work was to employ an exudate gum obtained from a South American wild tree (Prosopis alba), as wall material component to enhance the oxidative stability of fish oil encapsulated in alginate-chitosan beads. For this purpose, beads were vacuum-dried and stored under controlled conditions. Oxidation products, fatty acid profiles and lipid health indices were measured during storage. Alginate-chitosan interactions and the effect of gum were manifested in the FT-IR spectra. The inclusion of the gum in the gelation media allowed decreasing the oxidative damage during storage in comparison to the free oil and alginate-chitosan beads. The gum also improved wall material properties, providing higher oil retention during the drying step and subsequent storage. Fatty acids quality and lipid health indices were widely preserved in beads containing the gum. Present results showed a positive influence of the gum on oil encapsulation and stability, being the main mechanism attributed to a physical barrier effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

UV-screening chitosan nanocontainers: increasing the photostability of encapsulated materials and controlled release

NASA Astrophysics Data System (ADS)

Anumansirikul, Nattaporm; Wittayasuporn, Mayura; Klinubol, Patcharawalai; Tachaprutinun, A.; Wanichwecharungruang, Supason P.

2008-05-01

Methyl ether terminated poly(ethylene glycol)-4-methoxycinnamoylphthaloylchitosan (PCPLC), a UV absorptive polymer, and methyl ether terminated poly(ethylene glycol)-phthaloylchitosan (PPLC) were synthesized, characterized and self-assembled into stable water-dispersible spherical nanoparticles. The encapsulation of a model compound, 2-ethylhexyl-4-methoxycinnamate (EHMC), was carried out to give particles with 67% (w/w) EHMC loading. The E to Z photoisomerization of EHMC encapsulated inside both particles was monitored and compared to non-encapsulated EHMC. Minimal E to Z photoisomerization was observed when EHMC was encapsulated in PCPLC particles prepared from a polymer with a maximum degree of 4-methoxycinnamoyl substitution. The results indicated that the grafted UVB absorptive chromophore, 4-methoxycinnamoyl moieties, situated at the shell of PCPLC nanoparticles acted as a UV-filtering barrier, protecting the encapsulated EHMC from the UVB radiation, thus minimizing its photoisomerization. In vitro experiments revealed the pH-dependent controlled release of EHMC from PCPLC and PPLC particles. Ex vivo experiments, using a Franz diffusion cell with baby mouse skin, indicated that neither PPLC nor PCPLC particles could penetrate the skin into the receptor medium after a 24 h topical application. When applied on the baby mouse skin, both EHMC-encapsulated PPLC and EHMC-encapsulated PCPLC showed comparable controlled releases of the EHMC. The released EHMC could transdermally penetrate the baby mouse skin.

Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: Characterization and cytotoxic effect on MCF-7 breast cancer cell lines.

PubMed

Nayak, Debasis; Minz, Aliva Prity; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Chopra, Pankaj; Nayak, Bismita

2016-05-15

Chitosan (Cs) is a biocompatible, biodegradable cationic polymer having the ability of targeted drug delivery. Vitamin E and C are not synthesized in our body thus, when encapsulated within a carrier system these vitamins in combination with/alone can be utilized for their anti-cancer potentials. The present investigation was conducted to develop a stable nanoparticle based formulation encapsulating antioxidants (Vitamin E, catechol) and silver nanoparticles synthesized from Hibiscus rosa-sinensis (HRS) petal extracts within a chitosan matrix. The prepared nanoformulations were characterized using Field emission scanning electron microscopy (Fe-SEM), X-ray diffraction (XRD) and Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR). They were further tested for their antioxidant potentials using DPPH assay, hydrogen peroxide scavenging assay, nitric oxide scavenging assay and ferrous antioxidant reducing potential assay. The nanoformulations were found to be highly hemocompatible and showed high encapsulation efficiency up to 76%. They also showed higher antioxidant activity than their base materials. Further, their anti-cancer efficacy was observed against MCF-7 breast cancer cells having IC50 values of 53.36±0.36μg/mL (chitosan-ascorbic acid-glucose), 55.28±0.85μg/mL (chitosan-Vitamin E), 63.72±0.27μg/mL (Chitosan-catechol) and 58.53±0.55μg/mL (chitosan-silver nanoparticles). Thus, the prepared formulations can be therapeutically applied for effective and targeted delivery in breast cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Chitosan microparticles: influence of the gelation process on the release profile and oral bioavailability of albendazole, a class II compound.

PubMed

Piccirilli, Gisela N; García, Agustina; Leonardi, Darío; Mamprin, María E; Bolmaro, Raúl E; Salomón, Claudio J; Lamas, María C

2014-11-01

Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy. The efficiency of encapsulation was found to be between 60 and 85% depending on the internal or external gelation process. Almost spherically spray dried microparticles were observed using scanning electron microscopy. In vitro dissolution results indicated that the microparticles prepared by internal gelation released 8% of the drug within 30 min, while the microparticles prepared by external gelation released 67% within 30 min. It was observed that the AUC and Cmax values of ABZ from microparticles were greatly improved, in comparison with the non-encapsulated drug. In conclusion, the release properties and oral bioavailability of albendazole were greatly improved by using spraydried chitosan-sodium lauryl sulphate microparticles.

Photooxidation of Trimethyl Phosphite in Nitrogen, Oxygen, and para-Hydrogen Matrixes at Low Temperatures.

PubMed

Ramanathan, N; Sundararajan, K; Gopi, R; Sankaran, K

2017-03-16

Trimethyl phosphite (TMPhite) was photooxidized to trimethyl phosphate (TMP) in N 2 , O 2 , and para-H 2 matrixes at low temperatures to correlate the conformational landscape of these two molecules. The photooxidation produced the trans (TGG)-rich conformer with respect to the ground state gauche (GGG) conformer of TMP in N 2 and O 2 matrixes, which has diverged from the conformational composition of freshly deposited pure TMP in the low-temperature matrixes. The enrichment of the trans conformer in preference to the gauche conformer of TMP during photooxidation is due to the TMPhite precursor, which exists exclusively in the trans conformer. Interestingly, whereas the photooxidized TMP molecule suffers site effects possibly due to the local asymmetry in N 2 and O 2 matrixes, in the para-H 2 matrix owing to the quantum crystal nature the site effects were observed to be self-repaired.

The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

PubMed Central

Wang, Yun; Lin, Fu-xing; Zhao, Yu; Wang, Mo-zhen; Ge, Xue-wu; Gong, Zheng-xing; Bao, Dan-dan; Gu, Yu-fang

2014-01-01

Novel submicron core-shell-structured chitosan-based composite particles encapsulated with enhanced green fluorescent protein plasmids (pEGFP) were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS) and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC). pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. PMID:25364253

The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles.

PubMed

Wang, Yun; Lin, Fu-xing; Zhao, Yu; Wang, Mo-zhen; Ge, Xue-wu; Gong, Zheng-xing; Bao, Dan-dan; Gu, Yu-fang

2014-01-01

Novel submicron core-shell-structured chitosan-based composite particles encapsulated with enhanced green fluorescent protein plasmids (pEGFP) were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS) and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC). pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection.

Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal microbubble gel.

PubMed

Chen, Daquan; Yu, Hongyun; Mu, Hongjie; Wei, Junhua; Song, Zhenkun; Shi, Hong; Liang, Rongcai; Sun, Kaoxiang; Liu, Wanhui

2013-04-15

In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the NCHOSC was characterized by FTIR and (1)H NMR. The liposomal microbubble gel based on NCHOSC with a high encapsulation efficiency of curcumin was formed and improved the solubility of curcumin. The diameter of most liposomal microbubble was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room temperature and would form a gel at body temperature. Simultaneously, the ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G by ultrasound suppressed tumor growth most efficiently. These findings have shed some light on the potential NCHOSC material used to liposome-loaded microbubble gel for temperature and ultrasound dual-sensitive drug delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adsorption properties of congo red from aqueous solution onto N,O-carboxymethyl-chitosan.

PubMed

Wang, Li; Wang, Aiqin

2008-03-01

N,O-carboxymethyl-chitosans (N,O-CMC) with different degree of substitution (DS) were synthesized under heterogeneous conditions by controlling the reaction temperature. The factors influencing adsorption capacity of N,O-CMC such as the DS of N,O-CMC, initial pH value of the dye solution and adsorption temperature for anionic dye congo red (CR) were investigated. Compared with chitosan (78.90 mg/g), N,O-CMC with the DS of 0.35 exhibited much higher adsorption capacity (330.62 mg/g) for CR at the same adsorption conditions. The adsorption kinetics and isotherms showed that the sorption processes were better fitted by pseudo-second-order equation and the Langmuir equation, respectively. The adsorption mechanism of N,O-CMC was also discussed by means of IR and XPS spectra. The results in this study indicated that N,O-CMC was an attractive candidate for removing CR from the dye wastewater.

N-Allylation of amines with allyl acetates using chitosan-immobilized palladium

EPA Science Inventory

A simple procedure for N-Allylation of allyl Acetates has been developed using a biodegradable and easily recyclable heterogeneous chitosan-supported palladium catalyst. The general methodology, applicable to wide range of substrates, has sustainable features that include a ligan...

Transport mechanism of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan decorated coumarin-6 loaded nanostructured lipid carriers across the rabbit ocular.

PubMed

Li, Jinyu; Tan, Guoxin; Cheng, Bingchao; Liu, Dandan; Pan, Weisan

2017-11-01

To facilitate the hydrophobic drugs modeled by coumarin-6 (Cou-6) acrossing the cornea to the anterior chamber of the rabbit eye, chitosan (CS) derivatives including chitosan-N-acetyl-l-cysteine (CS-NAC), chitosan oligosaccharides (COS) and carboxymethyl chitosan (CMCS) modified nanostructured lipid carriers (NLCs) were designed and characterized. We found that, with similar size distribution and positivecharges, different CS derivatives based on NLCs led to distinctive delivery performance. In vivo precorneal retention study on rabbits revealed that these CS derivatives coating exhibited a stronger resistant effect than Cou-6 eye drops and Cou-6-NLC (P<0.05), moreover, the AUC (0-∞) , C max and MRT (0-∞) of them followed the sequence of CMCS-Cou-6-NLC

PELA microspheres with encapsulated arginine-chitosan/pBMP-2 nanoparticles induce pBMP-2 controlled-release, transfected osteoblastic progenitor cells, and promoted osteogenic differentiation.

PubMed

Xu, Xiaolong; Qiu, Sujun; Zhang, Yuxian; Yin, Jie; Min, Shaoxiong

2017-03-01

Repair of the bone injury remains a challenge in clinical practices. Recent progress in tissue engineering and therapeutic gene delivery systems have led to promising new strategies for successful acceleration of bone repair process. The aim of this study was to create a controlled-release system to slowly release the arginine-chitosan/plasmid DNA nanoparticles encoding BMP-2 gene (Arg-CS/pBMP-2 NPs), efficiently transfect osteoblastic progenitor cells, secrete functional BMP-2 protein, and promote osteogenic differentiation. In this study, chitosan was conjugated with arginine to generate arginine-chitosan polymer (Arg-CS) for gene delivery. Mix the Arg-CS with pBMP-2 to condense pBMP-2 into nano-sized particles. In vitro transfection assays demonstrated that the transfection efficiency of Arg-CS/pBMP-2 nanoparticles and the expression level of BMP-2 was obviously exceed control groups. Further, PELA microspheres as the controlled-release carrier for the nanoparticles were used to encapsulate Arg-CS/pBMP-2 NPs. We demonstrated that the Arg-CS/pBMP-2 NPs could slowly release from the PELA microspheres at least for 42 d. During the co-culture with the PELA microspheres, the content of BMP-2 protein secreted by MC3T3-E1 reached the peak at 7 d. After 21d, the secretion of BMP-2 protein still maintain a higher level. The alkaline phosphatase activity, alizarin red staining, and osteogenesis-related gene expression by real-time quantitative PCR analysis all showed the PELA microspheres entrapping with Arg-CS/pBMP-2 NPs can obviously induce the osteogenic differentiation. The results indicated that the Arg-CS is a suitable gene vector which can promote the gene transfection. And the novel PELA microspheres-nanoparticle controlled-release system has potential clinical application in the future after further research.

Chitosan microspheres as candidate plasmid vaccine carrier for oral immunisation of Japanese flounder (Paralichthys olivaceus).

PubMed

Tian, Jiyuan; Yu, Juan; Sun, Xiuqin

2008-12-15

Oral DNA-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, because of the existence of the nucleases and severe gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured. In our laboratory, a plasmid DNA (pDNA) containing major capsid protein (MCP) gene of lymphocystis disease virus (LCDV) was prepared, and then pDNA was encapsulated in chitosan microspheres through an emulsion-based methodology. The yield, loading percent and encapsulation efficiency of microspheres were 93.6%, 0.3% and 94.5%, respectively. Scanning electron microscopy (SEM) showed that pDNA-loaded microspheres yielded a spherical shape with smooth surfaces. The disproportion of super-coiled to open circle and linear pDNA suggested that high transfection efficiencies of pDNA in microspheres were retained. The cumulative release of pDNA showed that chitosan microspheres were resistant to degradation in simulated gastrointestinal tract environment. The release profile at PBS buffer (pH 7.4) displayed that pDNA-loaded chitosan microspheres had a release up to 42 days after intestinal imbibition. RT-PCR showed that RNA containing information of MCP gene existed in various tissues 10-90 days post-vaccination. SDS-PAGE and immunofluorescent images indicated that pDNA expressed MCP in tissues of fish 10-90 days after oral administration. In addition, indirect ELISA displayed that the immune responses of sera were positive (O.D.> or =0.3) from week 1 to week 16 for fish vaccinated with microspheres, in comparison with fish vaccinated with naked pDNA. Data obtained suggested that chitosan microspheres were promising carriers for oral pDNA vaccine. Because this encapsulation technique was easy to operate and immunisation efficacy of microspheres loaded with pDNA was significant, it had potential to be used in drug delivery applications.

Chitosan-folate decorated carbon nanotubes for site specific lung cancer delivery.

PubMed

Singh, Rahul Pratap; Sharma, Gunjan; Sonali; Singh, Sanjay; Bharti, Shreekant; Pandey, Bajarangprasad L; Koch, Biplob; Muthu, Madaswamy S

2017-08-01

The aim of this work was to formulate chitosan-folate conjugated multi-walled carbon nanotubes for the lung cancer targeted delivery of docetaxel. The chitosan-folate conjugate was synthesized and the conjugation was confirmed by Fourier transform infrared spectroscopy. The multi-walled carbon nanotubes were characterized for their particle size, polydispersity, zeta potential, surface morphology, drug encapsulation efficiency and in vitro release study. The in vitro cellular uptake, cytotoxicity, and cell cycle analysis of the docetaxel/coumarin-6 loaded multi-walled carbon nanotubes were carried out to compare the effectiveness of the formulations. The biocompatibility and safety of chitosan-folate conjugated multi-walled carbon nanotubes was analyzed by lung histopathology in comparison with marketed docetaxel formulation (Docel™) and acylated multi-walled carbon nanotubes. The cellular internalization study shown that the chitosan-folate conjugated multi-walled carbon nanotubes could be easily internalized into the lung cancer cells through a folate receptor-mediated endocytic pathway. The IC 50 values exhibited that chitosan-folate conjugated multi-walled carbon nanotubes could be 89-fold more effective than Docel™ in human lung cancer cells (A549 cells). Copyright © 2017 Elsevier B.V. All rights reserved.

Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations.

PubMed

Yahyaei, Mohammad; Mehrnejad, Faramarz; Naderi-Manesh, Hossein; Rezayan, Ali Hossein

2017-09-30

Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian stimulation techniques. However, it must be administered daily because of its short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels have attracted significant interest as promising controlled release protein delivery because of their ability to minimize the aggregation and irreversible denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS nanogels. The MD simulations have been performed using the GROMACS software for up to 200ns simulation time. Furthermore, the binding free energy has been calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings suggest that the main driving force of the formation of the CS-CTS nanogels is the hydrophobic interactions between the CS-CS moieties in water. The results have also indicated that the CS-CTS nanogel formation can occur through the hydrogen bonding in addition to the hydrophobic interactions. The obtained data demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual process driven by the hydrophobic interactions between the hydrophobic patch of FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that except in the hydrophobic patch region, the flexibility of FSH was reduced in the presence of the nanogel. This study provides the elucidation of the nanogel-FSH interactions at the molecular level and presents new perspective for the ideal design and applications of the CS-CTS nanogel in protein delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of the parameters of binding between lipopolysaccharide and chitosan and its N-acetylated derivative using a gravimetric piezoquartz biosensor.

PubMed

Naberezhnykh, G A; Gorbach, V I; Kalmykova, E N; Solov'eva, T F

2015-03-01

The interaction of endotoxin (lipopolysaccharide - LPS) with low molecular weight chitosan (5.5 kDa), its N-acylated derivative and chitoliposomes was studied using a gravimetric piezoelectric quartz crystal microbalance biosensor. The optimal conditions for the formation of a biolayer based on immobilized LPS on the resonator surface and its regeneration were elaborated. The association and dissociation rate constants for LPS binding to chitosans were determined and the affinity constants (Kaf) were calculated based on the data on changes in the oscillation frequency of the quartz crystal resonator. The Kaf values correlated with the ones obtained using other methods. The affinity of N-acylated chitosan binding to LPS was higher than that of the parent chitosan binding to LPS. Based on the results obtained, we suggest that water-soluble N-acylated derivatives of chitosan with low degree of substitution of amino groups could be useful compounds for endotoxin binding and neutralization. Copyright © 2015 Elsevier B.V. All rights reserved.

Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate chitosan nanoparticles improves the immunogenicity of the antigen after nasal administration.

PubMed

Liu, Qingfeng; Zheng, Xiaoyao; Zhang, Chi; Shao, Xiayan; Zhang, Xi; Zhang, Qizhi; Jiang, Xinguo

2015-11-01

As one of the most serious infectious respiratory diseases, influenza A (H1N1) is a great threat to human health, and it has created an urgent demand for effective vaccines. Nasal immunization can induce both systemic and mucosal immune responses against viruses, and it can serve as an ideal route for vaccination. However, the low immunogenicity of antigens on nasal mucosa is a high barrier for the development of nasal vaccines. In this study, we covalently conjugated an influenza A (H1N1) antigen to the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles (H1N1-TMC/NP) through thioester bonds to increase the immunogenicity of the antigen after nasal administration. SDS-PAGE revealed that most of the antigen was conjugated on TMC nanoparticles, and an in vitro biological activity assay confirmed the stability of the antigen after conjugation. After three nasal immunizations, the H1N1-TMC/NP induced significantly higher levels of serum IgG and mucosal sIgA compared with free antigen. A hemagglutination inhibition assay showed that H1N1-TMC/NP induced much more protective antibodies than antigen-encapsulated nanoparticles or alum-precipitated antigen (I.M.). In the mechanistic study, H1N1-TMC/NP was shown to stimulate macrophages to produce IL-1β and IL-6 and to stimulate spleen lymphocytes to produce IL-2 and IFN-γ. These results indicated that H1N1-TMC/NP may be an effective vaccine against influenza A (H1N1) viruses for use in nasal immunization. © 2015 Wiley Periodicals, Inc.

Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

PubMed

Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

2017-05-01

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

Entirely S-protected chitosan: A promising mucoadhesive excipient for metronidazole vaginal tablets.

PubMed

Lupo, Noemi; Fodor, Benjamin; Muhammad, Ijaz; Yaqoob, Muhammad; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

2017-12-01

Synthesis and evaluation of an entirely S-protected chitosan as mucoadhesive excipient for vaginal drug delivery. N-acetyl-cysteine was linked to 6-mercaptonicotinamide via disulphide exchange reaction. The obtained ligand, NAC-6-MNA, was subsequently attached to chitosan by carbodiimide mediated amide bond formation in two concentrations. The synthesized S-protected chitosan was chemically characterized and mucoadhesive properties and stability against oxidation were investigated. Moreover, metronidazole tablets comprising the S-protected chitosan were evaluated regarding water uptake capacity, disintegration behaviour, residence time on vaginal mucosa, release of the encapsulated drug and antimicrobial activity. S-protected chitosan displayed 160±19 (CS-MNA-160) and 320±38 (CS-MNA-320)µmol of ligand per gram of polymer. At pH 4.2, CS-MNA-160 and CS-MNA-320 showed 5.2-fold and 6.2-fold increase in mucus viscosity in comparison to unmodified chitosan (One-way ANOVA, p<.001), whereas, 9.9-fold (CS-MNA-160) and 15.6-fold (CS-MNA-320) (One-way ANOVA, p<.001) increase in viscosity was measured at pH 6. The S-protected chitosan remained stable against oxidation in presence of 0.5%v/v hydrogen peroxide. Metronidazole tablets consisting in S-protected chitosan showed prolonged residence time on vaginal mucosa and improved water uptake capacity and disintegration time in comparison to tablets consisting of unmodified chitosan. Moreover, CS-MNA-320 metronidazole tablets displayed prolonged drug release and antimicrobial activity. On the basis of the achieved results, entirely S-protected chitosan represents a promising excipient for the development of metronidazole vaginal tablets. S-protected thiomers are polymers modified with thiol groups protected by aromatic ligands and characterized by strong mucoadhesive properties and high stability against oxidation. Up to date, the entirely S-protection of thiol groups was achieved via the synthesis of the ligand 2-((2-amino-2

Chitosan-Coated Cinnamon/Oregano-Loaded Solid Lipid Nanoparticles to Augment 5-Fluorouracil Cytotoxicity for Colorectal Cancer: Extract Standardization, Nanoparticle Optimization, and Cytotoxicity Evaluation.

PubMed

Kamel, Kamel M; Khalil, Islam A; Rateb, Mostafa E; Elgendy, Hosieny; Elhawary, Seham

2017-09-13

This study aimed to coat lipid-based nanocarriers with chitosan to encapsulate nutraceuticals, minimize opsonization, and facilitate passive-targeting. Phase one was concerned with standardization according to the World Health Organization. Qualitative analysis using liquid chromatography-high-resolution mass spectrometry (LC-HRMS/MS) investigated the active constituents, especially reported cytotoxic agents. Cinnamaldehyde and rosmarinic acid were selected to be quantified using high-performance liquid chromatography. Phase two was aimed to encapsulate both extracts in solid lipid nanoparticles (core) and chitosan (shell) to gain the advantages of both materials properties. The developed experimental model suggested an optimum formulation with 2% lipid, 2.3% surfactant, and 0.4% chitosan to achieve a particle size of 254.77 nm, polydispersity index of 0.28, zeta potential of +15.26, and entrapment efficiency percentage of 77.3% and 69.1% for cinnamon and oregano, respectively. Phase three was focused on the evaluation of cytotoxic activity unencapsulated/encapsulated cinnamon and oregano extracts with/without 5-fluorouracil on HCT-116 cells. This study confirmed the success of the suggested combination with 5-fluorouracil for treating human colon carcinoma with a low dose leading to decreasing side effects and allowing uninterrupted therapy.

Cellular Encapsulation Enhances Cardiac Repair

PubMed Central

Levit, Rebecca D.; Landázuri, Natalia; Phelps, Edward A.; Brown, Milton E.; García, Andrés J.; Davis, Michael E.; Joseph, Giji; Long, Robert; Safley, Susan A.; Suever, Jonathan D.; Lyle, Alicia N.; Weber, Collin J.; Taylor, W. Robert

2013-01-01

Background Stem cells for cardiac repair have shown promise in preclinical trials, but lower than expected retention, viability, and efficacy. Encapsulation is one potential strategy to increase viable cell retention while facilitating paracrine effects. Methods and Results Human mesenchymal stem cells (hMSC) were encapsulated in alginate and attached to the heart with a hydrogel patch in a rat myocardial infarction (MI) model. Cells were tracked using bioluminescence (BLI) and cardiac function measured by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR). Microvasculature was quantified using von Willebrand factor staining and scar measured by Masson's Trichrome. Post‐MI ejection fraction by CMR was greatly improved in encapsulated hMSC‐treated animals (MI: 34±3%, MI+Gel: 35±3%, MI+Gel+hMSC: 39±2%, MI+Gel+encapsulated hMSC: 56±1%; n=4 per group; P<0.01). Data represent mean±SEM. By TTE, encapsulated hMSC‐treated animals had improved fractional shortening. Longitudinal BLI showed greatest hMSC retention when the cells were encapsulated (P<0.05). Scar size at 28 days was significantly reduced in encapsulated hMSC‐treated animals (MI: 12±1%, n=8; MI+Gel: 14±2%, n=7; MI+Gel+hMSC: 14±1%, n=7; MI+Gel+encapsulated hMSC: 7±1%, n=6; P<0.05). There was a large increase in microvascular density in the peri‐infarct area (MI: 121±10, n=7; MI+Gel: 153±26, n=5; MI+Gel+hMSC: 198±18, n=7; MI+Gel+encapsulated hMSC: 828±56 vessels/mm2, n=6; P<0.01). Conclusions Alginate encapsulation improved retention of hMSCs and facilitated paracrine effects such as increased peri‐infarct microvasculature and decreased scar. Encapsulation of MSCs improved cardiac function post‐MI and represents a new, translatable strategy for optimization of regenerative therapies for cardiovascular diseases. PMID:24113327

Fabrication of biodegradable micelles with sheddable poly(ethylene glycol) shells as the carrier of 7-ethyl-10-hydroxy-camptothecin.

PubMed

Guo, Qian; Luo, Ping; Luo, Yu; Du, Fang; Lu, Wei; Liu, Shiyuan; Huang, Jin; Yu, Jiahui

2012-12-01

Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate Vaginal Delivery System—Development, Characterization and Cytotoxicity Studies

PubMed Central

Szymańska, Emilia; Szekalska, Marta; Czarnomysy, Robert; Lavrič, Zoran; Srčič, Stane; Miltyk, Wojciech; Winnicka, Katarzyna

2016-01-01

Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug loading and encapsulation efficacy in chitosan microparticles. By increasing the cross-linking ratio, the microparticles with lower diameter, moisture content and smoother surface were observed. Mucoadhesive studies displayed that all formulations possessed mucoadhesive properties. The in vitro release profile of clotrimazole was found to alter considerably by changing the glycerol 2-phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of apoptotic cells in the presence of chitosan and ion cross-linked chitosan microparticles, followed by a loss of membrane potential suggesting that cell death might go through the mitochondrial apoptotic pathway. PMID:27690062

Ab initio computational study of –N-C and –O-C bonding formation : functional group modification reaction based chitosan

NASA Astrophysics Data System (ADS)

Siahaan, P.; Salimah, S. N. M.; Sipangkar, M. J.; Hudiyanti, D.; Djunaidi, M. C.; Laksitorini, M. D.

2018-04-01

Chitosan application in pharmaceutics and cosmeceutics industries is limited by its solubility issue. Modification of -NH2 and -OH fuctional groups of chitosan by adding carboxyl group has been shown to improve its solubility and application. Attempt to synthesize carboxymethyl chitosan (CMC) from monocloroacetic acid (MCAA) has been done prior this report. However no information is available wether –OH (-O-C bonding formation) or -NH2 (-N-C bonding formation) is the preference for - CH2COOH to attach. In the current study, the reaction mechanism between chitosan and MCAA reactants into carboxymethyl chitosan (CMC) was examined by computational approach. Dimer from of chitosan used as a molecular model in calculation All the molecular structure involved in the reaction mechanism was optimized by ab initio computational on the theory and basis set HF/6-31G(d,p). The results showed that the - N-C bonding formation via SN2 than the -O-C bonding formation via SN2 which have activation energy 469.437 kJ/mol and 533.219 kJ/mol respectively. However, the -O-C bonding formation more spontaneous than the -N-C bonding formation because ΔG the formation of O-CMC-2 reaction is more negative than ΔG of formation N-CMC-2 reaction is -4.353 kJ/mol and -1.095 kJ/mol respectively. The synthesis of N,O-CMC first forms -O-CH2COOH, then continues to form -NH-CH2COOH. This information is valuable to further optimize the reaction codition for CMC synthesis.

Effects of tripolyphosphate on cellular uptake and RNA interference efficiency of chitosan-based nanoparticles in Raw 264.7 macrophages.

PubMed

Xiao, Bo; Ma, Panpan; Ma, Lijun; Chen, Qiubing; Si, Xiaoying; Walter, Lewins; Merlin, Didier

2017-03-15

Tumor necrosis factor-α (TNF-α) is a major pro-inflammatory cytokine that is mainly secreted by macrophages during inflammation. Here, we synthesized a series of N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chlorides (HTCCs), and then used a complex coacervation technique or tripolyphosphate (TPP)-assisted ionotropic gelation strategy to complex the HTCCs with TNF-α siRNA (siTNF) to form nanoparticles (NPs). The resultant NPs had a desirable particle size (210-279nm), a slightly positive zeta potential (14-22mV), and negligible cytotoxicity against Raw 264.7 macrophages and colon-26 cells. Subsequent cellular uptake tests demonstrated that the introduction of TPP to the NPs markedly increased their cellular uptake efficiency (to nearly 100%) compared with TPP-free NPs, and yielded a correspondingly higher intracellular concentration of siRNA. Critically, in vitro gene silencing experiments revealed that all of the TPP-containing NPs showed excellent efficiency in inhibiting the mRNA expression level of TNF-α (by approximately 85-92%, which was much higher than that obtained using Oligofectamine/siTNF complexes). Collectively, these results obviously suggest that our non-toxic TPP-containing chitosan-based NPs can be exploited as efficient siTNF carriers for the treatment of inflammatory diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Chitosan Nanoparticles Prepared by Ionotropic Gelation: An Overview of Recent Advances.

PubMed

Desai, Kashappa Goud

2016-01-01

The objective of this review is to summarize recent advances in chitosan nanoparticles prepared by ionotropic gelation. Significant progress has occurred in this area since the method was first reported. The gelation technique has been improved through a number of creative methodological modifications. Ionotropic gelation via electrospraying and spinning disc processing produces nanoparticles with a more uniform size distribution. Large-scale manufacturing of the nanoparticles can be achieved with the latter approach. Hydrophobic and hydrophilic drugs can be simultaneously encapsulated with high efficiency by emulsification followed by ionic gelation. The turbulent mixing approach facilitates nanoparticle formation at a relatively high polymer concentration (5 mg/mL). The technique can be easily tuned to achieve the desired polymer/surface modifications (e.g., blending, coating, and surface conjugation). Using factorial-design-based approaches, optimal conditions for nanoparticle formation can be determined with a minimum number of experiments. New insights have been gained into the mechanism of chitosan-tripolyphosphate nanoparticle formation. Chitosan nanoparticles prepared by ionotropic gelation tend to aggregate/agglomerate in unfavorable environments. Factors influencing this phenomenon and strategies that can be adopted to minimize the instability are discussed. Ionically cross-linked nanoparticles based on native chitosan and modified chitosan have shown excellent efficacy for controlled and targeted drug-delivery applications.

Nasal delivery of chitosan-coated poly(lactide-co-glycolide)-encapsulated honeybee (Apis mellifera) venom promotes Th 1-specific systemic and local intestinal immune responses in weaned pigs.

PubMed

Lee, Jin-A; Kim, Yun-Mi; Kim, Tae-Hoon; Lee, Sang-Ho; Lee, Cho-A; Cho, Cheong-Weon; Jeon, Jong-Woon; Park, Jin-Kyu; Kim, Sang-Ki; Jung, Bock-Gie; Lee, Bong-Joo

2016-10-01

Nasal delivery is a convenient and acceptable route for drug administration, and has been shown to elicit a much more potent local and systemic response compared with other drug delivery routes. We previously demonstrated that rectal administration of poly(lactide-co-glycolide)-encapsulated honeybee venom (P-HBV) could enhance systemic Th 1-specific immune responses. We therefore synthesized chitosan-coated P-HBV (CP-HBV) and then evaluated the immune-boosting efficacy of nasally administered CP-HBV on systemic and local intestinal immunity compared with non-chitosan-coated P-HBV. The nasally delivered CP-HBV effectively enhanced Th 1-specific responses, eliciting a significant increase in the CD3(+)CD4(+)CD8(-) Th cell population, lymphocyte proliferation capacity, and expression of Th 1 cytokines (IFN-γ, IL-12, and IL-2) in peripheral blood mononuclear cells. Furthermore, these immune-boosting effects persisted up to 21days post CP-HBV administration. Nasal administration of CP-HBV also led to an increase of not only the CD4(+) Th 1 and IFN-γ secreting CD4(+) Th 1 cell population but also Th 1-specific cytokines and transcription factors, including IL-12, IFN-γ, STAT4, and T-bet, in isolated mononuclear cells from the spleen and ileum. Copyright © 2016 Elsevier B.V. All rights reserved.

Aqua­(1,10-phenanthroline-κ2 N,N′)bis­(trimethyl­acetato)-κ2 O,O′;κO-cobalt(II)

PubMed Central

Chen, Xiao-Dan; Chen, Hong-Xian; Li, Zhong-Shu; Zhang, Huai-Hong; Sun, Bai-Wang

2009-01-01

In the title compound, [Co(C5H9O2)2(C12H8N2)(H2O)], the CoII atom is coordinated in a distorted octahedral environment by three carboxyl O atoms of two trimethyl­acetate ligands, one aqua O atom and two N atoms from 1,10-phen­anthroline. The crystal structure is stabilized by O—H⋯O hydrogen bonds and π–π stacking inter­actions [inter­planar distance between inter­digitating 1,10-phenanthroline ligands = 3.378 (2) Å]. PMID:21583436

Tetra­butyl­ammonium tetra­kis­(trimethyl­silanolato-κO)ferrate(III)

PubMed Central

Hay, Michael; Staples, Richard; Lee, Andre

2012-01-01

In the title salt, (C16H36N)[Fe(C3H9OSi)4], the cation contains a central N atom bonded to four n-butyl alkyl groups in a tetra­hedral arrangement, while the anion contains a central FeIII atom tetra­hedrally coordinated by four trimethyl­silanolate ligands. PMID:22969479

Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virus

NASA Astrophysics Data System (ADS)

Mori, Yasutaka; Ono, Takeshi; Miyahira, Yasushi; Nguyen, Vinh Quang; Matsui, Takemi; Ishihara, Masayuki

2013-02-01

Silver nanoparticle (Ag NP)/chitosan (Ch) composites with antiviral activity against H1N1 influenza A virus were prepared. The Ag NP/Ch composites were obtained as yellow or brown floc-like powders following reaction at room temperature in aqueous medium. Ag NPs (3.5, 6.5, and 12.9 nm average diameters) were embedded into the chitosan matrix without aggregation or size alternation. The antiviral activity of the Ag NP/Ch composites was evaluated by comparing the TCID50 ratio of viral suspensions treated with the composites to untreated suspensions. For all sizes of Ag NPs tested, antiviral activity against H1N1 influenza A virus increased as the concentration of Ag NPs increased; chitosan alone exhibited no antiviral activity. Size dependence of the Ag NPs on antiviral activity was also observed: antiviral activity was generally stronger with smaller Ag NPs in the composites. These results indicate that Ag NP/Ch composites interacting with viruses exhibit antiviral activity.

Chitosan-catechol: a writable bioink under serum culture media.

PubMed

Lee, Daiheon; Park, Joseph P; Koh, Mi-Young; Kim, Pureum; Lee, Junhee; Shin, Mikyung; Lee, Haeshin

2018-05-01

Mussel-inspired adhesive coatings on biomedical devices have attracted significant interest due to their unique properties such as substrate independency and high efficiency. The key molecules for mussel-inspired adhesive coatings are catechol and amine groups. Along with the understanding of catechol chemistry, chitosan-catechol has also been developed as a representative mussel-inpired adhesive polymer that contains catechol and amine groups for adhesiveness. Herein, we demonstrated the direct writability of chitosan-catechol as a bioink for 3D printing, one of the additive techniques. The use of chitosan-catechol bioink results in the formation of 3D constructs in normal culture media via rapid complexation of this bioink with serum proteins; in addition, the metal/catechol combination containing tiny amounts of vanadyl ions, in which the ratio of metal to catechol is 0.0005, dramatically enhances the mechanical strength and printability of the cell-encapsulated inks, showing a cell viability of approximately 90%. These findings for mussel-inspired bioinks will be a promising way to design a biocompatible 3D bioink cross-linked without any external stimuli.

Potential advantages of a novel chitosan-N-acetylcysteine surface modified nanostructured lipid carrier on the performance of ophthalmic delivery of curcumin

PubMed Central

Liu, Dandan; Li, Jinyu; Pan, Hao; He, Fengwei; Liu, Zhidong; Wu, Qingyin; Bai, Chunping; Yu, Shihui; Yang, Xinggang

2016-01-01

The transient precorneal retention time and low penetration capacity into intraocular tissues are the key obstacles that hinder the ophthalmic drug delivery of many therapeutic compounds, especially for drugs with poor solubility and permeability. To break the stalemate, N-acetyl-L-cysteine functionalized chitosan copolymer (CS-NAC), which exhibit marked bioadhesion and permeation enhancing effect, was synthesized. The curcumin encapsulated NLC (CUR-NLC) was produced and optimized followed by surface absorption of CS-NAC. After coating, changed particle size from 50.76 ± 2.21 nm to 88.64 ± 1.25 nm and reversed zeta potential from −20.38 ± 0.39 mV to 22.51 ± 0.34 mV was observed. The in vitro CUR release from NLC was slower than that of CUR-NLC and chitosan hydrochlorides (CH) coated NLC due to the inter and/or intramolecular disulfide formation of thiomers on the surface of nanocarriers. The modification also significantly enhanced transcorneal penetration compared with CH-NLC and the uncoated ones. The effect on bioadhesion and precorneal retention were evaluated by in vivo imaging technique and ocular pharmacokinetics studies revealing that the clearance of the formulations was significantly delayed in the presence of CS-NAC and the effect was positively related to the degree of thiolation. In summary, CS-NAC-NLC presented a series of notable advantages for ophthalmic drug application. PMID:27350323

Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

NASA Astrophysics Data System (ADS)

Khajuria, Deepak Kumar; Konnur, Manish C.; Vasireddi, Ramakrishna; Roy Mahapatra, D.

2015-02-01

By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

Development of novel encapsulated formulations using albumin-chitosan as a polymer matrix for ocular drug delivery

NASA Astrophysics Data System (ADS)

Addo, Richard Tettey

Designing formulations for ophthalmic drug delivery is one of the most challenging endeavors facing the pharmaceutical scientist due to the unique anatomy, physiology, and biochemistry of the eye. Current treatment protocols for administration of drugs in eye diseases are primarily solution formulations, gels or ointments. However, these modes of delivery have several drawbacks such as short duration of exposure, need for repeated administrations and non-specific toxicity. We hypothesize that development of ocular drugs in microparticles will overcome the deficiencies of the current modalities of treatment. We based the hypothesis on the preliminary studies conducted with encapsulated tetracaine, an anesthetic used for surgical purposes and atropine, a medication used for several ophthalmic indications including mydriatic and cycloplegic effects. However, atropine is well absorbed into the systemic circulation and has been reported to exert severe systemic side effects after ocular administration (Hoefnagel D. 1961, Morton H. G. 1939 and Lang J. C. 1995) and may lead to serious side effects including death in extreme cases with pediatric use. Based on these observations, the focus of this dissertation is to formulate microparticulate drug carrier for treatment of various conditions of the eye. Purpose: To prepare, characterize, study the in vitro and in vivo interaction of albumin-chitosan microparticles (BSA-CSN MS), a novel particulate drug carrier for ocular drug delivery. Method: Microparticle formulations were prepared by method of spray drying. The percentage drug loading and efficiency were assessed using USP (I) dissolution apparatus. Using Malvern Zeta-Sizer, we determined size and surface charge of the fabrication. Surface morphology of the microparticles was examined using Scanning Electron Microscopy. Microparticles were characterized in terms of thermal properties using Differential Scanning Calorimetry. Human corneal epithelial cells (HCET-1) were

Effect of Eudragit S100 nanoparticles and alginate chitosan encapsulation on the viability of Lactobacillus acidophilus and Lactobacillus rhamnosus.

PubMed

Ansari, Fereshteh; Pourjafar, Hadi; Jodat, Vahid; Sahebi, Javad; Ataei, Amir

2017-12-01

In this study, we examined a novel method of microencapsulation with calcium alginate-chitosan and Eudragit S100 nanoparticles for the improving viability of probiotic bacteria, Lactobacillus acidophilus and Lactobacillus rhamnosus. Extrusion technique was carried out in microencapsulation process. The viability of two probiotics in single coated beads (with only chitosan), double coated beads (with chitosan and Eudragit nanoparticles), and as free cells (unencapsulated) were conducted in simulated gastric juice (pH 1.55, without pepsin) followed by incubation in simulated intestinal juice (pH 7.5, with 1% bile salt). In case of single coated beads, presumably, lack of sufficient strength of chitosan under simulated gastric condition was the main reason of 4-log and 5-log reduction of the counts of the L. acidophilus and L. rhamnosus respectively. The results showed that with the second coat forming (Eudragit nanoparticles) over the first coat (chitosan), the strength of the beads and then viability rate of the bacteria were increased in comparison with the single coated beads.

Characterization and carboplatin loaded chitosan nanoparticles for the chemotherapy against breast cancer in vitro studies.

PubMed

Khan, Md Asad; Zafaryab, Md; Mehdi, Syed Hassan; Quadri, Javed; Rizvi, M Moshahid A

2017-04-01

Aim of the studies to synthesized chitosan nanoparticles by an ionic interaction procedure. The nanoparticles were characterized by physicochemical methods like, DLS, TEM, Surface potential measurements, FT-IR and DSC. The average particle size of chitosan and carboplatin nanoparticles was found to be 277.25±11.37nm and 289.30±8.15nm and zeta potential was found to be 31±3.14mV and 33±2.15mV respectively with low polydispersity index. The maximum entrapment of carboplatin in nanoparticles was a spherical shape with a positive charge. The maximum encapsulation and loading efficiencies of carboplatin (5mg/ml) were obtained to be 58.43% and 13.27% respectively. The nanocarboplatin was better blood compatibility as compared to chitosan nanoparticles. Finally, the cytotoxic effects of the carboplatin loaded chitosan nanoparticles were tested in-vitro against breast cancer (MCF-7) cell lines. Our studies showed that the chitosan nanoparticles could be used as a promising candidate for drug delivery for the therapeutic treatment of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled release behaviors of chitosan/α, β-glycerophosphate thermo-sensitive hydrogels

NASA Astrophysics Data System (ADS)

Liu, Wei-Fang; Kang, Chuan-Zhen; Kong, Ming; Li, Yang; Su, Jing; Yi, An; Cheng, Xiao-Jie; Chen, Xi-Guang

2012-09-01

Chitosan/α, β-glycerophosphate (CS/α, β-GP) thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronidazole encapsulated, CS and α, β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α, β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows: 1.8% (w/v) CS in HAc solvent, 5.6% (w/v) α, β-GP and 5 g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applications.

An Overview of the Protective Effects of Chitosan and Acetylated Chitosan Oligosaccharides against Neuronal Disorders.

PubMed

Hao, Cui; Wang, Wei; Wang, Shuyao; Zhang, Lijuan; Guo, Yunliang

2017-03-23

Chitin is the second most abundant biopolymer on Earth and is mainly comprised of a marine invertebrate, consisting of repeating β-1,4 linked N-acetylated glucosamine units, whereas its N-deacetylated product, chitosan, has broad medical applications. Interestingly, chitosan oligosaccharides have therapeutic effects on different types of neuronal disorders, including, but not limited to, Alzheimer's disease, Parkinson's disease, and nerve crush injury. A common link among neuronal disorders is observed at a sub-cellular level, such as atypical protein assemblies and induced neuronal death. Chronic activation of innate immune responses that lead to neuronal injury is also common in these diseases. Thus, the common mechanisms of neuronal disorders might explain the general therapeutic effects of chitosan oligosaccharides and their derivatives in these diseases. This review provides an update on the pathogenesis and therapy for neuronal disorders and will be mainly focused on the recent progress made towards the neuroprotective properties of chitosan and acetylated chitosan oligosaccharides. Their structural features and the underlying molecular mechanisms will also be discussed.

Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles.

PubMed

Keawchaoon, Lalita; Yoksan, Rangrong

2011-05-01

The fabrication of carvacrol-loaded chitosan nanoparticles was achieved by a two-step method, i.e., oil-in-water emulsion and ionic gelation of chitosan with pentasodium tripolyphosphate. The obtained particles possessed encapsulation efficiency (EE) and loading capacity (LC) in the ranges of 14-31% and 3-21%, respectively, when the initial carvacrol content was 0.25-1.25 g/g of chitosan. The individual particles exhibited a spherical shape with an average diameter of 40-80 nm, and a positively charged surface with a zeta potential value of 25-29 mV. The increment of initial carvacrol content caused a reduction of surface charge. Carvacrol-loaded chitosan nanoparticles showed antimicrobial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli with an MIC of 0.257 mg/mL. The release of carvacrol from chitosan nanoparticles reached plateau level on day 30, with release amounts of 53% in acetate buffer solution with pH of 3, and 23% and 33% in phosphate buffer solutions with pH of 7 and 11, respectively. The release mechanism followed a Fickian behavior. The release rate was superior in an acidic medium to either alkaline or neutral media, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

Amphiphilically modified chitosan cationic nanoparticles for drug delivery

NASA Astrophysics Data System (ADS)

You, Jie; Li, Wenfeng; Yu, Chang; Zhao, Chengguang; Jin, Langping; Zhou, Yili; Xu, Xuzhong; Dong, Siyang; Lu, Xincheng; Wang, Ouchen

2013-12-01

A series of amphiphilic N-(2-hydroxy)propyl-3-trimethylammonium-chitosan-cholic acid (HPTA-CHI-CA) polymers were synthesized by grafting cholic acid (CA) and glycidyltrimethylammonium chloride onto chitosan. The self-assembly behavior of HPTA-CHI-CA was studied by fluorescence technique. The polymers were able to self-assemble into NPs in phosphate buffered saline with a critical aggregation concentration (CAC) in the range of 66-26 mg/L and the CAC decreased with the increasing of the degree of substitution (DS) of CA. The size of cationic HPTA-CHI-CA NPs ranges from 170 to 220 nm (PDI < 0.2). It was found that doxorubicin (DOX) could be encapsulated into HPTA-CHI-CA NPs based on self-assembly. The drug loading content and efficiency varies depending on the DS of CA and feeding ratio of DOX to polymer. In vitro release studies suggested that DOX released slowly from HPTA-CHI-CA NPs without any burst initial release. Besides, the confocal microscopic measurements indicated that DOX-HPTA-CHI-CA NPs could easily be uptaken by breast cancer (MCF-7) cells and release DOX in cytoplasm. Anti-tumor efficacy results showed that DOX-HPTA-CHI-CA NPs have a significant activity of inhibition MCF-7 cells growth. These results suggest cationic HPTA-CHI-CA may have great potential for anticancer drug delivery.

Preparation, physical characterization, and stability of Ferrous-Chitosan microcapsules using different iron sources

NASA Astrophysics Data System (ADS)

Handayani, Noer Abyor; Luthfansyah, M.; Krisanti, Elsa; Kartohardjono, Sutrasno; Mulia, Kamarza

2017-11-01

Dietary modification, supplementation and food fortification are common strategies to alleviate iron deficiencies. Fortification of food is an effective long-term approach to improve iron status of populations. Fortification by adding iron directly to food will cause sensory problems and decrease its bioavailability. The purpose of iron encapsulation is: (1) to improve iron bioavailability, by preventing oxidation and contact with inhibitors and competitors; and (2) to disguise the rancid aroma and flavor of iron. A microcapsule formulation of two suitable iron compounds (iron II fumarate and iron II gluconate) using chitosan as a biodegradable polymer will be very important. Freeze dryer was also used for completing the iron microencapsulation process. The main objective of the present study was to prepare and characterize the iron-chitosan microcapsules. Physical characterization, i.e. encapsulation efficiency, iron loading capacity, and SEM, were also discussed in this paper. The stability of microencapsulated iron under simulated gastrointestinal conditions was also investigated, as well. Both iron sources were highly encapsulated, ranging from 71.5% to 98.5%. Furthermore, the highest ferrous fumarate and ferrous gluconate loaded were 1.9% and 4.8%, respectively. About 1.04% to 9.17% and 45.17% to 75.19% of Fe II and total Fe, were released in simulated gastric fluid for two hours and in simulated intestinal fluid for six hours, respectively.

Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model.

PubMed

Amado, S; Simões, M J; Armada da Silva, P A S; Luís, A L; Shirosaki, Y; Lopes, M A; Santos, J D; Fregnan, F; Gambarotta, G; Raimondo, S; Fornaro, M; Veloso, A P; Varejão, A S P; Maurício, A C; Geuna, S

2008-11-01

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to use in peripheral nerve reconstruction, either alone or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in vitro, to assess their ability in supporting N1E-115 cell survival and differentiation, and in vivo to assess biocompatibility as well as to evaluate their effects on nerve fiber regeneration and functional recovery after a standardized rat sciatic nerve crush injury. Functional recovery was evaluated using the sciatic functional index (SFI), the static sciatic index (SSI), the extensor postural thrust (EPT), the withdrawal reflex latency (WRL) and ankle kinematics. Nerve fiber regeneration was assessed by quantitative stereological analysis and electron microscopy. All chitosan membranes showed good biocompatibility and proved to be a suitable substrate for plating the N1E-115 cellular system. By contrast, in vivo nerve regeneration assessment after crush injury showed that the freeze-dried chitosan type III, without N1E-115 cell addition, was the only type of membrane that significantly improved posttraumatic axonal regrowth and functional recovery. It can be thus suggested that local enwrapping with this type of chitosan membrane may represent an effective approach for the improvement of the clinical outcome in patients receiving peripheral nerve surgery.

Encapsulated boron as an osteoinductive agent for bone scaffolds.

PubMed

Gümüşderelioğlu, Menemşe; Tunçay, Ekin Ö; Kaynak, Gökçe; Demirtaş, Tolga T; Aydın, Seda Tığlı; Hakkı, Sema S

2015-01-01

The aim of this study was to develop boron (B)-releasing polymeric scaffold to promote regeneration of bone tissue. Boric acid-doped chitosan nanoparticles with a diameter of approx. 175 nm were produced by tripolyphosphate (TPP)-initiated ionic gelation process. The nanoparticles strongly attached via electrostatic interactions into chitosan scaffolds produced by freeze-drying with approx. 100 μm pore diameter. According to the ICP-OES results, following first 5h initial burst release, fast release of B from scaffolds was observed for 24h incubation period in conditioned medium. Then, slow release of B was performed over 120 h. The results of the cell culture studies proved that the encapsulated boron within the scaffolds can be used as an osteoinductive agent by showing its positive effects on the proliferation and differentiation of MC3T3-E1 preosteoblastic cells. Copyright © 2015 Elsevier GmbH. All rights reserved.

Experimental study of trimethyl aluminum decomposition

NASA Astrophysics Data System (ADS)

Zhang, Zhi; Pan, Yang; Yang, Jiuzhong; Jiang, Zhiming; Fang, Haisheng

2017-09-01

Trimethyl aluminum (TMA) is an important precursor used for metal-organic chemical vapor deposition (MOCVD) of most Al-containing structures, in particular of nitride structures. The reaction mechanism of TMA with ammonia is neither clear nor certain due to its complexity. Pyrolysis of trimethyl metal is the start of series of reactions, thus significantly affecting the growth. Experimental study of TMA pyrolysis, however, has not yet been conducted in detail. In this paper, a reflectron time-of-flight mass spectrometer is adopted to measure the TMA decomposition from room temperature to 800 °C in a special pyrolysis furnace, activated by soft X-ray from the synchrotron radiation. The results show that generation of methyl, ethane and monomethyl aluminum (MMA) indicates the start of the pyrolysis process. In the low temperature range from 25 °C to 700 °C, the main product is dimethyl aluminum (DMA) from decomposition of TMA. For temperatures larger than 700 °C, the main products are MMA, DMA, methyl and ethane.

Antibacterial Loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder Aerosol for the Treatment of Lung Infections

PubMed Central

Mishra, Brahmeshwar; Mishra, Madhusmita; Yadav, Sarita Kumari

2017-01-01

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections. Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr’s index, solid state interaction by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis. The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution. The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection. PMID:28496463

Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material.

PubMed

Güneş, Seda; Tıhmınlıoğlu, Funda

2017-09-01

Recent studies in wound dressing applications offer new therapies and promote wound healing process. The aim of this study was to develop Hypericum perforatum (St John's Wort) oil incorporated chitosan films for wound dressing applications. H. perforatum oil as a potential therapeutic agent was encapsulated in chitosan film to achieve a better wound dressing material. Oil incorporated chitosan films were successfully prepared by solvent casting method in different oil concentrations (0.25-1.5%v/v). Water vapor permeability (WVP), mechanical test, swelling behavior and surface hydrophobicity were performed in order to characterize the prepared films. Antimicrobial test was performed by disc diffusion method and the growth inhibition effects of the films including different amount of H. perforatum oil were investigated on Escherichia coli and Staphylococcus aureus. WVP increased with oil incorporation and the highest value was obtained for 0.25% oil concentration.The highest strain value was obtained in 0.25% oil content films although tensile stress decreased with increasing oil content. H. perforatum oil incorporated films had antimicrobial effect on both microorganisms. Chitosan based films had no cytotoxic effects on NIH3T3fibroblast cells and provided a good surface for cell attachment and proliferation. The results showed that the H. perforatum incorporated chitosan films seems to be a potential and novel biomaterial for wound healing applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis, characterization and cytotoxicity of S-nitroso-mercaptosuccinic acid-containing alginate/chitosan nanoparticles

NASA Astrophysics Data System (ADS)

Seabra, Amedea B.; Fabbri, Giulia K.; Pelegrino, Milena T.; Silva, Letícia C.; Rodrigues, Tiago

2017-06-01

Nitric oxide (NO) is an endogenous free radical, which plays key roles in several biological processes including vasodilation, neurotransmission, inhibition of platelet adhesion, cytotoxicity against pathogens, wound healing, and defense against cancer. Due to the relative instability of NO in vivo (half-life of ca. 0.5 seconds), there is an increasing interest in the development of low molecular weight NO donors, such as S-nitrosothiols (RSNOs), which are able to prolong and preserve the biological activities of NO in vivo. In order to enhance the sustained NO release in several biomedical applications, RSNOs have been successfully allied to nanomaterials. In this context, this work describes the synthesis and characterization of the NO donor S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), which belongs to the class of RSNOs, and its incorporation in polymeric biodegradable nanoparticles composed by alginate/chitosan. First, chitosan nanoparticles were obtained by gelation process with sodium tripolyphosphate (TPP), followed by the addition of the alginate layer, to enhance the nanoparticle protection. The obtained nanoparticles presented a hydrodynamic diameter of 343 ± 38 nm, polydispersity index (PDI) of 0.36 ± 0.1, and zeta potential of - 30.3 ± 0.4 mV, indicating their thermal stability in aqueous suspension. The negative zeta potential value was assigned to the presence of alginate chains on the surface of chitosan/TPP nanoparticles. The encapsulation efficiency of the NO donor into the polymeric nanoparticles was found to be 98 ± 0.2%. The high encapsulation efficiency value was attributed to the positive interactions between the NO donor and the polymeric content of the nanoparticles. Kinetics of NO release from the nanoparticles revealed a spontaneous and sustained release of therapeutic amounts of NO, for several hours under physiological temperature. The incubation of NO-releasing alginate/chitosan nanoparticles with human hepatocellular carcinoma

Structure of a Multilayer Nanofilm To Increase the Encapsulation Efficiency of Basic Fibroblast Growth Factor.

PubMed

Han, Uiyoung; Hong, Jinkee

2018-03-05

In this study, we established the structure of a multilayer nanofilm that more efficiently encapsulates basic fibroblast growth factor (bFGF). First, a positively charged layer material was selected from biocompatible polymers such as collagen (Col), poly(beta-amino ester) (Poly2), and chitosan (Chi), while considering the film thickness. We then investigated the change in bFGF encapsulation efficiency when the multilayer structure was changed from a tetralayer to a trilayer. As a result, we obtained a highly improved bFGF encapsulation efficiency in the nanofilm using a positively charged layer formed by a blend of Col and Poly2 and a negatively charged poly(acrylic acid) (PAA) layer within a trilayered structure. In particular, we found that a significant amount of adsorbed bFGF was desorbed again during the film fabrication process of a tetralayered nanofilm. In the conventional nanofilm, bFGF was regarded as a polycation and formed a multilayer nanofilm that was composed of a tetralayered structure and was represented as (polycation/polyanion/bFGF/polyanion) n where n = number of repeated tetralayers. Here, we suggested that bFGF should not be considered a polycation, rather it should be considered as a small quantity of molecule that exists between the polyanion and polycation layers. In this case, the nanofilm is composed of repeating units of (polycation/polyanion/bFGF/polycation/polyanion), because the amount of adsorbed bFGF is considerably lower than that of other building blocks.

Ultrasonically synthesized organic liquid-filled chitosan microcapsules: part 2: characterization using AFM (atomic force microscopy) and combined AFM-confocal laser scanning fluorescence microscopy.

PubMed

Mettu, Srinivas; Ye, Qianyu; Zhou, Meifang; Dagastine, Raymond; Ashokkumar, Muthupandian

2018-04-25

Atomic Force Microscopy (AFM) is used to measure the stiffness and Young's modulus of individual microcapsules that have a chitosan cross-linked shell encapsulating tetradecane. The oil filled microcapsules were prepared using a one pot synthesis via ultrasonic emulsification of tetradecane and crosslinking of the chitosan shell in aqueous solutions of acetic acid. The concentration of acetic acid in aqueous solutions of chitosan was varied from 0.2% to 25% v/v. The effect of acetic acid concentration and size of the individual microcapsules on the strength was probed. The deformations and forces required to rupture the microcapsules were also measured. Three dimensional deformations of microcapsules under large applied loads were obtained by the combination of Laser Scanning Confocal Microscopy (LSCM) with Atomic Force Microscopy (AFM). The stiffness, and hence the modulus, of the microcapsules was found to decrease with an increase in size with the average stiffness ranging from 82 to 111 mN m-1 and average Young's modulus ranging from 0.4 to 6.5 MPa. The forces required to rupture the microcapsules varied from 150 to 250 nN with deformations of the microcapsules up to 62 to 110% relative to their radius, respectively. Three dimensional images obtained using laser scanning confocal microscopy showed that the microcapsules retained their structure and shape after being subjected to large deformations and subsequent removal of the loads. Based on the above observations, the oil filled chitosan crosslinked microcapsules are an ideal choice for use in the food and pharmaceutical industries as they would be able to withstand the process conditions encountered.

Inactivated infectious bronchitis virus vaccine encapsulated in chitosan nanoparticles induces mucosal immune responses and effective protection against challenge.

PubMed

Lopes, Priscila Diniz; Okino, Cintia Hiromi; Fernando, Filipe Santos; Pavani, Caren; Casagrande, Viviane Mariguela; Lopez, Renata F V; Montassier, Maria de Fátima Silva; Montassier, Helio José

2018-05-03

Avian infectious bronchitis virus (IBV) is one of the most important viral diseases of poultry. The mucosa of upper respiratory tract, specially the trachea, is the primary replication site for this virus. However, conventional inactivate IBV vaccines usually elicit reduced mucosal immune responses and local protection. Thus, an inactivated IBV vaccine containing BR-I genotype strain encapsulated in chitosan nanoparticles (IBV-CS) was produced by ionic gelation method to be administered by oculo-nasal route to chickens. IBV-CS vaccine administered alone resulted in markedly mucosal immune responses, characterized by high levels of anti-IBV IgA isotype antibodies and IFNγ gene expression at 1dpi. The association of live attenuated Massachusetts IBV and IBV-CS vaccine also induced strong mucosal immune responses, though a switch from IgA isotype to IgG was observed, and IFNγ gene expression peak was late (at 5 dpi). Efficacy of IBV-CS was evaluated by tracheal ciliostasis analysis, histopathology examination, and viral load determination in the trachea and kidney. The results indicated that IBV-CS vaccine administered alone or associated with a live attenuated heterologous vaccine induced both humoral and cell-mediated immune responses at the primary site of viral replication, and provided an effective protection against IBV infection at local (trachea) and systemic (kidney) sites. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chitosan films incorporated with nettle (Urtica dioica L.) extract-loaded nanoliposomes: I. Physicochemical characterisation and antimicrobial properties.

PubMed

Haghju, Sara; Beigzadeh, Sara; Almasi, Hadi; Hamishehkar, Hamed

2016-07-17

The objective of this study was to characterise and compare physical, mechanical and antimicrobial properties of chitosan-based films, containing free or nanoencapsulated nettle (Urtica dioica L.) extract (NE) at concentrations of 0, 0.5, 1 and 1.5% w/w. Nanoliposomes were prepared using soy-lecithin by thin-film hydration and sonication method to generate an average size of 107-136 nm with 70% encapsulation efficiency. The information on FT-IR reflected that some new interaction have occurred between chitosan and nanoliposomes. Despite the increasing yellowness and decreasing whiteness indexes, the nanoliposomes incorporation improved the thermal properties and mechanical stiffness and caused to decrease water vapour permeability (WVP), moisture uptake and water solubility. The possible antimicrobial activity of the films containing NE-loaded nanoliposomes against Staphylococcus aureus was decreased in comparison to free NE-incorporated films, which could be due to the inhibition effect of the encapsulation that prevents the release of NE from the matrix.

Impact of molecular weight on the formation of electrosprayed chitosan microcapsules as delivery vehicles for bioactive compounds.

PubMed

Gómez-Mascaraque, Laura G; Sanchez, Gloria; López-Rubio, Amparo

2016-10-05

The molecular weight of chitosan is one of its most determinant characteristics, which affects its processability and its performance as a biomaterial. However, information about the effect of this parameter on the formation of electrosprayed chitosan microcapsules is scarce. In this work, the impact of chitosan molecular weight on its electrosprayability was studied and correlated with its effect on the viscosity, surface tension and electrical conductivity of solutions. A Discriminant Function Analysis revealed that the morphology of the electrosprayed chitosan materials could be correctly predicted using these three parameters for almost 85% of the samples. The suitability of using electrosprayed chitosan capsules as carriers for bioactive agents was also assessed by loading them with a model active compound, (-)-epigallocatechin gallate (EGCG). This encapsulation, with an estimated efficiency of around 80% in terms of preserved antioxidant activity, showed the potential to prolong the antiviral activity of EGCG against murine norovirus via gradual bioactive release combined with its protection against degradation in simulated physiological conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis of biodegradable plastic from tapioca with N-Isopropylacrylamid and chitosan using glycerol as plasticizer

NASA Astrophysics Data System (ADS)

Syaubari; Safwani, S.; Riza, M.

2018-04-01

One of natural polymers that can be used as raw material in the manufacture of biodegradable plastic is tapioca and chitosan. The addition of other compounds such as glycerol as plasticizer is to improve the characteristics of the plastic that already produced. N- Isopropylacrylamid (NIPAm) is an organic compound that can be synthesized into a polymer or polymer grafting which also biodegradable too. This research aims tostudy the synthesis of biodegradable plastics from tapioca with the addition of chitosan, NIPAm, poly(NIPAm) and analyze the characteristics of biodegradable plastics that already produced. This research was done in three stages, there are (1) polymerization NIPAm, (2) the grafting of chitosan-poly NIPAm and (3) the synthesis of biodegradable plastics from starch mixture with variation of addition chitosan, NIPAm, poly(NIPAm), chitosan-graft-poly(NIPAm) and also variations of glycerol as plasticizer. The results of this research is a thin sheet of plastic which is will get analyzed for the characteristics of functional groups, mechanical, morphological and its biodegradability. FTIR spectra showed the grafting process with the new group formation of CO single-bond at 850 cm-1. Plastic with the addition of NIPAm and 1 ml glycerol has the highest tensile strength value about 31.1 MPa. Plastic with poly(NIPAm) and 4 ml glycerol produces the highest elongation value about 153.72%. Plastic with Chitosan-graft-poly(NIPAm) with 1 ml glycerol has the longest biodegradation because of the small mass-loss for six weeks which is about 6.6%.

Synthesis and characterization of a stable humic-urease complex: application to barley seed encapsulation for improving N uptake.

PubMed

Mvila, Beaufray G; Pilar-Izquierdo, María C; Busto, María D; Perez-Mateos, Manuel; Ortega, Natividad

2016-07-01

Most N fertilizers added to soil are not efficiently used by plants and are lost to the atmosphere or leached from the soil, causing environmental pollution and increasing cost. Barley seed encapsulation in calcium alginate gels containing free or immobilized urease to enhance plant utilization of soil N was investigated. Urease was immobilized with soil humic acids (HA). A central composite face-centered design was applied to optimize the immobilization process, reaching an immobilization yield of 127%. Soil stability of urease was enhanced after the immobilization. Seed encapsulation with free urease (FU) and humic-urease complex (HUC) resulted in a urease activity retention in the coating layer of 46% and 24%, and in germination rates of 87% and 92%, respectively. Under pot culture conditions, the pots planted with seeds encapsulated with FU and HUC showed higher ammonium N (NH4 (+) -N) (26% and 64%, respectively) than the control soil at 28 days after planting (DAP). Moreover, the seed encapsulation with FU and HUC increased the N uptake 83% and 97%, respectively, at 35 DAP. Seed encapsulation with urease could substantially contribute to enhancing plant N nutrition in the early stages of seedling establishment. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Preparation and optimization of submicron chitosan capsules by water-based electrospraying for food and bioactive packaging applications.

PubMed

Sreekumar, Sruthi; Lemke, Philipp; Moerschbacher, Bruno M; Torres-Giner, Sergio; Lagaron, Jose M

2017-10-01

In the present study, a well-defined set of chitosans, with different degrees of acetylation (DA) and degrees of polymerization (DP), were processed by solution electrospraying from a water-based solvent. The solution properties, in terms of surface tension, conductivity, viscosity, and pH, were characterized and related to the physico-chemical properties of the chitosans. It was observed that both DA and DP values of a given chitosan, in combination with biopolymer concentration, mainly determined solution viscosity. This was, in turn, the major driving factor that defined the electrosprayability of chitosan. In addition, the physico-chemical properties of chitosans highly influenced solution conductivity and results indicated that the chitosan solutions with low or low-to-medium values of conductivity were the most optimal for electrospraying. The results obtained here also demonstrate that a good process control can be achieved by adjusting the working conditions, i.e. applied voltage, flow-rate, and tip-to-collector distance. Finally, it was also shown that electrosprayability of chitosan with inadequate physico-chemical properties can be improved by solution mixing of very different kinds of this polysaccharide. The resultant electrosprayed submicron chitosan capsules can be applied for encapsulation of food additives and to develop bioactive coatings of interest in food packaging, where these particles alone or containing functional ingredients can be released from the package into the food to promote a health benefit.

Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

PubMed

David, Karolyn Infanta; Jaidev, Leela Raghav; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

2015-11-01

Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Vitamin D-fortified chitosan films from mushroom waste

USDA-ARS?s Scientific Manuscript database

Brown mushroom (Agaricus bisporus) stalk bases from mushroom waste were treated with UV-B light to rapidly increase vitamin D2 content. Chitin was also recovered from this waste and converted into chitosan by N-deacetylation. FTIR spectra showed that the mushroom chitosan were similar to chitosan fr...

Preparation and anti-cancer activity of polymer-encapsulated curcumin nanoparticles

NASA Astrophysics Data System (ADS)

Thu Ha, Phuong; Huong Le, Mai; Nhung Hoang, Thi My; Thu Huong Le, Thi; Quang Duong, Tuan; Tran, Thi Hong Ha; Tran, Dai Lam; Phuc Nguyen, Xuan

2012-09-01

Curcumin (Cur) is a yellow compound isolated from rhizome of the herb curcuma longa. Curcumin possesses antioxidant, anti-inflammatory, anti-carcinogenic and antimicrobial properties, and suppresses proliferation of many tumor cells. However, the clinical application of curcumin in cancer treatment is considerably limited due to its serious poor delivery characteristics. In order to increase the hydrophilicity and drug delivery capability, we encapsulated curcumin into copolymer PLA-TPGS, 1,3-beta-glucan (Glu), O-carboxymethyl chitosan (OCMCs) and folate-conjugated OCMCs (OCMCs-Fol). These polymer-encapsulated curcumin nanoparticles (Cur-PLA-TPGS, Cur-Glu, Cur-OCMCs and Cur-OCMCs-Fol) were characterized by infrared (IR), fluorescence (FL), photoluminescence (PL) spectra, field emission scanning electron microscopy (FE-SEM), and found to be spherical particles with an average size of 50-100 nm, being suitable for drug delivery applications. They were much more soluble in water than not only free curcumin but also other biodegradable polymer-encapsulated curcumin nanoparticles. The anti-tumor promoting assay was carried out, showing the positive effects of Cur-Glu and Cur-PLA-TPGS on tumor promotion of Hep-G2 cell line in vitro. Confocal microscopy revealed that the nano-sized curcumin encapsulated by polymers OCMCs and OCMCs-Fol significantly enhanced the cellular uptake (cancer cell HT29 and HeLa).

Thiolated chitosans.

PubMed

Bernkop-Schnürch, Andreas; Hornof, Margit; Guggi, Davide

2004-01-01

The derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions leads to the formation of thiolated chitosans. So far, three types of thiolated chitosans have been generated: chitosan-cysteine conjugates, chitosan-thioglycolic acid conjugates and chitosan-4-thio-butyl-amidine conjugates. Various properties of chitosan are improved by this immobilization of thiol groups. Due to the formation of disulfide bonds with mucus glycoproteins, the mucoadhesiveness is 6--100-fold augmented (I). The permeation of paracellular markers through intestinal mucosa can be enhanced 1.6--3-fold utilizing thiolated instead of unmodified chitosan (II). Moreover, thiolated chitosans display in situ-gelling features, due to the pH-dependent formation of inter- as well as intra-molecular disulfide bonds (III). This latter process provides a strong cohesion and stability of carrier matrices being based on thiolated chitosans (IV). Consequently, thiolated chitosans can guarantee a prolonged controlled release of embedded therapeutic ingredients (V). The potential of thiolated chitosans has meanwhile also been demonstrated in vivo. A significant pharmacological efficacy of 1.3% of orally given salmon calcitonin, for instance, could be achieved utilizing thiolated chitosan as polymeric drug carrier matrix, while no effect was reached using unmodified chitosan. According to these results thiolated chitosans represent a promising new category of polymeric excipients in particular for the non-invasive administration of hydrophilic macromolecules. Further applications such as their use as scaffold materials in tissue engineering or as coating material for stents seem feasible.

Effect of alginate composition on profile release and characteristics of chitosan-alginate microparticles loaded with mangosteen extract

NASA Astrophysics Data System (ADS)

Mulia, Kamarza; Halimah, Nur; Krisanti, Elsa

2017-03-01

Preparation of mangostin-loaded chitosan-alginate microparticles, chemical and physical characterization of the particles, and mangostin release profiles, are described herein. Mangostin rich fraction was obtained from Garcinia mangostana L. pericarp by extraction followed by fractionation. Mangostin-loaded chitosan-alginate microparticles were prepared by ionic gelation method using tripolyphosphate as the linking agent and various concentration of alginate. Mangostin was effectively loaded in all microparticle formulations, resulting in ˜97% encapsulation efficiencies. The loading of mangostin and the in-vitro release profiles in simulated gastrointestinal fluids were affected by the chitosan to alginate ratios used in the preparation of the microparticles. Increased alginate concentration resulted in lowered release of mangostin from microparticles immersed in simulated gastric fluid (pH 1.2) up to two hours. Low release of mangostin in acidic fluid but high release in simulated colon fluid, indicated that the chitosan-alginate microparticles are prospective carrier for extended release of active compound in gastrointestinal system.

Nitric Oxide-Releasing Chitosan Oligosaccharides as Antibacterial Agents

PubMed Central

Lu, Yuan; Slomberg, Danielle L.; Schoenfisch, Mark H.

2014-01-01

Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ~2500, 5000, 10000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro. PMID:24268196

Preparation and characterization of chitosan-natural nano hydroxyapatite-fucoidan nanocomposites for bone tissue engineering.

PubMed

Lowe, Baboucarr; Venkatesan, Jayachandran; Anil, Sukumaran; Shim, Min Suk; Kim, Se-Kwon

2016-12-01

Solid three dimensional (3D) composite scaffolds for bone tissue engineering were prepared using the freeze-drying method. The scaffolds were composed of chitosan, natural nano-hydroxyapatite (nHA) and fucoidan in the following combinations: chitosan, chitosan-fucoidan, chitosan-nHA, and chitosan-nHA-fucoidan. Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and optical microscopy (OM) were used to determine the physiochemical constituents and the morphology of the scaffolds. The addition of nHA into the chitosan-fucoidan composite scaffold reduced the water uptake and water retention. FT-IR analysis confirmed the presence of a phosphate group in the chitosan-nHA-fucoidan scaffold. This group is present because of the presence of nHA (isolated via alkaline hydrolysis from salmon fish bones). Microscopic results indicated that the dispersion of nHA and fucoidan in the chitosan matrix was uniform with a pore size of 10-400μm. The composite demonstrated a suitable micro architecture for cell growth and nutrient supplementation. This compatibility was further elucidated in vitro using periosteum-derived mesenchymal stem cells (PMSCs). The cells demonstrated high biocompatibility and excellent mineralization for the chitosan-nHA-fucoidan scaffold. We believe that a chitosan-nHA-fucoidan composite is a promising biomaterial for the scaffold that can be used for bone tissue regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Encapsulation on Antimicrobial Activity of
Herbal Extracts with Lysozyme

PubMed Central

Matouskova, Petra; Bokrova, Jitka; Benesova, Pavla

2016-01-01

Summary Resistance of microorganisms to antibiotics has increased. The use of natural components with antimicrobial properties can be of great significance to reduce this problem. The presented work is focused on the study of the effect of encapsulation of selected plant and animal antimicrobial substances (herbs, spices, lysozyme and nisin) on their activity and stability. Antimicrobial components were packaged into liposomes and polysaccharide particles (alginate, chitosan and starch). Antimicrobial activity was tested against two Gram-positive (Bacillus subtilis and Micrococcus luteus) and two Gram-negative (Escherichia coli and Serratia marcescens) bacteria. Encapsulation was successful in all types of polysaccharide particles and liposomes. The prepared particles exhibited very good long-term stability, especially in aqueous conditions. Antimicrobial activity was retained in all types of particles. Liposomes with encapsulated herb and spice extracts exhibited very good inhibitory effect against all tested bacterial strains. Most of herbal extracts had very good antimicrobial effect against the tested Gram-negative bacterial strains, while Gram-positive bacteria were more sensitive to lysozyme particles. Thus, particles with co-encapsulated herbs and lysozyme are more active against different types of bacteria, and more stable and more effective during long-term storage. Particles with encapsulated mixture of selected plant extracts and lysozyme could be used as complex antimicrobial preparation with controlled release in the production of food and food supplements, pharmaceutical and cosmetic industries. PMID:27956862

Effect of Green Tea Extract Encapsulated Into Chitosan Nanoparticles on Hepatic Fibrosis Collagen Fibers Assessed by Atomic Force Microscopy in Rat Hepatic Fibrosis Model.

PubMed

Safer, Abdel-Majeed A; Hanafy, Nomany A; Bharali, Dhruba J; Cui, Huadong; Mousa, Shaker A

2015-09-01

The present study examined the effect of Green Tea Extract (GTE) encapsulated into Chitosan Nanoparticles (CS-NPs) on hepatic fibrosis in rat model as determined by atomic force microscopy (AFM). The bioactive compounds in GTE encapsulated into CS-NPs were determined using LC-MS/MS method. Additionally, the uptake of GTE-CS NPs in HepG2 cells showed enhanced uptake. In experimental fibrosis model, AFM was used as a high resolution microscopic tool to investigate collagen fibers as an indicator of hepatic fibrosis induced by treatment with CCl4. Paraffin sections of fibrotic liver tissues caused by CC4 treatment of rats and the effect of GTE-CS NPs treatment with or without CCl4 on hepatic fibrosis were examined. Liver tissues from the different groups of animals were de-waxed and processed as for normal H/E staining and Masson's trichrome staining to locate the proper area of ECM collagen in the CCl4 group versus collagen in liver tissues treated with the GTE-CS NPs with or without CCl4. Selected areas of paraffin sections were trimmed off and fixed flat on top of mica and inserted in the AFM stage. H/E staining, Masson's trichrome stained slides, and AFM images revealed that collagen fibers of 250 to 300 nm widths were abundant in the fibrotic liver samples while those of GTE-CS NPs were clear as in the control group. Data confirmed the hypothesis that GTE-CS NPs are effective in removing all the extracellular collagen caused by CCl4 in the hepatic fibrosis rat liver.

Low toxic and high soluble camptothecin derivative 2–47 effectively induces apoptosis of tumor cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Yao; Zhao, Hong-Ye; Jiang, Du

The cytotoxic activity of camptothecin derivatives is so high that these compounds need to be further modified before their successful application as anti-cancer agents clinically. In this study, we reported the synthesis and biological evaluation of a novel camptothecin derivative called compound 2–47. The changes in structure did not reduce its activity to inhibit DNA topoisomerase I. Compound 2–47 induced apoptosis of many tumor cells including leukemia cells K562, Jurkat, HL-60, breast cancer cell BT-549, colon cancer cell HT-29 and liver cancer cell HepG2 with a half maximal inhibitory concentration (IC{sub 50}) of 2- to 3-fold lower than HCPT asmore » a control. In particular, 2–47 inhibited the proliferation of Jurkat cells with an IC{sub 50} of as low as 40 nM. By making use of Jurkat cell as a model, following treatment of Jurkat cells, compound 2–47 activated caspase-3 and PARP, resulting in a decreased Bcl-2/Bax ratio. These data showed that compound 2–47 induces Jurkat cell death through the mitochondrial apoptotic pathway. In addition, compound 2–47 showed a decreased cytotoxic activity against normal cells and an improved solubility in low-polar solvent. For example, compound 2–47 solutes in CHCl{sub 3} 130-fold higher than HCPT. Taken together, our data demonstrated that camptothecin derivative 2–47 notably inhibits the tumor cell proliferation through mitochondrial-mediated apoptosis in vitro. - Highlights: • Compound 2–47 showed a wide inhibitory effect on the tested tumor cell lines with an IC{sub 50} of 3 times lower than that of HCPT in general. • Compound 2–47 inhibited the proliferation of the human leukemia cell Jurkat at an IC{sub 50} of as low as 40 nM. • As compared to HCPT, compound 2–47 showed much reduced cytotoxicity on normal human cells. • As compared to others, compound 2–47 showed a hundreds-fold higher solubility in non-polar organic solution.« less

Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles.

PubMed

Qasim, Muhammad; Udomluck, Nopphadol; Chang, Jihyun; Park, Hansoo; Kim, Kyobum

2018-01-01

In this study, we analyzed the antimicrobial activities of poly- N -isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH 2 -based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO 3 using NaBH 4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus ) bacteria depending on the nanoparticle size and amount of AgNO 3 used during fabrication.

Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles

PubMed Central

Qasim, Muhammad; Udomluck, Nopphadol; Chang, Jihyun; Park, Hansoo; Kim, Kyobum

2018-01-01

In this study, we analyzed the antimicrobial activities of poly-N-isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH2-based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO3 using NaBH4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria depending on the nanoparticle size and amount of AgNO3 used during fabrication. PMID:29379284

Selective crystallization of calcium salts by poly(acrylate)-grafted chitosan.

PubMed

Neira-Carrillo, Andrónico; Yazdani-Pedram, Mehrdad; Retuert, Jaime; Diaz-Dosque, Mario; Gallois, Sebastien; Arias, José L

2005-06-01

The biopolymer chitosan was chemically modified by grafting polyacrylamide or polyacrylic acid in a homogeneous aqueous phase using potassium persulfate (KPS) as redox initiator system in the presence of N,N-methylene-bis-acrylamide as a crosslinking agent. The influence of the grafted chitosan on calcium salts crystallization in vitro was studied using the sitting-drop method. By using polyacrylamide grafted chitosan as substrate, rosette-like CaSO4 crystals were observed. This was originated by the presence of sulfate coming from the initiator KPS. By comparing crystallization on pure chitosan and on grafted chitosan, a dramatic influence of the grafted polymer on the crystalline habit of both salts was observed. Substrates prepared by combining sulfate with chitosan or sulfate with polyacrylamide did not produce similar CaSO4 morphologies. Moreover, small spheres or donut-shaped CaCO3 crystals on polyacrylic acid grafted chitosan were generated. The particular morphology of CaCO3 crystals depends also on other synthetic parameters such as the molecular weight of the chitosan sample and the KPS concentration.

Thymol nanoemulsions incorporated in quinoa protein/chitosan edible films; antifungal effect in cherry tomatoes.

PubMed

Robledo, Nancy; Vera, Paola; López, Luis; Yazdani-Pedram, Mehrdad; Tapia, Cristian; Abugoch, Lilian

2018-04-25

Thymol nanoemulsions were produced by spontaneous emulsification, ultrasound, and a combination of both methods. The best result in terms of size and polydispersion was spontaneous emulsification where thymol was efficiently encapsulated, the nanoemulsions inhibited Botrytis cinerea at 110 ppm of thymol. A 10% dilution of this nanoemulsion in water was used to prepare quinoa-chitosan films. The film microstructure was porous and heterogeneous. The tensile strength of the film was significantly lower but its mean elongation at break was similar to that of the control film. The water vapour permeability was similar to that of the control film. The effect of nanoemulsion-thymol-quinoa protein/chitosan coating on mould growth in inoculated cherry tomatoes was evaluated. Compared with control samples (tomatoes without coating and those coated with quinoa protein/chitosan), tomatoes with this coating and inoculated with B. cinerea showed a significant decrease in fungal growth after 7 days at 5 °C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nerve transection repair using laser-activated chitosan in a rat model.

PubMed

Bhatt, Neel K; Khan, Taleef R; Mejias, Christopher; Paniello, Randal C

2017-08-01

Cranial nerve transection during head and neck surgery is conventionally repaired with microsuture. Previous studies have demonstrated recovery with laser nerve welding (LNW), a novel alternative to microsuture. LNW has been reported to have poorer tensile strength, however. Laser-activated chitosan, an adhesive biopolymer, may promote nerve recovery while enhancing the tensile strength of the repair. Using a rat posterior tibial nerve injury model, we compared four different methods of nerve repair in this pilot study. Animal study. Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by potassium titanyl phosphate (KTP) laser alone (n = 20), KTP + chitosan (n = 12), microsuture + chitosan (n = 12), and chitosan alone (n = 14). Weekly walking tracks were conducted to measure functional recovery (FR). Tensile strength (TS) was measured at 6 weeks. At 6 weeks, KTP laser alone had the best recovery (FR = 93.4% ± 8.3%). Microsuture + chitosan, KTP + chitosan, and chitosan alone all showed good FR (87.4% ± 13.5%, 84.6% ± 13.0%, and 84.1% ± 10.0%, respectively). One-way analysis of variance was performed (F(3,56) = 2.6, P = .061). A TS threshold of 3.8 N was selected as a control mean recovery. Three groups-KTP alone, KTP + chitosan, and microsuture + chitosan-were found to meet threshold 60% (95% confidence interval [CI]: 23.1%-88.3%), 75% (95% CI: 46.8%-91.1%), and 100% (95% CI: 75.8%-100.0%), respectively. In the posterior tibial nerve model, all repair methods promoted nerve recovery. Laser-activated chitosan as a biopolymer anchor provided good TS and appears to be a novel alternative to microsuture. This repair method may have surgical utility following cranial nerve injury during head and neck surgery. NA Laryngoscope, 127:E253-E257, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Microfluidics and BIO-encapsulation for drug- and cell-therapy

NASA Astrophysics Data System (ADS)

Aloisi, A.; Toma, C. C.; Di Corato, R.; Rinaldi, R.

2017-08-01

We present the construction and the application of biocompatible micro- and nano-structures that can be administered systemically and transport in a targeted and effective way drugs, small molecules, stem cells or immune system cells. These polymeric nano-systems represent a primary goal for the treatment of a wide family of neurological/systemic disorders, as well as tumors and/or acute injuries. As natural, biocompatible, biodegradable and non-immunogenic building blocks, alginate and chitosan are been currently exploited. Ionotropic pre-gelation of the alginate core, followed by chitosan polyelectrolyte complexation, allows to encapsulate selected active molecules by means of physical entrapment and electrostatic interactions within sub-micron sized hydrogel vesicles. Here we present a microfluidicassisted assembly method of nano- and micro-vesicles -under sterile, closed environment and gas exchange adjustable conditions, which is a critical issue, when the cargo to be uploaded is very sensitive. Polymer/polymer and polymer/drug mass ratio relationship are crucial in order to attain the optimum in terms of shuttle size and cargo concentration. By modulating polymer reticulation conditions, it become possible to control drug loading efficiency as well as drug delivery dynamics. Recent results on the application of these vesicles for the encapsulation and delivery of Inhibin-A and Decorin, proteins involved in acute kidney injury (AKI), for Renal tubular cell regeneration will be presented. Finally, the impact of these polysaccharide sub-micron vesicles on Human Immune cells and the metabolic and functional activity of cells embedded in the assembled vesicles will be presented and discussed.

Metabolite fingerprinting of Camptotheca acuminata and the HPLC-ESI-MS/MS analysis of camptothecin and related alkaloids.

PubMed

Montoro, Paola; Maldini, Mariateresa; Piacente, Sonia; Macchia, Mario; Pizza, Cosimo

2010-01-20

The major phytochemical constituents, namely, alkaloids, flavonoids and ellagic acid derivatives, of leaves of Camptotheca acuminata were identified using high performance liquid chromatography (HPLC) coupled with electrospray mass spectrometry (ESI-MS) in extracts of plants cultivated in Italy and collected at different growth stages. Alkaloids related to camptothecin were identified and quantified by HPLC coupled with ESI-tandem mass spectrometry (MS/MS) employing, respectively, an ion trap and a triple quadrupole mass analyser. The fragmentation patterns of alkaloids related to camptothecin were analysed and a specific Multiple Reaction Monitoring HPLC-MS/MS method was developed for the quantitative determination of these constituents. The described method provides high sensitivity and specificity for the characterisation and quantitative determination of the alkaloids in C. acuminata.

Microencapsulation in Alginate and Chitosan Microgels to Enhance Viability of Bifidobacterium longum for Oral Delivery

PubMed Central

Yeung, Timothy W.; Üçok, Elif F.; Tiani, Kendra A.; McClements, David J.; Sela, David A.

2016-01-01

Probiotic microorganisms are incorporated into a wide variety of foods, supplements, and pharmaceuticals to promote human health and wellness. However, maintaining bacterial cell viability during storage and gastrointestinal transit remains a challenge. Encapsulation of bifidobacteria within food-grade hydrogel particles potentially mitigates their sensitivity to environmental stresses. In this study, Bifidobacterium longum subspecies and strains were encapsulated in core-shell microgels consisting of an alginate core and a microgel shell. Encapsulated obligate anaerobes Bifidobacterium longum subsp. infantis and Bifidobacterium longum subsp. longum exhibited differences in viability in a strain-dependent manner, without a discernable relationship to subspecies lineage. This includes viability under aerobic storage conditions and modeled gastrointestinal tract conditions. Coating alginate microgels with chitosan did not improve viability compared to cells encapsulated in alginate microgels alone, suggesting that modifying the surface charge alone does not enhance delivery. Thus hydrogel beads have great potential for improving the stability and efficacy of bifidobacterial probiotics in various nutritional interventions. PMID:27148184

Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice

PubMed Central

Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

2016-01-01

Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

Facile Synthesis of Radial-Like Macroporous Superparamagnetic Chitosan Spheres with In-Situ Co-Precipitation and Gelation of Ferro-Gels

PubMed Central

Yang, Chih-Hui; Wang, Chih-Yu; Huang, Keng-Shiang; Yeh, Chen-Sheng; Wang, Andrew H. -J.; Wang, Wei-Ting; Lin, Ming-Yu

2012-01-01

Macroporous chitosan spheres encapsulating superparamagnetic iron oxide nanoparticles were synthesized by a facile and effective one-step fabrication process. Ferro-gels containing ferrous cations, ferric cations and chitosan were dropped into a sodium hydroxide solution through a syringe pump. In addition, a sodium hydroxide solution was employed for both gelation (chitosan) and co-precipitation (ferrous cations and ferric cations) of the ferro-gels. The results showed that the in-situ co-precipitation of ferro-ions gave rise to a radial morphology with non-spheroid macro pores (large cavities) inside the chitosan spheres. The particle size of iron oxide can be adjusted from 2.5 nm to 5.4 nm by tuning the concentration of the sodium hydroxide solution. Using Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra, the synthesized nanoparticles were illustrated as Fe3O4 nanoparticles. In addition, the prepared macroporous chitosan spheres presented a super-paramagnetic behaviour at room temperature with a saturation magnetization value as high as ca. 18 emu/g. The cytotoxicity was estimated using cell viability by incubating doses (0∼1000 µg/mL) of the macroporous chitosan spheres. The result showed good viability (above 80%) with alginate chitosan particles below 1000 µg/mL, indicating that macroporous chitosan spheres were potentially useful for biomedical applications in the future. PMID:23226207

Antimicrobial Activity of Chitosan Derivatives Containing N-Quaternized Moieties in Its Backbone: A Review

PubMed Central

Martins, Alessandro F.; Facchi, Suelen P.; Follmann, Heveline D. M.; Pereira, Antonio G. B.; Rubira, Adley F.; Muniz, Edvani C.

2014-01-01

Chitosan, which is derived from a deacetylation reaction of chitin, has attractive antimicrobial activity. However, chitosan applications as a biocide are only effective in acidic medium due to its low solubility in neutral and basic conditions. Also, the positive charges carried by the protonated amine groups of chitosan (in acidic conditions) that are the driving force for its solubilization are also associated with its antimicrobial activity. Therefore, chemical modifications of chitosan are required to enhance its solubility and broaden the spectrum of its applications, including as biocide. Quaternization on the nitrogen atom of chitosan is the most used route to render water-soluble chitosan-derivatives, especially at physiological pH conditions. Recent reports in the literature demonstrate that such chitosan-derivatives present excellent antimicrobial activity due to permanent positive charge on nitrogen atoms side-bonded to the polymer backbone. This review presents some relevant work regarding the use of quaternized chitosan-derivatives obtained by different synthetic paths in applications as antimicrobial agents. PMID:25402643

Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies.

PubMed

Yoon, Kyoung Jin P; Krull, Erik J; Morton, Christopher L; Bornmann, William G; Lee, Richard E; Potter, Philip M; Danks, Mary K

2003-11-01

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (irinotecan, CPT-11) is a camptothecin prodrug that is metabolized by carboxylesterases (CE) to the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), a topoisomerase I inhibitor. CPT-11 has shown encouraging antitumor activity against a broad spectrum of tumor types in early clinical trials, but hematopoietic and gastrointestinal toxicity limit its administration. To increase the therapeutic index of CPT-11 and to develop other prodrug analogues for enzyme/prodrug gene therapy applications, our laboratories propose to develop camptothecin prodrugs that will be activated by specific CEs. Specific analogues might then be predicted to be activated, for example, predominantly by human liver CE(hCE1), by human intestinal CE (hiCE), or in gene therapy approaches using a rabbit liver CE (rCE). This study describes a molecular modeling approach to relate the structure of rCE-activated camptothecin prodrugs with their biological activation. Comparative molecular field analysis, comparative molecular similarity index analysis, and docking studies were used to predict the biological activity of a 4-benzylpiperazine derivative of CPT-11 [7-ethyl-10-[4-(1-benzyl)-1-piperazino]carbonyloxycamptothecin (BP-CPT)] in U373MG glioma cell lines transfected with plasmids encoding rCE or hiCE. BP-CPT has been reported to be activated more efficiently than CPT-11 by a rat serum esterase activity; however, three-dimensional quantitative structure-activity relationship studies predicted that rCE would activate BP-CPT less efficiently than CPT-11. This was confirmed by both growth inhibition experiments and kinetic studies. The method is being used to design camptothecin prodrugs predicted to be activated by specific CEs.

Antimicrobial coating of modified chitosan onto cotton fabrics

NASA Astrophysics Data System (ADS)

Cheng, Xiaoli; Ma, Kaikai; Li, Rong; Ren, Xuehong; Huang, T. S.

2014-08-01

Chitosan has been applied as an antibacterial agent to provide biocidal function for textiles but has limitations of application condition and durability. In this study, a new N-halamine chitosan derivative was synthesized by introducing N-halamine hydantoin precursor. The synthesized chitosan derivative 1-Hydroxymethyl-5,5-dimethylhydantoin chitosan (chitosan-HDH) was coated onto cotton fabric with 1,2,3,4-butanetetracarboxylic acid (BTCA) as a crosslinking agent. The coatings were characterized and confirmed by FT-IR and SEM. The treated cotton fabrics can be rendered excellent antimicrobial activity upon exposure to dilute household bleach. The chlorinated coated swatches can inactivate 100% of the Staphylococcus aureus and E. coli O157:H7 with a contact time of 5 min. Almost all the lost chlorine after a month of storage could be recharged upon rechlorination. The crease recovery property of the treated swatches improved while the breaking strength decreased compared with uncoated cotton.

Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets.

PubMed

Huanbutta, Kampanart; Cheewatanakornkool, Kamonrak; Terada, Katsuhide; Nunthanid, Jurairat; Sriamornsak, Pornsak

2013-08-14

Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chitosan-carboxymethylcellulose based microcapsules formulation for controlled release of active ingredients from cosmeto textile

NASA Astrophysics Data System (ADS)

Roy, J. C.; Ferri, A.; Salaün, F.; Giraud, S.; Chen, G.; Jinping, G.

2017-10-01

Chitosan-based emulsions were prepared at pH from 4.0 to 6.0. The zeta potential and droplet size were monitored at different pH. Double emulsions (wateroil- water) were observed due to the stiff conformation of chitosan at pH 4.0. At pH 5.0, the emulsion droplets were the smallest (2.9 μm) of the experimental pH range. The emulsion droplets were well dispersed due to high surface charge of chitosan (for example, +50 mV at pH 5.5) in entire pH range. The emulsion was treated with carboxymethyl cellulose (CMC) for neutralizing the charged chitosan on the surface of emulsion droplets. Above 10×10-2 mg/ml of CMC, no change in zeta potential was observed indicating no more free chitosan existed after neutralization with CMC. The emulsion was then crosslinked with different amount of glutaraldehyde. Upon increasing the amount of glutaraldehyde, the amount of core content inside the microcapsule and encapsulation efficiency of shell materials decreased gradually. The Dynamic Scanning Calorimetry data confirmed no interaction between core and shell material in the microencapsulation process. The thermal degradation of the microcapsules was examined by thermogravimetric analysis and a gradual decrease in the degradation temperature upon increasing glutaraldehyde concentration was found. The tuning of CMC concentration can provide valuable information regarding stable emulsion and efficient microcapsule formulation via coacervation.

Synthesis and characterization of chitosan alkyl urea.

PubMed

Wang, Jing; Jiang, Ji-Zhou; Chen, Wei; Bai, Zheng-Wu

2016-07-10

Chitosan is a versatile material employed for various purposes in many fields including the development of chiral stationary phases for enantioseparation. Chitosan alkyl urea is a kind of intermediate used to prepare enantioseparation materials. In order to synthesize the intermediates, in the present work, a new way to prepare chitosan alkyl urea has been established: chitosan was first reacted with methyl chloroformate yielding N-methoxyformylated chitosan, which was then converted to chitosan alkyl urea through amine-ester exchange reaction. With a large excess of methyl chloroformate and primary amine of low stereohindrance, the amino group in chitosan could be almost completely converted to ureido group. The as-prepared chitosan alkyl urea derivatives were characterized by IR, (1)H NMR, (13)C NMR,(1)H-(1)H COSY and (1)H-(13)C HSQC NMR spectra. The chemical shifts of hydrogen and carbon atoms of glucose unit were assigned. It was found that the degree of substitution was obviously lower if cyclopropyl amine, aniline, tert-butyl amine and diethyl amine were used as reactants for the amine-ester exchange reaction. The reason was explained with the aid of theoretical calculations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Applying quality by design (QbD) concept for fabrication of chitosan coated nanoliposomes.

PubMed

Pandey, Abhijeet P; Karande, Kiran P; Sonawane, Raju O; Deshmukh, Prashant K

2014-03-01

In the present investigation, a quality by design (QbD) strategy was successfully applied to the fabrication of chitosan-coated nanoliposomes (CH-NLPs) encapsulating a hydrophilic drug. The effects of the processing variables on the particle size, encapsulation efficiency (%EE) and coating efficiency (%CE) of CH-NLPs (prepared using a modified ethanol injection method) were investigated. The concentrations of lipid, cholesterol, drug and chitosan; stirring speed, sonication time; organic:aqueous phase ratio; and temperature were identified as the key factors after risk analysis for conducting a screening design study. A separate study was designed to investigate the robustness of the predicted design space. The particle size, %EE and %CE of the optimized CH-NLPs were 111.3 nm, 33.4% and 35.2%, respectively. The observed responses were in accordance with the predicted response, which confirms the suitability and robustness of the design space for CH-NLP formulation. In conclusion, optimization of the selected key variables will help minimize the problems related to size, %EE and %CE that are generally encountered when scaling up processes for NLP formulations. The robustness of the design space will help minimize both intra-batch and inter-batch variations, which are quite common in the pharmaceutical industry.

Chitosan nanoparticles for the linear release of model cationic Peptide.

PubMed

Piras, Anna Maria; Sandreschi, Stefania; Maisetta, Giuseppantonio; Esin, Semih; Batoni, Giovanna; Chiellini, Federica

2015-07-01

The present study is focused on the development of a model drug delivery system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI) as model agent. RSI shares the main chemical-physical features of several biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic potential that is hampered by their lability in the biological fluids and as such they are perfect candidates for DDS. The development studies of quality DDS loaded with AMPs would require highly sensitive and specific quantification assays. The use of RSI allowed for the fine-tuning and optimization of the formulation parameters to promote the hydrophobic interactions between CS and the cationic peptide, favour the loading of the active ingredient and enhance the release properties of the carrier. RSI was encapsulated in chitosan NPs by mean of ionic gelation and a chromogenic enzymatic essay was carried out for the release kinetics evaluation. The developed formulations displayed almost 100% of encapsulation efficacy, low burst percentages, and a linear release of the model peptide. A release model was created showing a direct dependence on both the amount of RSI and NPs radius. Although CS has always been formulated with negatively charged active agents (e.g. oligonucleotides or anionic proteins), the use of ionotropic gelation in presence of a small cationic active agent promoted the formation of "core-shell" NPs. The described model, with tuneable linear release rates, appears eligible for further exploitation such as the loading of therapeutically active AMPs.

pH-responsive self-healing injectable hydrogel based on N-carboxyethyl chitosan for hepatocellular carcinoma therapy.

PubMed

Qu, Jin; Zhao, Xin; Ma, Peter X; Guo, Baolin

2017-08-01

Injectable hydrogels with pH-responsiveness and self-healing ability have great potential for anti-cancer drug delivery. Herein, we developed a series of polysaccharide-based self-healing hydrogels with pH-sensitivity as drug delivery vehicles for hepatocellular carcinoma therapy. The hydrogels were prepared by using N-carboxyethyl chitosan (CEC) synthesized via Michael reaction in aqueous solution and dibenzaldehyde-terminated poly(ethylene glycol) (PEGDA). Doxorubicin (Dox), as a model of water-soluble small molecule anti-cancer drug was encapsulated into the hydrogel in situ. Self-healing behavior of the hydrogels was investigated at microscopic and macroscopic levels, and the hydrogels showed rapid self-healing performance without any external stimulus owing to the dynamic covalent Schiff-base linkage between amine groups from CEC and benzaldehyde groups from PEGDA. The chemical structures, rheological property, in vitro gel degradation, morphology, gelation time and in vitro Dox release behavior from the hydrogels were characterized. Injectability was verified by in vitro injection and in vivo subcutaneous injection in a rat. pH-responsive behavior was verified by in vitro Dox release from hydrogels in PBS solutions with different pH values. Furthermore, the activity of Dox released from hydrogel matrix was evaluated by employing human hepatocellular liver carcinoma (HepG2). Cytotoxicity test of the hydrogels using L929 cells confirmed their good cytocompatibility. Together, these pH-responsive self-healing injectable hydrogels are excellent candidates as drug delivery vehicles for liver cancer treatment. STATEMENT OF SIGNIFICANCE: pH-responsive drug delivery system could release drug efficiently in targeted acid environment and minimalize the amount of drug release in normal physiological environment. pH-sensitive injectable hydrogels as smart anti-cancer drug delivery carriers show great potential application for cancer therapy. The hydrogels with self

Green synthesis approach: extraction of chitosan from fungus mycelia.

PubMed

Dhillon, Gurpreet Singh; Kaur, Surinder; Brar, Satinder Kaur; Verma, Mausam

2013-12-01

Chitosan, copolymer of glucosamine and N-acetyl glucosamine is mainly derived from chitin, which is present in cell walls of crustaceans and some other microorganisms, such as fungi. Chitosan is emerging as an important biopolymer having a broad range of applications in different fields. On a commercial scale, chitosan is mainly obtained from crustacean shells rather than from the fungal sources. The methods used for extraction of chitosan are laden with many disadvantages. Alternative options of producing chitosan from fungal biomass exist, in fact with superior physico-chemical properties. Researchers around the globe are attempting to commercialize chitosan production and extraction from fungal sources. Chitosan extracted from fungal sources has the potential to completely replace crustacean-derived chitosan. In this context, the present review discusses the potential of fungal biomass resulting from various biotechnological industries or grown on negative/low cost agricultural and industrial wastes and their by-products as an inexpensive source of chitosan. Biologically derived fungal chitosan offers promising advantages over the chitosan obtained from crustacean shells with respect to different physico-chemical attributes. The different aspects of fungal chitosan extraction methods and various parameters having an effect on the yield of chitosan are discussed in detail. This review also deals with essential attributes of chitosan for high value-added applications in different fields.

Protection of dopamine towards autoxidation reaction by encapsulation into non-coated- or chitosan- or thiolated chitosan-coated-liposomes.

PubMed

Trapani, A; Mandracchia, D; Tripodo, G; Cometa, S; Cellamare, S; De Giglio, E; Klepetsanis, P; Antimisiaris, S G

2018-05-26

The aim of this work is to evaluate the potential of non-coated-, chitosan-(CS)- or chitosan-glutathione conjugate- (CS-GSH)-coated liposomes to protect the neurotransmitter Dopamine (DA) from the autoxidation reaction in neutral/alkaline conditions. This may be of interest in the development of nanotechnology-based approaches to improve Parkinson's disease treatment because decreased ROS production and reduced DA associated neurotoxicity are expected. For the mentioned purposes, DA-loaded vesicles were prepared by the Dried Reconstituted Vesicles (DRV) method, and were subsequently coated using solutions of polycations. As for the mean diameters of liposomes so prepared, the CS-GSH coated liposomes showed a significant decrease in size compared to the corresponding non-coated and CS-coated vesicles. The surface charge of DA-loaded non-coated liposomes was -10.8 mV, whereas the CS or CS-GSH coated vesicles showed a slightly positive ζ-potential. The capability of the herein studied vesicles to prevent DA autoxidation was evaluated by visual inspection, monitoring DA/lipid ratio as such and under stressed conditions. The results suggest that liposome formulations partially protect the neurotransmitter from the autoxidation reaction. In particular, the CS-GSH coated liposomes were more stable than the corresponding CS-coated and non-coated ones against the oxidative damage and were found to deliver the neurotransmitter in a sustained manner. Probably, this is due to the localization of the neurotransmitter in the core of the vesicles as indicated by XPS which confirmed the absence of the neurotransmitter on the surface of these vesicles. Copyright © 2018 Elsevier B.V. All rights reserved.

Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation

PubMed Central

Kim, Sungwoo; Kang, Yunqing; Krueger, Chad A.; Sen, Milan; Holcomb, John B.; Chen, Di; Wenke, Joseph C.; Yang, Yunzhi

2012-01-01

The purpose of this study was to develop and characterize a chitosan gel/gelatin microspheres (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1 containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system than other treatments (p<0.05) after a week of culture. PMID:22293583

Dual responsive PNIPAM-chitosan targeted magnetic nanopolymers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yadavalli, Tejabhiram; Ramasamy, Shivaraman; Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal; Chennakesavulu, Ramasamy

2015-04-01

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation.

Effective production of resistant starch using pullulanase immobilized onto magnetic chitosan/Fe3O4 nanoparticles.

PubMed

Long, Jie; Zhang, Bao; Li, Xingfei; Zhan, Xiaobei; Xu, Xueming; Xie, Zhengjun; Jin, Zhengyu

2018-01-15

In this study, pullulanase was firstly immobilized by covalent bonding onto chitosan/Fe 3 O 4 nanoparticles or encapsulation in sol-gel after bonding onto chitosan/Fe 3 O 4 nanoparticles, and then the immobilized pullulanase was used for the effective production of resistant starch (RS). The highest RS content (35.1%) was obtained under the optimized condition of pH 4.4, enzyme concentration of 10ASPU/g and hydrolysis time of 12h when debranched by free pullulsanase, indicating that RS content was significantly (p<0.05) increased when compared to native starch (4.3%) and autoclaved starch (12.5%). Under these conditions, the immobilized pullulanase (10ASPU/g dry starch) yielded higher RS content compared to free enzyme (10ASPU/g dry starch), especially, the pullulanse immobilized by sol-gel encapsulation yielded the highest RS content (43.4%). Moreover, compared to starches hydrolyzed by free pullulanase, starches hydrolyzed by immobilized pullulanase showed a different saccharide profile of starch hydrolysate, including a stronger peak C (MW=5.0×10 3 ), as well as exhibited an additional absorption peak around 140°C. Reusability results demonstrated that pullulanase immobilized by sol-gel encapsulation had the advantages of producing higher RS content as well as better operational stability compared to pullulanase immobilized by cross-linking. The resulting enhanced RS content generated by the process described in this work could be used as an adjunct in food processing industries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Poly(d,l-lactide-co-glycolide)–chitosan composite particles for the treatment of lung cancer

PubMed Central

Arya, Neha; Katti, Dhirendra S

2015-01-01

Tumor heterogeneity makes combination chemotherapy one of the preferred modes of treatment regimens. In this work, sequential exposure of two anticancer agents, paclitaxel (Tx) followed by topotecan (TPT), was shown to have a synergistic effect on non-small cell lung cancer (NSCLC) cell line, NCI-H460. In order to improve patient compliance, the aforementioned concept was translated into a drug delivery system comprising of poly(d,l-lactide-co-glycolide) (PLGA)–chitosan composite particles. TPT-containing chitosan micro-/nanoparticles were prepared by the facile technique of electrospraying and encapsulated within PLGA microparticles using emulsion-solvent evaporation technique for delayed release of TPT. The formulation containing Tx- and TPT-loaded composite particles demonstrated synergism when exposed to NCI-H460 cellular aggregates (tumoroids) generated in vitro. Overall, the results of this study demonstrated the potential of the formulation containing Tx and PLGA–chitosan (TPT-loaded) composite particles for the treatment of lung cancer. PMID:25945047

Polyamidoamine dendrimer conjugated chitosan nanoparticles for the delivery of methotrexate.

PubMed

Leng, Zhen-Hua; Zhuang, Qian-Fen; Li, Yan-Chao; He, Zeng; Chen, Zhao; Huang, Sai-Peng; Jia, Hong-Ying; Zhou, Jian-Wei; Liu, Yang; Du, Li-Bo

2013-10-15

Encapsulating anticancer drugs to synthetic polymer is a promising approach to improve the efficiency and reduce the side effects of anticancer drugs. In this study, novel chitosan derivatives with polyamidoamine moieties (CS-PAMAM) were synthesized and characterized by morphology, particle size, and zeta potential. Then the anticancer drug-methotrexate-encapsulated CS-PAMAM was prepared by hydrophobic-hydrophilic interactions. The drug release assay showed that the amount of the methotrexate release from CS-PAMAM was pH depended. Meanwhile, the cell viability assay illustrated that CS-PAMAM was suitable for the drug delivery because of its low cytotoxicity on cells. Moreover, our results showed that the CS-PAMAM could significantly improve the cytotoxicity of free methotrexate on A549 cells. These results demonstrate that CS-PAMAM may provide a suitable platform for the water-insoluble drug delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

CH stretching overtone spectra of trimethyl amine and dimethyl sulfide

NASA Astrophysics Data System (ADS)

Billinghurst, Brant E.; Gough, Kathleen M.; Low, Geoffrey R.; Kjaergaard, Henrik G.

2004-01-01

Trimethyl amine (TMA) exhibits the largest known difference in CH bond lengths within a methyl group, due to what is known as the lone pair trans effect. Dimethyl sulfide also exhibits this effect, but to a far lesser extent, making it ideal for comparison to TMA. In this paper, the first through fourth overtone spectra of N(CH3)3, N(CD3)3, N(CD2H)(CD3)2, N(CH3)(CD3)2, N(CD3)(CH3)2 and S(CH3)2 are reported and all major bands are assigned. The intensities of the observed bands are compared to intensities predicted by the harmonically coupled anharmonic oscillator local mode model. Good correlation is found between the experimental intensities and those predicted with the local mode model and HF/6-311++G(2d,2p) calculated dipole moment functions. An increase in the ability to resolve peaks as methyl groups are deuterated suggests that the lone pair mediates increased coupling between methyl groups.

Chitosan-based biocatalytic nanoparticles for pollutant removal from wastewater.

PubMed

Alarcón-Payán, Dulce A; Koyani, Rina D; Vazquez-Duhalt, Rafael

2017-05-01

Chitosan, a renewable biopolymer has the prospective applications in different fields due to its gelation capacity. Nanoconfiguration of chitosan through ionotropic gelation to encapsulate enzymatic activity offers numerous potential applications. In the present study, the preparation and characterization of chitosan nanoparticles loaded with versatile peroxidase are reported. Their performance in bioremediation process and the resistance enhancement against natural microbial biodegradation were studied. The average diameter of enzymatic nanoparticles was 120nm and showed a high enzyme loading capacity. The kinetic parameters of nanoparticles exhibited a slightly lower catalytic activity (k cat ), similar affinity constant (Km) for hydrogen peroxide and higher Km value for the phenolic compound when compared with the free enzyme. The enzymatic nanoparticles showed higher thermostability and the same pH activity profile than those from free enzyme. Ten phenolic compounds, including pesticides, halogenated compounds, endocrine disruptors and antibacterials were transformed by the enzymatic nanoparticles. The transformation rate was lower than those obtained with free enzyme suggesting mass transfer limitations. But very importantly, the enzymatic nanoparticles showed a significant increase of the operational stability in real conditions of wastewater treatment process. Moreover, chemical modification of nanoparticles with different aldehydes still enhanced the operational stability of nanoparticulated enzymes. This enhancement of stability in real conditions and the potential use of biocatalytic nanoparticles in bioremediation processes are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Injectable In Situ Forming Biodegradable Chitosan-Hyaluronic acid Based Hydrogels for Cartilage Tissue Engineering

PubMed Central

Tan, Huaping; Chu, Constance R.; Payne, Karin; Marra, Kacey G.

2009-01-01

Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAG). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications. PMID:19167750

Characterization of physicochemical and colloidal properties of hydrogel chitosan-coated iron-oxide nanoparticles for cancer therapy

NASA Astrophysics Data System (ADS)

Catalano, E.; Di Benedetto, A.

2017-05-01

Superparamagnetic iron oxide nanoparticles have recently been investigated for their potential to kill cancer cells with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe3O4 magnetic nanoparticles were synthesized to induce magnetic hyperthermia, and targeted delivering of chemotherapeutics in the cancer microenvironment. The characteristic properties of synthesized bare and CS-MNPs were analyzed by various analytical methods: X-ray diffraction, Fourier transformed infrared spectroscopy, Scanning electron microscopy and Thermo-gravimetric analysis/differential thermal analysis. Magnetic nanoparticles were successfully synthesized using the co-precipitation method. This synthesis technique resulted in nanoparticles with an average particle size of 16 nm. The pure obtained nanoparticles were then successfully encapsulated with 4-nm-thick chitosan coating. The formation of chitosan on the surface of nanoparticles was confirmed by physicochemical analyses. Heating experiments at safe magnetic field (f = 100 kHz, H =10-20 kA m-1) revealed that the maximum achieved temperature of water stable chitosan-coated nanoparticles (50 mg ml-1) is fully in agreement with cancer therapy and biomedical applications.

An overview of chitin or chitosan/nano ceramic composite scaffolds for bone tissue engineering.

PubMed

Deepthi, S; Venkatesan, J; Kim, Se-Kwon; Bumgardner, Joel D; Jayakumar, R

2016-12-01

Chitin and chitosan based nanocomposite scaffolds have been widely used for bone tissue engineering. These chitin and chitosan based scaffolds were reinforced with nanocomponents viz Hydroxyapatite (HAp), Bioglass ceramic (BGC), Silicon dioxide (SiO 2 ), Titanium dioxide (TiO 2 ) and Zirconium oxide (ZrO 2 ) to develop nanocomposite scaffolds. Plenty of works have been reported on the applications and characteristics of the nanoceramic composites however, compiling the work done in this field and presenting it in a single article is a thrust area. This review is written with an aim to fill this gap and focus on the preparations and applications of chitin or chitosan/nHAp, chitin or chitosan/nBGC, chitin or chitosan/nSiO 2 , chitin or chitosan/nTiO 2 and chitin or chitosan/nZrO 2 in the field of bone tissue engineering in detail. Many reports so far exemplify the importance of ceramics in bone regeneration. The effect of nanoceramics over native ceramics in developing composites, its role in osteogenesis etc. are the gist of this review. Copyright © 2016 Elsevier B.V. All rights reserved.

Chelators influenced synthesis of chitosan-carboxymethyl cellulose microparticles for controlled drug delivery

NASA Astrophysics Data System (ADS)

Samrot, Antony V.; Akanksha; Jahnavi, Tatipamula; Padmanaban, S.; Philip, Sheryl-Ann; Burman, Ujjala; Rabel, Arul Maximus

2016-11-01

In this study, polyphenolic curcumin is entrapped within microcomposites made of biopolymers chitosan (CS) and carboxymethyl cellulose (CMC) formulated by ionic gelation method. Here, different concentrations of two chelating agents, barium chloride and sodium tripolyphosphate, are used to make microcomposites. Thus, the synthesized microparticles were characterized by FTIR, and their surface morphology was studied by SEM. Drug encapsulation efficiency and the drug release kinetics of CS-CMC composites are also studied. The produced microcomposites were used to study antibacterial activity in vitro.

Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

PubMed

Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

2011-09-01

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

Engineering Tenofovir Loaded Chitosan Nanoparticles

PubMed Central

Meng, Jianing; Sturgis, Timothy F.; Youan, Bi-Botti C.

2011-01-01

The objective of this study was to engineer a model anti-HIV microbicide (Tenofovir) loaded chitosan based nanoparticles (NPs). Box-Behnken design allowed to assess the influence of formulation variables on the size of NPs and drug encapsulation efficiency (EE%) that were analyzed by dynamic light scattering and UV spectroscopy, respectively. The effect of the NPs on vaginal epithelial cells and Lactobacillus crispatus viability and their mucoadhesion to porcine vaginal tissue were assessed by cytotoxicity assays and fluorimetry, respectively. In the optimal aqueous conditions, the EE% and NPs size was 5.83% and 207.97nm, respectively. With 50% (v/v) ethanol/water as alternative solvent, these two responses increased to 20% and 602 nm, respectively. Drug release from medium (281 nm) and large size (602 nm)-sized NPs fitted the Higuchi (r2=0.991) and first-order release (r2=0.999) models, respectively. These NPs were not cytotoxic to both the vaginal epithelial cell line and Lactobacillus for 48 hours. When the diameter of the NPs decreased from 900 nm to 188 nm, the mucoadhesion increased from 6% to 12%. However, the combinatorial effect of EE% × mucoadhesion for larger size NPs was the highest. Overall, large-size, microbicide loaded chitosan NPs appeared to be promising nanomedicines for the prevention of HIV transmission. PMID:21704704

Functionalization of chitosan by click chemistry

NASA Astrophysics Data System (ADS)

Cheaburu-Yilmaz, Catalina Natalia; Karavana, Sinem Yaprak; Yilmaz, Onur

2017-12-01

Chitosan modification represents a challenge nowadays. The variety of compounds which can be obtained with various architectures and different functionalities made it attractive to be used in fields like pharmacy and material science. Presents study deals with the chemical modification of chitosan by using click chemistry technique. The study adopted the approach of clicking azidated chitosan with a synthesized alkyne terminated polymer i.e. poly N isopropylacrylamide with thermoresponsive properties. Structures were confirmed by the FT-IR and HNMR spectra. Thermal characterization was performed showing different thermal behaviour with the chemical modification. The final synthesized graft copolymer can play important role within pharmaceutical formulations carrying drugs for topical or oral treatments.

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

PubMed Central

Tchou-Wong, Kam-Meng; Kluz, Thomas; Arita, Adriana; Smith, Phillip R.; Brown, Stuart; Costa, Max

2011-01-01

Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3), a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s) underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq) and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq). The effect of NiCl2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs) on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl2. This study may provide insights into the epigenetic mechanism(s) underlying the carcinogenicity of nickel compounds. PMID:21455298

Sorption of Cu(II) Ions on Chitosan-Zeolite X Composites: Impact of Gelling and Drying Conditions.

PubMed

Djelad, Amal; Morsli, Amine; Robitzer, Mike; Bengueddach, Abdelkader; di Renzo, Francesco; Quignard, Françoise

2016-01-19

Chitosan-zeolite Na-X composite beads with open porosity and different zeolite contents were prepared by an encapsulation method. Preparation conditions had to be optimised in order to stabilize the zeolite network during the polysaccharide gelling process. Composites and pure reference components were characterized using X-ray diffraction (XRD); scanning electron microscopy (SEM); N₂ adsorption-desorption; and thermogravimetric analysis (TG). Cu(II) sorption was investigated at pH 6. The choice of drying method used for the storage of the adsorbent severely affects the textural properties of the composite and the copper sorption effectiveness. The copper sorption capacity of chitosan hydrogel is about 190 mg·g(-1). More than 70% of this capacity is retained when the polysaccharide is stored as an aerogel after supercrititcal CO₂ drying, but nearly 90% of the capacity is lost after evaporative drying to a xerogel. Textural data and Cu(II) sorption data indicate that the properties of the zeolite-polysaccharide composites are not just the sum of the properties of the individual components. Whereas a chitosan coating impairs the accessibility of the microporosity of the zeolite; the presence of the zeolite improves the stability of the dispersion of chitosan upon supercritical drying and increases the affinity of the composites for Cu(II) cations. Chitosan-zeolite aerogels present Cu(II) sorption properties.

Comparative study of chitosan and chitosan-gelatin scaffold for tissue engineering

NASA Astrophysics Data System (ADS)

Kumar, Pawan; Dehiya, Brijnandan S.; Sindhu, Anil

2017-12-01

A number of orthopedic disorders and bone defect issues are solved by scaffold-based therapy in tissue engineering. The biocompatibility of chitosan (polysaccharide) and its similarity with glycosaminoglycan makes it a bone-grafting material. The current work focus on the synthesis of chitosan and chitosan-gelatin scaffold for hard tissue engineering. The chitosan and chitosan-gelatin scaffold have shown improved specific surface area, density, porosity, mechanical properties, biodegradability and absorption. These scaffolds can lead to the development or artificial fabrication of hard tissue alternates. The porous scaffold samples were prepared by freeze-drying method. The microstructure, mechanical and degradable properties of chitosan and chitosan-gelatin scaffolds were analyzed and results revealed that the scaffolds prepared from chitosan-gelatin can be utilized as a useful matrix for tissue engineering.

Effect of hydroxyapatite nano-particles on morphology, rheology and thermal behavior of poly(caprolactone)/chitosan blends.

PubMed

Ghorbani, Fereshte Mohammad; Kaffashi, Babak; Shokrollahi, Parvin; Akhlaghi, Shahin; Hedenqvist, Mikael S

2016-02-01

The effect of hydroxyapatite nano-particles (nHA) on morphology, and rheological and thermal properties of PCL/chitosan blends was investigated. The tendency of nHA to reside in the submicron-dispersed chitosan phase is determined using SEM and AFM images. The presence of electrostatic interaction between amide sites of chitosan and ionic groups on the nHA surface was proved by FTIR. It is shown that the chitosan phase is thermodynamically more favorable for the nano-particles to reside than the PCL phase. Lack of implementation of Cox-Merz theory for this system shows that the polymer-nano-particle network is destructed by the flow. Results from dynamic rheological measurements and Zener fractional model show that the presence of nHA increases the shear moduli and relaxation time of the PCL/chitosan blends. DSC measurements showed that nHA nano-particles are responsible for the increase in melting and crystallization characteristics of the PCL/chitosan blends. Based on thermogravimetric analysis, the PCL/chitosan/nHA nano-composites exhibited a greater thermal stability compared to the nHA-free blends. Copyright © 2015 Elsevier B.V. All rights reserved.

Electrosprayed chitosan nanoparticles: facile and efficient approach for bacterial transformation

NASA Astrophysics Data System (ADS)

Abyadeh, Morteza; Sadroddiny, Esmaeil; Ebrahimi, Ammar; Esmaeili, Fariba; Landi, Farzaneh Saeedi; Amani, Amir

2017-12-01

A rapid and efficient procedure for DNA transformation is a key prerequisite for successful cloning and genomic studies. While there are efforts to develop a facile method, so far obtained efficiencies for alternative methods have been unsatisfactory (i.e. 105-106 CFU/μg plasmid) compared with conventional method (up to 108 CFU/μg plasmid). In this work, for the first time, we prepared chitosan/pDNA nanoparticles by electrospraying methods to improve transformation process. Electrospray method was used for chitosan/pDNA nanoparticles production to investigate the non-competent bacterial transformation efficiency; besides, the effect of chitosan molecular weight, N/P ratio and nanoparticle size on non-competent bacterial transformation efficiency was evaluated too. The results showed that transformation efficiency increased with decreasing the molecular weight, N/P ratio and nanoparticles size. In addition, transformation efficiency of 1.7 × 108 CFU/μg plasmid was obtained with chitosan molecular weight, N/P ratio and nanoparticles size values of 30 kDa, 1 and 125 nm. Chitosan/pDNA electrosprayed nanoparticles were produced and the effect of molecular weight, N/P and size of nanoparticles on transformation efficiency was evaluated. In total, we present a facile and rapid method for bacterial transformation, which has comparable efficiency with the common method.

Arabidopsis COMPASS-Like Complexes Mediate Histone H3 Lysine-4 Trimethylation to Control Floral Transition and Plant Development

PubMed Central

Jiang, Danhua; Kong, Nicholas C.; Gu, Xiaofeng; Li, Zicong; He, Yuehui

2011-01-01

Histone H3 lysine-4 (H3K4) methylation is associated with transcribed genes in eukaryotes. In Drosophila and mammals, both di- and tri-methylation of H3K4 are associated with gene activation. In contrast to animals, in Arabidopsis H3K4 trimethylation, but not mono- or di-methylation of H3K4, has been implicated in transcriptional activation. H3K4 methylation is catalyzed by the H3K4 methyltransferase complexes known as COMPASS or COMPASS-like in yeast and mammals. Here, we report that Arabidopsis homologs of the COMPASS and COMPASS-like complex core components known as Ash2, RbBP5, and WDR5 in humans form a nuclear subcomplex during vegetative and reproductive development, which can associate with multiple putative H3K4 methyltransferases. Loss of function of ARABIDOPSIS Ash2 RELATIVE (ASH2R) causes a great decrease in genome-wide H3K4 trimethylation, but not in di- or mono-methylation. Knockdown of ASH2R or the RbBP5 homolog suppresses the expression of a crucial Arabidopsis floral repressor, FLOWERING LOCUS C (FLC), and FLC homologs resulting in accelerated floral transition. ASH2R binds to the chromatin of FLC and FLC homologs in vivo and is required for H3K4 trimethylation, but not for H3K4 dimethylation in these loci; overexpression of ASH2R causes elevated H3K4 trimethylation, but not H3K4 dimethylation, in its target genes FLC and FLC homologs, resulting in activation of these gene expression and consequent late flowering. These results strongly suggest that H3K4 trimethylation in FLC and its homologs can activate their expression, providing concrete evidence that H3K4 trimethylation accumulation can activate eukaryotic gene expression. Furthermore, our findings suggest that there are multiple COMPASS-like complexes in Arabidopsis and that these complexes deposit trimethyl but not di- or mono-methyl H3K4 in target genes to promote their expression, providing a molecular explanation for the observed coupling of H3K4 trimethylation (but not H3K4 dimethylation

CdS QDs-chitosan microcapsules with stimuli-responsive property generated by gas-liquid microfluidic technique.

PubMed

Chen, Yanjun; Yao, Rongyi; Wang, Yifeng; Chen, Ming; Qiu, Tong; Zhang, Chaocan

2015-01-01

This article describes a straightforward gas-liquid microfluidic approach to generate uniform-sized chitosan microcapsules containing CdS quantum dots (QDs). CdS QDs are encapsulated into the liquid-core of the microcapsules. The sizes of the microcapsules can be conveniently controlled by gas flow rate. QDs-chitosan microcapsules show good fluorescent stability in water, and exhibit fluorescent responses to chemical environmental stimuli. α-Cyclodextrin (α-CD) causes the microcapsules to deform and even collapse. More interestingly, α-CD induces obvious changes on the fluorescent color of the microcapsules. However, β-cyclodextrin (β-CD) has little influence on the shape and fluorescent color of the microcapsules. Based on the results of scanning electron microscopy, the possible mechanism about the effects of α-CD on the chitosan microcapsules is analyzed. These stimuli-responsive microcapsules are low-cost and easy to be prepared by gas-liquid microfluidic technique, and can be applied as a potential micro-detector to chemicals, such as CDs. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation and characterization of PEGylated chitosan nanocapsules as a carrier for pharmaceutical application

NASA Astrophysics Data System (ADS)

Najafabadi, Alireza Hassani; Abdouss, Majid; Faghihi, Shahab

2014-03-01

A new method to conjugate methoxy polyethylene glycol (mPEG) to C6 position of chitosan under the mild condition is introduced that improves the biocompatibility and water solubility of chitosan. Harsh deprotecting step and several purification cycles are two major disadvantages of the current methods for preparing PEGylated chitosan. In this study, the amine groups at C2 position of chitosan are protected using SDS followed by grafting the PEG. The protecting group of chitosan is simply removed by dialyzing against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and 1H NMR spectroscopy. Fourier transformed-infrared (FT-IR) and 1H NMR spectra confirmed that the mPEG is successfully grafted to C6 position of chitosan. Prepared methoxy polyethylene glycol (mPEG) is then employed to prepare the nanocapsules for the encapsulation of poor water-soluble drug, propofol. The TEM, AFM, and DLS techniques are used to characterize the prepared nanocapsules size and morphology. The results show a size of about 80 nm with spherical shape for nanocapsules. In vitro drug release is carried out to evaluate the potential of nanocarriers for the intravenous delivery of drugs. The profile of release from formulated nanocapsules is similar to those of commercial lipid emulsion (CLE). In vivo animal sleep-recovery test on rats shows a close similarity between the time of unconsciousness and recovery of righting reflex between nanoparticles and CLE. This study provides an efficient, novel, and easy method for preparing a carrier system that requires less intensive reaction conditions, fewer reaction steps, and less purification steps. In addition, the nanocapsules introduced here could be a promising nano carrier for the delivery of poor water-soluble drugs.

Nitrate decontamination through functionalized chitosan in brackish water.

PubMed

Appunni, Sowmya; Rajesh, Mathur P; Prabhakar, Sivaraman

2016-08-20

N, N, N-Triethyl ammonium functionalized cross-linked chitosan beads (TEACCB) was prepared by alkylation of glutaraldehyde cross-linked chitosan beads to remove nitrate from brackish water. Physico-chemical characteristics of TEACCB were analyzed using FTIR, SEM, EDAX, TGA, DTA, BET surface area, swelling ratio and pHzpc. The maximum nitrate removal capacity of TEACCB was 2.26meq/g and is higher than other reported chitosan based adsorbents. Nitrate removal ratio in the presence and absence of common anions like chloride and sulphate demonstrated the selectively of TEACCB towards nitrate. The kinetic data of nitrate removal fitted well with the pseudo-second-order kinetic model. The thermodynamic parameters indicated that nitrate removal could be spontaneous and exothermic in nature. TEACCB was reused with 100% efficiency after regenerating with 0.05N HCl. Column study was carried out to remove nitrate from brackish water. These results are very significant to develop TEACCB based nitrate removal technology with great efficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

Understanding the properties of chitosan aryl substituted thioureas in their role and potential as antibacterial agents

NASA Astrophysics Data System (ADS)

Khairul, Wan M.; Daud, Adibah Izzati; Ismail, Noraznawati

2018-02-01

In this study, the effort was to design and synthesize a series of thiourea-chitosan derivatives featuring five aryl substituted members namely N-chitosan-N'-(4-nitrobenzoyl) thiourea (1), N-chitosan-N'-(4-chlorobenzoyl) thiourea (2), N-chitosan-N'-(4-methylbenzoyl) thiourea (3), N-chitosan-N'-(2-iodobenzoyl) thiourea (4), and N-chitosan-N'-(2-methylbenzoyl) thiourea (5) via SN2 reaction pathway having different donating and withdrawing groups. Their molecular structures were then characterised by FT-IR, UV-Vis, and thermogravimetric analysis (TGA). The antimicrobial activities of these derivatives against four species bacteria Bacillus cereus, Staphylococcus aureus, Salmonella typhi, and Escherichia coli of both Gram-positive and Gram-negative type bacteria at minimum concentration 6mg/ml were carried out to investigate their potential as antibacterial agents. Compound 1 exhibited specific activity as it can only inhibit Gram-positive bacteria while other compounds 2-5 showed broad range spectrum activity as they were able to inhibit both Gram-positive and Gram-negative bacteria. Therefore, 1-5 showed good antibacterial activity and have high potential to be further developed as active materials in pharmaceutical interests.

Microwave-Assisted Hydrolysis of Chitosan from Shrimp Shell Waste for Glucosammine Hydrochlorid Production

NASA Astrophysics Data System (ADS)

Zaeni, Ahmad; Safitri, Endang; Fuadah, Badrotul; Nyoman Sudiana, I.

2017-05-01

Chitin is the most widespread renewable natural sources following cellulose as the main source of chitosan. Chitin is isolated from crustacean waste and shrimp shells. Chitosan is derived from chitin throuhgt demineralisation, deproteination, decolorisation and deacetylation process using chemicals such as sodium hydroxide, hydrogen chloride and acetone. Glucosamine hydrochloride (GlcN-Cl) can be produced by hydrolysis of chitosan by using hydrogen chloride. During deacetylation and hydrolysis the solution is heated by hotplate or furnace. In this paper we use microwave instead of hotplate for production chitosan and GlcN-Cl. The research investigates effect of microwaves to amount of rendemen and their property. The chitosan was characterized its moisture content, solubility, and degree of deacetylation (DDA). Whereas the glucosammine hydrochloride characterized its functional groups using FTIR and crystallization by using X-Ray Difraction (XRD). The experimental results show that the use of microwave energy on deacetilation of chitosan and hydrolisis processes can decrease time consuming and reactant concentration during production. the DDA value obtained was very high from 70 to 85%. The results also show that microwaves meet chitosan and GlcN-Cl standards.

Synthesis, physiochemical and optical properties of chitosan based dye containing naphthalimide group.

PubMed

Kumar, Santosh; Koh, Joonseok

2013-04-15

A new biopolymer dye containing naphthalimide moiety was synthesized by reaction of N-naphthaloyl chitosan with 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazino-3-quinolinecarboxylic acid. N-naphthaloyl chitosan was synthesized by reaction of chitosan with 4-bromo-1,8-naphthalic anhydride in aqueous media by greener approach. The degree of substitution of chitosan biopolymer dye is 0.55 with a yield of 70%. The synthesized materials were characterized by using UV-vis, (1)H NMR, FTIR, and FT-Raman spectroscopy. Some physical properties and surface morphology were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Optical properties of chitosan biopolymer dye were evaluated by photoluminescence (PL) spectroscopy that showed red shift (λ(em)) peak at 442 nm and 551 nm at excitation wavelength 325 nm in comparison to chitosan. The solubility of chitosan biopolymer dye increased in most of the organic solvents. These results may provide new perspectives in biomedical applications as an optical and sensitive biosensor material. Copyright © 2013 Elsevier Ltd. All rights reserved.

Robotic laser tissue welding of sclera using chitosan films.

PubMed

Garcia, Pablo; Mines, Michael J; Bower, Kraig S; Hill, J; Menon, J; Tremblay, Eric; Smith, Benjamin

2009-01-01

To demonstrate the feasibility of scleral wound closure using a novel adhesive made of chitosan film. Five-millimeter scleral lacerations were created in enucleated pig eyes. Casted chitosan films were sized to 7x7 mm patches. Lacerations were sealed with chitosan film alone (7 eyes) or chitosan film followed by laser irradiation using a near infrared laser (1,455 nm) at 350 mW for 6 minutes (7 eyes). Seven eyes were closed with 9-0 nylon suture for comparison (7 eyes). Outcome measures included watertight closure, closure time, and leak pressure. Leak pressure was measured with a pressure transducer attached to tubing continuously monitored intraocular pressure during saline infusion. Watertight closure testing was performed immediately following closure (n = 3 per group) and after 24 hours (n = 3 per group). One eye in each group was fixed in formalin for histology. All wounds were watertight for each closure method. Mean closure time with unlasered chitosan film was 2.24 minutes (range 1.80-3.26, 7 eyes) with a mean leak pressure of 303 mm Hg (range 217-364, 3 eyes). Mean closure time with lasered chitosan was 12.47 minutes (range 11.45-14.15, 7 eyes) with a mean leak pressure of 454.7 mm Hg (range 152-721, 3 eyes). Suture closure required a mean of 4.83 minutes (range 4.03-7.30, 7 eyes) and resulted in a mean leak pressure of 570.3 mm Hg (range 460-646, 3 eyes). Both lasered and unlasered chitosan eyes remained watertight after 24 hours. Histology revealed minimal laser tissue damage in lasered eyes. In this preliminary study chitosan film successfully closed scleral lacerations with and without the application of laser energy. While laser appears to strengthen the closure, it significantly increases the closure time. Chitosan based adhesives hold promise as a scleral wound closure technique.

Comperative study of catalase immobilization on chitosan, magnetic chitosan and chitosan-clay composite beads.

PubMed

Başak, Esra; Aydemir, Tülin; Dinçer, Ayşe; Becerik, Seda Çınar

2013-12-01

Catalase was immobilized on chitosan and modified chitosan. Studies were carried out on free-immobilized catalase concerning the determination of optimum temperature, pH, thermal, storage stability, reusability, and kinetic parameters. Optimum temperature and pH for free catalase and catalase immobilized were found as 35°C and 7.0, respectively. After 100 times of repeated tests, the immobilized catalases on chitosan-clay and magnetic chitosan maintain over 50% and 60% of the original activity, respectively. The ease of catalase immobilization on low-cost matrices and good stability upon immobilization in the present study make it a suitable product for further use in the food industry.

Fabrication of antibacterial blend film from poly (vinyl alcohol) and quaternized chitosan for packaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Dongying; Wang, Lijuan, E-mail: donglinwlj@163.com

Highlights: • HTCC/PVA blend films were prepared through a simple mixing method. • The blend films had greater elongation at break and good optical transmittance. • The blend films had low oxygen permeability and water vapor permeability. • The films had good activity against Escherichia coli and Staphylococcus aureus. - Abstract: Blend films from poly (vinyl alcohol) (PVA) containing N-(2-hydroxy) propyl-3-trimethyl ammonium chloride chitosan (HTCC) were prepared via a simple mixing and casting method. The films were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction measurements (XRD), scanning electron microscopy and ultraviolet-visible measurements (UV–vis). The effects of HTCC amountmore » on mechanical properties, oxygen permeability, water vapor permeation, and antibacterial properties against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) of the films were investigated. FTIR and XRD analysis show that HTCC and PVA in the blend films interacted by hydrogen bonding. SEM and UV–vis analysis reveal the good compatibility between HTCC and PVA. Compared with pure PVA film, the blend films had greater elongation at break, lower water permeability, and higher antibacterial activity. The HTCC addition decreased the tensile strength and the light transmittance. The results suggest that HTCC/PVA blend films have a potential as packaging materials.« less

Echogenic Glycol Chitosan Nanoparticles for Ultrasound-Triggered Cancer Theranostics

PubMed Central

Min, Hyun Su; You, Dong Gil; Son, Sejin; Jeon, Sangmin; Park, Jae Hyung; Lee, Seulki; Kwon, Ick Chan; Kim, Kwangmeyung

2015-01-01

Theranostic nanoparticles hold great promise for simultaneous diagnosis of diseases, targeted drug delivery with minimal toxicity, and monitoring of therapeutic efficacy. However, one of the current challenges in developing theranostic nanoparticles is enhancing the tumor-specific targeting of both imaging probes and anticancer agents. Herein, we report the development of tumor-homing echogenic glycol chitosan-based nanoparticles (Echo-CNPs) that concurrently execute cancer-targeted ultrasound (US) imaging and US-triggered drug delivery. To construct this novel Echo-CNPs, an anticancer drug and bioinert perfluoropentane (PFP), a US gas precursor, were simultaneously encapsulated into glycol chitosan nanoparticles using the oil in water (O/W) emulsion method. The resulting Echo-CNPs had a nano-sized particle structure, composing of hydrophobic anticancer drug/PFP inner cores and a hydrophilic glycol chitosan polymer outer shell. The Echo-CNPs had a favorable hydrodynamic size of 432 nm, which is entirely different from the micro-sized core-empty conventional microbubbles (1-10 μm). Furthermore, Echo-CNPs showed the prolonged echogenicity via the sustained microbubble formation process of liquid-phase PFP at the body temperature and they also presented a US-triggered drug release profile through the external US irradiation. Interestingly, Echo-CNPs exhibited significantly increased tumor-homing ability with lower non-specific uptake by other tissues in tumor-bearing mice through the nanoparticle's enhanced permeation and retention (EPR) effect. Conclusively, theranostic Echo-CNPs are highly useful for simultaneous cancer-targeting US imaging and US-triggered delivery in cancer theranostics. PMID:26681985

[Effects of cell-mediated immunity induced by intramuscular chitosan-pJME/ GM-CSF nano-DNA vaccine in BAlb/c mice].

PubMed

Zhai, Yong-Zhen; Zhou, Yan; Ma, Li; Feng, Guo-He

2014-07-01

This study aimed to investigate the immune adjuvant effect and mechanism induced by chitosan nanoparticles carrying pJME/GM-CSF. In this study, plasmid DNA (pJME/GM-CSF) was encapsulated in chitosan to prepare chitosan-pJME/GM-CSF nanoparticles using a complex coacervation process. Immunohistochemistry was used to detect the type of infiltrating cells at the site of intramuscular injection. The phenotype and functional changes of splenic DCs were measured by flow cytometry after different immunogens were injected intramuscularly. The killing activity of CTLs was assessed using the lactate dehydrogenase (LDH) release assay. The preparation of chitosan-pJME/GM-CSF nanoparticles matched the expected theoretical results. Our results also found that, after pJME/GM-CSF injection, the incoming cells were a mixture of macrophages, neutrophils, and immature DCs. Meanwhile, pJME/GM-CSF increased the expression of MHC class II molecules on splenic DCs, and enhanced their Ag capture and presentation functions. Cell-mediated immunity was induced by the vaccine. Furthermore, chitosan-pJME/GM-CSF nanoparticles outperformed the administration of standard pJME/GM-CSF in terms of DC recruitment, antigen processing and presentation, and vaccine enhancement. These findings reveal that chitosan could be used as delivery vector for DNA vaccine intramuscular immunizations, and enhance pJME/GM-CSF-induced cellular immune responses.

Environmentally friendly surface modification of silk fiber: Chitosan grafting and dyeing

NASA Astrophysics Data System (ADS)

Davarpanah, Saideh; Mahmoodi, Niyaz Mohammad; Arami, Mokhtar; Bahrami, Hajir; Mazaheri, Firoozmehr

2009-01-01

In this paper, the surface modification of silk fiber using anhydrides to graft the polysaccharide chitosan and dyeing ability of the grafted silk were studied. Silk fiber was degummed and acylated with two anhydrides, succinic anhydride (SA) and phthalic anhydride (PA), in different solvents (dimethyl sulfoxide (DMSO) and N, N-dimethyl formamide (DMF)). The effects of anhydrides, solvents, anhydride concentration, liquor ratio (L:R) and reaction time on acylation of silk were studied. The polysaccharide chitosan was grafted to the acylated silk fiber and dyed by acid dye (Acid Black NB.B). The effects of pH, chitosan concentration, and reaction time on chitosan grafting of acylated silk were investigated. The physical properties show sensible changes regardless of weight gain. Scanning electron microscopy (SEM) analysis showed the presence of foreign materials firmly attached to the surface of silk. FTIR spectroscopy provided evidence that chitosan was grafted onto the acylated silk through the formation of new covalent bonds. The dyeing of the chitosan grafted-acylated silk fiber indicated the higher dye ability in comparison to the acylated and degummed silk samples. The mechanism of chitosan grafting over degummed silk through anhydride linkage was proposed. The findings of this research support the potential production of new environmentally friendly textile fibers. It is worthwhile to mention that the grafted samples have antibacterial potential due to the antibacterial property of chitosan molecules.

Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System.

PubMed

Onishi, Hiraku; Tokuyasu, Ayako

2016-09-13

The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. All microparticles before and after enteric coating had a submicron size (600-800 nm) and micrometer size (1300-1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.

Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System

PubMed Central

Onishi, Hiraku; Tokuyasu, Ayako

2016-01-01

Background: The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Methods: Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. Results: All microparticles before and after enteric coating had a submicron size (600–800 nm) and micrometer size (1300–1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs. PMID:27649146

Nano-scale characterization of nano-hydroxyapatite incorporated chitosan particles for bone repair.

PubMed

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C

2018-05-01

In this study, injectable porous spherical particles were fabricated using chitosan (CS) biopolymer, sodium tripolyphosphate (TPP), and nano-hydroxyapatite (nHA). TPP was primarily used as an ionic crosslinker to crosslink 2% (w/v) CS droplets. 2% (w/v) nHA was used to prepare nHA incorporated particles. The surface morphological properties and nanomechanical properties such as topography, deformation, adhesion, and dissipation of CS particles with and without nHA were studied using contact mode and peakforce quantitative nanomechanical property mapping mode in atomic force microscopy. The nHA spots have higher density than CS which leads to higher forces acting on the probe tip and higher energy dissipation to lift the tip from nHA areas. The cumulative release data showed that about 87% of total BMP-2 encapsulated within the particles was released by third week of experiment period. Degradation study was conducted to understand how the particles degradation occurs in the presence of phosphate buffered saline with continues shaking in an incubator at 37° C. In addition, BMP-2 release from the 2% nHA/CS particles was studied over a three weeks period and found that BMP-2 release was governed by the simple diffusion rather than the degradation of particles. Copyright © 2018 Elsevier B.V. All rights reserved.

Poly(N-isopropylacrylamide) hydrogel/chitosan scaffold hybrid for three-dimensional stem cell culture and cartilage tissue engineering.

PubMed

Mellati, Amir; Kiamahalleh, Meisam Valizadeh; Madani, S Hadi; Dai, Sheng; Bi, Jingxiu; Jin, Bo; Zhang, Hu

2016-11-01

Providing a controllable and definable three-dimensional (3D) microenvironment for chondrogenic differentiation of mesenchymal stem cells (MSCs) remains a great challenge for cartilage tissue engineering. In this work, poly(N-isopropylacrylamide) (PNIPAAm) polymers with the degrees of polymerization of 100 and 400 (NI100 and NI400) were prepared and the polymer solutions were introduced into the preprepared chitosan porous scaffolds (CS) to form hybrids (CSNI100 and CSNI400, respectively). SEM images indicated that the PNIPAAm gel partially occupied chitosan pores while the interconnected porous structure of chitosan was preserved. MSCs were incorporated within the hybrid and cell proliferation and chondrogenic differentiation were monitored. After 7-day incubation of the cell-laden constructs in a growth medium, the cell viability in CSNI100 and CSNI400 were 54 and 108% higher than that in CS alone, respectively. Glycosaminoglycan and total collagen contents increased 2.6- and 2.5-fold after 28-day culture of cell-laden CSNI400 in the chondrogenic medium. These results suggest that the hybrid structure composed of the chitosan porous scaffold and the well-defined PNIPAAm hydrogel, in particular CSNI400, is suitable for 3D stem cell culture and cartilage tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2764-2774, 2016. © 2016 Wiley Periodicals, Inc.

Investigation of Mechanistic Pathway for Trimethyl Borate Mediated Amidation of (R)-Mandelic Acid for the Synthesis of Mirabegron, an Antimuscarinic Agent.

PubMed

Deshmukh, Dattatray G; Bangal, Mukund N; Patekar, Mukunda R; Medhane, Vijay J; Mathad, Vijayavitthal Thippannachar

2018-03-01

The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active α-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing α-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods. The developed approach is rapid and efficient for the preparation of 4 with an overall yield of 85-87% and around 99.0% purity by HPLC at scale.

Preparation of Robust Metal-Free Magnetic Nanoemulsions Encapsulating Low-Molecular-Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery.

PubMed

Nagura, Kota; Takemoto, Yusa; Moronaga, Satori; Uchida, Yoshiaki; Shimono, Satoshi; Shiino, Akihiko; Tanigaki, Kenji; Amano, Tsukuru; Yoshino, Fumi; Noda, Yohei; Koizumi, Satoshi; Komatsu, Naoki; Kato, Tatsuhisa; Yamauchi, Jun; Tamura, Rui

2017-11-07

With a view to developing a theranostic nanomedicine for targeted drug delivery systems visible by magnetic resonance (MR) imaging, robust metal-free magnetic nanoemulsions (mean particle size less than 20 nm) consisting of a biocompatible surfactant and hydrophobic, low molecular weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals were prepared in pH 7.4 phosphate-buffered saline (PBS). The structure of the nanoemulsions was characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small-angle neutron-scattering measurements. The nanoemulsions showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T 1 ) weighted MR images in PBS in vitro (and preliminarily in vivo). Furthermore, the hydrophobic anticancer drug paclitaxel could be encapsulated inside the nanoparticles, and the resulting paclitaxel-loaded nanoemulsions were efficiently incorporated into HeLa cells to suppress cell growth. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional modification of chitosan for biomedical application

NASA Astrophysics Data System (ADS)

Tang, Ruogu

Chitosan is a linear polysaccharide. Normally commercial chitosan consists of randomly distributed beta-(1-4)-linked D-glucosamine (deacetylated proportion) and N-acetyl-D-glucosamine (acetylated proportion) together. Chitosan has been proved to be a multifunctional biopolymer that presents several unique properties due to free amino groups in the repeating unit therefore chitosan has been widely applied in various areas. To be specific, provided by the excellent biocompatibility, chitosan is expected to be used in biological and medical applications including wound dressing, implants, drug carrier/delivery, etc. In this thesis, we worked on chitosan functionalization for biomedical application. The thesis are composed of three parts: In the first part, we focused on modifying the chitosan thin film, chemically introducing the nitric oxide functional groups on chitosan film. We covalently bonded small molecule diazeniumdiolates onto the chitosan films and examined the antimicrobial function and biocompatibility. Commercial chitosan was cast into films from acidic aqueous solutions. Glutaraldehyde reacted with the chitosan film to introduce aldehyde groups onto the chitosan film (GA-CS film). GA-CS reacted with a small molecule NO donor, NOC-18, to covalently immobilize NONO groups onto the polymer (NO-CS film). The-CHO and [NONO] group were verified by FT IR, UV and Griess reagent. The NO releasing rate in aqueous solution and and thermal stability were studied quantitatively to prove its effectiveness. A series of antimicrobial tests indicated that NO-CS films have multiple functions: 1. It could inhibit the bacteria growth in nutrient rich environment; 2. It could directly inactivate bacteria and biofilm; 3. It could reduce the bacteria adherence on the film surface as well as inhibit biofilm formation. In addition, the NO-CS film was proved to be biocompatible with cell and it was also compatible with other antibiotics like Amoxicillin. In the second part, we

Evaluation of antioxidant activities and chemical analysis of sulfated chitosan from Sepia prashadi.

PubMed

Seedevi, Palaniappan; Moovendhan, Meivelu; Vairamani, Shanmugam; Shanmugam, Annaian

2017-06-01

The chitin and chitosan of S. prashadi was prepared through demineralization, deproteinzation, deacetylation process and sulfation were carried by chlorosulfonic acid in N,N-dimethylformamide. The sulfate content in chitosan was found to be 18.9%. The carbon, hydrogen and nitrogen composition of the sulfated chitosan were recorded 39.09%, 6.95% and 6.58% respectively. The structural analysis was done by using FT-IR and NMR spectroscopy technique. The DSC curves of sulfated chitosan showed a large endothermic peak resolved with T o value of 54.57°C and T P value of 97.46°C. The morphology of sulfated chitin and sulfated chitosan were studied by SEM. The Further in vitro antioxidant activity of sulfated chitosan was screened by scavenging activity of superoxide radical assay, hydroxyl radical scavenging assay, metal-ion chelating effect and reducing power. Its anticoagulant activity was tested for human plasma with respect to Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT). Results prove that sulfated chitosan has potent antioxidant and anticoagulant activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurospora crassa transcriptomics reveals oxidative stress and plasma membrane homeostasis biology genes as key targets in response to chitosan

PubMed Central

Lopez-Moya, Federico; Kowbel, David; Nueda, Ma José; Palma-Guerrero, Javier; Glass, N. Louise; Lopez-Llorca, Luis Vicente

2016-01-01

Chitosan is a natural polymer with antimicrobial activity. Chitosan causes plasma membrane permeabilization and induction of intracellular reactive oxygen species (ROS) in Neurospora crassa. We have determined the transcriptional profile of N. crassa to chitosan and identified the main gene targets involved in the cellular response to this compound. Global network analyses showed membrane, transport and oxidoreductase activity as key nodes affected by chitosan. Activation of oxidative metabolism indicates the importance of ROS and cell energy together with plasma membrane homeostasis in N. crassa response to chitosan. Deletion strain analysis of chitosan susceptibility pointed, NCU03639 encoding a class 3 lipase, involved in plasma membrane repair by lipid replacement and NCU04537 a MFS monosaccharide transporter related with assimilation of simple sugars, as main gene targets of chitosan. NCU10521, a glutathione S-transferase-4 involved in the generation of reducing power for scavenging intracellular ROS is also a determinant chitosan gene target. Ca2+ increased tolerance to chitosan in N. crassa. Growth of NCU10610 (fig 1 domain) and SYT1 (a synaptotagmin) deletion strains was significantly increased by Ca2+ in presence of chitosan. Both genes play a determinant role in N. crassa membrane homeostasis. Our results are of paramount importance for developing chitosan as antifungal. PMID:26694141

Removal of nitrate and phosphate using chitosan/Al2O3/Fe3O4 composite nanofibrous adsorbent: Comparison with chitosan/Al2O3/Fe3O4 beads.

PubMed

Bozorgpour, Farahnaz; Ramandi, Hossein Fasih; Jafari, Pooya; Samadi, Saman; Yazd, Shabnam Sharif; Aliabadi, Majid

2016-12-01

In the present study the chitosan/Al 2 O 3 /Fe 3 O 4 composite nanofibrous adsorbent was prepared by electrospinning process and its application for the removal of nitrate and phosphate were compared with chitosan/Al 2 O 3 /Fe 3 O 4 composite bead adsorbent. The influence of Al 2 O 3 /Fe 3 O 4 composite content, pH, contact time, nitrate and phosphate initial concentrations and temperature on the nitrate and phosphate sorption using synthesized bead and nanofibrous adsorbents was investigated in a single system. The reusability of chitosan/Al 2 O 3 /Fe 3 O 4 composite beads and nanofibers after five sorption-desorption cycles were carried out. The Box-Behnken design was used to investigate the interaction effects of adsorbent dosage, nitrate and phosphate initial concentrations on the nitrate and phosphate removal efficiency. The pseudo-second-order kinetic model and known Freundlich and Langmuir isotherm models were used to describe the kinetic and equilibrium data of nitrate and phosphate sorption using chitosan/Al 2 O 3 /Fe 3 O 4 composite beads and nanofibers. The influence of other anions including chloride, fluoride and sulphate on the sorption efficiency of nitrate and phosphate was examined. The obtained results revealed the higher potential of chitosan/Al 2 O 3 /Fe 3 O 4 composite nanofibers for nitrate and phosphate compared with chitosan/Al 2 O 3 /Fe 3 O 4 composite beads. Copyright © 2016 Elsevier B.V. All rights reserved.

Chitin, Chitosan, and Its Derivatives for Wound Healing: Old and New Materials

PubMed Central

Azuma, Kazuo; Izumi, Ryotaro; Osaki, Tomohiro; Ifuku, Shinsuke; Morimoto, Minoru; Saimoto, Hiroyuki; Minami, Saburo; Okamoto, Yoshiharu

2015-01-01

Chitin (β-(1-4)-poly-N-acetyl-d-glucosamine) is widely distributed in nature and is the second most abundant polysaccharide after cellulose. It is often converted to its more deacetylated derivative, chitosan. Previously, many reports have indicated the accelerating effects of chitin, chitosan, and its derivatives on wound healing. More recently, chemically modified or nano-fibrous chitin and chitosan have been developed, and their effects on wound healing have been evaluated. In this review, the studies on the wound-healing effects of chitin, chitosan, and its derivatives are summarized. Moreover, the development of adhesive-based chitin and chitosan are also described. The evidence indicates that chitin, chitosan, and its derivatives are beneficial for the wound healing process. More recently, it is also indicate that some nano-based materials from chitin and chitosan are beneficial than chitin and chitosan for wound healing. Clinical applications of nano-based chitin and chitosan are also expected. PMID:25780874

Effect of sodium tripolyphosphate concentration and simulated gastrointestinal fluids on release profile of paracetamol from chitosan microsphere

NASA Astrophysics Data System (ADS)

Mulia, Kamarza; Andrie; Krisanti, Elsa A.

2018-03-01

The problem to overcome in oral drug administration is the significant pH changes present in the human digestive system. In this study, ionotropic gelation method employing 2-8% (w/v) tripolyphosphate solutions were used to crosslink chitosan microspheres for a controlled release of paracetamol as a model drug. The release profiles of paracetamol from chitosan microspheres were determined using simulated gastrointestinal fluids having pH values of 1.2, 6.8, and 7.4. The results showed that the paracetamol loading and the encapsulation efficiency values increased with increasing concentration of tripolyphosphate solutions used in the preparation step. Paracetamol released at pH 1.2 and 6.8 buffer solutions was significantly higher than that at pH 7.4; also, more paracetamol was released in the presence of α-amylase and β-glucosidase enzymes. The release profiles showed zero-order release behaviour up to 8 hours where the highest drug release was 39% of the paracetamol loaded in the chitosan microspheres, indicating a strong crosslinking between chitosan and TPP anions. The relatively low accumulated drug release could be compensated by employing suitable enzymes, lower TPP solution concentration, and addition of other biodegradable polymer to reduce the TPP crosslink.

3D- Printed Poly(ε-caprolactone) Scaffold Integrated with Cell-laden Chitosan Hydrogels for Bone Tissue Engineering.

PubMed

Dong, Liang; Wang, Shao-Jie; Zhao, Xin-Rong; Zhu, Yu-Fang; Yu, Jia-Kuo

2017-10-17

Synthetic polymeric scaffolds are commonly used in bone tissue engineering (BTE) due to their biocompatibility and adequate mechanical properties. However, their hydrophobicity and the lack of specific cell recognition sites confined their practical application. In this study, to improve the cell seeding efficiency and osteoinductivity, an injectable thermo-sensitive chitosan hydrogel (CSG) was incorporated into a 3D-printed poly(ε-caprolactone) (PCL) scaffold to form a hybrid scaffold. To demonstrate the feasibility of this hybrid system for BTE application, rabbit bone marrow mesenchymal stem cells (BMMSCs) and bone morphogenetic protein-2 (BMP-2) were encapsulated in CSG. Pure PCL scaffolds were used as controls. Cell proliferation and viability were investigated. Osteogenic gene expressions of BMMSCs in various scaffolds were determined with reverse transcription polymerase chain reaction (RT-PCR). Growth factor releasing profile and mechanical tests were performed. CCK-8 assay confirmed greater cell retention and proliferation in chitosan and hybrid groups. Confocal microscopy showed even distribution of cells in the hybrid system. After 2-week osteogenic culture in vitro, BMMSCs in hybrid and chitosan scaffolds showed stronger osteogenesis and bone-matrix formation. To conclude, chitosan/PCL hybrid scaffolds are a favorable platform for BTE due to its capacity to carry cells and drugs, and excellent mechanical strength.

Hydrophobic lapatinib encapsulated dextran-chitosan nanoparticles using a toxic solvent free method: fabrication, release property & in vitro anti-cancer activity.

PubMed

Mobasseri, Rezvan; Karimi, Mahdi; Tian, Lingling; Naderi-Manesh, Hossein; Ramakrishna, Seeram

2017-05-01

Dextran sulfate-chitosan (DS-CS) nanoparticles, which possesses properties such as nontoxicity, biocompatibility and biodegradability have been employed as drug carriers in cancer therapy. In this study, DS-CS nanoparticles were synthesized and their sizes were controlled by a modification of the divalent cations cross-linkers (Ca 2+ , Zn 2+ or Mg 2+ ). Based on the optimized processing parameters, lapatinib encapsulated nanoparticles were developed and characterized by Dynamics Light Scattering (DLS) measurements, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). Calcium chloride (CaCl 2 ) facilitated the formation of bare (100.3±0.80nm) and drug-loaded nanoparticles (134.3±1.3nm) with narrow size distributions being the best cross-linker. The surface potential of drug-loaded nanoparticles was -16.8±0.47mV and its entrapment and loading efficiency were 76.74±1.73% and 47.36±1.27%, respectively. Cellular internalization of nanoparticles was observed by fluorescence microscopy and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay was used to determine cytotoxicity of bare and drug-loaded nanoparticles in comparison to the free drug lapatinib. The MTT assay showed that drug-loaded nanoparticles had comparable anticancer activity to free drug within a duration of 48h. The aforementioned results showed that the DS-CS nanoparticles were able to entrap, protect and release the hydrophobic drug, lapatinib in a controlled pattern and could further serve as a suitable drug carrier for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Chitosan-tripolyphosphate nanoparticles as Arrabidaea chica standardized extract carrier: synthesis, characterization, biocompatibility, and antiulcerogenic activity.

PubMed

Servat-Medina, Leila; González-Gómez, Alvaro; Reyes-Ortega, Felisa; Sousa, Ilza Maria Oliveira; Queiroz, Nubia de Cássia Almeida; Zago, Patricia Maria Wiziack; Jorge, Michelle Pedrosa; Monteiro, Karin Maia; de Carvalho, João Ernesto; San Román, Julio; Foglio, Mary Ann

2015-01-01

Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential

Mucoadhesion mechanism of chitosan and thiolated chitosan-poly(isobutyl cyanoacrylate) core-shell nanoparticles.

PubMed

Bravo-Osuna, Irene; Vauthier, Christine; Farabollini, Alessandra; Palmieri, Giovanni Filippo; Ponchel, Gilles

2007-04-01

The study is focused on the evaluation of the potential bioadhesive behaviour of chitosan and thiolated chitosan (chitosan-TBA)-coated poly(isobutyl cyanoacrylates) (PIBCA) nanoparticles. Nanoparticles were obtained by radical emulsion polymerisation with chitosan of different molecular weight and with different proportions of chitosan/chitosan-TBA. Mucoadhesion was ex vivo evaluated under static conditions by applying nanoparticle suspensions on rat intestinal mucosal surfaces and evaluating the amount of nanoparticles remaining attached to the mucosa after incubation. The analysis of the results obtained demonstrated that the presence of either chitosan or thiolated chitosan on the PIBCA nanoparticle surface clearly enhanced the mucoadhesion behaviour thanks to non-covalent interactions (ionic interaction and hydrogen bonds) with mucus chains. Both, the molecular weight of chitosan and the proportion of chitosan-TBA in the formulation influenced the nanoparticle hydrodynamic diameter and hence their transport through the mucus layer. Improved interpenetration ability with the mucus chain during the attachment process was suggested for the chitosan of high molecular weight, enhancing the bioadhesiveness of the system. The presence of thiol groups on the nanoparticle surface at high concentration (200 x 10(-6) micromol SH/cm2) increased the mucoadhesion capacity of nanoparticles by forming covalent bonds with the cysteine residues of the mucus glycoproteins.

Fabrication, characterization and antimicrobial activities of thymol-loaded zein nanoparticles stabilized by sodium caseinate-chitosan hydrochloride double layers.

PubMed

Zhang, Yaqiong; Niu, Yuge; Luo, Yangchao; Ge, Mei; Yang, Tian; Yu, Liangli Lucy; Wang, Qin

2014-01-01

Thymol-loaded zein nanoparticles stabilized with sodium caseinate (SC) and chitosan hydrochloride (CHC) were prepared and characterized. The SC stabilized nanoparticles had well-defined size range and negatively charged surface. Due to the presence of SC, the stabilized zein nanoparticles showed a shift of isoelectric point from 6.18 to 5.05, and had a desirable redispersibility in water at neutral pH after lyophilization. Coating with CHC onto the SC stabilized zein nanoparticles resulted in increased particle size, reversal of zeta potential value from negative to positive, and improved encapsulation efficiency. Both thymol-loaded zein nanoparticles and SC stabilized zein nanoparticles had a spherical shape and smooth surface, while the surfaces of CHC-SC stabilized zein nanoparticles seemed rough and had some clumps. Encapsulated thymol was more effective in suppressing gram-positive bacterium than un-encapsulated thymol for a longer time period. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chitosan films incorporated with nettle (Urtica Dioica L.) extract-loaded nanoliposomes: II. Antioxidant activity and release properties.

PubMed

Almasi, Hadi; Zandi, Mohsen; Beigzadeh, Sara; Haghju, Sara; Mehrnow, Nazila

2016-07-14

Chitosan films were loaded with NE nettle (Urtica dioica L.) extract (NE) at concentrations of 0, 0.5, 1 and 1.5%w/w in the free or nanoliposomal form to obtain active and nanoactive films, respectively. The antioxidant potential of the films containing NE-loaded nanoliposomes was decreased in comparison of free NE incorporated films. Diffusion of NE to soybean oil was enough to delay the induction of the oxidation of soybean oil stored for 60 days in contact with chitosan based films. Release studies indicated that the release rate of NE in 95% ethanol simulant significantly decreased by the nanoencapsulation of NE. The diffusion coefficient (D) for chitosan films containing 1.5%w/w of free and encapsulated NE at 25 °C was 18.80 and 3.68 × 10 -7 cm 2  s -1 , respectively. Moreover, the formation of nanoliposomes diminished the increasing effect of temperature on the release rate as when storage temperature increased from 4 °C to 40 °C.

Ex vivo permeation of tamoxifen and its 4-OH metabolite through rat intestine from lecithin/chitosan nanoparticles.

PubMed

Barbieri, S; Buttini, F; Rossi, A; Bettini, R; Colombo, P; Ponchel, G; Sonvico, F; Colombo, G

2015-08-01

Tamoxifen citrate is an anticancer drug slightly soluble in water. Administered orally, it shows great intra- and inter-patient variations in bioavailability. We developed a nanoformulation based on phospholipid and chitosan able to efficiently load tamoxifen and showing an enzyme triggered release. In this work the permeation of tamoxifen released from lecithin/chitosan nanoparticles across excised rat intestinal wall mounted in an Ussing chamber was investigated. Compared to tamoxifen citrate suspension, the amount of the drug permeated using the nanoformulation was increased from 1.5 to 90 times, in absence or in presence of pancreatin or lipase, respectively. It was also evidenced the formation of an active metabolite of tamoxifen, 4-hydroxy tamoxifen, however, the amount of metabolite permeated remained roughly constant in all experiments. The effect of enzymes on intestinal permeation of tamoxifen was shown only when tamoxifen-loaded nanoparticles were in intimate contact with the mucosal surface. The encapsulation of tamoxifen in lecithin/chitosan nanoparticles improved the non-metabolized drug passing through the rat intestinal tissue via paracellular transport. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis of carboxymethylated and quaternized chitosans and their therapeutic effect on nonalcoholic Fatty liver disease.

PubMed

Liu, Xiaofei; Yang, Fan; Song, Tao; Zeng, Anrong; Wang, Qi; Sun, Zhong; Shen, Jun

2011-10-12

O-Carboxymethyl chitosan (O-CMCs) and N-((2-hydroxy-3-N,N-dimethylhexadecylammonium)propyl)chitosan chloride (N-CQCs) were synthesized for nonalcoholic fatty liver disease (NAFLD) treatment. The weight-average weight and substitution degree of O-CMCs and N-CQCs were 6.5 × 10(4) and 0.72 and 7.9 × 10(4) and 0.21, respectively. O-CMCs was negatively charged with a zeta-potential value of -31.82 mV, whereas that of N-CQCs was +36.1 mV, and both showed low cytotoxcity. Serum lipid level and liver fat accumulation were reduced with chitosan and its two derivatives. Furthermore, mRNA and protein expression assay of hepatic lipid metabolism enzymes and low-density lipoprotein receptor (LDL-R) were observed by RT-PCR and Western blot. Results showed that N-CQCs exhibited a more evident desired effect than chitosan and O-CMCs, indicating that amphiphilicity, solubility, and surface charge of chitosan and its two derivatives played roles in the expression of hepatic lipid metabolism enzymes and LDL-R. Therefore, dietary supplementation of O-CMCs and N-CQCs can alleviate the high fat diet induced aberrations related to NAFLD by their antilipidemic property.

Thermal degradation kinetics of phycocyanin encapsulation as an antioxidant agent

NASA Astrophysics Data System (ADS)

Nilamsari, A. M.; Yunanda, A.; Hadiyanto, H.

2018-01-01

Phycocyanin is a blue-light pigment that found in Cyanobacteria and two Eukaryotics algae such as Rhodophyta and Crytophyta. Phycocyanin is soluble in water and has a strong fluorescent properties as an antioxidant and normally used in food industry, cosmetic, biotechnology, and drug. However, Phycocyanin is easily damaged by a heating process. The aim of this study is to obtain the optimal condition of phycocyanin encapsulation with different coating materials, Chitosan and Carrageenan, by the calculation of heat resistance of antioxidant activity (D), range of temperature that increase the rate of degradation (Z), rate constant of degradation (k), and activation energy (Ea). The ratio of phycocyanin and the coating material are 2% (w/v) and 2 % (w/v).

Chitosan

PubMed Central

Smith, Alan; Perelman, Michael; Hinchcliffe, Michael

2014-01-01

The nasal route is attractive for the delivery of vaccines in that it not only offers an easy to use, non-invasive, needle-free alternative to more conventional parenteral injection, but it also creates an opportunity to elicit both systemic and (crucially) mucosal immune responses which may increase the capability of controlling pathogens at the site of entry. Immune responses to “naked” antigens are often modest and it is widely accepted that incorporation of an adjuvant is a prerequisite for the achievement of clinically effective nasal vaccines. Many existing adjuvants are sub-optimal or unsuitable because of local toxicity or poor enhancement of immunogenicity. Chitosan, particularly chitosan salts, have now been used in several preclinical and clinical studies with good tolerability, excellent immune stimulation and positive clinical results across a number of infections. Particularly significant evidence supporting chitosan as an adjuvant for nasal vaccination comes from clinical investigations on a norovirus vaccine; this demonstrated the ability of chitosan (ChiSys®), when combined with monophosphoryl lipid, to evoke robust immunological responses and confer protective immunity following (enteral) norovirus challenge. This article summarizes the totality of the meaningful information (including key unpublished data) supporting the development of chitosan-adjuvanted vaccines. PMID:24346613

Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds.

PubMed

Bonferoni, Maria Cristina; Sandri, Giuseppina; Rossi, Silvia; Dellera, Eleonora; Invernizzi, Alessandro; Boselli, Cinzia; Cornaglia, Antonia Icaro; Del Fante, Claudia; Perotti, Cesare; Vigani, Barbara; Riva, Federica; Caramella, Carla; Ferrari, Franca

2018-02-09

Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds.

Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds

PubMed Central

Bonferoni, Maria Cristina; Dellera, Eleonora; Invernizzi, Alessandro; Cornaglia, Antonia Icaro; Perotti, Cesare; Vigani, Barbara; Caramella, Carla; Ferrari, Franca

2018-01-01

Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds. PMID:29425164

Long-lifetime thin-film encapsulated organic light-emitting diodes

NASA Astrophysics Data System (ADS)

Wong, F. L.; Fung, M. K.; Tao, S. L.; Lai, S. L.; Tsang, W. M.; Kong, K. H.; Choy, W. M.; Lee, C. S.; Lee, S. T.

2008-07-01

Multiple fluorocarbon (CFx) and silicon nitride (Si3N4) bilayers were applied as encapsulation cap on glass-based organic light-emitting diodes (OLEDs). When CFx/Si3N4 bilayers were deposited onto the OLED structure, the devices showed performance worse than one without any encapsulation. The adverse effects were attributed to the damage caused by reaction species during the thin-film deposition processes. To solve this problem, a CuPc interlayer was found to provide effective protection to the OLED structure. With a structure of CuPc/(CFx/Si3N4)×5, the encapsulated device showed an operation lifetime over 8000 h (higher than 80% of that achieved with a conventional metal encapsulation).

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

NASA Astrophysics Data System (ADS)

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-11-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.

Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

NASA Astrophysics Data System (ADS)

Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

2016-08-01

Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

Neurospora crassa transcriptomics reveals oxidative stress and plasma membrane homeostasis biology genes as key targets in response to chitosan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez-Moya, Federico; Kowbel, David; Nueda, Ma Jose

Chitosan is a natural polymer with antimicrobial activity. Chitosan causes plasma membrane permeabilization and induction of intracellular reactive oxygen species (ROS) in Neurospora crassa. In this paper, we have determined the transcriptional profile of N. crassa to chitosan and identified the main gene targets involved in the cellular response to this compound. Global network analyses showed membrane, transport and oxidoreductase activity as key nodes affected by chitosan. Activation of oxidative metabolism indicates the importance of ROS and cell energy together with plasma membrane homeostasis in N. crassa response to chitosan. Deletion strain analysis of chitosan susceptibility pointed NCU03639 encoding amore » class 3 lipase, involved in plasma membrane repair by lipid replacement, and NCU04537 a MFS monosaccharide transporter related to assimilation of simple sugars, as main gene targets of chitosan. NCU10521, a glutathione S-transferase-4 involved in the generation of reducing power for scavenging intracellular ROS is also a determinant chitosan gene target. Ca 2+ increased tolerance to chitosan in N. crassa. Growth of NCU10610 (fig 1 domain) and SYT1 (a synaptotagmin) deletion strains was significantly increased by Ca 2+ in the presence of chitosan. Both genes play a determinant role in N. crassa membrane homeostasis. Finally, our results are of paramount importance for developing chitosan as an antifungal.« less

Neurospora crassa transcriptomics reveals oxidative stress and plasma membrane homeostasis biology genes as key targets in response to chitosan

DOE PAGES

Lopez-Moya, Federico; Kowbel, David; Nueda, Ma Jose; ...

2015-12-01

Chitosan is a natural polymer with antimicrobial activity. Chitosan causes plasma membrane permeabilization and induction of intracellular reactive oxygen species (ROS) in Neurospora crassa. In this paper, we have determined the transcriptional profile of N. crassa to chitosan and identified the main gene targets involved in the cellular response to this compound. Global network analyses showed membrane, transport and oxidoreductase activity as key nodes affected by chitosan. Activation of oxidative metabolism indicates the importance of ROS and cell energy together with plasma membrane homeostasis in N. crassa response to chitosan. Deletion strain analysis of chitosan susceptibility pointed NCU03639 encoding amore » class 3 lipase, involved in plasma membrane repair by lipid replacement, and NCU04537 a MFS monosaccharide transporter related to assimilation of simple sugars, as main gene targets of chitosan. NCU10521, a glutathione S-transferase-4 involved in the generation of reducing power for scavenging intracellular ROS is also a determinant chitosan gene target. Ca 2+ increased tolerance to chitosan in N. crassa. Growth of NCU10610 (fig 1 domain) and SYT1 (a synaptotagmin) deletion strains was significantly increased by Ca 2+ in the presence of chitosan. Both genes play a determinant role in N. crassa membrane homeostasis. Finally, our results are of paramount importance for developing chitosan as an antifungal.« less

Cytotoxicity and biocompatibility evaluation of N,O-carboxymethyl chitosan/oxidized alginate hydrogel for drug delivery application.

PubMed

Li, Xingyi; Kong, Xiangye; Zhang, Zhaoliang; Nan, Kaihui; Li, LingLi; Wang, XianHou; Chen, Hao

2012-06-01

In this paper, covalently cross-linked hydrogel composed of N,O-carboxymethyl chitosan and oxidized alginate was developed intending for drug delivery application. In vitro/vivo cytocompatibility and biocompatibility of the developed hydrogel were preliminary evaluated. In vitro cytocompatibility test showed that the developed hydrogel exhibited good cytocompatibility against NH3T3 cells after 3-day incubation. According to the results of acute toxicity test, there was no obvious cytotoxicity for major organs during the period of 21-day intraperitoneal administration. Meanwhile, the developed hydrogel did not induce any cutaneous reaction within 72 h of subcutaneous injection followed by slow degradation and adsorption with the time evolution. Moreover, the extraction of developed hydrogel had nearly 0% of hemolysis ratio, which indicated the good hemocompatibility of hydrogel. Based on the above results, it may be concluded that the developed N,O-carboxymethyl chitosan/oxidized alginate hydrogel with non-cytotoxicity and good biocompatibility might suitable for the various drug delivery applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Release of tissue inhibitor of metalloproteinase-2 from alginate microcapsule encapsulating genetically engineered cells

PubMed Central

Kim, Yeon Seong; Jeong, Young-II; Jin, Shu-Guang; Pei, Jian; Wen, Min; Kim, In-Young; Moon, Kyung-Sub; Jung, Tae-Young; Ryu, Hyang-Hwa; Jung, Shin

2013-01-01

Background In this study, 293T cells were genetically engineered to secrete tissue inhibitor of metalloproteinase-2 (TIMP2) and encapsulated into alginate microcapsules to continuously release TIMP2 protein. Methods The anti-invasive potential of the microcapsules was studied in vitro using brain tumor cells. The TIMP2 gene was transfected to 293T cells, and genetically engineered 293TIMP2 cells were encapsulated into alginate microcapsules. Release of TIMP2 protein was detected with Western blot analysis and the anti-invasive potential against U87MG cells was tested using gelatin zymography and a Matrigel assay. Results Cell viability within the alginate microcapsules was maintained at a cell density of 5 × 106. Because polycationic polymers are helpful for maintaining the mechanical strength of microcapsules with good cell viability, the alginate microcapsules were reinforced with chitosan (0.1% w/v). Expression of TIMP2 protein in cell lysates and secretion of TIMP2 into the conditioned medium was confirmed by Western blot analysis. Alginate microcapsules encapsulating 293TIMP2 cells released TIMP2 protein into the medium efficiently, where the TIMP2 protein participated in degradation of the matrix metalloproteinase-2 enzyme and inhibited invasion of U87MG cells. Conclusion Alginate microcapsules encapsulating 293TIMP2 cells are promising candidates for anti-invasive treatment of glioma. PMID:24231999

Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect.

PubMed

Mantripragada, Venkata P; Jayasuriya, Ambalangodage C

2016-06-01

Injectable chitosan microparticles were prepared using a simple coacervation method under physiologically friendly conditions by eliminating oil or toxic chemical, and employing low temperature and pressure for growth factor stability. Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the chitosan microparticles by two methods: encapsulating and coating techniques. These microparticles were tested in vivo to determine the biological response in a rat femoral bone defect at 6 and 12 weeks. Four groups (n=10) were tested which include two groups for BMP-7 incorporated microparticles (by two techniques), microparticles without BMP-7, and defect itself (negative control). Healthy bone formation was observed around the microparticles, which were only confined to the defect site and did not disperse. Histology indicated minor inflammatory response around the microparticles at 6 weeks, which reduced by 12 weeks. Micro-CT analysis of bone surface density and porosity was found to be significantly more (p<0.05) for microparticles containing groups, in comparison with controls, which suggests that the new bone formed in the presence of microparticles is more interconnected and porous. Collagen fibrils analysis conducted using multiphoton microscopy showed significant improvement in the formation of bundled collagen area (%) in microparticles containing groups in comparison with controls, indicating higher cross-linking between the fibrils. Microparticles were biocompatible and did not degrade in the 12 week implant period. Copyright © 2016 Elsevier B.V. All rights reserved.

Bone-Induced Chondroinduction in Sheep Jamshidi Biopsy Defects with and without Treatment by Subchondral Chitosan-Blood Implant

PubMed Central

Bell, Angela D.; Lascau-Coman, Viorica; Sun, Jun; Chen, Gaoping; Lowerison, Mark W.; Hurtig, Mark B.

2013-01-01

Objective: Delivery of chitosan to subchondral bone is a novel approach for augmented marrow stimulation. We evaluated the effect of 3 presolidified chitosan-blood implant formulations on osteochondral repair progression compared with untreated defects. Design: In N = 5 adult sheep, six 2-mm diameter Jamshidi biopsy holes were created bilaterally in the medial femoral condyle and treated with presolidified chitosan-blood implant with fluorescent chitosan tracer (10 kDa, 40 kDa, or 150k Da chitosan, left knee) or left to bleed (untreated, right knee). Implant residency and osteochondral repair were assessed at 1 day (N = 1), 3 weeks (N = 2), or 3 months (N = 2) postoperative using fluorescence microscopy, histomorphometry, stereology, and micro–computed tomography. Results: Chitosan implants were retained in 89% of treated Jamshidi holes up to 3 weeks postoperative. At 3 weeks, biopsy sites were variably covered by cartilage flow, and most bone holes contained cartilage flow fragments and heterogeneous granulation tissues with sparse leukocytes, stromal cells, and occasional adipocytes (volume density 1% to 3%). After 3 months of repair, most Jamshidi bone holes were deeper, remodeling at the edges, filled with angiogenic granulation tissue, and lined with variably sized chondrogenic foci fused to bone trabeculae or actively repairing bone plate. The 150-kDa chitosan implant elicited more subchondral cartilage formation compared with 40-kDa chitosan-treated and control defects (P < 0.05, N = 4). Treated defects contained more mineralized repair tissue than control defects at 3 months (P < 0.05, N = 12). Conclusion: Bone plate–induced chondroinduction is an articular cartilage repair mechanism. Jamshidi biopsy repair takes longer than 3 months and can be influenced by subchondral chitosan-blood implant. PMID:26069656

Synthesis and Characterization of a Chitosan Derivative for Electro-Optical Applications

NASA Technical Reports Server (NTRS)

Prastofer, Thomas

1996-01-01

Chitin is a naturally occurring polymer of alpha(1-4) poly N-acetylglucosamine found primarily in the shells of crustaceans and insects. This polymer is chemically and thermally stable and physically durable as a consequence of hydrogen bonding which causes the alignment and ordering of the polymer chains into microcrystals which aggregate into sheets with chiral nematic order. Industry has attempted to take advantage of chitin's properties and low cost (chitin is a waste product of the shellfish industry) to produce durable fibers and other products. This has been largely unsuccessful because of chitin's non reactivity and insolubility. Chitosan is the deacetylation product of chitin and retains many of the structural properties of chitin. Unlike chitin, chitosan is soluble in aqueous solution at reduced pH making it easier to be processed into fibers and films than chitin. Chitosan and its derivatives are now used in such commercial applications as wound dressings, waste water treatment, and in pharmaceuticals. In this study, we have synthesized a chitosan derivative, N-para-nitrophenyl chitosan (NPNPC), as a model material with potential applications in electro optics.

Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

PubMed Central

Ahmed, Tarek A; Aljaeid, Bader M

2016-01-01

Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles.

PubMed

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2013-12-01

Peptide (insulin) loaded nanoparticles (NPs) have been embedded into buccal chitosan films (Ch-films-NPs). These films were produced by solvent casting and involved incorporating in chitosan gel (1.25% w/v), NPs-Insulin suspensions at three different concentrations (1, 3, and 5mg of NPs per film) using glycerol as plasticiser. Film swelling and mucoadhesion were investigated using 0.01M PBS at 37°C and texture analyzer, respectively. Formulations containing 3mg of NPs per film produced optimised films with excellent mucoadhesion and swelling properties. Dynamic laser scattering measurements showed that the erosion of the chitosan backbone controlled the release of NPs from the films, preceding in vitro drug (insulin) release from Ch-films-NPs after 6h. Modulated release was observed with 70% of encapsulated insulin released after 360h. The use of chitosan films yielded a 1.8-fold enhancement of ex vivo insulin permeation via EpiOral™ buccal tissue construct relative to the pure drug. Flux and apparent permeation coefficient of 0.1μg/cm(2)/h and 4×10(-2)cm(2)/h were respectively obtained for insulin released from Ch-films-NPs-3. Circular dichroism and FTIR spectroscopy demonstrated that the conformational structure of the model peptide drug (insulin) released from Ch-films-NPs was preserved during the formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

Magnetic- and pH-responsive κ-carrageenan/chitosan complexes for controlled release of methotrexate anticancer drug.

PubMed

Mahdavinia, Gholam Reza; Mosallanezhad, Amirabbas; Soleymani, Moslem; Sabzi, Mohammad

2017-04-01

The aim of the present work was to develop green carriers for methotrexate using κ-carrageenan/chitosan complexes. Magnetic Fe 3 O 4 nanoparticles were first synthesized in the presence of κ-carrageenan through in situ method. Then, the obtained magnetic κ-carrageenan was crosslinked using the polycation chitosan biopolymer. The physical and structural properties of hydrogels were investigated by FTIR, XRD, SEM, TEM, TGA, and VSM techniques. The pH-dependent swelling behavior of hydrogels was examined in various buffer solutions. All of the prepared hydrogels showed a high swelling capacity in basic solutions. The introduction of magnetite nanoparticles into κ-carrageenan/chitosan complexes had a significant effect on the swelling capacity of magnetic hydrogels, as the water absorbency of hydrogels decreased with increasing magnetite content. Methotrexate as an anticancer and model drug was loaded on hydrogels and the release profiles were investigated at pH=7.4 and 5.3. The methotrexate encapsulation efficiency was increased by increasing magnetite and chitosan contents. The results demonstrated that the release of methotrexate from magnetic hydrogels is pH-dependent with a high release content at pH=7.4. The release profiles were analyzed by Peppas's empirical model and the release of drug from hydrogels followed Fickian type of diffusion mechanism at both pHs. Copyright © 2017 Elsevier B.V. All rights reserved.

Resveratrol-3-O-glucuronide and resveratrol-4'-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin.

PubMed

Zunino, Susan J; Storms, David H

2017-08-01

Resveratrol has been reported to inhibit or induce DNA damage, depending upon the type of cell and the experimental conditions. Dietary resveratrol is present in the body predominantly as metabolites and limited data is available concerning the activities of these metabolic products. In the present study, physiologically obtainable levels of the resveratrol metabolites resveratrol-3-O-glucuronide, resveratrol-4'-O-glucuronide and resveratrol-3-O-sulfate were evaluated for their ability to protect Jurkat T cells against DNA damage induced by the topoisomerase I inhibitors camptothecin and topotecan. The cells were pretreated for 24 h with 10 µM resveratrol aglycone or each resveratrol metabolite prior to the induction of DNA damage with camptothecin or topotecan. In separate experiments, the cells were co-treated with resveratrol or its metabolites, and a topoisomerase I inhibitor. The detection of histone 2AX phosphorylation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) were used to determine DNA damage, and apoptosis was measured using an antibody against cleaved poly ADP-ribose polymerase. It was identified that pretreatment of the cells with resveratrol-3-O-glucuronide and resveratrol-4'-O-glucuronide reduced the mean fluorescence intensity of staining for DNA strand breaks following treatment with camptothecin, while the percentage of cells undergoing apoptosis was unchanged. However, pretreatment of the cells with resveratrol aglycone increased the DNA damage and apoptosis induced by the drugs. These results suggest that the glucuronide metabolites of resveratrol partially protected the cells from DNA damage, but did not influence the induction of cell death by camptothecin and topotecan. These data suggest that resveratrol aglycone treatment may be beneficial for treating types of cancer that have direct contact with resveratrol prior to its metabolism, including gastrointestinal cancers, which are routinely treated with

Design, characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin.

PubMed

Mortazavian, Elaheh; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza

2014-05-01

The purpose of this study is to optimize and characterize of chitosan buccal film for delivery of insulin nanoparticles that were prepared from thiolated dimethyl ethyl chitosan (DMEC-Cys). Insulin nanoparticles composed of chitosan and dimethyl ethyl chitosan (DMEC) were also prepared as control groups. The release of insulin from nanoparticles was studied in vitro in phosphate buffer solution (PBS) pH 7.4. Optimization of chitosan buccal films has been carried out by central composite design (CCD) response surface methodology. Independent variables were different amounts of chitosan and glycerol as mucoadhesive polymer and plasticizer, respectively. Tensile strength and bioadhesion force were considered as dependent variables. Ex vivo study was performed on excised rabbit buccal mucosa. Optimized insulin nanoparticles were obtained with acceptable physicochemical properties. In vitro release profile of insulin nanoparticles revealed that the highest solubility of nanoparticles in aqueous media is related to DMEC-Cys nanoparticles. CCD showed that optimized buccal film containing 4% chitosan and 10% glycerol has 5.81 kg/mm(2) tensile strength and 2.47 N bioadhesion forces. Results of ex vivo study demonstrated that permeation of insulin nanoparticles through rabbit buccal mucosa is 17.1, 67.89 and 97.18% for chitosan, DMEC and DMEC-Cys nanoparticles, respectively. Thus, this study suggests that DMEC-Cys can act as a potential enhancer for buccal delivery of insulin.

Protein arginine (N)-methyl transferase 7 (PRMT7) as a potential target for the sensitization of tumor cells to camptothecins.

PubMed

Verbiest, Vincent; Montaudon, Danièle; Tautu, Michel T; Moukarzel, Joyce; Portail, Jean-Pierre; Markovits, Judith; Robert, Jacques; Ichas, François; Pourquier, Philippe

2008-04-30

PRMT7 belongs to the protein arginine methyl-transferases family. We show that downregulation of PRMT7alpha and beta isoforms in DC-3F hamster cells was associated with increased sensitivity to the Top1 inhibitor camptothecin (CPT). This effect was not due to a change in Top1 contents or catalytic activity, or to a difference in the reversal of DNA breaks. Overexpression of PRMT7alpha and beta in DC-3F cells had no effect on CPT sensitivity, whereas it conferred a resistance to DC-3F/9-OH-E cells for which both isoforms are reduced by two- to three-fold as compared to DC-3F parental cells. Finally, downregulation of the human PRMT7 could also sensitize HeLa cells to CPT, suggesting that it could be used as a target to potentiate CPT derivatives.

Comparison of cadmium adsorption onto chitosan and epichlorohydrin crosslinked chitosan/eggshell composite

NASA Astrophysics Data System (ADS)

Rahmi; Marlina; Nisfayati

2018-05-01

The use of chitosan and epichlorohydrin crosslinked chitosan/eggshell composite for cadmium adsorption from water were investigated. The factors affecting adsorption such as pH and contact time were considered. The results showed that the optimum pH of adsorption was pH = 6.0 and the equilibrium time of adsorption was 40 min. The adsorption isotherm of Cd ions onto chitosan and composite were well fitted to Langmuir equation. The maximum adsorption capacity (fitting by Langmuir model) of chitosan and composite were 1.008 and 11.7647 mg/g, respectively. Adsorption performance of composite after regeneration was better than chitosan.

Encapsulation of selenium in chitosan nanoparticles improves selenium availability and protects cells from selenium-induced DNA damage response

USDA-ARS?s Scientific Manuscript database

Selenium, an essential mineral, plays important roles in optimizing human health. Chitosan is an effective, naturally oriented material for synthesizing nanoparticles with polyanions and exhibit preferable properties such as biocompatibility, biodegradation and resistance to certain enzymes. We have...

Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis

PubMed Central

Wang, Maowei; Yue, Yan; Dong, Chunsheng; Li, Xiaoyun; Xu, Wei

2013-01-01

Coxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to the Picornaviridae family. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P < 0.05) enhanced CVB3-specific fecal secretory IgA levels and promoted mucosal T cell immune responses. In accordance, reduced severity of myocarditis was observed in coimmunized mice, as evidenced by significantly (P < 0.05) reduced viral loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis. PMID:24027262

Dextran vesicular carriers for dual encapsulation of hydrophilic and hydrophobic molecules and delivery into cells.

PubMed

Pramod, P S; Takamura, Kathryn; Chaphekar, Sonali; Balasubramanian, Nagaraj; Jayakannan, M

2012-11-12

Dextran vesicular nanoscaffolds were developed based on polysaccharide and renewable resource alkyl tail for dual encapsulation of hydrophilic and hydrophobic molecules (or drugs) and delivery into cells. The roles of the hydrophobic segments on the molecular self-organization of dextran backbone into vesicles or nanoparticles were investigated in detail. Dextran vesicles were found to be a unique dual carrier in which water-soluble molecules (like Rhodamine-B, Rh-B) and polyaromatic anticancer drug (camptothecin, CPT) were selectively encapsulated in the hydrophilic core and hydrophobic layer, respectively. The dextran vesicles were capable of protecting the plasma-sensitive CPT lactone pharmacophore against the hydrolysis by 10× better than the CPT alone in PBS. The aliphatic ester linkage connecting the hydrophobic tail with dextran was found to be cleaved by esterase under physiological conditions for fast releasing of CPT or Rh-B. Cytotoxicity of the dextran vesicle and its drug conjugate were tested on mouse embryonic fibroblast cells (MEFs) using MTT assay. The dextran vesicular scaffold was found to be nontoxic to living cells. CPT loaded vesicles were found to be 2.5-fold more effective in killing fibroblasts compared to that of CPT alone in PBS. Confocal microscopic images confirmed that both Rh-B and CPT loaded vesicles to be taken up by fibroblasts compared to CPT alone, showing a distinctly perinuclear localization in cells. The custom designed dextran vesicular provides new research opportunities for dual loading and delivering of hydrophilic and hydrophobic drug molecules.

Preparation and Characterization of Facilitated Transport Membranes Composed of Chitosan-Styrene and Chitosan-Acrylonitrile Copolymers Modified by Methylimidazolium Based Ionic Liquids for CO2 Separation from CH4 and N2

PubMed Central

Otvagina, Ksenia V.; Mochalova, Alla E.; Sazanova, Tatyana S.; Petukhov, Anton N.; Moskvichev, Alexandr A.; Vorotyntsev, Andrey V.; Afonso, Carlos A. M.; Vorotyntsev, Ilya V.

2016-01-01

CO2 separation was found to be facilitated by transport membranes based on novel chitosan (CS)–poly(styrene) (PS) and chitosan (CS)–poly(acrylonitrile) (PAN) copolymer matrices doped with methylimidazolium based ionic liquids: [bmim][BF4], [bmim][PF6], and [bmim][Tf2N] (IL). CS plays the role of biodegradable film former and selectivity promoter. Copolymers were prepared implementing the latest achievements in radical copolymerization with chosen monomers, which enabled the achievement of outstanding mechanical strength values for the CS-based membranes (75–104 MPa for CS-PAN and 69–75 MPa for CS-PS). Ionic liquid (IL) doping affected the surface and mechanical properties of the membranes as well as the gas separation properties. The highest CO2 permeability 400 Barrers belongs to CS-b-PS/[bmim][BF4]. The highest selectivity α (CO2/N2) = 15.5 was achieved for CS-b-PAN/[bmim][BF4]. The operational temperature of the membranes is under 220 °C. PMID:27294964

Air-tolerant Fabrication and Enhanced Thermoelectric Performance of n-Type Single-walled Carbon Nanotubes Encapsulating 1,1'-Bis(diphenylphosphino)ferrocene.

PubMed

Nonoguchi, Yoshiyuki; Iihara, Yu; Ohashi, Kenji; Murayama, Tomoko; Kawai, Tsuyoshi

2016-09-06

The thermally-triggered n-type doping of single-walled carbon nanotubes is demonstrated using 1,1'-bis(diphenylphosphino)ferrocene, a novel n-type dopant. Through a simple thermal vacuum process, the phosphine compounds are moderately encapsulated inside single-walled carbon nanotubes. The encapsulation into SWNTs is carefully characterized using Raman/X-ray spectroscopy and transmission electron microscopy. This easy-to-handle doping with air-stable precursors for n-type SWNTs enables the large-scale fabrication of thermoelectric materials showing an excellent power factor exceeding approximately 240 μW mK(-2) . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms

PubMed Central

Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby

2017-01-01

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections. PMID:28362873

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

PubMed

Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby; Davamani, Fabian

2017-01-01

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

Chitosan(PEO)/silica hybrid nanofibers as a potential biomaterial for bone regeneration.

PubMed

Toskas, Georgios; Cherif, Chokri; Hund, Rolf-Dieter; Laourine, Ezzeddine; Mahltig, Boris; Fahmi, Amir; Heinemann, Christiane; Hanke, Thomas

2013-05-15

New hybrid nanofibers prepared with chitosan (CTS), containing a total amount of polyethylene oxide (PEO) down to 3.6wt.%, and silica precursors were produced by electrospinning. The solution of modified sol-gel particles contained tetraethoxysilane (TEOS) and the organosilane 3-glycidyloxypropyltriethoxysilane (GPTEOS). This is rending stable solution toward gelation and contributing in covalent bonding with chitosan. The fibers encompass advantages of biocompatible polymer template silicate components to form self-assembled core-shell structure of the polymer CTS/PEO encapsulated by the silica. Potential applicability of this hybrid material to bone tissue engineering was studied examining its cellular compatibility and bioactivity. The nanofiber matrices were proved cytocompatible when seeded with bone-forming 7F2-cells, promoting attachment and proliferation over 7 days. These found to enhance a fast apatite formation by incorporation of Ca(2+) ions and subsequent immersion in modified simulated body fluid (m-SBF). The tunable properties of these hybrid nanofibers can find applications as active biomaterials in bone repair and regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

HDPE/Chitosan Blends Modified with Organobentonite Synthesized with Quaternary Ammonium Salt Impregnated Chitosan

PubMed Central

de Araújo, Maria José G.; Barbosa, Rossemberg C.; Fook, Marcus Vinícius L.; Canedo, Eduardo L.; Silva, Suédina M. L.; Medeiros, Eliton S.; Leite, Itamara F.

2018-01-01

In this study, blends based on a high density polyethylene (HDPE) and chitosan (CS) were successfully prepared by melt processing, in a laboratory internal mixer. The CS biopolymer content effect (up to maximum of 40%), and, the addition of bentonite clay modified with quaternary ammonium salt (CTAB) impregnated chitosan as a compatibilizing agent, on the properties of the blends was analyzed by Fourier transform-infrared spectroscopy (FT-IR), wide angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), thermogravimetric analyses (TG), tensile strength, and scanning electron microscopy (SEM). The use of clay modified with CTAB impregnated chitosan, employing a method developed here, improved the compatibility of HDPE with chitosan, and therefore the thermal and some of the mechanical properties were enhanced, making HDPE/chitosan blends suitable candidates for food packaging. It was possible to obtain products of synthetic polymer, HDPE, with natural polymer, chitosan, using a method very used industrially, with acceptable and more friendly properties to the environment, when compared to conventional synthetic polymers. In addition, due to the possibility of impregnated chitosan with quaternary ammonium salt exhibit higher antibacterial activity than neat chitosan, the HDPE/chitosan/organobentonite blends may be potentially applied in food containers to favor the preservation of food for a longer time in comparison to conventional materials. PMID:29438286

HDPE/Chitosan Blends Modified with Organobentonite Synthesized with Quaternary Ammonium Salt Impregnated Chitosan.

PubMed

de Araújo, Maria José G; Barbosa, Rossemberg C; Fook, Marcus Vinícius L; Canedo, Eduardo L; Silva, Suédina M L; Medeiros, Eliton S; Leite, Itamara F

2018-02-13

In this study, blends based on a high density polyethylene (HDPE) and chitosan (CS) were successfully prepared by melt processing, in a laboratory internal mixer. The CS biopolymer content effect (up to maximum of 40%), and, the addition of bentonite clay modified with quaternary ammonium salt (CTAB) impregnated chitosan as a compatibilizing agent, on the properties of the blends was analyzed by Fourier transform-infrared spectroscopy (FT-IR), wide angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), thermogravimetric analyses (TG), tensile strength, and scanning electron microscopy (SEM). The use of clay modified with CTAB impregnated chitosan, employing a method developed here, improved the compatibility of HDPE with chitosan, and therefore the thermal and some of the mechanical properties were enhanced, making HDPE/chitosan blends suitable candidates for food packaging. It was possible to obtain products of synthetic polymer, HDPE, with natural polymer, chitosan, using a method very used industrially, with acceptable and more friendly properties to the environment, when compared to conventional synthetic polymers. In addition, due to the possibility of impregnated chitosan with quaternary ammonium salt exhibit higher antibacterial activity than neat chitosan, the HDPE/chitosan/organobentonite blends may be potentially applied in food containers to favor the preservation of food for a longer time in comparison to conventional materials.

The targeted behavior of folate-decorated N-succinyl-N'-octyl chitosan evaluated by NIR system in mouse model

NASA Astrophysics Data System (ADS)

Zhu, Hongyan; Deng, Dawei; Chen, Haiyan; Qian, Zhiyu; Gu, Yueqing

2010-11-01

The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to construct and evaluate the folate-decorated, self-assembled nanoparticles as candidates to deliver near infrared fluorescent dyes into tumors and to investigate the mechanisms underlying the tumor targeting with folate-decorated, self-assembled nanoparticles. Folate-decorated N-succinyl-N'-octyl chitosan (folate-SOC) were synthesized. The chemical modification chitosan could self-assemble into stable micelles in aqueous medium. Micelle size determined by size analysis was around 140 nm in a phosphate-buffered saline (PBS, PH 7.4). Folate-SOC could maintain their structure for up to 15 days in PBS. Near infrared dye ICG-Der-01 as a mode drug was loaded in the micelles, and the entrapment efficiency (EE) and drug loading (DL) were investigated. The targeted behavior of folate-SOC was evaluated by near-infrared fluorescence imaging in vivo on different groups of denuded mice, with A549 or Bel-7402 tumors. The optical imaging results indicated that folated-decorated SOC showed an excellent tumor specificity in Bel-7402 tumor-bearing mice, and weak tumor specificity in A549 tumor bearing mice. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

Resveratrol-3-O-glucuronide and resveratrol-4′-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin

PubMed Central

Zunino, Susan J.; Storms, David H.

2017-01-01

Resveratrol has been reported to inhibit or induce DNA damage, depending upon the type of cell and the experimental conditions. Dietary resveratrol is present in the body predominantly as metabolites and limited data is available concerning the activities of these metabolic products. In the present study, physiologically obtainable levels of the resveratrol metabolites resveratrol-3-O-glucuronide, resveratrol-4′-O-glucuronide and resveratrol-3-O-sulfate were evaluated for their ability to protect Jurkat T cells against DNA damage induced by the topoisomerase I inhibitors camptothecin and topotecan. The cells were pretreated for 24 h with 10 µM resveratrol aglycone or each resveratrol metabolite prior to the induction of DNA damage with camptothecin or topotecan. In separate experiments, the cells were co-treated with resveratrol or its metabolites, and a topoisomerase I inhibitor. The detection of histone 2AX phosphorylation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) were used to determine DNA damage, and apoptosis was measured using an antibody against cleaved poly ADP-ribose polymerase. It was identified that pretreatment of the cells with resveratrol-3-O-glucuronide and resveratrol-4′-O-glucuronide reduced the mean fluorescence intensity of staining for DNA strand breaks following treatment with camptothecin, while the percentage of cells undergoing apoptosis was unchanged. However, pretreatment of the cells with resveratrol aglycone increased the DNA damage and apoptosis induced by the drugs. These results suggest that the glucuronide metabolites of resveratrol partially protected the cells from DNA damage, but did not influence the induction of cell death by camptothecin and topotecan. These data suggest that resveratrol aglycone treatment may be beneficial for treating types of cancer that have direct contact with resveratrol prior to its metabolism, including gastrointestinal cancers, which are routinely treated with

Design of a potentially prebiotic and responsive encapsulation material for probiotic bacteria based on chitosan and sulfated β-glucan.

PubMed

Yucel Falco, Cigdem; Sotres, Javier; Rascón, Ana; Risbo, Jens; Cárdenas, Marité

2017-02-01

Chitosan and sulfated oat β-glucan are materials suitable to create a prebiotic coating for targeted delivery to gastrointestinal system, using the layer by layer technology. Quartz crystal microbalance with dissipation (QCM-D), spectroscopic ellipsometry (SE) and atomic force microscopy (AFM) were used to assess the multilayer formation capacity and characterize the resulting coatings in terms of morphology and material properties such as structure and rigidity. The coating of colloidal materials was proven, specifically on L. acidophilus bacteria as measured by changes in the bacterial suspension zeta potential. Viability of coated cells was shown using plate counting method. The coatings on solid surfaces were examined after exposure to mimics of gastrointestinal fluids and a commercially available β-glucanase. Successful build-up of multilayers was confirmed with QCM-D and SE. Zeta potential values proved the coating of cells. There was 2 log CFU/mL decrease after coating cells with four alternating layers of chitosan and sulfated β-glucan when compared to viability of uncoated cells. The coatings were partially degraded after exposure to simulated intestinal fluid and restructured as a result of β-glucanase treatment, mimicking enzymes present in the microflora of the human gut, but seemed to resist acidic gastric conditions. Therefore, coatings of chitosan and sulfated β-glucan can potentially be exploited as carriers for probiotics and delicate nutraceuticals. Copyright © 2016 Elsevier Inc. All rights reserved.

A method for determining the composition of methanol-trimethyl borate mixtures

NASA Technical Reports Server (NTRS)

Kaye, Samuel; Sordyl, Frank

1955-01-01

A study of mixtures of pure methanol and trimethyl borate showed that the composition can be accurately obtained by a simple density determination. The refractive-index determination gives the composition with much less accuracy. The potentiometric titration of boric acid is also discussed.

Enzymatic degradation of thiolated chitosan.

PubMed

Laffleur, Flavia; Hintzen, Fabian; Rahmat, Deni; Shahnaz, Gul; Millotti, Gioconda; Bernkop-Schnürch, Andreas

2013-10-01

The objective of this study was to evaluate the biodegradability of thiolated chitosans in comparison to unmodified chitosan. Mediated by carbodiimide, thioglycolic acid (TGA) and mercaptonicotinic acid (MNA) were covalently attached to chitosan via formation an amide bond. Applying two different concentrations of carbodiimide 50 and 100 mM, two chitosan TGA conjugates (TGA A and TGA B) were obtained. According to chitosan solution (3% m/v) thiomer solutions were prepared and chitosanolytic enzyme solutions were added. Lysozyme, pectinase and cellulase were examined in chitosan degrading activity. The enzymatic degradability of these thiomers was investigated by viscosity measurements with a plate-plate viscometer. The obtained chitosan TGA conjugate A displayed 267.7 µmol and conjugate B displayed 116.3 µmol of immobilized thiol groups. With 325.4 µmol immobilized thiol groups, chitosan MNA conjugate displayed the most content of thiol groups. In rheological studies subsequently the modification proved that chitosan TGA conjugates with a higher coupling rate of thiol groups were not only degraded to a lesser extent by 20.9-26.4% but also more slowly. Chitosan mercaptonicotinic acid was degraded by 31.4-50.1% depending the investigated enzyme and even faster than unmodified chitosan. According to these results the biodegradability can be influenced by various modifications of the polymer which showed in particular that the rate of biodegradation is increased when MNA is the ligand, whereas the degradation is hampered when TGA is used as ligand for chitosan.

Trimethylated homoserine functions as the major compatible solute in the globally significant oceanic cyanobacterium Trichodesmium.

PubMed

Pade, Nadin; Michalik, Dirk; Ruth, Wolfgang; Belkin, Natalia; Hess, Wolfgang R; Berman-Frank, Ilana; Hagemann, Martin

2016-11-15

The oceanic N 2 -fixing cyanobacterium Trichodesmium spp. form extensive surface blooms and contribute significantly to marine carbon and nitrogen cycles in the oligotrophic subtropical and tropical oceans. Trichodesmium grows in salinities from 27 to 43 parts per thousand (ppt), yet its salt acclimation strategy remains enigmatic because the genome of Trichodesmium erythraeum strain IMS101 lacks all genes for the biosynthesis of any known compatible solute. Using NMR and liquid chromatography coupled to mass spectroscopy, we identified the main compatible solute in T. erythraeum strain IMS101 as the quaternary ammonium compound N,N,N-trimethyl homoserine (or homoserine betaine) and elucidated its biosynthetic pathway. The identification of this compatible solute explains how Trichodesmium spp. can thrive in the marine system at varying salinities and provides further insight into the diversity of microbial salt acclimation.

Matrix Effect on the Spray Drying Nanoencapsulation of Lippia sidoides Essential Oil in Chitosan-Native Gum Blends.

PubMed

Paula, Haroldo C B; Oliveira, Erick F; Carneiro, Maria J M; de Paula, Regina C M

2017-03-01

Essential oils have many applications in the pharmaceutical, chemical, and food fields, however, their use is limited to the fact that they are very labile, requiring their a priori encapsulation, aiming to preserve their properties.This work reports on the preparation of chitosan-gum nanoparticles loaded with thymol containing Lippia sidoides essential oil, using exudates of Anacardium Occidentale (cashew gum), Sterculia striata (chichá gum), and Anadenanthera macrocarpa trees (angico gum). Nanoparticles were produced by spray drying an emulsion of L. sidoides essential oil and aqueous solution of gums with different chitosan : gum ratios. Samples were characterized by FTIR and UV/VIS spectroscopy, particle size, volume distribution, and zeta potential. The FTIR spectrum showed the main signals of chitosan and the gums. Data obtained revealed that the samples had sizes in the nano range, varying from 17 nm to 800 nm. The zeta potential varied from + 30 mV to - 40 mV. Nanoparticle loading values varied from 6.7 % to 15.6 %, with an average encapsulating efficiency of 62 %, where the samples with high ratios of cashew gum and chichá gum presented high oil loading values. The data revealed that both the chitosan : gum ratio and polysaccharide characteristics play major roles in nanoencapsulation processes. Georg Thieme Verlag KG Stuttgart · New York.

Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications.

PubMed

Ono, K; Ishihara, M; Ozeki, Y; Deguchi, H; Sato, M; Saito, Y; Yura, H; Sato, M; Kikuchi, M; Kurita, A; Maehara, T

2001-11-01

In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.

Water-Based Suspensions of Iron Oxide Nanoparticles with Electrostatic or Steric Stabilization by Chitosan: Fabrication, Characterization and Biocompatibility

PubMed Central

Litvinova, Larisa S.; Safronov, Alexander P.; Schupletsova, Valeria V.; Tyukova, Irina S.; Khaziakhmatova, Olga G.; Slepchenko, Galina B.; Yurova, Kristina A.; Cherempey, Elena G.; Kulesh, Nikita A.; Andrade, Ricardo; Beketov, Igor V.; Khlusov, Igor A.

2017-01-01

Present day biomedical applications, including magnetic biosensing, demand better understanding of the interactions between living systems and magnetic nanoparticles (MNPs). In this work spherical MNPs of maghemite were obtained by a highly productive laser target evaporation technique. XRD analysis confirmed the inverse spinel structure of the MNPs (space group Fd-3m). The ensemble obeyed a lognormal size distribution with the median value 26.8 nm and dispersion 0.362. Stabilized water-based suspensions were fabricated using electrostatic or steric stabilization by the natural polymer chitosan. The encapsulation of the MNPs by chitosan makes them resistant to the unfavorable factors for colloidal stability typically present in physiological conditions such as pH and high ionic force. Controlled amounts of suspensions were used for in vitro experiments with human blood mononuclear leukocytes (HBMLs) in order to study their morphofunctional response. For sake of comparison the results obtained in the present study were analyzed together with our previous results of the study of similar suspensions with human mesenchymal stem cells. Suspensions with and without chitosan enhanced the secretion of cytokines by a 24-h culture of HBMLs compared to a control without MNPs. At a dose of 2.3, the MTD of chitosan promotes the stimulating effect of MNPs on cells. In the dose range of MNPs 10–1000 MTD, chitosan “inhibits” cellular secretory activity compared to MNPs without chitosan. Both suspensions did not caused cell death by necrosis, hence, the secretion of cytokines is due to the enhancement of the functional activity of HBMLs. Increased accumulation of MNP with chitosan in the cell fraction at 100 MTD for 24 h exposure, may be due to fixation of chitosan on the outer membrane of HBMLs. The discussed results can be used for an addressed design of cell delivery/removal incorporating multiple activities because of cell capability to avoid phagocytosis by immune cells

Optimizing deacetylation process for chitosan production from green mussel (perna viridis) shell

NASA Astrophysics Data System (ADS)

Danarto, Y. C.; Distantina, Sperisa

2016-02-01

The green mussel (perna viridis) shell waste could be utilized for chitosan production because it contained chitin. Chitin can be derived into chitosan through the deacetylation process. Chitosan is a polysaccharides polymer that is readily soluble in dilute acid solution and easily modified into other useful compounds. This research aimed to study the chitosan production from green mussel shells. This experiment had the following stages, deproteinization process aimed to eliminate the protein content using 1N NaOH solution, demineralization process aimed to remove minerals in green mussel shells as CaCO3 using 1 N HCl solution and decolorization process aimed to eliminate the color pigments and other impurities using ethanol solvent. All process above resulted chitin. Furthermore, chemical modification of chitin into chitosan by deacetylation process. This stage was very important because it greatly affected the chitosan properties. This research studied two different treatment for deacetylation process. The first treatment was the deacetylation process using concentrated NaOH solution (50% w), at high temperatures (90 - 100 °C) for 2 hours extraction, whilw the second treatment was deacetylation process using a low concentration of NaOH solution (15% w), at room temperature for 24 hours. The results showed that deproteinization, demineralization, and decolorizaton was capable of removing protein, mineral, and pigment. This experiment yield chitin 41.6 %wt. Chitosan yield from second treatment was 39.5%w and it was better than first treatment. Chitosan from first treatment had 79.8% degree of deacetylation and 16.5 kDa molecular weight. It was better than first treatment.

Oxidation-mediated chitosan as additives for creation of chitosan aerogels with diverse three-dimensional interconnected skeletons

NASA Astrophysics Data System (ADS)

Zhang, Sizhao; Feng, Jian; Feng, Junzong; Jiang, Yonggang

2017-02-01

Naturally occurring polymer-based aerogels have myriad practical utilizations due to environmentally benign and fruitful resources. However, engineering morphology-controllable biomass aerogels still represents a great challenge. Here we present a facile solution to synthesize chitosan aerogels having distinguished textures by reacting oxidized chitosan with formaldehyde and chitosan sol. In more detail, chitosan was chemically oxidized using two types of oxidation agents such as ammonium persulphate (SPD) and sodium periodate (APS) to obtain corresponding oxidized chitosan, subsequently cross-linked with chitosan solution containing formaldehyde to harvest SPD-oxidized chitosan aerogels (SCAs) and APS-SPD-oxidized ones (ASCAs) after aging, solvent exchange and supercritical drying processes. We found that the morphologies of as-prepared chitosan aerogels are strongly dependent upon the oxidation pattern towards chitosan. The structural textures of SCAs and ASCAs appear nanoflake-like and nanofiber-like structures, which may be related to spatial freedom of active groups located in chitosan. Selected area electron diffraction analysis reveals that the crystalline properties of chitosan aerogels generally appear the serious deterioration comparing to raw chitosan owing to their interconnected skeletal structure formation. The occurrence of characteristic groups displays cross-linked chain construction by using chemical state measurements such as FT-IR and XPS. Further, a plausible mechanism for controlling morphology of chitosan aerogels is also established. This new family of method for creation of chitosan aerogels may open up a perspective for biomass aerogels with controllable textures.

Development of silver/titanium dioxide/chitosan adipate nanocomposite as an antibacterial coating for fruit storage

USDA-ARS?s Scientific Manuscript database

A novel nanocomposite of silver/titanium dioxide/chitosan adipate (Ag/TiO2/CS) was developed through photochemical reduction using a chitosan adipate template. Chitosan served as a reducing agent for the metal ions, and anchored metal ions by forming Ag–N coordination bonds and electrostatic attract...

Effect of chitosan content on gel content of epoxized natural rubber grafted with chitosan in latex form.

PubMed

Riyajan, Sa-Ad; Sukhlaaied, Wattana

2013-04-01

The epoxidized natural rubber (ENR) latex-g-chitosan (ENR-g-chitosan) was prepared in latex form using potassium persulphate as an initiator. Firstly, the reduction in molecular weight of chitosan was subjected to the addition of K2S2O8 at 70 °C for 15 min. The structure of the modified chitosan was characterized by ATR-FTIR. Secondarily, the influence of chitosan contents, reaction time, and temperature and K2S2O8 concentrations on the gel content of the modified ENR was investigated. The chemical structure of the ENR-g-chitosan was confirmed by (1)H-NMR and ATR-FTIR. The ether linkage of the ENR-g-chitosan was conformed at 1154 an 1089 cm(-1) by ATR-FTIR and 3.60 ppm by (1)H-NMR. The gel content of ENR-g-chitosan at 5% chitosan showed the highest value compared with other samples. But when chitosan increased from 5% to 10% or 20%, the gel content of ENR-g-chitosan dramatically decreased. The ENR-g-chitosan showed good thermal resistance due to incorporation of chitosan. The morphology of ENR-g-chitosan particle showed the core-shell structure observed by TEM. The optimum condition of grafting ENR with chitosan was found at 65°C for 3h of reaction time, ratio of ENR/chitosan at 9:1. Copyright © 2012 Elsevier B.V. All rights reserved.

In vivo assessment of chitosan/β-glycerophosphate as a new liquid embolic agent.

PubMed

Wang, Y; Xu, N; Luo, Q; Li, Y; Sun, L; Wang, H; Xu, K; Wang, B; Zhen, Y

2011-03-01

We sought to assess the feasibility of using thermosensitive chitosan/β-glycerophosphate forembolotherapy. The renal arteries in nine rabbits were embolized with chitosan/β-glycero-phosphate. The animals were studied angiographically and sacrificed at one week (n = 3), four weeks (n = 3), and eight weeks (n = 3) after embolotherapy. Histology was obtained at these three time points. Delivery of chitosan/β-glycerophosphate was successful in all cases. Complete occlusion was achieved in all cases. No recanalization was observed in the follow-up angiograms. No untoward inflammatory reactions were observed in the target renal arteries and infarcted kidneys during the histological examinations. Our preliminary feasibility evaluation in rabbit renal arteries indicates that C/GP is a satisfactory embolization agent.

Rifaximin - Chitosan Nanoparticles for Inflammatory Bowel Disease (IBD).

PubMed

Kumar, Jatinder; Newton, Amaldoss M J

2017-01-01

Inflammatory Bowel Disease (IBD) cannot be controlled easily and the recurrence is the most challenging issue for the physicians. There are various controlled and colon targeted drug delivery systems available for the treatment with limited success rate. Nanoparticles prepared by using the colon targeted polymers such as chitosan may improve the IBD due to their smaller size, unique physico chemical properties and targeting potential. The aim of this investigation was designed to formulate and develop a colon targeted polysaccharide nanoparticles of rifaximin (RFX) by using linear polysaccharide chitosan, for the improvement of rifaximin solubility, overall therapeutic efficacy and colon targeting. The research was focused on developing RFX nanoparticles for the treatment of Inflammatory Bowel Disease (IBD) by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as XRD, FTIR and mean particle size (MPS) by Master Sizer and Zeta Sizer. Transmission Electron Microscopy (TEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The efficiency of drug release from prepared formulation was studied in vitro by using a dialysis bag diffusion technique in the buffer condition mimicking stomach, intestine and colonic pH conditions. The prepared nanoparticles demonstrated the size in the nano range. The drug release profile was controlled in the upper GI tract and the maximum amount of drug was released in the colonic conditions. The prepared nanoparticles significantly improved the solubility of rifaximin. The zeta potential of the best chitosan preparation was found to be 37.79, which confirms the stability of prepared nanosuspension. Nanoparticles with small particle size found to have high encapsulation efficiency and relatively high loading capacity and predetermined in vitro release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antimicrobial effect of emulsion-encapsulated isoeugenol against biofilms of food pathogens and spoilage bacteria.

PubMed

Krogsgård Nielsen, Christina; Kjems, Jørgen; Mygind, Tina; Snabe, Torben; Schwarz, Karin; Serfert, Yvonne; Meyer, Rikke Louise

2017-02-02

Food-related biofilms can cause food-borne illnesses and spoilage, both of which are problems on a global level. Essential oils are compounds derived from plant material that have a potential to be used in natural food preservation in the future since they are natural antimicrobials. Bacterial biofilms are particularly resilient towards biocides, and preservatives that effectively eradicate biofilms are therefore needed. In this study, we test the antibacterial properties of emulsion-encapsulated and unencapsulated isoeugenol against biofilms of Lis. monocytogenes, S. aureus, P. fluorescens and Leu. mesenteroides in tryptic soy broth and carrot juice. We show that emulsion encapsulation enhances the antimicrobial properties of isoeugenol against biofilms in media but not in carrot juice. Some of the isoeugenol emulsions were coated with chitosan, and treatment of biofilms with these emulsions disrupted the biofilm structure. Furthermore, we show that addition of the surfactant Tween 80, which is commonly used to disperse oils in food, hampers the antibacterial properties of isoeugenol. This finding highlights that common food additives, such as surfactants, may have an adverse effect on the antibacterial activity of preservatives. Isoeugenol is a promising candidate as a future food preservative because it works almost equally well against planktonic bacteria and biofilms. Emulsion encapsulation has potential benefits for the efficacy of isoeugenol, but the effect of encapsulation depends on the properties of food matrix in which isoeugenol is to be applied. Copyright © 2016 Elsevier B.V. All rights reserved.

Suitability of Different Food Grade Materials for the Encapsulation of Some Functional Foods Well Reported for Their Advantages and Susceptibility.

PubMed

Wani, Touseef Ahmed; Shah, Adil Gani; Wani, Sajad Mohd; Wani, Idrees Ahmed; Masoodi, Farooq Ahmad; Nissar, Nazia; Shagoo, Mudasir Ahmad

2016-11-17

Functional foods find a very important place in the modern era, where different types of cancer, diabetes, cardiovascular diseases, etc. are on a high. Irrespective of the abundance of bioactive components in different fruits and vegetables, their low solubility in aqueous solution, vulnerability to destruction in different environmental and gastrointestinal conditions and a low intestinal absorption becomes a concern. Because it is quite difficult to commercialize non food materials for the food encapsulation purposes due to their safety concerns in the human body, scientists in the recent times have come up with the idea of encapsulating the different bioactive components in different food grade materials that are able to safeguard these bioactive components against the different environmental and gastrointestinal conditions and ensure their safe and targeted delivery at their absorption sites. Different food grade encapsulation materials including various oligosaccharides, polysaccharides (starch, cyclodextrins, alginates, chitosan, gum arabic, and carboxymethyl cellulose) and proteins and their suitability for encapsulating various bioactive components like flavonoids (catechins, rutin, curcumin, hesperetin, and vanillin), nonflavonoids (resveratrol), carotenoids (β-carotene, lycopene, and lutein), and fatty acids (fish oil, flaxseed oil, and olive oil) of high medical and nutritional value are reviewed here.

How Trypanosoma cruzi handles cell cycle arrest promoted by camptothecin, a topoisomerase I inhibitor.

PubMed

Zuma, Aline Araujo; Mendes, Isabela Cecília; Reignault, Lissa Catherine; Elias, Maria Carolina; de Souza, Wanderley; Machado, Carlos Renato; Motta, Maria Cristina M

2014-02-01

The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease, which affects approximately 8 million people in Latin America. This parasite contains a single nucleus and a kinetoplast, which harbors the mitochondrial DNA (kDNA). DNA topoisomerases act during replication, transcription and repair and modulate DNA topology by reverting supercoiling in the DNA double-strand. In this work, we evaluated the effects promoted by camptothecin, a topoisomerase I inhibitor that promotes protozoan proliferation impairment, cell cycle arrest, ultrastructure alterations and DNA lesions in epimastigotes of T. cruzi. The results showed that inhibition of cell proliferation was reversible only at the lowest drug concentration (1μM) used. The unpacking of nuclear heterochromatin and mitochondrion swelling were the main ultrastructural modifications observed. Inhibition of parasite proliferation also led to cell cycle arrest, which was most likely caused by nuclear DNA lesions. Following camptothecin treatment, some of the cells restored their DNA, whereas others entered early apoptosis but did not progress to late apoptosis, indicating that the protozoa stay alive in a "senescence-like" state. This programmed cell death may be associated with a decrease in mitochondrial membrane potential and an increase in the production of reactive oxygen species. Taken together, these results indicate that the inhibition of T. cruzi proliferation is related to events capable of affecting cell cycle, DNA organization and mitochondrial activity. Copyright © 2014. Published by Elsevier B.V.

Influence of chitosan concentration on mechanical and barrier properties of corn starch/chitosan films.

PubMed

Ren, Lili; Yan, Xiaoxia; Zhou, Jiang; Tong, Jin; Su, Xingguang

2017-12-01

The active packaging films based on corn starch and chitosan were prepared through mixing the starch solution and the chitosan solution (1:1) by casting. The aim of this work was to characterize and analyze the effects of the chitosan concentrations (0, 21, 41, 61 and 81wt% of starch) on physicochemical, mechanical and water vapor barrier properties as well as morphological characteristics of the corn starch/chitosan (CS/CH) films. Starch molecules and chitosan could interact through hydrogen bonding as confirmed from the shift of the main peaks to higher wavenumbers in FTIR and the reduction of crystallinity in XRD. Results showed that the incorporation of chitosan resulted in an increase in film solubility, total color differences, tensile strength and elongation at break and a decrease in Young's modulus and water vapor permeability (WVP). Elongation at break of the CS/CH films increased with increasing of chitosan concentration, and reached a maximum at 41 wt%, then declined at higher chitosan concentration. The WVP of CS/CH films increased with an increase of chitosan concentration and the same tendency observed for the moisture content. The results suggest that this biodegradable CS/CH films could potentially be used as active packaging films for food and pharmaceutical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of Chitin and Chitosan Molecular Structure in Aqueous Solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franca, Eduardo D.; Lins, Roberto D.; Freitas, Luiz C.

Molecular dynamics simulations have been used to characterize the structure of chitin and chitosan fibers in aqueous solutions. Chitin fibers, whether isolated or in the form of a β-chitin nanoparticle, adopt the so-called 2-fold helix with Φ and φ values similar to its crystalline state. In solution, the intramolecular hydrogen bond HO3(n)•••O5(n+1) responsible for the 2-fold helical motif is stabilized by hydrogen bonds with water molecules in a well-defined orientation. On the other hand, chitosan can adopt five distinct helical motifs and its conformational equilibrium is highly dependent on pH. The hydrogen bond pattern and solvation around the O3 atommore » of insoluble chitosan (basic pH) are nearly identical to these quantities in chitin. Our findings suggest that the solubility and conformation of these polysaccharides are related to the stability of the intrachain HO3(n)•••O5(n+1) hydrogen bond, which is affect by the water exchange around the O3-HO3 hydroxyl group.« less

Coupling Deep Transcriptome Analysis with Untargeted Metabolic Profiling in Ophiorrhiza pumila to Further the Understanding of the Biosynthesis of the Anti-Cancer Alkaloid Camptothecin and Anthraquinones

PubMed Central

Yamazaki, Mami; Mochida, Keiichi; Asano, Takashi; Nakabayashi, Ryo; Chiba, Motoaki; Udomson, Nirin; Yamazaki, Yasuyo; Goodenowe, Dayan B.; Sankawa, Ushio; Yoshida, Takuhiro; Toyoda, Atsushi; Totoki, Yasushi; Sakaki, Yoshiyuki; Góngora-Castillo, Elsa; Buell, C. Robin; Sakurai, Tetsuya; Saito, Kazuki

2013-01-01

The Rubiaceae species, Ophiorrhiza pumila, accumulates camptothecin, an anti-cancer alkaloid with a potent DNA topoisomerase I inhibitory activity, as well as anthraquinones that are derived from the combination of the isochorismate and hemiterpenoid pathways. The biosynthesis of these secondary products is active in O. pumila hairy roots yet very low in cell suspension culture. Deep transcriptome analysis was conducted in O. pumila hairy roots and cell suspension cultures using the Illumina platform, yielding a total of 2 Gb of sequence for each sample. We generated a hybrid transcriptome assembly of O. pumila using the Illumina-derived short read sequences and conventional Sanger-derived expressed sequence tag clones derived from a full-length cDNA library constructed using RNA from hairy roots. Among 35,608 non-redundant unigenes, 3,649 were preferentially expressed in hairy roots compared with cell suspension culture. Candidate genes involved in the biosynthetic pathway for the monoterpenoid indole alkaloid camptothecin were identified; specifically, genes involved in post-strictosamide biosynthetic events and genes involved in the biosynthesis of anthraquinones and chlorogenic acid. Untargeted metabolomic analysis by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) indicated that most of the proposed intermediates in the camptothecin biosynthetic pathway accumulated in hairy roots in a preferential manner compared with cell suspension culture. In addition, a number of anthraquinones and chlorogenic acid preferentially accumulated in hairy roots compared with cell suspension culture. These results suggest that deep transcriptome and metabolome data sets can facilitate the identification of genes and intermediates involved in the biosynthesis of secondary products including camptothecin in O. pumila. PMID:23503598

Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation

PubMed Central

Thornton, Janet L.; Westfield, Gerwin H.; Takahashi, Yoh-hei; Cook, Malcolm; Gao, Xin; Woodfin, Ashley R.; Lee, Jung-Shin; Morgan, Marc A.; Jackson, Jessica; Smith, Edwin R.; Couture, Jean-Francois; Skiniotis, Georgios; Shilatifard, Ali

2014-01-01

The stimulation of trimethylation of histone H3 Lys4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied, with multiple mechanisms having been proposed for this form of histone cross-talk. Cps35/Swd2 within COMPASS (complex of proteins associated with Set1) is considered to bridge these different processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation (H3K4me3) without interacting with Cps35/Swd2, and such cross-talk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we used biochemical, structural, in vivo, and chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) approaches to demonstrate that Cps40/Spp1 and the n-SET domain of Set1 are required for the stability of Set1 and not the cross-talk. Furthermore, the apparent wild-type levels of H3K4me3 in the 762-Set1 strain are due to the rogue methylase activity of this mutant, resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to the gene bodies and intergenic regions. We also performed detailed screens and identified yeast strains lacking H2Bub but containing intact H2Bub enzymes that have normal levels of H3K4me3, suggesting that monoubiquitination may not directly stimulate COMPASS but rather works in the context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the monoubiquitination machinery and Cps35/Swd2 function to focus COMPASS's H3K4me3 activity at promoter-proximal regions in a context-dependent manner. PMID:24402317

Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan nanoparticles for pain relief.

PubMed

Patel, Deepa; Naik, Sachin; Chuttani, Krishna; Mathur, Rashi; Mishra, Anil K; Misra, Ambikanandan

2013-09-01

The purpose of present investigation was to formulate and characterize the cyclobenzaprine HCl (CBZ)-loaded thiolated chitosan nanoparticles and assessment of in-vitro cell viability, trans-mucosal permeability on RPMI2650 cell monolayer, in-vivo pharmacokinetic and pharmacodynamic study of thiolated chitosan nanoparticles on Swiss albino mice after intranasal administration. A significant high permeation of drug was observed from thiolated chitosan nanoparticles with less toxicity on nasal epithelial cells. Brain uptake of the drug after (99m)Tc labeling was significantly enhanced after thiolation of chitosan. CBZ-loaded thiolated chitosan NPs significantly reverse the N-Methyl-.-Aspartate (NMDA)-induced hyperalgesia by intranasal administration than the CBZ solution. The studies of present investigation revealed that thiolation of chitosan significantly reduce trans-mucosal toxicity with enhanced trans-mucosal permeability via paracellular pathway and brain uptake of a hydrophilic drug (normally impermeable across blood brain barrier) and pain alleviation activity via intranasal route.

Chitosan coated carbon fiber microelectrode for selective in vivo detection of neurotransmitters in live zebrafish embryos

PubMed Central

Özel, Rıfat Emrah; Wallace, Kenneth N.; Andreescu, Silvana

2011-01-01

We report the development of a chitosan modified carbon fiber microelectrode for in vivo detection of serotonin. We find that chitosan has the ability to reject physiological levels of ascorbic acid interferences and facilitate selective and sensitive detection of in vivo levels of serotonin, a common catecholamine neurotransmitter. Presence of chitosan on the microelectrode surface was investigated using scanning electron microscopy (SEM) and cyclic voltammetry (CV). The electrode was characterized using differential pulse voltammetry (DPV). A detection limit of 1.6 nM serotonin with a sensitivity of 5.12 nA/µM, a linear range from 2 to 100 nM and a reproducibility of 6.5 % for n=6 electrodes were obtained. Chitosan modified microelectrodes selectively measure serotonin in presence of physiological levels of ascorbic acid. In vivo measurements were performed to measure concentration of serotonin in the live embryonic zebrafish intestine. The sensor quantifies in vivo intestinal levels of serotonin while successfully rejecting ascorbic acid interferences. We demonstrate that chitosan can be used as an effective coating to reject ascorbic acid interferences at carbon fiber microelectrodes, as an alternative to Nafion, and that chitosan modified microelectrodes are reliable tools for in vivo monitoring of changes in neurotransmitter levels. PMID:21601035

Curcumin-containing chitosan nanoparticles as a potential mucoadhesive delivery system to the colon.

PubMed

Chuah, Lay Hong; Billa, Nashiru; Roberts, Clive J; Burley, Jonathan C; Manickam, Sivakumar

2013-01-01

In the present study, we investigate the mucoadhesive characteristics and release of the anticancer agent curcumin, contained in chitosan nanoparticles (CS-NPs). Such a system has potential therapeutic benefits in the treatment of colon cancer through prolonged retention and delivery. The CS-NPs were ionically gelled with tripolyphosphate (TPP) and registered an isoelectric pH of 6.2 (z-average diameter of 214 nm ± 1.0 nm). pH variations around the isoelectric point caused a reduction in CS-NPs electrical charge which correspondingly increased the z-average due to agglomeration. Curcumin release from CS-NPs was slowest at chitosan to TPP weight ratio of 3:1, with a significant retention (36%) at the end of 6 h. Adsorption isotherms of mucin on CS-NPs fitted both the Freundlich and Langmuir models, suggesting a monolayer-limited adsorption on heterogeneous sites with varied affinities. Encapsulated curcumin exerted an influence on the adsorption of mucin due to H-bonding as well as π-π interactions between the phenolic moieties of curcumin and mucin.

Transfection efficiency of chitosan and thiolated chitosan in retinal pigment epithelium cells: A comparative study

PubMed Central

Oliveira, Ana V.; Silva, Andreia P.; Bitoque, Diogo B.; Silva, Gabriela A.; Rosa da Costa, Ana M.

2013-01-01

OBJECTIVE: Gene therapy relies on efficient vector for a therapeutic effect. Efficient non-viral vectors are sought as an alternative to viral vectors. Chitosan, a cationic polymer, has been studied for its gene delivery potential. In this work, disulfide bond containing groups were covalently added to chitosan to improve the transfection efficiency. These bonds can be cleaved by cytoplasmic glutathione, thus, releasing the DNA load more efficiently. MATERIALS AND METHODS: Chitosan and thiolated chitosan nanoparticles (NPs) were prepared in order to obtain a NH3+:PO4− ratio of 5:1 and characterized for plasmid DNA complexation and release efficiency. Cytotoxicity and gene delivery studies were carried out on retinal pigment epithelial cells. RESULTS: In this work, we show that chitosan was effectively modified to incorporate a disulfide bond. The transfection efficiency of chitosan and thiolated chitosan varied according to the cell line used, however, thiolation did not seem to significantly improve transfection efficiency. CONCLUSION: The apparent lack of improvement in transfection efficiency of the thiolated chitosan NPs is most likely due to its size increase and charge inversion relatively to chitosan. Therefore, for retinal cells, thiolated chitosan does not seem to constitute an efficient strategy for gene delivery. PMID:23833516

Photochemical tissue bonding with chitosan adhesive films

PubMed Central

2010-01-01

Background Photochemical tissue bonding (PTB) is a promising sutureless technique for tissue repair. PTB is often achieved by applying a solution of rose bengal (RB) between two tissue edges, which are irradiated by a green laser to crosslink collagen fibers with minimal heat production. In this study, RB has been incorporated in chitosan films to create a novel tissue adhesive that is laser-activated. Methods Adhesive films, based on chitosan and containing ~0.1 wt% RB were manufactured and bonded to calf intestine by a solid state laser (λ = 532 nm, Fluence~110 J/cm2, spot size~0.5 cm). A single-column tensiometer, interfaced with a personal computer, tested the bonding strength. K-type thermocouples recorded the temperature (T) at the adhesive-tissue interface during laser irradiation. Human fibroblasts were also seeded on the adhesive and cultured for 48 hours to assess cell growth. Results The RB-chitosan adhesive bonded firmly to the intestine with adhesion strength of 15 ± 2 kPa, (n = 31). The adhesion strength dropped to 0.5 ± 0.1 (n = 8) kPa when the laser was not applied to the adhesive. The average temperature of the adhesive increased from 26°C to 32°C during laser exposure. Fibroblasts grew confluent on the adhesive without morphological changes. Conclusion A new biocompatible chitosan adhesive has been developed that bonds photochemically to tissue with minimal temperature increase. PMID:20825632

Improvement in hemocompatibility of chitosan/soy protein composite membranes by heparinization.

PubMed

Wang, Xiaomei; Shi, Na; Chen, Yan; Li, Chen; Du, Xinshen; Jin, Weihua; Chen, Yun; Chang, Peter R

2012-01-01

To improve the hemocompatibility of chitosan/soy protein isolate composite membranes by heparinization. Chitosan/soy protein isolate membranes (ChS-n, n=0, 10 and 30, corresponding to the soy protein isolate content in the membranes) and heparinized ChS-n membranes (HChS-n) were prepared by blending in dilute HAc/NaAc solution. The hemocompatibility of ChS-n and HChS-n membranes were comparatively evaluated by measuring surface heparin density, blood platelet adhesion, plasma recalcification time (PRT), thrombus formation and hemolysis assay. The surface heparin density analysis showed that heparinized chitosan/SPI soy protein isolate membranes have been successfully prepared by blending. The density of heparin on the surface of HChS-n membranes was in the range of 0.67-1.29 μg/cm2. The results of platelet adhesion measurement showed that the platelet adhesion numbers of HChS-n membranes were lower than those of the corresponding ChS-n membranes. The PRT of the HChS-0, HChS-10 and HChS-30 membranes were around 292, 306 and 295 s, respectively, which were longer than the corresponding ChS-0 (152 s), ChS-10 (204 s) and ChS-30 (273 s) membranes. The hemolysis rate of HChS-n membranes was lower than 1%. The hemocompatibility of ChS membranes could be improved by blending with heparin. Compared with ChS membranes, HChS membranes showed lower platelet adhesion, longer PRT, higher BCI, significant thromboresistivity and a lower hemolysis rate due to the heparinization. This widens the application of chitosan and soy protein-based biomaterials that may come in contact with blood.

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

PubMed Central

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-01-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate. PMID:27869192

Folate-conjugated chitosan-polylactide nanoparticles for enhanced intracellular uptake of anticancer drug

NASA Astrophysics Data System (ADS)

Huang, Shengtang; Wan, Ying; Wang, Zheng; Wu, Jiliang

2013-12-01

Chitosan was conjugated with folic acid (FA) and the resulting chitosan derivatives with a FA-substitution degree of around 6 % was used to synthesize FA-conjugated chitosan-polylactide (FA-CH-PLA) copolymers to build a drug carrier with active targeting characteristics for the anticancer drug of paclitaxel (PTX). Selected FA-CH-PLAs with various polylactide percentages of about 40 wt% or lower were employed to fabricate nanoparticles using sodium tripolyphosphate as a crosslinker, and different types of nanoparticles were endued with similar average particle-sizes located in a range between 100 and 200 nm. Certain types of PTX-loaded FA-CH-PLA nanoparticles having encapsulation efficiency of around 90 % and initial load of about 12 % were able to release PTX in a controlled manner with significant regulation by polylactide content in FA-CH-PLAs. Targeting characteristic of achieved nanoparticles was confirmed using FA-receptor-expressed MCF-7 breast cancer cells. The uptake of PTX revealed that optimized FA-CH-PLA nanoparticles with an equivalent PTX-dose of around 1 μg/mL could have more than sixfold increasing abilities to facilitate intracellular paclitaxel accumulation in MCF-7 cells after 24 h treatment as compared to free PTX. At a relatively safe equivalent PTX-dose for normal MCF-10A mammary epithelial cells, the obtained results from Hoechst 33342 staining indicated that optimized PTX-loaded FA-CH-PLA nanoparticles had more than threefold increasing abilities to induce MCF-7 cell apoptosis in comparison to free PTX.

Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer

PubMed Central

Lee, Hung-Yen; Mohammed, Kamal A; Kaye, Fredric; Sharma, Parvesh; Moudgil, Brij M; Clapp, William L; Nasreen, Najmunnisa

2013-01-01

MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1–LNP) and let-7a miR encapsulated LNP (miR–LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR–ephrin-A1–LNP) was determined on MPM and NSCLC tumor growth in vitro. miR–ephrin-A1–LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR–ephrin-A1–LNP treatment. Furthermore, the miR–ephrin-A1–LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered mi

Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent.

PubMed

Ilk, Sedef; Saglam, Necdet; Özgen, Mustafa

2017-08-01

Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 ± 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture.

Development of Poly(lactic acid)/Chitosan Fibers Loaded with Essential Oil for Antimicrobial Applications

PubMed Central

Liu, Yaowen; Wang, Shuyao; Zhang, Rong; Lan, Wenting; Qin, Wen

2017-01-01

Cinnamon essential oil (CEO) was successfully encapsulated into chitosan (CS) nanoparticles at different loading amounts (1%, 1.5%, 2%, and 2.5% v/v) using oil-in-water (o/w) emulsion and ionic-gelation methods. In order to form active packaging, poly(lactic acid) (PLA) was used to fabricate PLA/CS-CEO composite fibers using a simple electrospinning method. The shape, size, zeta potential, and encapsulation efficacy of the CS-CEO nanoparticles were investigated. The composition, morphology, and release behavior of the composite fibers were investigated. PLA/CS-CEO-1.5 showed good stability and favorable sustained release of CEO, resulting in improved antimicrobial activity compared to the other blends. The PLA/CS-CEO fibers showed high long-term inactivation rates against Escherichia coli and Staphylococcus aureus due to the sustained release of CEO, indicating that the developed PLA/CS-CEO fibers have great potential for active food packaging applications. PMID:28737719

The dispersion of fine chitosan particles by beads-milling

NASA Astrophysics Data System (ADS)

Rochima, Emma; Utami, Safira; Hamdani, Herman; Azhary, Sundoro Yoga; Praseptiangga, Danar; Joni, I. Made; Panatarani, Camellia

2018-02-01

This research aimed to produce fine chitosan particles from a crab shell waste by beads-milling method by two different concentration of PEG as dispersing agent (150 and 300 wt. %). The characterization was performed to obtain the size and size distribution, the characteristics of functional groups and the degree of deacetylation. The results showed that the chitosan fine particles was obtained with a milling time 120 minutes with the best concentration of PEG 400 150 wt. %. The average particle size of the as-prepared suspension is 584 nm after addition of acetic acid solution (1%, v/v). Beads milling process did not change the glucosamine and N-acetylglucosamine content on chitosan structure which is indicated by degree of deacetylation higher than 70%. It was concluded that beads milling process can be applied to prepare chitosan fineparticles by proper adjustment in the milling time, pH and dosage of dispersing agent.

In Vivo Assessment of Chitosan/ β-Glycerophosphate as a New Liquid Embolic Agent

PubMed Central

Wang, Y.; Xu, N.; Luo, Q.; Li, Y.; Sun, L.; Wang, H.; Xu, K.; Wang, B.; Zhen, Y.

2011-01-01

Summary We sought to assess the feasibility of using thermosensitive chitosan/β-glycerophosphate for embolotherapy. The renal arteries in nine rabbits were embolized with chitosan/β-glycerophosphate. The animals were studied angiographically and sacrificed at one week (n = 3), four weeks (n = 3), and eight weeks (n = 3) after embolotherapy. Histology was obtained at these three time points. Delivery of chitosan/β-glycerophosphate was successful in all cases. Complete occlusion was achieved in all cases. No recanalization was observed in the follow-up angiograms. No untoward inflammatory reactions were observed in the target renal arteries and infarcted kidneys during the histological examinations. Our preliminary feasibility evaluation in rabbit renal arteries indicates that C/GP is a satisfactory embolization agent. PMID:21561564

Two-Ply Composite Membranes with Separation Layers from Chitosan and Sulfoethylcellulose on a Microporous Support Based on Poly(diphenylsulfone-N-phenylphthalimide).

PubMed

Kononova, Svetlana V; Kruchinina, Elena V; Petrova, Valentina A; Baklagina, Yulia G; Romashkova, Kira A; Orekhov, Anton S; Klechkovskaya, Vera V; Skorik, Yury A

2017-12-14

Two-ply composite membranes with separation layers from chitosan and sulfoethylcellulose were developed on a microporous support based on poly(diphenylsulfone- N -phenylphthalimide) and investigated by use of X-ray diffraction and scanning electron microscopy methods. The pervaporation properties of the membranes were studied for the separation of aqueous alcohol (ethanol, propan-2-ol) mixtures of different compositions. When the mixtures to be separated consist of less than 15 wt % water in propan-2-ol, the membranes composed of polyelectrolytes with the same molar fraction of ionogenic groups (-NH₃⁺ for chitosan and -SO₃ - for sulfoethylcellulose) show high permselectivity (the water content in the permeate was 100%). Factors affecting the structure of a non-porous layer of the polyelectrolyte complex formed on the substrate surface and the contribution of that complex to changes in the transport properties of membranes are discussed. The results indicate significant prospects for the use of chitosan and sulfoethylcellulose for the formation of highly selective pervaporation membranes.

Ni0 encapsulated in N-doped carbon nanotubes for catalytic reduction of highly toxic hexavalent chromium

NASA Astrophysics Data System (ADS)

Yao, Yunjin; Zhang, Jie; Chen, Hao; Yu, Maojing; Gao, Mengxue; Hu, Yi; Wang, Shaobin

2018-05-01

N-doped carbon nanotubes encapsulating Ni0 nanoparticles (Ni@N-C) were fabricated via thermal reduction of dicyandiamide and NiCl2·6H2O, and used to remove CrVI in polluted water. The resultant products present an excellent catalytic activity for CrVI reduction using formic acid under relatively mild conditions. The CrVI reduction efficiency of Ni@N-C was significantly affected by the preparation conditions including the mass of nickel salt and synthesis temperatures. The impacts of several reaction parameters, such as initial concentrations of CrVI and formic acid, solution pH and temperatures, as well as inorganic anions in solution on CrVI reduction efficiency were also evaluated in view of scalable industrial applications. Owing to the synergistic effects amongst tubes-coated Ni0, doped nitrogen, oxygen containing groups, and the configuration of carbon nanotubes, Ni@N-C catalysts exhibit excellent catalytic activity and recyclable capability for CrVI reduction. Carbon shell can efficiently protect inner Ni0 core and N species from corrosion and subsequent leaching, while Ni0 endows the Ni@N-C catalysts with ferromagnetism, so that the composites can be easily separated via a permanent magnet. This study opens up an avenue for design of N-doped carbon nanotubes encapsulating Ni0 nanoparticles with high CrVI removal efficiency and magnetic recyclability as low-cost catalysts for industrial applications.

Blood contact properties of ascorbyl chitosan.

PubMed

Yalinca, Z; Yilmaz, E; Taneri, B; Bullici, F; Tuzmen, S

2013-01-01

Ascorbyl chitosan was synthesized by heating chitosan with ascorbic acid in isopropanol. The products were characterized by FTIR and C-13 NMR spectroscopies, SEM, and elemental analysis. Blood contact properties of ascorbyl chitosans were evaluated. The ascorbyl chitosans demonstrated to have increased lipid-lowering activity in comparison to chitosan alone upon contact with human blood serum in in vitro conditions. Furthermore, the total cholesterol/HDL ratio was improved towards the desirable ideal values after three hours contact with ascorbyl chitosan samples. The lipid-lowering activity increased with ascorbyl substitution. The inherent nonspecific adsorption capability of chitosan due to its chelating power with several different functional groups was exhibited by ascorbyl chitosans as well. This behavior was exemplified in a simultaneous decrease in the total iron values of the volunteers together with lower lipid levels. Furthermore, ascorbyl chitosans were observed to have less hemocompatibility but increased anticoagulant activity when compared to chitosan alone. Additional in vivo studies are necessary to support these results and to investigate further the advantages and disadvantages of these materials to prove their safety prior to clinical applications.

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.

PubMed

Salade, Laurent; Wauthoz, Nathalie; Deleu, Magali; Vermeersch, Marjorie; De Vriese, Carine; Amighi, Karim; Goole, Jonathan

2017-01-01

The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose-brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N -(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose-brain delivery of ghrelin.

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia

PubMed Central

Salade, Laurent; Wauthoz, Nathalie; Deleu, Magali; Vermeersch, Marjorie; De Vriese, Carine; Amighi, Karim; Goole, Jonathan

2017-01-01

The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose–brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose–brain delivery of ghrelin. PMID:29238190

Growth and dissolution of an encapsulated contrast microbubble: effects of encapsulation permeability

PubMed Central

Sarkar, Kausik; Katiyar, Amit; Jain, Pankaj

2009-01-01

Gas diffusion from an encapsulated microbubble is modeled using an explicit linear relation for gas permeation through the encapsulation. Both the cases of single gas (air) and multiple gases (perfluorocarbon inside the bubble and air dissolved in surrounding liquid) are considered. An analytical expression for the dissolution time for an encapsulated air bubble is obtained; it showed that for small permeability the dissolution time increases linearly with decreasing permeability. A perfluorocarbon-filled contrast microbubble such as Definity was predicted to experience a transient growth due to air infusion before it dissolves in conformity with previous experimental findings. The growth phase occurs only for bubbles with a critical value of initial partial mole fraction of perfluorocarbon relative to air. With empirically obtained property values, the dissolution time of a 2.5 micron diameter (same as that of Definity) lipid coated octafluoropropane bubble with surface tension 25 mN/m predicts a lifetime of 42 minutes in an air saturated medium. The properties such as shell permeability, surface tension, relative mole fraction of octafluoropropane are varied to investigate their effects on the time scales of bubble growth and dissolution including their asymptotic scalings where appropriate. The dissolution dynamics scales with permeability, in that when the time is nondimensioanlized with permeability, curves for different permeabilities collapse on a single curve. Investigation of bubbles filled with other gases (non-octafluoropropane perfluorocarbon and sulfur hexafluoride) indicates longer dissolution time due to lower solubility and lower diffusivity for larger gas molecules. For such micron size encapsulated bubbles, lifetime of hours is possible only at extremely low surface tension (<1mN/m) or at extreme oversaturation. PMID:19616160

Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

PubMed Central

Li, Xiaosong; Min, Min; Du, Nan; Gu, Ying; Hode, Tomas; Naylor, Mark; Chen, Dianjun; Nordquist, Robert E.; Chen, Wei R.

2013-01-01

With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development. PMID:23533454

Antimicrobial activity of chitosan coatings and films against Listeria monocytogenes on black radish.

PubMed

Jovanović, Gordana D; Klaus, Anita S; Nikšić, Miomir P

2016-01-01

The antibacterial activity of chitosan coatings prepared with acetic or lactic acid, as well as of composite chitosan-gelatin films prepared with essential oils, was evaluated in fresh shredded black radish samples inoculated with Listeria monocytogenes ATCC 19115 and L. monocytogenes ATCC 19112 during seven days of storage at 4°C. The chitosan coating prepared with acetic acid showed the most effective antibacterial activity. All tested formulations of chitosan films exhibited strong antimicrobial activity on the growth of L. monocytogenes on black radish, although a higher inhibition of pathogens was achieved at higher concentrations of chitosan. The antimicrobial effect of chitosan films was even more pronounced with the addition of essential oils. Chitosan-gelatin films with thyme essential oils showed the most effective antimicrobial activity. A reduction of 2.4log10CFU/g for L. monocytogenes ATCC 19115 and 2.1log10CFU/g for L. monocytogenes ATCC 19112 was achieved in the presence of 1% chitosan film containing 0.2% of thyme essential oil after 24h of storage. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Synthesis of a novel amphiphilic quaternized chitosan and its distribution in rats.

PubMed

Liu, Xiaofei; Zeng, Anrong; Li, Lin; Yang, Fan; Wang, Qi; Sun, Zhong; Shen, Jun

2011-01-01

A novel amphiphilic chitosan derivative, N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl]chitosan chloride (N-CQCs), was prepared with a degree of substitution (DS) of 15.58%. N-CQCs was positively charged and its zeta potential was +28.4 mV. The introduction of a long carbon chain with a quaternary ammonium salt group into the chitosan backbone enabled N-CQCs to be lipotropic and hydrophilic. According to the hypothesis of the hypocholesterolemic effect of N-CQCs, its organ distribution in rats was investigated 48 h after administration via gavage using fluorescein isothiocyanate labeling. N-CQCs showed lower cytotoxicity. The plasma half-life of N-CQCs in rats was 48 h and the plasma AUC0-48 h (P) was 371.70 μg/ml per h, suggesting that N-CQCs remained in body for a long time. The results also showed that the accumulation in adipose tissue and gastrointestinal tract was higher than in thymus, kidney, liver and spleen at 48 h after administration. It could be presumed that N-CQCs play an important part in the metabolic process of body fat. Adipose tissue and gastrointestinal tract were the probable interaction sites of N-CQCs and body fat.

Dense chitosan surgical membranes produced by a coincident compression-dehydration process

PubMed Central

Dooley, Thomas P.; Ellis, April L.; Belousova, Maria; Petersen, Don; DeCarlo, Arthur A.

2012-01-01

High density chitosan membranes were produced via a novel manufacturing process for use as implantable resorbable surgical membranes. The innovative method utilizes the following three sequential steps: (1) casting an acidic chitosan solution within a silicon mold, followed by freezing; (2) neutralizing the frozen acidic chitosan solution in alkaline solution to facilitate polymerization; and (3) applying coincident compression-dehydration under a vacuum. Resulting membranes of 0.2 – 0.5 mm thickness have densities as high as 1.6 g/cm3. Inclusion of glycerol prior to the compression-dehydration step provides additional physical and clinical handling benefits. The biomaterials exhibit tensile strength with a maximum load as high as 10.9 N at ~ 2.5 mm width and clinically-relevant resistance to suture pull-out with a maximum load as high as 2.2 N. These physical properties were superior to those of a commercial reconstituted collagen membrane. The dense chitosan membranes have excellent clinical handling characteristics, such as pliability and “memory” when wet. They are semi-permeable to small molecules, biodegradable in vitro in lysozyme solution, and the rates of degradation are inversely correlated to the degree of deacetylation. Furthermore, the dense chitosan membranes are biocompatible and resorbable in vivo as demonstrated in a rat oral wound healing model. The unique combination of physical, in vitro, in vivo, and clinical handling properties demonstrate the high utility of dense chitosan membranes produced by this new method. The materials may be useful as surgical barrier membranes, scaffolds for tissue engineering, wound dressings, and as delivery devices for active ingredients. PMID:23565872

Compound Specific Extraction of Camptothecin from Nothapodytes nimmoniana and Piperine from Piper nigrum Using Accelerated Solvent Extractor

PubMed Central

Upadhya, Vinayak; Pai, Sandeep R.; Sharma, Ajay K.; Hegde, Harsha V.; Kholkute, Sanjiva D.; Joshi, Rajesh K.

2014-01-01

Effects of varying temperatures with constant pressure of solvent on extraction efficiency of two chemically different alkaloids were studied. Camptothecin (CPT) from stem of Nothapodytes nimmoniana (Grah.) Mabb. and piperine from the fruits of Piper nigrum L. were extracted using Accelerated Solvent Extractor (ASE). Three cycles of extraction for a particular sample cell at a given temperature assured complete extraction. CPT and piperine were determined and quantified by using a simple and efficient UFLC-PDA (245 and 343 nm) method. Temperature increased efficiency of extraction to yield higher amount of CPT, whereas temperature had diminutive effect on yield of piperine. Maximum yield for CPT was achieved at 80°C and for piperine at 40°C. Thus, the study determines compound specific extraction of CPT from N. nimmoniana and piperine from P. nigrum using ASE method. The present study indicates the use of this method for simple, fast, and accurate extraction of the compound of interest. PMID:24527258

Functionalized and graft copolymers of chitosan and its pharmaceutical applications.

PubMed

Bhavsar, Chintan; Momin, Munira; Gharat, Sankalp; Omri, Abdelwahab

2017-10-01

Chitosan is the second most abundant natural polysaccharide. It belongs a family of polycationic polymers comprised of repetitive units of glucosamine and N-acetylglucosamine. Its biodegradability, nontoxicity, non-immunogenicity and biocompatibility along with properties like mucoadhesion, fungistatic and bacteriogenic have made chitosan an appreciated polymer with numerous applications in the pharmaceutical, comestics and food industry. However, the limited solubility of chitosan at alkaline and neutral pH limits its widespread commercial use. This can be circumvented by fabrication of chitosan by graft copolymerization with acyl, alkyl, monomeric and polymeric moieties. Areas covered: Modifications like quarterization, thiolation, acylation and grafting result in copolymers with higher mucoadhesion strength, increased hydrophobic interactions (advantageous in hydrophobic drug entrapment), and increased solubility in alkaline pH, the ability for adsorption of metal ions, protein and peptide delivery and nutrient delivery. Insights on methods of polymerization, including atomic transfer radical polymerization and click chemistry are discussed. Applications of such modified chitosan copolymers in medical and surgical, and drug delivery, including nasal, oral and buccal delivery have also been covered. Expert opinion: Despite a number of successful investigations, commercialization of chitosan copolymers still remains a challenge. Further advancements in polymerization techniques may address the unmet needs of the healthcare industry.

Synthesis and anticoagulant activity of the quaternary ammonium chitosan sulfates.

PubMed

Fan, Lihong; Wu, Penghui; Zhang, Jinrong; Gao, Song; Wang, Libo; Li, Mingjia; Sha, Mingming; Xie, Weiguo; Nie, Min

2012-01-01

Quaternary ammonium chitosan sulfates with diverse degrees of substitution (DS) ascribed to sulfate groups between 0.52 and 1.55 were synthesized by reacting quaternary ammonium chitosan with an uncommon sulfating agent (N(SO(3)Na)(3)) that was prepared from sodium bisulfite (NaHSO(3)) through reaction with sodium nitrite (NaNO(2)) in the aqueous system homogeneous. The structures of the derivatives were characterized by FTIR, (1)H NMR and (13)C NMR. The factors affecting DS of quaternary ammonium chitosan sulfates which included the molar ratio of NaNO(2) to quaternary ammonium chitosan, sulfated temperature, sulfated time and pH of sulfated reaction solution were investigated in detail. Its anticoagulation activity in vitro was determined by an activated partial thromboplastin time (APTT) assay, a thrombin time (TT) assay and a prothrombin time (PT) assay. Results of anticoagulation assays showed quaternary ammonium chitosan sulfates significantly prolonged APTT and TT, but not PT, and demonstrated that the introduction of sulfate groups into the quaternary ammonium chitosan structure improved its anticoagulant activity obviously. The study showed its anticoagulant properties strongly depended on its DS, concentration and molecular weight. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Fusion of a Novel Genetically Engineered Chitosan Affinity Protein and Green Fluorescent Protein for Specific Detection of Chitosan In Vitro and In Situ

PubMed Central

Nampally, Malathi; Moerschbacher, Bruno Maria

2012-01-01

Chitin is the second most abundant polysaccharide, present, e.g., in insect and arthropod exoskeletons and fungal cell walls. In some species or under specific conditions, chitin appears to be enzymatically de-N-acetylated to chitosan—e.g., when pathogenic fungi invade their host tissues. Here, the deacetylation of chitin is assumed to represent a pathogenicity mechanism protecting the fungus from the host's chitin-driven immune response. While highly specific chitin binding lectins are well known and easily available, this is not the case for chitosan-specific probes. This is partly due to the poor antigenicity of chitosan so that producing high-affinity, specific antibodies is difficult. Also, lectins with specificity to chitosan have been described but are not commercially available, and our attempts to reproduce the findings were not successful. We have, therefore, generated a fusion protein between a chitosanase inactivated by site-directed mutagenesis, the green fluorescent protein (GFP), and StrepII, as well as His6 tags for purification and detection. The recombinant chitosan affinity protein (CAP) expressed in Escherichia coli was shown to specifically bind to chitosan, but not to chitin, and the affinity increased with decreasing degree of acetylation. In vitro, CAP detection was possible either based on GFP fluorescence or using Strep-Tactin conjugates or anti-His5 antibodies. CAP fluorescence microscopy revealed binding to the chitosan exposing endophytic infection structures of the wheat stem rust fungus, but not the chitin exposing ectophytic infection structures, verifying its suitability for in situ chitosan staining. PMID:22367086

Radiation-induced graft copolymerization of poly(ethylene glycol) monomethacrylate onto deoxycholate-chitosan nanoparticles as a drug carrier

NASA Astrophysics Data System (ADS)

Pasanphan, Wanvimol; Rattanawongwiboon, Thitirat; Rimdusit, Pakjira; Piroonpan, Thananchai

2014-01-01

Poly(ethylene glycol) monomethacrylate-grafted-deoxycholate chitosan nanoparticles (PEGMA-g-DCCSNPs) were successfully prepared by radiation-induced graft copolymerization. The hydrophilic poly(ethylene glycol) monomethacrylate was grafted onto deoxycholate-chitosan in an aqueous system. The radiation-absorbed dose is an important parameter on degree of grafting, shell thickness and particle size of PEGMA-g-DCCSNPs. Owing to their amphiphilic architecture, PEGMA-g-DCCSNPs self-assembled into spherical core-shell nanoparticles in aqueous media. The particle size of PEGMA-g-DCCSNPs measured by TEM varied in the range of 70-130 nm depending on the degree of grafting as well as the irradiation dose. Berberine (BBR) as a model drug was encapsulated into the PEGMA-g-DCCSNPs. Drug release study revealed that the BBR drug was slowly released from PEGMA-g-DCCSNPs at a mostly constant rate of 10-20% in PBS buffer (pH 7.4) at 37 °C over a period of 23 days.

Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres.

PubMed

Song, Kedong; Liu, Yingchao; Macedo, Hugo M; Jiang, Lili; Li, Chao; Mei, Guanyu; Liu, Tianqing

2013-04-01

Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27-55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99±2.51) %, (89.66±0.66) % and (73.77±3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24±0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44±1.81)×10(-2) mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a promising technique

Optimization of chitosan nanoparticles for colon tumors using experimental design methodology.

PubMed

Jain, Anekant; Jain, Sanjay K

2016-12-01

Purpose Colon-specific drug delivery systems (CDDS) can improve the bio-availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer.

Pseudo-thermosetting chitosan hydrogels for biomedical application.

PubMed

Berger, J; Reist, M; Chenite, A; Felt-Baeyens, O; Mayer, J M; Gurny, R

2005-01-20

To prepare transparent chitosan/beta-glycerophosphate (betaGP) pseudo-thermosetting hydrogels, the deacetylation degree (DD) of chitosan has been modified by reacetylation with acetic anhydride. Two methods (I and II) of reacetylation have been compared and have shown that the use of previously filtered chitosan, dilution of acetic anhydride and reduction of temperature in method II improves efficiency and reproducibility. Chitosans with DD ranging from 35.0 to 83.2% have been prepared according to method II under homogeneous and non-homogeneous reacetylation conditions and the turbidity of chitosan/betaGP hydrogels containing homogeneously or non-homogeneously reacetylated chitosan has been investigated. Turbidity is shown to be modulated by the DD of chitosan and by the homogeneity of the medium during reacetylation, which influences the distribution mode of the chitosan monomers. The preparation of transparent chitosan/betaGP hydrogels requires a homogeneously reacetylated chitosan with a DD between 35 and 50%.

Pseudo-thermosetting chitosan hydrogels for biomedical application.

PubMed

Berger, J; Reist, M; Chenite, A; Felt-Baeyens, O; Mayer, J M; Gurny, R

2005-01-06

To prepare transparent chitosan/beta-glycerophosphate (betaGP) pseudo-thermosetting hydrogels, the deacetylation degree (DD) of chitosan has been modified by reacetylation with acetic anhydride. Two methods (I and II) of reacetylation have been compared and have shown that the use of previously filtered chitosan, dilution of acetic anhydride and reduction of temperature in method II improves efficiency and reproducibility. Chitosans with DD ranging from 35.0 to 83.2% have been prepared according to method II under homogeneous and non-homogeneous reacetylation conditions and the turbidity of chitosan/betaGP hydrogels containing homogeneously or non-homogeneously reacetylated chitosan has been investigated. Turbidity is shown to be modulated by the DD of chitosan and by the homogeneity of the medium during reacetylation, which influences the distribution mode of the chitosan monomers. The preparation of transparent chitosan/betaGP hydrogels requires a homogeneously reacetylated chitosan with a DD between 35 and 50%.

Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects

PubMed Central

Zhou, Ding; Qi, Chao; Chen, Yi-Xuan; Zhu, Ying-Jie; Sun, Tuan-Wei; Chen, Feng; Zhang, Chang-Qing

2017-01-01

Hydroxyapatite (HAP; Ca10(PO4)6(OH)2) and whitlockite (WH; Ca18Mg2(HPO4)2(PO4)12) are widely utilized in bone repair because they are the main components of hard tissues such as bones and teeth. In this paper, we synthesized HAP and WH hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through microwave-assisted hydrothermal method. Then, we prepared HAP/chitosan and WH/chitosan composite membranes to evaluate their biocompatibility in vitro and prepared porous HAP/chitosan and WH/chitosan scaffolds by freeze drying to compare their effects on bone regeneration in calvarial defects in a rat model. The experimental results indicated that the WH/chitosan composite membrane had a better biocompatibility, enhancing proliferation and osteogenic differentiation ability of human mesenchymal stem cells than HAP/chitosan. Moreover, the porous WH/chitosan scaffold can significantly promote bone regeneration in calvarial defects, and thus it is more promising for applications in tissue engineering such as calvarial repair compared to porous HAP/chitosan scaffold. PMID:28435251

Investigation of the effects of local glutathione and chitosan administration on incisional oral mucosal wound healing in rabbits.

PubMed

Kılıç, Ciğdem; Güleç Peker, Emine Gülçeri; Acartürk, Füsun; Kılıçaslan, Seda M Sarı; Çoşkun Cevher, Şule

2013-12-01

The aim of the present study was to investigate the effects of local glutathione (GSH) and chitosan applications on the oxidant events and histological changes that occur, during healing processes in rabbits with incisional intraoral mucosal wounds. For this purpose, discs containing glutathione and chitosan (1:1) were prepared and their physicochemical characteristics were evaluated. New Zealand white rabbits were used in in vivo studies. A standard incision was applied to the oral mucosa of rabbits. The rabbits were divided into four groups, being: an untreated incisional group (n=6), a group treated with discs containing GSH+chitosan (n=6), a group treated with discs containing solely chitosan (n=5) and a group treated with discs containing solely GSH (n=5). The levels of malondialdehyde (MDA), glutathione and nitric oxide (NOx) in the oral wound tissues were measured on the fifth day after the injury. Histological changes in the wound tissues were also investigated. The tissue MDA levels in the group treated with the disc containing GSH+chitosan were found to be lower than those in the other groups. There were no statistically significant differences in terms of tissue GSH and NOx levels between the group treated with the disc comprising GSH+chitosan and the control group that had untreated incision wounds. According to the histological findings, wound healing in the group treated with the disc containing solely chitosan was found to be better than in the other groups. The results of the experiments showed that the local application to the intraoral incision wounds of chitosan+GSH, and chitosan alone, can be effective in the wound healing processes of soft tissues and dental implants. Copyright © 2013 Elsevier B.V. All rights reserved.