Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery.

PubMed

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

PubMed Central

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

PubMed

Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

2017-09-01

Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer.

PubMed

Shikata, Futoshi; Tokumitsu, Hiroyuki; Ichikawa, Hideki; Fukumori, Yoshinobu

2002-01-01

The accumulation of gadolinium loaded as gadopentetic acid (Gd-DTPA) in chitosan nanoparticles (Gd-nanoCPs), which were designed for gadolinium neutron-capture therapy (Gd-NCT) for cancer, was evaluated in vitro in cultured cells. Using L929 fibroblast cells, the Gd accumulation for 12 h at 37 degrees C was investigated at Gd concentrations lower than 40 ppm. The accumulation leveled above 20 ppm and reached 18.0+/-2.7 (mean+/-S.D.) microg Gd/10(6) cells at 40 ppm. Furthermore, the corresponding accumulations in B16F10 melanoma cells and SCC-VII squamous cell carcinoma, which were used in the previous Gd-NCT trials in vivo, were 27.1+/-2.9 and 59.8+/-9.8 microg Gd/10(6) cells, respectively, hence explaining the superior growth-suppression in the in vivo trials using SCC-VII cells. The accumulation of Gd-nanoCPs in these cells was 100-200 times higher in comparison to dimeglumine gadopentetate aqueous solution (Magnevist), a magnetic resonance imaging contrast agent. The endocytic uptake of Gd-nanoCPs, strongly holding Gd-DTPA, was suggested from transmission electron microscopy and comparative studies at 4 degrees C and with the solution system. These findings indicated that Gd-nanoCPs had a high affinity to the cells, probably contributing to the long retention of Gd in tumor tissue and leading to the significant suppression of tumor growth in the in vivo studies that were previously reported.

Chitosan-triclosan particles modulate inflammatory signaling in gingival fibroblasts.

PubMed

Pavez, L; Tobar, N; Chacón, C; Arancibia, R; Martínez, C; Tapia, C; Pastor, A; González, M; Martínez, J; Smith, P C

2018-04-01

An important goal of periodontal therapy is the modulation of the inflammatory response. To this end, several pharmacological agents have been evaluated. Triclosan corresponds to an antibacterial and anti-inflammatory agent currently used in periodontal therapy. Chitosan is a natural polymer that may act as a drug delivery agent and exerts antibacterial and anti-inflammatory activities. Therefore, an association between both molecules might be useful to prevent inflammation and tissue destruction in periodontal tissues. In the present study, we have generated chitosan-triclosan particles and evaluated their morphology, charge, biocompatibility and gene expression analysis in human gingival fibroblasts. The chitosan-triclosan particles size and Z potential were 129 ± 47 nm and 51 ± 17 mV respectively. Human gingival fibroblast viability was not affected by chitosan-triclosan. A total of 1533 genes were upregulated by interleukin (IL)-1β. On the other hand, 943 were downregulated in fibroblasts stimulated with IL-1β plus chitosan-triclosan particles. Fifty-one genes were identified as molecular targets upregulated by IL-1 β and downregulated by the chitosan-triclosan particles. The gene ontology analysis revealed that these genes were enriched in categories related to biological processes, molecular function and cellular components. Furthermore, using real-time reverse transcription-polymerase chain reaction beta-actin, fibronectin, interleukin-6 and IL-1b genes were confirmed as targets upregulated by IL-1β and downregulated by chitosan-triclosan particles. Our results show that chitosan-triclosan particles are able to modulate the inflammatory response in gingival fibroblasts. This effect might be useful in the prevention and/or treatment of inflammation in periodontal diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Eugenol-loaded chitosan nanoparticles: II. Application in bio-based plastics for active packaging.

PubMed

Woranuch, Sarekha; Yoksan, Rangrong

2013-07-25

The aim of the present research was to study the possibility of using eugenol-loaded chitosan nanoparticles as antioxidants for active bio-based packaging material. Eugenol-loaded chitosan nanoparticles were incorporated into thermoplastic flour (TPF) - a model bio-based plastic - through an extrusion process at temperatures above 150°C. The influences of eugenol-loaded chitosan nanoparticles on crystallinity, morphology, thermal properties, radical scavenging activity, reducing power, tensile properties and barrier properties of TPF were investigated. Although the incorporation of 3% (w/w) of eugenol-loaded chitosan nanoparticles significantly reduced the extensibility and the oxygen barrier property of TPF, it provided antioxidant activity and improved the water vapor barrier property. In addition, TPF containing eugenol-loaded chitosan nanoparticles exhibited superior radical scavenging activity and stronger reducing power compared with TPF containing naked eugenol. The results suggest the applicability of TPF containing eugenol-loaded chitosan nanoparticles as an antioxidant active packaging material. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

PubMed

Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P

2011-09-01

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

Gadolinium-loaded Plastic Scintillators for Thermal Neutron Detection using Compensation

NASA Astrophysics Data System (ADS)

Dumazert, Jonathan; Coulon, Romain; Hamel, Matthieu; Carrel, Frédérick; Sguerra, Fabien; Normand, Stéphane; Méchin, Laurence; Bertrand, Guillaume H. V.

2016-06-01

Plastic scintillator loading with gadolinium-rich organometallic complexes shows a high potential for the deployment of efficient and cost-effective neutron detectors. Due to the low-energy photon and electron signature of thermal neutron capture by Gd-155 and Gd-157, alternative treatment to pulse-shape discrimination has to be proposed in order to display a count rate. This paper discloses the principle of a compensation method applied to a two-scintillator system: a detection scintillator interacts with photon and fast neutron radiation and is loaded with gadolinium organometallic compound to become a thermal neutron absorber, while a not-gadolinium loaded compensation scintillator solely interacts with the fast neutron and photon part of incident radiation. After the nonlinear smoothing of the counting signals, a hypothesis test determines whether the resulting count rate post-background response compensation falls into statistical fluctuations or provides a robust indication of neutron activity. Laboratory samples are tested under both photon and neutron irradiations, allowing the authors to investigate the performance of the overall detection system in terms of sensitivity and detection limits, especially with regards to a similar-active volume He-3 based commercial counter. The study reveals satisfactory figures of merit in terms of sensitivity and directs future investigation toward promising paths.

Short- and long-term stability of lyophilised melatonin-loaded lecithin/chitosan nanoparticles.

PubMed

Hafner, Anita; Dürrigl, Marjana; Pepić, Ivan; Filipović-Grčić, Jelena

2011-01-01

The aim of this study was to establish a freeze-drying process for melatonin-loaded lecithin/chitosan nanoparticles (NPs) to preserve their chemical and physical stability for a longer time period that what is possible in an aqueous suspension. Glucose and trehalose were investigated as potential excipients during freeze-drying of NP suspensions. Lecithin/chitosan NPs were characterised by mean diameter and zeta potential, ranging between 117.4 and 328.5 nm and 6.7 and 30.2 mV, respectively, depending on the lecithin type and chitosan content in the preparation. Melatonin loadings were up to 7.1%. For all lecithin/chitosan NPs, no notable differences in the mean particle size, size distribution, zeta potential or melatonin content were observed before or immediately after the lyophilisation process or after 7 months of storage at 4 °C. The residual moisture contents of lyophilisates with glucose and trehalose immediately after the lyophilisation process varied between 4.0-4.8% and 2.4-3.0%, respectively. All lecithin/chitosan NPs had a fully amorphous nature after the freeze-drying process, as indicated by modulated differential scanning calorimetry. NP lyophilisates with glucose had a low glass transition temperature (ca. 5 °C), confirming that lyophilisation with glucose as a cryoprotectant was not appropriate. All lyophilisates with trehalose had a glass transition temperature above the room temperature, allowing formation of the cake without a collapse of the structure, which was capable of preserving its characteristics and appearance following 7 months of storage at 4 °C.

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

In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites.

PubMed

Cui, Xu; Gu, Yifei; Li, Le; Wang, Hui; Xie, Zhongping; Luo, Shihua; Zhou, Nai; Huang, Wenhai; Rahaman, Mohamed N

2013-10-01

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

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).

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery.

PubMed

Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

2016-12-26

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w / w ), and a sodium deoxycholate gel (CP 0.05% w / w ) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery

PubMed Central

Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

2016-01-01

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w/w), and a sodium deoxycholate gel (CP 0.05% w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP. PMID:28035957

Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: loading, enzyme-trigger release and cell uptake.

PubMed

Barbieri, Stefano; Sonvico, Fabio; Como, Caterina; Colombo, Gaia; Zani, Franca; Buttini, Francesca; Bettini, Ruggero; Rossi, Alessandra; Colombo, Paolo

2013-05-10

Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60 mg/100 ml maintained the positive zeta potential value of about +45 mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.

PubMed

Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

2013-11-01

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.

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

Preparation of carboplatin-Fe@C-loaded chitosan nanoparticles and study on hyperthermia combined with pharmacotherapy for liver cancer.

PubMed

Li, Fu-rong; Yan, Wen-hui; Guo, Yue-hua; Qi, Hui; Zhou, Han-xin

2009-08-01

Magnetic fluid hyperthermia is a kind of technology for treating tumors based on nanotechnology. It is suitable to various types of tumors. The purpose of this study was to prepare carboplatin-Fe@C-loaded chitosan nanoparticles with Fe@C as a magnetic core and to investigate efficacy of hyperthermia combined with chemotherapy for transplanted liver cancer in rats. Fe@C nanopowder was treated with dilute hydrochloric acid to prepare Fe@C nanocage. Carboplatin-Fe@C-loaded chitosan nanoparticles were prepared by reverse microemulsion method with the nanocages as the magnetic cores, chitosan as the matrix. The shape, size, drug-loading rate, and in vitro cumulative release of the nanoparticles were observed and heat product under high frequency alternating electromagnetic field in vitro was explored. Eighty rats with transplanted liver cancer were randomly divided into 4 groups (group A: control group, group B: free carboplatin group, group C: nanoparticles with static magnetic field group, and group D: nanoparticles with static field and alternating magnetic field). Drug was injected into the hepatic artery. The therapeutic effect of hyperthermia combined with chemotherapy for tumor, toxicity and rat survival time were observed. Carboplatin-Fe@C-loaded chitosan nanoparticles were spherical in shape with an average size of (207 +/- 21) nm and high saturation magnetization. The drug-loading rate of the nanoparticles was 11.0 +/- 1.1%. The cumulative release percentage of carboplatin-Fe@C-loaded chitosan nanoparticles in vitro at different point time phase of 24 h, 48 h, 72 h, 96 h and 120 h were 51%, 68%, 80%, 87% and 91%, respectively. With an increase in carboplatin-Fe@C-loaded chitosan nanoparticle concentration and magnetic field strength, the heating rate and constant temperature of carboplatin-Fe@C-loaded chitosan nanoparticles dispersed in physiological saline were increased in an alternating magnetic field. In vivo experiments showed that after particle

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.

Development of silver nanoparticles loaded chitosan-alginate constructs with biomedical potentialities.

PubMed

Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M N; Li, Chuanlong; Hu, Hongbo; Zhang, Xuehong

2017-12-01

Herein, a facile biosynthesis of silver nanoparticles (AgNPs) and AgNPs-loaded chitosan-alginate constructs with biomedical potentialities is reported. The UV-vis spectroscopic profile confirmed the synthesis of AgNPs using methanolic leaves extract of Euphorbia helioscopia. The newly developed AgNPs were characterized using various analytical and imaging techniques including UV-vis and FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The optimally yielded AgNPs at 24h reaction period were loaded onto various chitosan-alginate constructs. A maximum of 95% loading efficiency (LE) was recorded with a chitosan: alginate ratio at 2:1, followed by 81% at 2:2 ratios. The anti-bacterial activities of AgNPs and AgNPs loaded chitosan-alginate constructs were tested against six bacterial strains i.e. Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Morganella morganii and Haemophilus influenza. A significant reduction in the log values was recorded for all test constructs, in comparison to the initial bacterial count (control value, i.e., 1.5×10 8 CFU/mL). The cytotoxicity profile revealed complete biocompatibility against normal cell line i.e. L929. Almost all constructs showed considerable cytotoxicity up to certain extant against human epithelial cells (HeLa) cancer cells. In summary, the highest antibacterial activities along with anti-cancer behavior both suggest the biomedical potentialities of newly engineered AgNPs and AgNPs-loaded chitosan-alginate constructs. Copyright © 2017 Elsevier B.V. All rights reserved.

Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles.

PubMed

Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

2017-01-01

Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration.

Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles

PubMed Central

Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

2017-01-01

Introduction Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). Methods In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Results Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. Conclusion This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration. PMID:29276386

Chitosan microparticles loaded with yeast-derived PCV2 virus-like particles elicit antigen-specific cellular immune response in mice after oral administration.

PubMed

Bucarey, Sergio A; Pujol, Myriam; Poblete, Joaquín; Nuñez, Ignacio; Tapia, Cecilia V; Neira-Carrillo, Andrónico; Martinez, Jonatán; Bassa, Oliver

2014-08-20

Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to improved management and husbandry practices, the availability of several anti-PCV2 vaccines provides an efficient immunological option for reducing the impact of these diseases. Most anti-PCV2 vaccines are marketed as injectable formulations. Although these are effective, there are problems associated with the use of injectable products, including laborious and time-consuming procedures, the induction of inflammatory responses at the injection site, and treatment-associated stress to the animals. Oral vaccines represent an improvement in antigen delivery technology; they overcome the problems associated with injection management and facilitate antigen boosting when an animals' immunity falls outside the protective window. Chitosan microparticles were used as both a vehicle and mucosal adjuvant to deliver yeast-derived PCV2 virus-like particles (VLPs) in an attempt to develop an oral vaccine. The physical characteristics of the microparticles, including size, Zeta potential, and polydispersity, were examined along with the potential to induce PCV2-specific cellular immune responses in mice after oral delivery. Feeding mice with PCV2 VLP-loaded, positively-charged chitosan microparticles with an average size of 2.5 μm induced the proliferation of PCV2-specific splenic CD4+/CD8+ lymphocytes and the subsequent production of IFN-γ to levels comparable with those induced by an injectable commercial formulation. Chitosan microparticles appear to be a safe, simple system on which to base PCV2 oral vaccines. Oral chitosan-mediated antigen delivery is a novel strategy that efficiently induces anti-PCV2 cellular responses in a mouse model. Further studies in swine are warranted.

Synthesis of Monodisperse Chitosan Nanoparticles and in Situ Drug Loading Using Active Microreactor.

PubMed

Kamat, Vivek; Marathe, Ila; Ghormade, Vandana; Bodas, Dhananjay; Paknikar, Kishore

2015-10-21

Chitosan nanoparticles are promising drug delivery vehicles. However, the conventional method of unregulated mixing during ionic gelation limits their application because of heterogeneity in size and physicochemical properties. Therefore, a detailed theoretical analysis of conventional and active microreactor models was simulated. This led to design and fabrication of a polydimethylsiloxane microreactor with magnetic micro needles for the synthesis of monodisperse chitosan nanoparticles. Chitosan nanoparticles synthesized conventionally, using 0.5 mg/mL chitosan, were 250 ± 27 nm with +29.8 ± 8 mV charge. Using similar parameters, the microreactor yielded small size particles (154 ± 20 nm) at optimized flow rate of 400 μL/min. Further optimization at 0.4 mg/mL chitosan concentration yielded particles (130 ± 9 nm) with higher charge (+39.8 ± 5 mV). The well-controlled microreactor-based mixing generated highly monodisperse particles with tunable properties including antifungal drug entrapment (80%), release rate, and effective activity (MIC, 1 μg/mL) against Candida.

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.

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

A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticles loaded with optical agent for animal imaging

NASA Astrophysics Data System (ADS)

Ranjan, Amalendu P.; Zeglam, Karim; Mukerjee, Anindita; Thamake, Sanjay; Vishwanatha, Jamboor K.

2011-07-01

The objective of this study was to develop optical imaging agent loaded biodegradable nanoparticles with indocynanine green (ICG) using chitosan modified poly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blended polymer. Nanoparticles were formulated with an emulsification solvent diffusion technique using PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan were used as stabilizers. The particle size, shape and zeta potential of the formulated nanoparticles and the release kinetics of ICG from these nanoparticles were determined. Further, biodistribution of these nanoparticles was studied in mice at various time points until 24 h following intravenous administration, using a non-invasive imaging system. The average particle size of the nanoparticles was found to be 146 ± 3.7 to 260 ± 4.5 nm. The zeta potential progressively increased from - 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles were studied using transmission electron microscopy (TEM) which revealed the particles to be smooth and spherical in shape. These nanoparticles were efficiently delivered to the cytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laser scanning microscopy. In vitro release studies indicated sustained release of ICG from the nanoparticles over a period of seven days. Nanoparticle distribution results in mice showing improved uptake and accumulation with chitosan modified nanoparticles in various organs and slower clearance at different time points over a 24 h period as compared to unmodified nanoparticles. The successful formulation of such cationically modified nanoparticles for encapsulating optical agents may lead to a potential deep tissue imaging technique for tumor detection, diagnosis and therapy.

Hollow latex particles functionalized with chitosan for the removal of formaldehyde from indoor air.

PubMed

Nuasaen, Sukanya; Opaprakasit, Pakorn; Tangboriboonrat, Pramuan

2014-01-30

Chitosan and polyethyleneimine (PEI) functionalized hollow latex (HL) particles were conveniently fabricated by coating poly(methyl methacrylate-co-divinyl benzene-co-acrylic acid) (P(MMA/DVB/AA)) HL particles with 5 wt% chitosan or 14 wt% PEI. The materials were used as formaldehyde adsorbent, where their adsorbent activity was examined by Fourier Transform Infrared (FTIR) spectroscopy. The nucleophilic addition of amines to carbonyls generated a carbinolamine intermediate with a characteristic band at 1,020 cm(-1) and Schiff base product at 1650 cm(-1), whose intensity increased with prolonged formaldehyde exposure times. The major products observed in HL-chitosan were carbinolamine and Schiff base, whereas a small amount of Schiff base was obtained in HL-PEI particles, confirming a chemical bond formation without re-emission of formaldehyde. Compared to HL-PEI, HL-chitosan possesses higher formaldehyde adsorption efficiency. Besides providing opacity and whiteness, the multilayer HL-chitosan particles can effectively remove indoor air pollutants, i.e., formaldehyde gas, and, hence, would be useful in special coating applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B.

PubMed

Khatri, Kapil; Goyal, Amit K; Gupta, Prem N; Mishra, Neeraj; Vyas, Suresh P

2008-04-16

This work investigates the preparation and in vivo efficacy of plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Chitosan pDNA nanoparticles were prepared using a complex coacervation process. Prepared nanoparticles were characterized for size, shape, surface charge, plasmid loading and ability of nanoparticles to protect DNA against nuclease digestion and for their transfection efficacy. Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level. However, intramuscular administration of naked DNA and alum adsorbed HBsAg did not elicit sIgA titre in mucosal secretions that was induced by nasal immunization with chitosan nanoparticles. Similarly, cellular responses (cytokine levels) were poor in case of alum adsorbed HBsAg. Chitosan nanoparticles thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. The study signifies the potential of chitosan nanoparticles as DNA vaccine carrier and adjuvant for effective immunization through non-invasive nasal route.

Development, optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box-Behnken experimental design.

PubMed

Adena, Sandeep Kumar Reddy; Upadhyay, Mansi; Vardhan, Harsh; Mishra, Brahmeshwar

2018-03-01

The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs). Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP. The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39 ± 1.82 nm, apparent drug content (ADC) of 72.06 ± 0.86%, and zeta potential (ZP) of -13.91 ± 1.21 mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48 h and followed Korsmeyer-Peppas release kinetic model. A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.

Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.

PubMed

Muddineti, Omkara Swami; Kumari, Preeti; Ray, Eupa; Ghosh, Balaram; Biswas, Swati

2017-06-02

To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.

Synthesis and anti-fungal effect of silver nanoparticles–chitosan composite particles

PubMed Central

Wang, Lung-Shuo; Wang, Chih-Yu; Yang, Chih-Hui; Hsieh, Chen-Ling; Chen, Szu-Yu; Shen, Chi-Yen; Wang, Jia-Jung; Huang, Keng-Shiang

2015-01-01

Silver nanoparticles have been used in various fields, and several synthesis processes have been developed. The stability and dispersion of the synthesized nanoparticles is vital. The present article describes a novel approach for one-step synthesis of silver nanoparticles–embedded chitosan particles. The proposed approach was applied to simultaneously obtain and stabilize silver nanoparticles in a chitosan polymer matrix in-situ. The diameter of the synthesized chitosan composite particles ranged from 1.7 mm to 2.5 mm, and the embedded silver nanoparticles were measured to be 15±3.3 nm. Further, the analyses of ultraviolet-visible spectroscopy, energy dispersive spectroscopy, and X-ray diffraction were employed to characterize the prepared composites. The results show that the silver nanoparticles were distributed over the surface and interior of the chitosan spheres. The fabricated spheres had macroporous property, and could be used for many applications such as fungicidal agents in the future. PMID:25878501

Fabrication of lactobionic-loaded chitosan microcapsules as potential drug carriers targeting the liver.

PubMed

Zhang, Jing; Li, Cao; Xue, Zhi-Yuan; Cheng, Hai-Wei; Huang, Fu-Wei; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2011-04-01

This paper demonstrates a general approach for fabrication of lactobionic chitosan microcapsules using layer-by-layer assembly via click chemistry. Chitosan was selectively modified with either azide (CHI-Az) or alkyne (CHI-Alk) groups. The growth of the CHI-Az/CHI-Alk click multilayer was studied experimentally by multilayer assembly on planar supports. Linear buildup of the film was observed. The chitosan click capsules were also analyzed with confocal laser scanning microscopy and transmission electron microscopy. Capsules were found to have regular spherical shapes. In addition, (CHI-Az/CHI-Alk)-coated particles were modified with fluorescein isothiocyanate to ensure that the particles can be easily post-functionalized. Finally, lactobionic acid was conjugated onto the (CHI-Az/CHI-Alk)-coated particles and the lactobionic particles exhibited hepatoma cell (HepG2) targeting behavior. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

PubMed

Fujimoto, T; Ichikawa, H; Akisue, T; Fujita, I; Kishimoto, K; Hara, H; Imabori, M; Kawamitsu, H; Sharma, P; Brown, S C; Moudgil, B M; Fujii, M; Yamamoto, T; Kurosaka, M; Fukumori, Y

2009-07-01

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

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.

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.

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells.

PubMed

Talaei, Fatemeh; Azizi, Ebrahim; Dinarvand, Rassoul; Atyabi, Fatemeh

2011-01-01

Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo.

Formation of Polyelectrolyte Complex Colloid Particles between Chitosan and Pectin with Different Degree of Esterification

NASA Astrophysics Data System (ADS)

Wang, Hui; Sun, Hongyuan; He, Jieyu

2017-12-01

The effects of degree of esterification, pectin/chitosan ratio and pH on the formation of polyelectrolyte complex colloid particles between chitosan (CS) and pectin (PE) were investigated. Low methoxyl pectin (LPE) was achieved by de-esterifying high methoxyl pectin (HPE) with pectin methyl esterase. Turbidity titration and colorimetric method was used to determine the stability of complex colloid particles. The structure and morphology of complex particles were characterized by FTIR and TEM. When pectin solution was dropped into chitosan solution, complex colloidal dispersion was stable as PE/CS mass ratio was no more than 3:2. Colloidal particles of HPE-CS complex coagulated at larger ratio of PE/CS than LPE-CS. The maximum complex occurred at pH 6.1 for HPE-CS and pH 5.7 for LPE-CS, and decreasing pH leaded to the dissociation of complex particles. Electrostatic interactions between carboxyl groups on pectin and amino groups on chitosan were confirmed by FTIR. Colloidal particle sizes ranged from about 100 nm to 400 nm with spherical shape.

Physical characterization and osteogenic activity of the quaternized chitosan-loaded PMMA bone cement.

PubMed

Tan, Honglue; Guo, Shengrong; Yang, Shengbing; Xu, Xiaofen; Tang, Tingting

2012-07-01

Gentamicin-loaded polymethylmethacrylate (PMMA), widely used for primary cemented arthroplasty and revision surgery for preventing or treating infections, may lead to the evolution of antibiotic-resistant bacteria and dysfunction of osteogenic cells, which further influence the osteointegration of bone cement. In a previous study, we reported that a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that was loaded into PMMA significantly inhibited the formation of biofilms caused by methicillin-resistant Staphylococcus strains. In the present study, we further investigated the surface morphology, hydrophilicity, apatite formation ability and osteogenic activity of HACC-loaded PMMA. Chitosan-loaded PMMA, gentamicin-loaded PMMA and PMMA without antibiotic were also investigated and compared. The results showed that, compared to other PMMA-based cements, HACC-loaded PMMA had improved properties such as a lower polymerization temperature, prolonged setting time, porous structures after immersion in phosphate-buffered saline, higher hydrophilicity, more apatite formation on the surface after immersion in simulated body fluid, and better attachment and spreading of the human-marrow-derived mesenchymal stem cells. We also found better stem cell proliferation, osteogenic differentiation, and osteogenesis-associated genes expression on the surface of the HACC-loaded PMMA compared to the gentamicin-loaded PMMA. Therefore, this new anti-infective bone cement had improved physical properties and osteogenic activity, which may lead to better osteointegration of the bone cement in cemented arthroplasty. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Drug release characteristics of quercetin-loaded TiO2 nanotubes coated with chitosan.

PubMed

Mohan, L; Anandan, C; Rajendran, N

2016-12-01

TiO 2 nanotubes formed by anodic oxidation of Ti-6Al-7Nb were loaded with quercetin (TNTQ) and chitosan was coated on the top of the quercetin (TNTQC) to various thicknesses. Field emission scanning electron microscopy (FESEM), 3D and 2D analyses were used to characterize the samples. The drug release studies of TNTQ and TNTQC were studied in Hanks' solution for 192h. The studies showed that the native oxide on the sample is substituted by self assembled nanotube arrays by anodisation. FESEM images of chitosan-loaded TNT samples showed that filling of chitosan takes place in inter-tubular space and pores. Drug release studies revealed that the release of drug into the local environment during that duration was constant. The local concentration of the drug can be controlled and tuned by controlling the thickness of the chitosan (0.6, 1 and 3μm) to fit into an optimal therapeutic window in order to treat postoperative infections, inflammation and for quick healing with better osseointegration of the titanium implants. Copyright © 2016 Elsevier B.V. All rights reserved.

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

PubMed Central

Talaei, Fatemeh; Azizi, Ebrahim; Dinarvand, Rassoul; Atyabi, Fatemeh

2011-01-01

Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo. PMID:21976973

In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma.

PubMed

Katiyar, Shefali; Pandit, Jayamanti; Mondal, Rabi S; Mishra, Anil K; Chuttani, Krishna; Aqil, Mohd; Ali, Asgar; Sultana, Yasmin

2014-02-15

The most important risk associated with glaucoma is the onset and progression of intraocular pressure. The objective of this study was to formulate in situ gel of chitosan nanoparticles to enhance the bioavailability and efficacy of dorzolamide in the glaucoma treatment. Optimized nanoparticles were spherical in shape (particle size: 164 nm) with a loading efficiency of 98.1%. The ex vivo release of the optimized in situ gel nanoparticle formulation showed a sustained drug release as compared to marketed formulation. The gamma scintigraphic study of prepared in situ nanoparticle gel showed good corneal retention compared to marketed formulation. HET-CAM assay of the prepared formulation scored 0.33 in 5 min which indicates the non-irritant property of the formulation. Thus in situ gel of dorzolamide hydrochloride loaded nanoparticles offers a more intensive treatment of glaucoma and a better patient compliance as it requires fewer applications per day compared to conventional eye drops. Copyright © 2013 Elsevier Ltd. All rights reserved.

Electrospinning of curcumin loaded chitosan/poly (lactic acid) nanofilm and evaluation of its medicinal characteristics

NASA Astrophysics Data System (ADS)

Dhurai, Bhaarathi; Saraswathy, Nachimuthu; Maheswaran, Ramasamy; Sethupathi, Ponnusamy; Vanitha, Palanisamy; Vigneshwaran, Sukumar; Rameshbabu, Venugopal

2013-12-01

The curcumin loaded chitosan/poly (lactic acid) (PLA) nanofibers were produced using electrospinning. Box—Behnken experimental design was used for the optimization of variables (-1, 0, + 1 coded level) like chitosan/PLA strength (% w/v), curcumin strength (% w/v) and applied voltage (kV) to obtain uniform fiber diameter. The morphology of nanofibers was shown by SEM. Molecular interactions and the presence of each chemical compound of curcumin loaded chitosan/PLA fibers were characterized by FTIR and EDX analysis. Antioxidant, drug release and in vitro cytotoxicity tests were performed to evaluate the suitability of nanofibers that would be used for wound healing. In vivo wound healing studies on excision and incision wounds created on rat model showed significant reduction of wound area when compared to untreated. The better healing efficiency can be attributed to the presence of curcumin and chitosan.

Cross-linkable liposomes stabilize a magnetic resonance contrast-enhancing polymeric fastener.

PubMed

Smith, Cartney E; Kong, Hyunjoon

2014-04-08

Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads.

Cross-Linkable Liposomes Stabilize a Magnetic Resonance Contrast-Enhancing Polymeric Fastener

PubMed Central

2015-01-01

Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads. PMID:24635565

Formation and characterization of chitosan-protein particles with fractal whey protein aggregates.

PubMed

Ahmed, Khouloud Fekih; Aschi, Adel; Nicolai, Taco

2018-05-15

Hybrid protein-polysaccharide particles were formed by complexation of fractal whey protein aggregates and the cationic polysaccharide chitosan. The fractal aggregates were preformed by heating native whey protein isolate at pH 7 and subsequently mixed with chitosan at pH 3 where these proteins and polysaccharides don't interact with each other. Stable dispersions of protein-polysaccharide particles were formed spontaneously when the pH was gradually increased between 4.1 and 6.8, whereas in the absence of chitosan the fractal aggregates precipitated between pH 4.1 and 5.4. Potentiometric titration of the mixtures showed that deprotonation of both components was affected by complexation. With increasing pH, the size of the complexes increased sharply between pH 4.1. and pH 4.5, remained constant up to pH 5.6 and then increased again. A minimum amount of chitosan was needed to form stable complexes at pH 5.0 and the size of the complexes decreased with increasing chitosan concentration. Light scattering showed that the complexes were stable to dilution and had a self similar structure with a fractal dimensions close to two. The effect of changing the pH on the size and stability of the complexes was investigated. Suspensions of complexes of preformed whey protein aggregates and chitosan are more stable up to high pH (6.8) than complexes between native WPI and chitosan as reported in the literature. Copyright © 2018. Published by Elsevier B.V.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

PubMed

Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

2015-01-01

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

PubMed Central

Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

2015-01-01

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N′-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. PMID:26316749

Tumor-Microenvironment Relaxivity-Changeable Gd-Loaded Poly(L-lysine)/Carboxymethyl Chitosan Nanoparticles as Cancer-Recognizable Magnetic Resonance Imaging Contrast Agents.

PubMed

Jiang, Dandan; Zhang, Xiaopeng; Yu, Dexin; Xiao, Yanan; Wang, Tianqi; Su, Zhihui; Liu, Yongjun; Zhang, Na

2017-03-01

Magnetic resonance imaging (MRI) contrast agents with tumor-microenvironment changeable relaxivity are effective to increase the sensitivity and selectivity of MRI in tumor diagnosis. In this study, pH-sensitive Gd-loaded Poly(L-lysine)/ Carboxymethyl Chitosan Nanoparticles (Gd-PCNPs) were developed as relaxivity-changeable MRI contrast agents based on the "on–off" switchable strategy. The "on–off" switchable nano-contrast agents were capable of releasing Gd3+ in response to physical stimulation, with structure transformed. Gd-PCNPs could responsively disassemble in an acidic tumor-microenvironment and increase the exchange of protons between water molecules and Gd3+ ions, thus selectively enhance the relaxivity in tumor area. Gd-PCNPs were self-assembled via electrostatic interaction between poly(L-lysine)-diethylenetriamine pentaacetic acid-gadolinium and pH-sensitive carboxymethyl chitosan (CMCS). Gd-PCNPs exhibited spherical shape with uniform particle size distribution (166.00 ± 1 .71 nm) and negative zeta potential (–13.2 ± 4.7 mV). The relaxivity of Gd-PCNPs increased from 6.618 mM–1 · s–1 to 10.008 mM–1 · s–1 when the pH values decrease from 7.4 to 6.0, which was higher than Magnevist® (3.924 mM–1 · s–1 at both pH 7.4 and 6.0 (p <0 05). The changeable relaxivity of Gd/PCNPs would result in enhanced tumor/normal tissue signal contrast, which was verified by in vivo MRI test. In vivo MRI test showed that the signal of Gd-PCNPs was significantly enhanced with prolonged imaging time in tumor tissue compared to Magnevist® (p <0 05). Furthermore, Gd-PCNPs exhibited unobvious in vitro cytotoxicity under the experimental concentrations in B16 cells. No obvious damage was observed in the different tissues of mice. These results indicated that the relaxivity-changeable Gd-PCNPs exhibited demonstrated sensitivity and selectivity in tumor diagnosis with a great potential as a novel MRI contrast agent.

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.

Electrophoretic deposition of gentamicin-loaded bioactive glass/chitosan composite coatings for orthopaedic implants.

PubMed

Pishbin, Fatemehsadat; Mouriño, Viviana; Flor, Sabrina; Kreppel, Stefan; Salih, Vehid; Ryan, Mary P; Boccaccini, Aldo R

2014-06-11

Despite their widespread application, metallic orthopaedic prosthesis failure still occurs because of lack of adequate bone-bonding and the incidence of post-surgery infections. The goal of this research was to develop multifunctional composite chitosan/Bioglass coatings loaded with gentamicin antibiotic as a suitable strategy to improve the surface properties of metallic implants. Electrophoretic deposition (EPD) was applied as a single-step technology to simultaneously deposit the biopolymer, bioactive glass particles, and the antibiotic on stainless steel substrate. The microstructure and composition of the coatings were characterized using SEM/EDX, XRD, FTIR, and TGA/DSC, respectively. The in vitro bioactivity of the coatings was demonstrated by formation of hydroxyapatite after immersion in simulated body fluid (SBF) in a short period of 2 days. High-performance liquid chromatography (HPLC) measurements indicated the release of 40% of the loaded gentamicin in phosphate buffered saline (PBS) within the first 5 days. The developed composite coating supported attachment and proliferation of MG-63 cells up to 10 days. Moreover, disc diffusion test showed improved bactericidal effect of gentamicin-loaded composite coatings against S. aureus compared to control non-gentamicin-loaded coatings.

Synthesis of curcumin-loaded chitosan phosphate nanoparticle and study of its cytotoxicity and antimicrobial activity.

PubMed

Deka, C; Aidew, L; Devi, N; Buragohain, A K; Kakati, D K

2016-11-01

Curcumin has acquired an important position in the treatment of various diseases. But its use, as a chemotherapeutic agent, is limited due to its low water solubility, poor bioavailability, and its sensitive nature at the physiological pH. To overcome this, curcumin was loaded into chitosan phosphate nanoparticles (CPNs). The loading efficiency was found to be 84%. DLS studies revealed the average particle size of CPNs and curcumin-loaded CPNs as 53 and 91 nm, respectively, and TEM results supplemented these values. A sustained release pattern was noticed and the amount of curcumin released in acidic pH was higher than at physiological pH. The curcumin nanoformulation exhibited proficient activity against both Gram-positive and Gram-negative bacteria as well as fungus. Cytocompatibility of the nanoformulations against peripheral blood mononuclear cells (PBMCs) and murine monocyte-macrophage cell line was confirmed by incubating with PBMCs and murine monocyte-macrophage cell line.

Optimized Preparation of Levofloxacin-loaded Chitosan Nanoparticles by Ionotropic Gelation

NASA Astrophysics Data System (ADS)

Guan, J.; Cheng, P.; Huang, S. J.; Wu, J. M.; Li, Z. H.; You, X. D.; Hao, L. M.; Guo, Y.; Li, R. X.; Zhang, H.

The present work investigates the feasibility of fabricating chitosan (CS)-levofloxacin (LOF) nanoparticles by ionotropic gelation technology. An orthogonal experiment was designed to optimize its preparing parameters and multi-index comprehensive weighed score analysis method was used to study the effects of various factors including concentration of CS, concentration of tripolyphosphate (TPP), mass ratio of CS to TPP, and mass ratio of CS to LOF on the properties of nanoparticles. The particles prepared under optimal condition of 2 mg/ml CS concentration, 2 mg/ml TPP concentration, 0.5:1 mass ratio of oil to water and 4:1 mass ratio of CS to TPP had 140 nm diameter, 0.95 span, 6.13% loading capacity (LC) and 24.91% encapsulation efficiency (EE). In vitro release profile showed that LOF released fast initially and then slowly with T90 occurring at 76.5 h. Future studies should focus on antibacterial and biocompatible properties in order to evaluate its potential as sustainable delivery system.

One-step analysis of DNA/chitosan complexes by field-flow fractionation reveals particle size and free chitosan content.

PubMed

Ma, Pei Lian; Buschmann, Michael D; Winnik, Françoise M

2010-03-08

The composition of samples obtained upon complexation of DNA with chitosan was analyzed by asymmetrical flow field flow fractionation (AF4) with online UV-visible, multiangle light scattering (MALS), and dynamic light scattering (DLS) detectors. A chitosan labeled with rhodamine B to facilitate UV-vis detection of the polycation was complexed with DNA under conditions commonly used for transfection (chitosan glucosamine to DNA phosphate molar ratio of 5). AF4 analysis revealed that 73% of the chitosan-rhodamine remained free in the dispersion and that the DNA/chitosan complexes had a broad size distribution ranging from 20 to 160 nm in hydrodynamic radius. The accuracy of the data was assessed by comparison with data from batch-mode DLS and scanning electron microscopy. The AF4 combined with DLS allowed the characterization of small particles that were not detected by conventional batch-mode DLS. The AF4 analysis will prove to be an important tool in the field of gene therapy because it readily provides, in a single measurement, three important physicochemical parameters of the complexes: the amount of unbound polycation, the hydrodynamic size of the complexes, and their size distribution.

Development of chitosan oleate ionic micelles loaded with silver sulfadiazine to be associated with platelet lysate for application in wound healing.

PubMed

Dellera, Eleonora; Bonferoni, Maria Cristina; Sandri, Giuseppina; Rossi, Silvia; Ferrari, Franca; Del Fante, Claudia; Perotti, Cesare; Grisoli, Pietro; Caramella, Carla

2014-11-01

In the treatment of chronic wounds, topical application of anti-infective drugs such as silver sulfadiazine (AgSD) is of primary importance to avoid infections and accelerate wound repair. AgSD is used in burns and chronic wounds for its wide antibacterial spectrum, but presents limitations due to poor solubility and cytotoxicity. In the present work polymeric micelles obtained by self-assembling of chitosan ionically modified by interaction with oleic acid were developed as carriers for AgSD to overcome the drawbacks of the drug. The AgSD loaded micelles were intended to be associated in wound healing with platelet lysate (PL), a hemoderivative rich in growth factors. Unloaded micelles demonstrated good compatibility with both fibroblasts and PL. The relevance of chitosan concentration and of the ratio between chitosan and oleic acid to the drug loading and the particle size of nanoparticles was studied. A marked increase (up to 100 times with respect to saturated solution) of AgSD concentration in micelle dispersion was obtained. Moreover, the encapsulation reduced the cytotoxic effect of the drug towards fibroblasts and the drug incompatibility with PDGF-AB (platelet derived growth factor), chosen as representative of platelet growth factors. Copyright © 2014. Published by Elsevier B.V.

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.

Room temperature ferromagnetic gadolinium silicide nanoparticles

DOEpatents

Hadimani, Magundappa Ravi L.; Gupta, Shalabh; Harstad, Shane; Pecharsky, Vitalij; Jiles, David C.

2018-03-06

A particle usable as T₁ and T₂ contrast agents is provided. The particle is a gadolinium silicide (Gd₅Si₄) particle that is ferromagnetic at temperatures up to 290 K and is less than 2 .mu.m in diameter. An MRI contrast agent that includes a plurality of gadolinium silicide (Gd.sub.5Si.sub.4) particles that are less than 1 .mu.m in diameter is also provided. A method for creating gadolinium silicide (Gd₅Si₄) particles is also provided. The method includes the steps of providing a Gd₅Si₄ bulk alloy; grinding the Gd₅Si₄ bulk alloy into a powder; and milling the Gd₅Si₄ bulk alloy powder for a time of approximately 20 minutes or less.

Entrapment of carbon dioxide with chitosan-based core-shell particles containing changeable cores.

PubMed

Dong, Yanrui; Fu, Yinghao; Lin, Xia; Xiao, Congming

2016-08-01

Water-soluble chitosan-based core-shell particles that contained changeable cores were successfully applied to anchor carbon dioxide. The entrapment capacity of the particles for carbon dioxide (EC) depended on the cores. It was found that EC of the particles contained aqueous cores was higher than that of the beads with water-soluble chitosan gel cores, which was confirmed with thermogravimetric analysis. In addition, calcium ions and sodium hydroxide were introduced within the particles to examine their effect on the entrapment. EC of the particles was enhanced with sodium hydroxide when the cores were WSC gel. The incorporation of calcium ions was helpful for stabilizing carbon dioxide through the formation of calcium carbonate, which was verified with Fourier transform infrared spectra and scanning electron microscopy/energy-dispersive spectrometry. This phenomenon meant the role of calcium ions for fixating carbon dioxide was significant. Copyright © 2016 Elsevier B.V. All rights reserved.

Gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan: optimization and release characteristics.

PubMed

Lee, Ji-Soo; Kim, Jong Soo; Lee, Hyeon Gyu

2009-05-01

Response surface methodology was used to optimize microparticle preparation conditions, including the ratio of pectin:gamma-oryzanol (OZ) (X(1)), agitation speed (X(2)), and the concentration of emulsifier (X(3)), for maximal entrapment efficiency (EE) of OZ-loaded Ca pectinate microparticles. The optimized values of X(1), X(2), and X(3) were found to be 2.72:5.28, 1143.5 rpm, and 2.61%, respectively. Experimental results obtained for the optimum formulation agreed favorably with the predicted results, indicating the usefulness of predicting models for EE. In order to evaluate the effect of chitosan-coating and blending on the release pattern of the entrapped OZ from microparticles, chitosan-coated and blended Ca pectinate microparticles were prepared. Release studies revealed that the chitosan treatments, especially the chitosan-coating, were effective in suppressing the release in both simulated gastric fluid (SGF) and intestinal fluid (SIF).

Development and Evaluation of Cefadroxil Drug Loaded Biopolymeric Films Based on Chitosan-Furfural Schiff Base

PubMed Central

Dixit, Ritu B.; Uplana, Rahul A.; Patel, Vishnu A.; Dixit, Bharat C.; Patel, Tarosh S.

2010-01-01

Cefadroxil drug loaded biopolymeric films of chitosan-furfural schiff base were prepared by reacting chitosan with furfural in presence of acetic acid and perchloric acid respectively for the external use. Prepared films were evaluated for their strength, swelling index, thickness, drug content, uniformity, tensile strength, percent elongation, FTIR spectral analysis and SEM. The results of in vitro diffusion studies revealed that the films exhibited enhanced drug diffusion as compared to the films prepared using untreated chitosan. The films also demonstrated good to moderate antibacterial activities against selective gram positive and gram negative bacteria. PMID:21179325

Gadolinium-loaded gel scintillators for neutron and antineutrino detection

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

Riddle, Catherine Lynn; Akers, Douglas William; Demmer, Ricky Lynn

A gadolinium (Gd) loaded scintillation gel (Gd-ScintGel) compound allows for neutron and gamma-ray detection. The unique gel scintillator encompasses some of the best features of both liquid and solid scintillators, yet without many of the disadvantages associated therewith. Preferably, the gel scintillator is a water soluble Gd-DTPA compound and water soluble fluorophores such as: CdSe/ZnS (or ZnS) quantum dot (Q-dot) nanoparticles, coumarin derivatives 7-hydroxy-4-methylcoumarin, 7-hydroxy-4-methylcoumarin-3-acetic acid, 7-hydroxycoumarin-3-carboxylic acid, and Alexa Fluor 350 as well as a carbostyril compound, carbostyril 124 in a stable water-based gel, such as methylcellulose or polyacrylamide polymers. The Gd-loaded ScintGel allows for a homogenious distribution ofmore » the Gd-DTPA and the fluorophores, and yields clean fluorescent emission peaks. A moderator, such as deuterium or a water-based clear polymer, can be incorporated in the Gd-ScintGel. The gel scintillators can be used in compact detectors, including neutron and antineutrino detectors.« less

Highly aligned porous Ti scaffold coated with bone morphogenetic protein-loaded silica/chitosan hybrid for enhanced bone regeneration.

PubMed

Jung, Hyun-Do; Yook, Se-Won; Han, Cheol-Min; Jang, Tae-Sik; Kim, Hyoun-Ee; Koh, Young-Hag; Estrin, Yuri

2014-07-01

Porous Ti has been widely investigated for orthopedic and dental applications on account of their ability to promote implant fixation via bone ingrowth into pores. In this study, highly aligned porous Ti scaffolds coated with a bone morphogenetic protein (BMP)-loaded silica/chitosan hybrid were produced, and their bone regeneration ability was evaluated by in vivo animal experiments. Reverse freeze casting allowed for the creation of highly aligned pores, resulting in a high compressive strength of 254 ± 21 MPa of the scaffolds at a porosity level of ∼51 vol %. In addition, a BMP-loaded silica/chitosan hybrid coating layer with a thickness of ∼1 μm was uniformly deposited on the porous Ti scaffold, which enabled the sustained release of the BMP over a prolonged period of time up to 26 days. The cumulative amount of the BMP released was ∼4 μg, which was much higher than that released from the specimen without a hybrid coating layer. In addition, the bone regeneration ability of the porous Ti scaffold with a BMP-loaded silica/chitosan coating layer was examined by in vivo animal testing using a rabbit calvarial defect model and compared with those of the as-produced porous Ti scaffold and porous Ti scaffold with a silica/chitosan coating layer. After 4 weeks of healing, the specimen coated with a BMP-loaded silica/chitosan hybrid showed a much higher bone regeneration volume (∼36%) than the as-produced specimen (∼15%) (p < 0.005) and even the specimen coated with a silica/chitosan hybrid (∼25%) (p < 0.05). © 2013 Wiley Periodicals, Inc.

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

Chitosan-based dressings loaded with neurotensin--an efficient strategy to improve early diabetic wound healing.

PubMed

Moura, Liane I F; Dias, Ana M A; Leal, Ermelindo C; Carvalho, Lina; de Sousa, Hermínio C; Carvalho, Eugénia

2014-02-01

One important complication of diabetes mellitus is chronic, non-healing diabetic foot ulcers (DFUs). This study aims to develop and use dressings based on chitosan derivatives for the sustained delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. Three different derivatives, namely N-carboxymethyl chitosan, 5-methyl pyrrolidinone chitosan (MPC) and N-succinyl chitosan, are presented as potential biomaterials for wound healing applications. Our results show that MPC has the best fluid handling capacity and delivery profile, also being non-toxic to Raw 264.7 and HaCaT cells. NT-loaded and non-loaded MPC dressings were applied to control/diabetic wounds to evaluate their in vitro/in vivo performance. The results show that the former induced more rapid healing (50% wound area reduction) in the early phases of wound healing in diabetic mice. A NT-loaded MPC foam also reduced expression of the inflammatory cytokine TNF-α (P<0.001) and decreased the amount of inflammatory infiltrate on day 3. On day 10 MMP-9 was reduced in diabetic skin (P<0.001), significantly increasing fibroblast migration and collagen (COL1A1, COL1A2 and COL3A1) expression and deposition. These results suggest that MPC-based dressings may work as an effective support for sustained NT release to reduce DFUs. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Melatonin-loaded lecithin/chitosan nanoparticles: physicochemical characterisation and permeability through Caco-2 cell monolayers.

PubMed

Hafner, Anita; Lovrić, Jasmina; Voinovich, Dario; Filipović-Grcić, Jelena

2009-11-03

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as a mucoadhesive colloidal nanosystem for transmucosal delivery of melatonin was investigated. The size, zeta potential and melatonin loading of the lecithin/chitosan NPs were investigated as a function of lecithin type (Lipoid S45, S75 and S100) and chitosan content in the preparation. The NPs were characterised by mean diameter and zeta potential ranging between 121.6 and 347.5 nm, and 7.5 and 32.7 mV, respectively, and increasing with lecithin-negative charge and chitosan content in the preparation. Melatonin loadings were up to 7.1%. All NPs were characterised by prolonged release profiles with an initial burst (approximately 25%), followed by a slow release phase. Approximately 60-70% of melatonin was released in 4h. The permeability of melatonin was investigated using Caco-2 cells as an in vitro model of the epithelial barrier. Melatonin permeability from an NP suspension prepared with Lipoid S45 lecithin and a lecithin-to-chitosan weight ratio (L/C) of 20:1 (sample C2) was significantly improved compared to the permeability of melatonin from the solution (P<0.001) and from all other NPs investigated (P<0.05). The results obtained by the cell viability studies (MTT and LDH leakage assays) showed that C2 NP suspension did not induce plasma membrane damage or decrease cell viability and could be safely applied to Caco-2 cells in the concentration range tested (<400 microg/ml).

Encapsulation of testosterone by chitosan nanoparticles.

PubMed

Chanphai, P; Tajmir-Riahi, H A

2017-05-01

The loading of testosterone by chitosan nanoparticles was investigated, using multiple spectroscopic methods, thermodynamic analysis, TEM images and modeling. Thermodynamic parameters showed testosterone-chitosan bindings occur mainly via H-bonding and van der Waals contacts. As polymer size increased more stable steroid-chitosan conjugates formed and hydrophobic contact was also observed. The loading efficacy of testosterone-nanocarrier was 40-55% and increased as chitosan size increased. Testosterone encapsulation markedly alters chitosan morphology. Chitosan nanoparticles are capable of transporting testosterone in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of hydrocortisone succinic acid/and 5-fluorouracil/chitosan microcapsules for oral and topical drug deliveries.

PubMed

Lam, Pik-Ling; Lee, Kenneth Ka-Ho; Wong, Raymond Siu-Ming; Cheng, Gregory Yin Ming; Cheng, Shuk Yan; Yuen, Marcus Chun-Wah; Lam, Kim-Hung; Gambari, Roberto; Kok, Stanton Hon-Lung; Chui, Chung-Hin

2012-05-01

Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules as a carrier for both oral and topical deliveries. We also reported the improved biological activity towards skin cells and Staphylococcus aureus of phyllanthin containing chitosan microcapsules. However, the possibility of both oral and topical applications was still necessary to be further studied. Here we investigated that both oral and topical applications of chitosan-based microcapsules were tested using hydrocortisone succinic acid (HSA) and 5-fluorouracil (5-FU), respectively. The drug loading efficiency, particle size, surface morphology and chemical compositions of both drug loaded microcapsules were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning electron microscope and Fourier transform infrared spectroscopy. The in vitro release studies revealed that both HSA and 5-FU could be released form chitosan microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded microcapsule mice plasma was detected to be lower than that of water control. One hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule treated textiles into nude mice skin. Further uses of the drug loaded microcapsules may provide an efficiency deliverable tool for both oral and topical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method.

PubMed

Zu, Yuangang; Zhao, Qi; Zhao, Xiuhua; Zu, Shuchong; Meng, Li

2011-01-01

Oligomycin-A (Oli-A), an anticancer drug, was loaded to the folate (FA)-conjugated chitosan as a tumor-targeted drug delivery system for the purpose of overcoming the nonspecific targeting characteristics and the hydrophobicity of the compound. The two-level factorial design (2-LFD) was applied to modeling the preparation process, which was composed of five independent variables, namely FA-conjugated chitosan (FA-CS) concentration, Oli-A concentration, sodium tripolyphosphate (TPP) concentration, the mass ratio of FA-CS to TPP, and crosslinking time. The mean particle size (MPS) and the drug loading rate (DLR) of the resulting Oli-loaded FA-CS nanoparticles (FA-Oli-CSNPs) were used as response variables. The interactive effects of the five independent variables on the response variables were studied. The characteristics of the nanoparticles, such as amount of FA conjugation, drug entrapment rate (DER), DLR, surface morphology, and release kinetics properties in vitro were investigated. The FA-Oli-CSNPs with MPS of 182.6 nm, DER of 17.3%, DLR of 58.5%, and zeta potential (ZP) of 24.6 mV were obtained under optimum conditions. The amount of FA conjugation was 45.9 mg/g chitosan. The FA-Oli-CSNPs showed sustained-release characteristics for 576 hours in vitro. The results indicated that FA-Oli-CSNPs obtained as a targeted drug delivery system could be effective in the therapy of leukemia in the future.

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.

Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery.

PubMed

Noor, Norhayati Mohamed; Sheikh, Khalid; Somavarapu, Satyanarayana; Taylor, Kevin M G

2017-08-01

Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1 H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 2 3 full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6±7.0nm to 220.1±11.9nm, and modified surface charge, with zeta potentials being -18.3±0.9mV and +25.8±1.1mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60days, when stored at 4-8°C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4-8°C after 30days. The measured particle size for all formulations stored at 25°C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p<0.05) for DST-NLCs (6.09±1.09μg/cm 2 ) without coating and those coated with 5% CSO-SA (2.82±0.40μg/cm 2 ), 10% CSO-SA (2.70±0.35μg/cm 2 ) and CSO (2.11±0.64μg/cm 2) . There was a significant difference (p<0.05) in the cytotoxicity (IC 50 ) between dutasteride alone and in the nanoparticles. DST-NLCs coated

Biocompatibility of Gd-Loaded Chitosan-Hyaluronic Acid Nanogels as Contrast Agents for Magnetic Resonance Cancer Imaging

PubMed Central

Gheran, Cecilia Virginia; Rigaux, Guillaume; Callewaert, Maité; Berquand, Alexandre; Chuburu, Françoise; Voicu, Sorina Nicoleta; Dinischiotu, Anca

2018-01-01

Although the research on nanogels incorporating Gd chelates for theranostic applications has grown exponentially in recent years, knowledge about their biocompatibility is limited. We compared the biocompatibility of Gd-loaded hyaluronic acid-chitosan-based nanogels (GdCA⊂CS-TPP/HA) with two chitosan concentrations (2.5 and 1.5 mg·mL−1 respectively) using SVEC4-10 murine lymph node endothelial cells. The sulforhodamine B method and released lactate dehydrogenase (LDH) activity were used as cell viability tests. Reactive oxygen species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) were measured by spectrophotometric and fluorimetric methods. Nrf-2 protein expression was evaluated by Western blot analysis and genotoxicity by alkaline comet assay. After 24 h, the cells viability was not affected by all types and doses of nanogels. The increase of ROS induced a low decrease of GSH concentration and a time-dependent raise of MDA one was produced by citric GdDOTA⊂CS-TPP/HA with a chitosan concentration of 1.5 mg·mL−1, at the highest dose applied. None of the tested nanogels induced changes in Nrf-2 protein expression. A slight but significant genotoxic effect was caused only by citric GdDOTA⊂CS-TPP/HA where CS concentration was 1.5 mg·mL−1. Our results showed a better biocompatibility with lymph node endothelial cells for Gd-loaded hyaluronic acid-chitosan based nanogels with a concentration in chitosan of 2.5 mg·mL−1. PMID:29597306

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

PubMed

Harisa, Gamaleldin I; Badran, Mohamed M; AlQahtani, Saeed A; Alanazi, Fars K; Attia, Sabry M

2016-01-01

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer.

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer

PubMed Central

Harisa, Gamaleldin I.; Badran, Mohamed M.; AlQahtani, Saeed A.; Alanazi, Fars K.; Attia, Sabry M.

2015-01-01

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin–chitosan nanogels (PR–CNG–ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR–CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR–CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR–CNG–ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR–CNG–ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR–CNG–ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR–CNG–ER are promising drug carriers to target liver cancer. PMID:26903771

Effect of tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue

NASA Astrophysics Data System (ADS)

Sukmawati, Anita; Utami, Wahyu; Yuliani, Ratna; Da'i, Muhammad; Nafarin, Akhmad

2018-02-01

Delivery of anticancer is facing several problems including unspecific delivery of active substance to the targeted cell. The conjugation between chitosan and folate (chitosan-FA) was used for nanoparticle preparation containing combination of doxorubicin (DOX) and curcumin analogue, 2,5-bis-(4-hydroxi,3,5-dimethyl)-benzylidincylopentanone, as active substances. The purpose of this research is investigating formulation aspect for chitosan-FA nanoparticle by addition various tween 80 to achieve desired nano-size particle. The ionic gelation method was used for nanoparticle preparation using 0.05% w/v chitosan-FA with addition of 0.1 and 0.5% v/v of tween 80. The result showed that the high concentration of tween 80 during nanoparticle preparation lead to formation of smaller size particle. The 111.8 ±4.11 nm particle size was revealed by addition of 0.5% v/v tween 80 during chitosan-FA nanoparticle preparation loaded with active substances.

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.

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.

Comparative evaluation of in vitro parameters of tamoxifen citrate loaded poly(lactide-co-glycolide), poly(epsilon-caprolactone) and chitosan nanoparticles.

PubMed

Cirpanli, Y; Yerlikaya, F; Ozturk, K; Erdogar, N; Launay, M; Gegu, C; Leturgez, T; Bilensoy, E; Calis, S; Capan, Y

2010-12-01

Tamoxifen (TAM), the clinical choice for the antiestrogen treatment of advanced or metastatic breast cancer, was formulated in nanoparticulate carrier systems in the form of poly(lactide-co-glycolide) (PLGA), poly-epsilon-caprolactone (PCL) and chitosan (CS) nanoparticles. The PLGA and PCL nanoparticles were prepared by a nanoprecipitation technique whereas the CS nanoparticles were prepared by the ionic gelation method. Mean particle sizes were under 260 nm for PLGA and PCL nanoparticles and around 400 nm for CS nanoparticles. Polydispersity indices were less than 0.4 for all formulations. Zeta potential values were positive for TAM loaded nanoparticles because of the positive charge of the drug. Drug loading values were significantly higher for PCL nanoparticles when compared to PLGA and CS nanoparticles. All nanoparticle formulations exhibited controlled release properties. These results indicate that TAM loaded PLGA, PCL and CS nanoparticles may provide promising carrier systems for tumor targeting.

Fabrication of monodispersive nanoscale alginate-chitosan core-shell particulate systems for controlled release studies

NASA Astrophysics Data System (ADS)

Körpe, Didem Aksoy; Malekghasemi, Soheil; Aydın, Uğur; Duman, Memed

2014-12-01

Biopolymers such as chitosan and alginate are widely used for controlled drug delivery systems. The present work aimed to develop a new protocol for preparation of monodisperse alginate-coated chitosan nanoparticles at nanoscale. Modifications of preparation protocol contain changing the pH of polymer solutions and adding extra centrifugation steps into the procedure. While chitosan nanoparticles were synthesized by ionic gelation method, they were coated with alginate by electrostatic interaction. The size, morphology, charge, and structural characterization of prepared core-shell nanoparticulated system were performed by AFM, Zeta sizer, and FTIR. BSA and DOX were loaded as test biomolecules to core and shell part of the nanoparticle, respectively. Release profiles of BSA and DOX were determined by spectrophotometry. The sizes of both chitosan and alginate-coated chitosan nanoparticles which were prepared by modified protocol were measured to be 50 ± 10 and 60 ± 3 nm, respectively. After loading BSA and DOX, the average size of the particles increased to 80 ± 7 nm. Moreover, while the zeta potential of chitosan nanoparticles was positive value, the value was inverted to negative after alginate coating. Release profile measurements of BSA and DOX were determined during 57 and 2 days, respectively. Our results demonstrated that monodisperse alginate-coated nanoparticles were synthesized and loaded successfully using our modified protocol.

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.

Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil.

PubMed

Di Martino, Antonio; Kucharczyk, Pavel; Capakova, Zdenka; Humpolicek, Petr; Sedlarik, Vladimir

2017-09-01

In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by 1 H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120-200nm and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing.

PubMed

Lord, Megan S; Ellis, April L; Farrugia, Brooke L; Whitelock, John M; Grenett, Hernan; Li, Chuanyu; O'Grady, Robert L; DeCarlo, Arthur A

2017-03-28

The repair of dermal wounds, particularly in the diabetic population, poses a significant healthcare burden. The impaired wound healing of diabetic wounds is attributed to low levels of endogenous growth factors, including vascular endothelial growth factor (VEGF), that normally stimulate multiple phases of wound healing. In this study, chitosan scaffolds were prepared via freeze drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for their ability to promote dermal wound healing. The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted dermal wound healing in normal and diabetic rats. This treatment resulted in an increase in the number of blood vessels and sub-epithelial connective tissue matrix components within the wound beds compared to wounds treated with chitosan scaffolds containing control DNA or wounded controls. These results suggest that chitosan scaffolds containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogenesis and wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Formulation and statistical optimization of gastric floating alginate/oil/chitosan capsules loading procyanidins: in vitro and in vivo evaluations.

PubMed

Chen, Rencai; Guo, Xiaomin; Liu, Xuecong; Cui, Haiming; Wang, Rui; Han, Jing

2018-03-01

The aim of the present work was to develop gastric floating capsules containing oil-entrapped beads loading procyanidins. The floating beads were prepared by ionotropic gelation method using sodium alginate, CaCl 2 and chitosan. The effect of three independent parameters (concentration of sodium alginate, CaCl 2 and chitosan) on entrapment efficiency were analyzed by Box-Behnken design. The floating beads were evaluated for surface morphology, particle size, density, entrapment efficiency, buoyancy, release behavior in vitro and floating ability in vivo. The prepared beads were grossly spherical in shape and the mean size was approximately 1.54±0.17mm. The density was 0.97g/cm 3 . And the optimal conditions were as follows: concentration of sodium alginate, CaCl 2 and chitosan were 33.75mg/mL, 9.84mg/mL and 9.05mg/mL, respectively. The optimized formulation showed entrapment efficiency of 88.84±1.04% within small error-value (0.65). The release mechanism of floating capsules followed Korsmeyer-Peppas model (r 2 =0.9902) with non-Fickian release. The gastric floating capsules exhibited 100% floating percentage in vitro and they could float on the top of gastric juice for 5h in vivo. Therefore, the floating capsules are able to prolong the gastroretentive delivery of procyanidins. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and characterization of nontoxic chitosan-coated Fe3O4 particles for patulin adsorption in a juice-pH simulation aqueous.

PubMed

Luo, Ying; Zhou, Zhengkun; Yue, Tianli

2017-04-15

Chitosan-coated Fe 3 O 4 particles were prepared as a magnetic adsorbent by reverse oil-in-water micro-emulsion system using Triton X-100 as the emulsifier. Coating chitosan onto the magnetic particles was confirmed by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectra and magnetic measurements. Chitosan-coated Fe 3 O 4 adsorbent was shown to be effective for patulin adsorption with a maximum adsorption capacity of 6.67mg/g within 5h by adding 300μg adsorbents into 10mL 200μg/L patulin aqueous. In addition, the recovery rate of chitosan-coated Fe 3 O 4 adsorbent reached to 99.95% within 60min, showed its excellent recoverable performance. Moreover, in vitro cytotoxicity and acute toxicity evaluation were also conducted, the results suggested that the chitosan-coated Fe 3 O 4 adsorbent was non-cytotoxic, and had no toxic response or histopathological changes on mice. The results of this study demonstrated that chitosan-coated Fe 3 O 4 particles are promising adsorbents for patulin removal in fruit juice industry. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mucoadhesive hydrogel microparticles based on poly (methacrylic acid-vinyl pyrrolidone)-chitosan for oral drug delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2011-05-01

The study was aimed at the evaluation of N-vinyl pyrrolidone (NVP) incorporated polymethacrylic acid-chitosan microparticles for oral drug delivery applications. Poly (methacrylic acid)-chitosan (PMC) and poly(methacrylic acid-vinyl pyrrolidone)-chitosan (PMVC) microparticles were prepared by an ionic-gelation method. Mucoadhesion behaviour of these particles was evaluated by ex-vivo adhesion method using freshly excised rat intestinal tissue. Cytotoxicity and absorption enhancing property of PMC and PMVC particles were evaluated on Caco 2 cell monolayers. Protease enzyme inhibition capability and insulin loading/release properties of these hydrogel particles was evaluated under in vitro experimental conditions. Addition of NVP units enhanced the mucoadhesion behavior of PMC particles on isolated rat intestinal tissue. Both PMC and PMVC particles were found non-toxic on Caco 2 cell monolayers and PMC particles was more effective in improving paracellular transport of fluorescent dextran across Caco 2 cell monolayers as compared to PMVC particles. However, protease inhibition efficacy of PMC particles was not significantly affected with NVP addition. NVP incorporation improved the insulin release properties of PMC microparticles at acidic pH. Hydrophilic modification seems to be an interesting approach in improving mucoadhesion capability of PMC microparticles.

In vitro fibroblast migration by sustained release of PDGF-BB loaded in chitosan nanoparticles incorporated in electrospun nanofibers for wound dressing applications.

PubMed

Piran, Mehrdad; Vakilian, Saeid; Piran, Mehran; Mohammadi-Sangcheshmeh, Abdollah; Hosseinzadeh, Simzar; Ardeshirylajimi, Abdolreza

2018-01-23

Migration of fibroblasts into wound area is a critical phenomenon in wound healing process. We used an appropriate system to fabricate an electrospun bioactive scaffold with controlled release of PDGF-BB in order to induce migration of primary skin fibroblast cells. First of all, protein-loaded chitosan nanoparticles based on ionic gelation interaction between chitosan and sodium tripolyphosphate were prepared. Then polycaprolactone electrospun fibers containing chitosan nanoparticles or PDGF-BB-loaded chitosan nanoparticles were prepared. Cellular attachment and morphology of cells seeded on scaffolds with or without PDGF-BB were evaluated by using a fluorescence microscope and scanning electron microscopy. Cells were well-oriented 72 h after seeding on the scaffolds containing PDGF-BB. The mean aspect ratio of populations on scaffold containing PDGF-BB-loaded chitosan nanoparticles was significantly greater than those on the scaffold containing chitosan nanoparticles but no PDGF-BB. Furthermore, the Arp2 gene, which is involved in cell protrusion formation, showed about three times more expression at mRNA level, in cells seeding on PDGF-BB-containing scaffold compared to cells seeding on scaffold containing only chitosan nanoparticles, using Real Time PCR test. Finally, under agarose migration assay results demonstrated that cells' chemotaxic behavior was more toward scaffold containing PDGF-BB compared to the PDGF-BB alone or FBS group. In addition, in terms of distance, the cell mass could grow faster, in response to scaffold containing PDGF-BB compared to FBS or PDGF-BB alone; however, the number of migrating cells might be the same or significantly higher in the latter groups.

Structural, optical and magnetic properties of gadolinium sesquioxide nanobars synthesized via thermal decomposition of gadolinium oxalate

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

Manigandan, R.; Giribabu, K.; Suresh, R.

2013-10-15

Graphical abstract: - Highlights: • The cubic Gd{sub 2}O{sub 3} nanobars are synthesized by decomposition of C{sub 6}H{sub 20}Gd{sub 2}O{sub 22}. • The nanoparticles are rectangular bar shape with high porous surface. • The combination of magnetic and optical properties within a single particle. • The Gd{sub 2}O{sub 3} nanobars have tailorable nanostructure, wide bandgap and are paramagnetic. - Abstract: Gadolinium oxide nanobars were obtained by thermal decomposition of gadolinium oxalate, which was synthesized by the chemical precipitation method along with glycerol. The functional group analysis and formation of gadolinium oxide from gadolinium oxalate were characterized by the Fourier transformmore » infrared spectroscopy and thermo gravimetric analyzer. The crystal structure, average crystallite size, and lattice parameter were analyzed by X-ray diffraction technique. Moreover, Raman shifts, elemental composition and morphology of the gadolinium oxide was widely investigated by the laser Raman microscope, X-ray photoelectron spectroscopy, FE-SEM-EDAX and HR-TEM, respectively. Furthermore, the optical properties like band gap, absorbance measurement of the gadolinium oxide were extensively examined. In addition, the paramagnetic property of gadolinium oxide nanobars was explored by the vibrating sample magnetometer.« less

Preparation of curcumin-loaded pluronic F127/chitosan nanoparticles for cancer therapy

NASA Astrophysics Data System (ADS)

Phuc Le, Thi Minh; Phuc Pham, Van; Lua Dang, Thi Minh; Huyen La, Thi; Hanh Le, Thi; Huan Le, Quang

2013-06-01

Nanoparticles (NPs) have been proven to be an effective delivery system with few side effects for anticancer drugs. In this study, curcumin-loaded NPs have been prepared by an ionic gelation method using chitosan (Chi) and pluronic®F-127 (PF) as carriers to deliver curcumin to the target cancer cells. Prepared NPs were characterized using Zetasizer, fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Our results showed that the encapsulation efficiency of curcumin was approximately 50%. The average size of curcumin-loaded PF/Chi NPs was 150.9 nm, while the zeta potential was 5.09 mV. Cellular uptake of curcumin-loaded NPs into HEK293 cells was confirmed by fluorescence microscopy.

Formulation, Characterization and Stability Assessment of a Food-Derived Tripeptide, Leucine-Lysine-Proline Loaded Chitosan Nanoparticles.

PubMed

Danish, Minna K; Vozza, Giuliana; Byrne, Hugh J; Frias, Jesus M; Ryan, Sinéad M

2017-09-01

The chicken- or fish-derived tripeptide, leucine-lysine-proline (LKP), inhibits the angiotensin converting enzyme and may be used as an alternative treatment for prehypertension. However, it has low permeation across the small intestine. The formulation of LKP into a nanoparticle (NP) has the potential to address this issue. LKP-loaded NPs were produced using an ionotropic gelation technique, using chitosan (CL113). Following optimization of unloaded NPs, a mixture amount design was constructed using variable concentration of CL113 and tripolyphosphate at a fixed LKP concentration. Resultant particle sizes ranged from 120 to 271 nm, zeta potential values from 29 to 37 mV, and polydispersity values from 0.3 to 0.6. A ratio of 6:1 (CL113:TPP) produced the best encapsulation of approximately 65%. Accelerated studies of the loaded NPs indicated stability under normal storage conditions (room temperature). Cytotoxicity assessment showed no significant loss of cell viability and in vitro release studies indicated an initial burst followed by a slower and sustained release. © 2017 Institute of Food Technologists®.

Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique.

PubMed

Rodriguez, Lidia B; Avalos, Abraham; Chiaia, Nicholas; Nadarajah, Arunan

2017-05-01

There are many studies about the synthesis of chitosan microparticles; however, most of them have very low production rate, have wide size distribution, are difficult to reproduce, and use harsh crosslinking agents. Uniform microparticles are necessary to obtain repeatable drug release behavior. The main focus of this investigation was to study the effect of the process and formulation parameters during the preparation of chitosan microparticles in order to produce particles with narrow size distribution. The technique evaluated during this study was emulsion crosslinking technique. Chitosan is a biocompatible and biodegradable material but lacks good mechanical properties; for that reason, chitosan was ionically crosslinked with sodium tripolyphosphate (TPP) at three different ratios (32, 64, and 100%). The model drug used was acetylsalicylic acid (ASA). During the preparation of the microparticles, chitosan was first mixed with ASA and then dispersed in oil containing an emulsifier. The evaporation of the solvents hardened the hydrophilic droplets forming microparticles with spherical shape. The process and formulation parameters were varied, and the microparticles were characterized by their morphology, particle size, drug loading efficiency, and drug release behavior. The higher drug loading efficiency was achieved by using 32% mass ratio of TPP to chitosan. The average microparticle size was 18.7 μm. The optimum formulation conditions to prepare uniform spherical microparticles were determined and represented by a region in a triangular phase diagram. The drug release analyses were evaluated in phosphate buffer solution at pH 7.4 and were mainly completed at 24 h.

Nano-Chitosan Particles in Anticancer Drug Delivery: An Up-to-Date Review.

PubMed

Kamath, Pooja R; Sunil, Dhanya

2017-01-01

Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment has exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access into the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive. This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery. • Efforts to improve cancer chemotherapy by exploiting the intrinsic differences between normal and neoplastic cells to achieve maximum effective drug delivery to target cancer cells through bioengineered chitosan nano delivery vectors are discussed. • The easy manipulation of surface characteristics of chitosan based nanoparticles by various functionalization methods to achieve targeted drug delivery proves its potential to be an essential tool for the advancement of anticancer drug-delivery vectors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Preparation and characterisation of alendronate-loaded chitosan microparticles obtained through the spray drying technique.

PubMed

Ochiuz, Lacramioara; Peris, José-Esteban

2009-03-01

Microparticles of chitosan (CHT) containing alendronate sodium (AL) were prepared in four drug:polymer ratios (1:1, 1:2, 1:4, 1:6) using the spray drying technique. The efficiency of the method was evaluated by determining production yield (about 70 %) and microencapsulation efficiency, which was almost 100 % in the case of all four of the formulations studied. Particles had a mean size of between 3.6 and 4.6 microm, and a near-spherical shape. The formulations with the highest content of AL (drug:polymer ratio 1:1 and 1:2) showed an asymmetrical distribution of particles, which were larger in size, and had a higher proportion of irregular particles than the other formulations. FT-IR analysis revealed an ionic interaction between AL and CHT. Differential scanning calorimetry and thermogravimetric analysis confirmed the microencapsulation of AL and the increased thermal stability of encapsulated AL. The dissolution profiles of AL from CHT microspheres, at pH values of 1.2 and 6.8, showed a delayed release of AL from microspheres, and the dissolution rate was dependent on the pH and the drug:polymer ratio. It can be concluded that spray drying is a suitable technique for preparing AL-loaded CHT microspheres, and that the drug:polymer ratio can be used to control the rate of AL release from microspheres.

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.

Colon-specific delivery of 5-aminosalicylic acid from chitosan-Ca-alginate microparticles.

PubMed

Mladenovska, K; Raicki, R S; Janevik, E I; Ristoski, T; Pavlova, M J; Kavrakovski, Z; Dodov, M G; Goracinova, K

2007-09-05

Chitosan-Ca-alginate microparticles for colon-specific delivery and controlled release of 5-aminosalicylic acid after peroral administration were prepared using spray drying method followed by ionotropic gelation/polyelectrolyte complexation. Physicochemical characterization pointed to the negatively charged particles with spherical morphology having a mean diameter less than 9 microm. Chitosan was localized dominantly in the particle wall, while for alginate, a homogeneous distribution throughout the particles was observed. (1)H NMR, FTIR, X-ray and DSC studies indicated molecularly dispersed drug within the particles with preserved stability during microencapsulation and in simulated in vivo drug release conditions. In vitro drug release studies carried out in simulated in vivo conditions in respect to pH, enzymatic and salt content confirmed the potential of the particles to release the drug in a controlled manner. The diffusional exponents according to the general exponential release equation indicated anomalous (non-Fickian) transport in 5-ASA release controlled by a polymer relaxation, erosion and degradation. Biodistribution studies of [(131)I]-5-ASA loaded chitosan-Ca-alginate microparticles, carried out within 2 days after peroral administration to Wistar male rats in which TNBS colitis was induced, confirmed the dominant localization of 5-ASA in the colon with low systemic bioavailability.

Effective immobilization of glucose oxidase on chitosan submicron particles from gladius of Todarodes pacificus for glucose sensing.

PubMed

Anusha, J R; Fleming, Albin T; Kim, Hee-Je; Kim, Byung Chul; Yu, Kook-Hyun; Raj, C Justin

2015-08-01

An effective enzymatic glucose biosensor was developed by immobilizing glucose oxidase on chitosan submicron particles synthesized from the gladius of Todarodes pacificus (GCSP). The chemically synthesized chitosan from gladius was pulverized to submicron particles by ball milling technique, which was further characterized and compared with the standard chitosan (SCS). The degree of deacetylation of GCSP was determined using FTIR spectroscopy which was comparable to the value of standard chitosan. The glucose oxidase (GOx) was immobilized over GCSP on porous zinc oxide/platinum nanoparticle (ZnO/Pt) based electrode. The morphological and structural properties of the electrodes were analyzed using scanning electron microscopy and X-ray diffraction analysis. The glucose sensing behavior of electrode was estimated using electrochemical analysis and showed an excellent analytical performance. The electrode ZnO/Pt/GCSP conjugated with GOx displayed high sensitivity (88.76 μA mM(-1) cm(-2)) with low detection limit in short response time. In addition, the very low value of Michaelis-Menten constant for GCSP based electrode contributes a better affinity of the electrode surface towards glucose oxidase. Copyright © 2015 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.

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.

Fabrication and characterization of Pickering emulsions and oil gels stabilized by highly charged zein/chitosan complex particles (ZCCPs).

PubMed

Wang, Li-Juan; Yin, Shou-Wei; Wu, Lei-Yan; Qi, Jun-Ru; Guo, Jian; Yang, Xiao-Quan

2016-12-15

Herein, we reported a facile method to fabricate ultra-stable, surfactant- and antimicrobial-free Pickering emulsions by designing and modulating emulsions' interfaces via zein/chitosan colloid particles (ZCCPs). Highly charged ZCCPs with neutral wettability were produced by a facile anti-solvent procedure. The ZCCPs were shown to be effective Pickering emulsifiers because the emulsions formed were highly resistant to coalescence over a 9-month storage period. The ZCCPs were adsorbed irreversibly at the interface during emulsification, forming a hybrid network framework in which zein particles were embedded within the chitosan network, yielding ultra-stable food-grade zein/chitosan colloid particles stabilized Pickering emulsions (ZCCPEs). Moreover, stable surfactant-free oil gels were obtained by a one-step freeze-drying process of the precursor ZCCPEs. This distinctive interfacial architecture accounted for the favourable physical performance, and potentially oxidative and microbial stability of the emulsions and/or oil gels. This work opens up a promising route via a food-grade Pickering emulsion-template approach to transform liquid oil into solid-like fats with zero trans-fat formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery.

PubMed

Kumar, Manoj; Pandey, Ravi Shankar; Patra, Kartik Chandra; Jain, Sunil Kumar; Soni, Muarai Lal; Dangi, Jawahar Singh; Madan, Jitender

2013-10-01

Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

PubMed

Ye, Bai-Liang; Zheng, Ru; Ruan, Xiao-Jiao; Zheng, Zhi-Hai; Cai, Hua-Jie

2018-01-01

Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and characterisation of PEG modified chitosan nanocapsules loaded with thymoquinone.

PubMed

Vignesh Kumar, Suresh Kumar; Renuka Devi, Ponnuswamy; Harish, Saru; Hemananthan, Eswaran

2017-02-01

Thymoquinone (TQ), a major bioactive compound of Nigella sativa seeds has several therapeutic properties. The main drawback in bringing TQ to therapeutic application is that it has poor stability and bioavailability. Hence a suitable carrier is essential for TQ delivery. Recent studies indicate biodegradable polymers are potentially good carriers of bioactive compounds. In this study, polyethylene glycol (PEG) modified chitosan (Cs) nanocapsules were developed as a carrier for TQ. Aqueous soluble low molecular weight Cs and PEG was selected among different biodegradable polymers based on their biocompatibility and efficacy as a carrier. Optimisation of synthesis of nanocapsules was done based on particle size, PDI, encapsulation efficiency and process yield. A positive zeta potential value of +48 mV, indicating good stability was observed. Scanning electron microscope and atomic-force microscopy analysis revealed spherical shaped and smooth surfaced nanocapsules with size between 100 to 300 nm. The molecular dispersion of the TQ in Cs PEG nanocapsules was studied using X-ray powder diffraction. The Fourier transform infrared spectrum of optimised nanocapsule exhibited functional groups of both polymer and drug, confirming the presence of Cs, PEG and TQ. In vitro drug release studies showed that PEG modified Cs nanocapsules loaded with TQ had a slow and sustained release.

One-step synthesis of magnetic chitosan for controlled release of 5-hydroxytryptophan

NASA Astrophysics Data System (ADS)

Santos Menegucci, Jucély dos; Santos, Mac-Kedson Medeiros Salviano; Dias, Diego Juscelino Santos; Chaker, Juliano Alexandre; Sousa, Marcelo Henrique

2015-04-01

In this work, nanoparticles of chitosan embedded with 25% (w/w) of iron oxide magnetic nanoparticles (magnetite/maghemite) with narrow size-distribution and with a loading efficiency of about 80% for 5-hydroxytryptophan (5-HTP), which is a chemical precursor in the biosynthesis of important neurotransmitters as serotonin, were synthesized with an initial mass ratio of 5-HTP/magnetic chitosan=1.2, using homogeneous precipitation by urea decomposition, in an efficient one-step procedure. Characterization of morphology, structure and surface were performed by XRD, TEM, FTIR, TGA, magnetization and zeta potential measurements, while drug loading and drug releasing were investigated using UV-vis spectroscopy. Kinetic drug release experiments under different pH conditions revealed a pH-sensitivecontrolled-release system, ruled by polymer swelling and/or particle dissolution.

Physicochemical aspects involved in methotrexate release kinetics from biodegradable spray-dried chitosan microparticles

NASA Astrophysics Data System (ADS)

Mesquita, Philippe C.; Oliveira, Alice R.; Pedrosa, Matheus F. Fernandes; de Oliveira, Anselmo Gomes; da Silva-Júnior, Arnóbio Antônio

2015-06-01

Spray dried methotrexate (MTX) loaded chitosan microparticles were prepared using different drug/copolymer ratios (9%, 18%, 27% and 45% w/w). The physicochemical aspects were assessed in order to select particles that were able to induce a sustained drug release effect. Particles were successfully produced which exhibited desired physicochemical aspects such as spherical shape and high drug loading. XRD and FT-IR analysis demonstrated that drug is not bound to copolymer and is only homogeneously dispersed in an amorphous state into polymeric matrix. Even the particles with higher drug loading levels presented a sustained drug release profile, which were mathematically modeled using adjusted Higuchi model. The drug release occurred predominantly with drug dissolution and diffusion through swollen polymeric matrix, with the slowest release occurring with particles containing 9% of drug, demonstrating an interesting and promising drug delivery system for MTX.

Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin.

PubMed

Chen, Shuangxi; Guo, Feng; Deng, Tiantian; Zhu, Siqi; Liu, Wenyu; Zhong, Haijun; Yu, Hua; Luo, Rong; Deng, Zeyuan

2017-05-01

In order to improve oral absorption of insulin, especially the absorption at the colon, Eudragit S100® (ES)-coated chitosan nanoparticles loading insulin and a trans-activating transcriptional peptide (Tat) were employed as the vehicle. In vitro releases of insulin and Tat from ES-coated chitosan nanoparticles had a pH-dependant characteristic. A small amount of the contents was released from the coated nanoparticles at pH 1.2 simulated gastric fluid, while a fairly fast and complete release was observed in pH 7.4 medium. Caco-2 cell was used as the model of cellular transport and uptake studies. The results showed that the cellular transport and uptake of insulin for ES-coated chitosan nanoparticles co-loading insulin and Tat (ES-Tat-cNPs) were about 3-fold and 4-fold higher than those for the nanoparticles loading only insulin (ES-cNPs), respectively. The evaluations in vivo of ES-Tat-cNPs were conducted on diabetic rats and normal minipigs, respectively. The experimental results on rats revealed that the pharmacodynamical bioavailability of ES-Tat-cNPs had 2.16-fold increase compared with ES-cNPs. After oral administration of nanoparticle suspensions to the minipigs, insulin bioavailability of ES-Tat-cNPs was 1.73-fold higher than that of ES-cNPs, and the main absorption site of insulin was probably located in the colon for the two nanoparticles. In summary, this report provided an exploratory means for the improvement of oral absorption of insulin.

A temperature-induced and shear-reversible assembly of latanoprost-loaded amphiphilic chitosan colloids: characterization and in vivo glaucoma treatment.

PubMed

Hsiao, Meng-Hsuan; Chiou, Shih-Hwa; Larsson, Mikael; Hung, Kuo-Hsuan; Wang, Yi-Ling; Liu, Catherine Jui-Ling; Liu, Dean-Mo

2014-07-01

Hydrogels composed of assembled colloids is a material class that is currently receiving much interest and shows great promise for use in biomedical applications. This emerging material class presents unique properties derived from the combination of nanosized domains in the form of colloidal particles with a continuous gel network and an interspersed liquid phase. Here we developed an amphiphilic chitosan-based, thermogelling, shear-reversible colloidal gel system for improved glaucoma treatment and addressed how preparation procedures and loading with the anti-glaucoma drug latanoprost and commonly used preservative benzalkonium chloride influenced the mechanical properties of and drug release from the colloidal gels. The results highlight that incorporated substances and preparation procedures have effects both on mechanical properties and drug release, but that the release of drug loaded in the colloidal carriers is mainly limited by transport out of the carriers, rather than by diffusion within the gel. The developed colloidal chitosan based gels hold outstanding biomedical potential, as confirmed by the ease of preparation and administration, low cytotoxicity in MTT assay, excellent biocompatibility and lowering of intraocular pressure for 40 days in a rabbit glaucoma model. The findings clearly justify further investigations towards clinical use in the treatment of glaucoma. Furthermore, the use of this shear-reversible colloidal gel could easily be extended to localized treatment of a number of critical conditions, from chronic disorders to cancer, potentially resulting in a number of new therapeutics with improved clinical performance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Simultaneous Effect of Thiolation and Carboxylation of Chitosan Particles Towards Mucoadhesive Oral Insulin Delivery Applications: An In Vitro and In Vivo Evaluation.

PubMed

Rekha, M R; Sharma, Chandra P

2015-01-01

Thiomalyl chitosan (TCS), a pH sensitive thiolated chitosan derivative, was developed and investigated towards oral protein delivery application. Particles of z-average 364 ± 5.6 nm with a negative zeta potential of 14.4 mV was obtained by tripolyphosphate cross linking of TCS. The release of insulin from TCS particles was significantly restricted at pH 1.2 minimizing up to about < 10% in 3 hours. The permeation enhancement ratio was found to 13 times higher than the FD4 alone and was 1.6 times higher than the unmodified chitosan particles. The protein protective properties of the matrix were established in presence of pepsin and pancreatic enzymes. Confocal microscopy studies proved the tight junction opening of Caco-2 cells by these thiolated chitosan particles and the in vivo studies on diabetic rats established its potential towards oral peptide delivery with pharmacological availability (PA) of 1.5%. The significance of this work is to establish that, the presence of multiple functional groups having similar property in the same matrix can improve its suitability as a promising candidate for oral peptide delivery with improved release characteristics, mucoadhesion as well as protecting the insulin activity and enhancing the permeability across the intestinal wall.

Constructing experimental devices for half-ton synthesis of gadolinium-loaded liquid scintillator and its performance.

PubMed

Park, Young Seo; Jang, Yeong Min; Joo, Kyung Kwang

2018-04-01

This paper describes in brief features of various experimental devices constructed for half-ton synthesis of gadolinium(Gd)-loaded liquid scintillator (GdLS) and also includes the performances and detailed chemical and physical results of a 0.5% high-concentration GdLS. Various feasibility studies on useful apparatus used for loading Gd into solvents have been carried out. The transmittance, Gd concentration, density, light yield, and moisture content were measured for quality control. We show that with the help of adequate automated experimental devices and tools, it is possible to perform ton scale synthesis of GdLS at moderate laboratory scale without difficulty. The synthesized GdLS was satisfactory to meet chemical, optical, and physical properties and various safety requirements. These synthesizing devices can be expanded into massive scale next-generation neutrino experiments of several hundred tons.

Constructing experimental devices for half-ton synthesis of gadolinium-loaded liquid scintillator and its performance

NASA Astrophysics Data System (ADS)

Park, Young Seo; Jang, Yeong Min; Joo, Kyung Kwang

2018-04-01

This paper describes in brief features of various experimental devices constructed for half-ton synthesis of gadolinium(Gd)-loaded liquid scintillator (GdLS) and also includes the performances and detailed chemical and physical results of a 0.5% high-concentration GdLS. Various feasibility studies on useful apparatus used for loading Gd into solvents have been carried out. The transmittance, Gd concentration, density, light yield, and moisture content were measured for quality control. We show that with the help of adequate automated experimental devices and tools, it is possible to perform ton scale synthesis of GdLS at moderate laboratory scale without difficulty. The synthesized GdLS was satisfactory to meet chemical, optical, and physical properties and various safety requirements. These synthesizing devices can be expanded into massive scale next-generation neutrino experiments of several hundred tons.

Synthesis and properties of platinum on multiwall carbon nanotube modified by chitosan

NASA Astrophysics Data System (ADS)

Fikriyyah, A. K.; Chaldun, E. R.; Indriyati

2018-03-01

Platinum nanoparticles on multiwall carbon nanotubes (Pt/MWCNT) play an important role in fuel cell to convert the chemical energy from a fuel into electricity. In this study, Pt/MWCNT electrocatalysts were prepared by chemical reduction of the metal salts in chitosan as the support. Firstly, commercial MWCNTs were functionalized by oxidative process using a mixture of nitric acid and sulfuric acid. Then, functionalized MWCNTs were mixed with chitosan-acetic acid solution to conduct grafting reaction with NH2 groups in chitosan by solution polymerization method. Platinum nanoparticles were loaded onto the surface of the MWCNTs after hexachloroplatinic acid was reduced by sodium hydroxide solution. The result showed that Pt was attached on MWCNT based on analysis from EDS, XRD, and UV Vis Spectroscopy. UV Vis analysis indicates the plasmon absorbance band of Pt nanoparticles in Pt/MWCNT, while XRD analysis confirmed the size of Pt particle in nanometer. This elucidates the potential procedure to synthesize Pt/MWCNT using chitosan.

Improved Chemical Stability and Antiproliferative Activities of Curcumin-Loaded Nanoparticles with a Chitosan Chlorogenic Acid Conjugate.

PubMed

Fan, Yuting; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

2017-12-13

A chitosan (CS)-chlorogenic acid (CA) conjugate was successfully prepared through free-radical-induced protocols with a substitution of CA on CS of 103.5 mg/g. ATR-FTIR and 1 H NMR results validated the covalent conjugation of CA onto CS. XRD results indicated the decrease of crystallinity after CA conjugation. DPPH-scavenging activity and reducing-power studies indicated that the CS-CA conjugate had stronger antioxidant activity than chitosan. The particle diameters of curcumin-loaded CS and CS-CA nanoparticles simultaneously formed by ionic gelling in the presence of tripolyphosphate (TPP) were less than 300 nm (243.6 and 256.5 nm, respectively), and zeta-potential values between 25 and 30 mV were obtained. TEM results showed that the nanoparticles were spherically shaped and homogeneously dispersed. Curcumin with the CS-CA conjugate showed better heat stability than with CA at both temperatures (25 and 95 °C) (p <0.05). Curcumin release was inhibited by the CS-CA conjugate. The total release amount of curcumin from CS and CS-CA-conjugate nanoparticles were 70.5 and 61.7%, respectively (p <0.05). A methyl thiazolyl tetrazolium (MTT) assay showed that the antiproliferative activity of curcumin in CS-CA nanoparticles was remarkably higher than that in CS nanoparticles because of the higher chemical stability. The results suggest that CS-CA-based nanoparticles are promising candidates for the encapsulation and controlled release of hydrophobic, bioactive compounds and can improve these compounds' chemical stabilities and anticancer activities.

Characterization and toxicology evaluation of chitosan nanoparticles on the embryonic development of zebrafish, Danio rerio.

PubMed

Wang, Yanbo; Zhou, Jinru; Liu, Lin; Huang, Changjiang; Zhou, Deqing; Fu, Linglin

2016-05-05

In the present study, chitosan nanoparticles were prepared, characterized and used to evaluate the embryonic toxicology on zebrafish (Danio rerio). The average particle size of chitosan nanoparticles was 84.86nm. The increased mortality and decreased hatching rate was found in the zebrafish embryo exposure to normal chitosan particles and chitosan nanoparticles with the increased addition concentration. At 120h post-fertilization (hpf), the rate of mortality were 25.0 and 44.4% in the groups treated with chitosan nanoparticles and normal chitosan particles at 250mg/L, respectively. At 72hpf, the hatching rate in the groups treated with normal chitosan particles were lower (P<0.01) at 300 and 400mg/L than those of the corresponding control groups, respectively. However, there were no significant differences between the groups treated with chitosan nanoparticles and the control groups across all the addition concentrations. More abundant typical malformation of embryos was observed in the groups treated with normal chitosan particles compared with those treated with chitosan nanoparticles. The LC50 (medium lethal concentration) of chitosan nanoparticles was 280mg/L at 96hpf and 270mg/L at 120hpf. As for normal chitosan particles, the LC50 was 257mg/L at both 96hpf and 120hpf. The TC50 (medium teratogenic concentration) of the zebrafish treated with chitosan nanoparticles and normal chitosan particles were 257mg/L and 137mg/L, respectively. It indicated that the chitosan nanoparticles were relatively more secure compared with normal chitosan particles. Copyright © 2016 Elsevier Ltd. All rights reserved.

"Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route* ".

PubMed

Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

2016-08-01

The objective of the present investigation was to optimize and develop quetiapine fumarate (QF) loaded chitosan nanoparticles (QF-NP) by ionic gelation method using Box-Behnken design. Three independent variables viz., X1-Concentration of chitosan, X2-Concentration of sodium tripolyphosphate and X3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y1-Size, Y2-PDI and Y3-%EE). Optimized formula of QF-NP was selected from the design space which was further evaluated for physicochemical, morphological, solid state characterization, nasal diffusion and in-vivo distribution for brain targeting following non-invasive intranasal administration. The average particle size, PDI, %EE and nasal diffusion were found to be 131.08±7.45nm, 0.252±0.064, 89.93±3.85% and 65.24±5.26% respectively. Neither toxicity nor structural damage on nasal mucosa was observed upon histopathological examination. Significantly higher brain/blood ratio and 2 folds higher nasal bioavailability in brain with QF-NP in comparison to drug solution following intranasal administration revealed preferential nose to brain transport bypassing blood-brain barrier and prolonged retention of QF at site of action suggesting superiority of chitosan as permeability enhancer. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of quaternised chitosan-loaded PMMA to inhibit biofilm formation and downregulate the virulence-associated gene expression of antibiotic-resistant staphylococcus.

PubMed

Tan, Honglue; Peng, Zhaoxiang; Li, Qingtian; Xu, Xiaofen; Guo, Shengrong; Tang, Tingting

2012-01-01

Biomaterial-associated infections remain a serious complication in orthopaedic surgery. Treatments, including the local use of antibiotic-loaded polymethylmethacrylate (PMMA) bone cement, are not always successful because of multiantibiotic-resistant organisms. In this study, we synthesised a new quaternised chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that contains a series of substitutions of quaternary ammonium and demonstrated that HACC with a 26% degree of substitution (DS; referred to as 26%HACC) had a strong antibacterial activity and simultaneously good biocompatibility with osteogenic cells. We loaded 26%HACC at 20% by weight into PMMA bone cement to investigate whether HACC in PMMA prevents bacterial biofilm formation on the surface of bone cements. Chitosan-loaded PMMA (at the same weight ratio), gentamicin-loaded PMMA and PMMA with no antibiotic were also investigated and compared. Two clinical isolates, Staphylococcus epidermidis 389 and methicillin-resistant S. epidermidis (MRSE287), and two standard strains, S. epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate the bacterial biofilm formation at 6, 12 and 24 h using the spread plate method, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The results showed that 26%HACC-loaded PMMA inhibited biofilm formation on its surface, while the PMMA control and chitosan-loaded PMMA were unable to inhibit biofilm formation. The gentamicin-loaded PMMA decreased the number of viable methicillin-resistant Staphylococcus strains, but its ability to inhibit biofilm formation was lower than 26%HACC-loaded PMMA. Real-time PCR demonstrated that 26%HACC-loaded PMMA markedly downregulated the expression of icaAD, which encodes essential enzymes for polysaccharide intercellular adhesion (PIA) biosynthesis, upregulated the expression level of icaR, which negatively mediates icaAD expression, and

Development of dorzolamide loaded 6-o-carboxymethyl chitosan nanoparticles for open angle glaucoma.

PubMed

Shinde, Ujwala; Ahmed, Mohammed Hadi; Singh, Kavita

2013-01-01

Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and (13)C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and (13)C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment.

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.

The effect of temperature and chitosan concentration during storage on the growth of chitosan nanoparticle produced by ionic gelation method

NASA Astrophysics Data System (ADS)

Handani, Wenny Rinda; Sediawan, Wahyudi Budi; Tawfiequrrahman, Ahmad; Wiratni, Kusumastuti, Yuni

2017-05-01

The objective of this research was to get the mechanism of nano size chitosan particle growth during storage by observing the effect of temperature and initial concentration of chitosan. The products were analyzed using PSA to have the average of particle radius. Nanochitosan solution was prepared by ionic gelation method. This method is described as an electrostatic interaction between positively charged amine with negatively charged polyanion, such as tripolyphosphate (TPP). Chitosan was dissolved in 1% acetic acid and was stirred for 30 minutes. Tween 80 was added to avoid agglomeration. TPP was prepared by dissolving 0.336 g into distilled water. The nano size chitosan was obtained by mixing TPP and chitosan solution dropwise while stirring for 30 minutes. This step was done at 15°C and ambient temperature (about 30°C) and chitosan concentration 0.2%, 0.4% and 0.6%. The results show that temperature during ionic gelation process (15°C and 30°C) does not affect the initial size of the nanoparticles produced as well as the growth of the nanoparticles during storage. On the other hand, initial chitosan concentration strongly affects initial size of the nanoparticles produced and the growth of the nanoparticles during storage. The concentration of chitosan at 0.2%, 0.4%, 0.6% gave initial size of nanoparticle chitosan of 175.3 nm, 337.9 nm, 643.3 nm respectively. On the other hand, the growth mechanism of chitosan nanoparticle depended on its radius(R). At R<500 nm, the growth rate of nanoparticles is controlled by adsorption at the surface of the particles, while at R>500 nm, it is controlled by diffusion in the liquid film around the particles.

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.

Measurement of mass stopping power of chitosan polymer loaded with TiO2 for relativistic electron interaction

NASA Astrophysics Data System (ADS)

Babu, S. Ramesh; Badiger, N. M.; Karidurgannavar, M. Y.; Varghese, Jolly. G.

2018-04-01

The Mass Stopping Power (MSP) of relativistic electrons in chitosan loaded with TiO2 of different proportions has been measured by recording the spectrum of internal conversion electrons. The internal conversion electrons of energies 614 keV from Cs137, 942 keV and 1016 keV from Bi207 source are allowed to pass through chitosan-TiO2 alloy and transmitted electrons are detected with a Si (Li) detector coupled to an 8 K multichannel analyzer. By knowing the energies of incident electrons and transmitted electrons, the energy loss and the MSP are determined. Thus measured MSP values of the alloys are compared with the values calculated using Braggs additivity rule. The disagreement between theory and experiment is found to increases with increasing TiO2 concentration in chitosan, indicating the influence of chemical environment in the properties of such polymeric membrane.

Doxorubicin Loaded Chitosan-W18 O49 Hybrid Nanoparticles for Combined Photothermal-Chemotherapy.

PubMed

Yuan, Shanmei; Hua, Jisong; Zhou, Yinyin; Ding, Yin; Hu, Yong

2017-08-01

Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan-W 18 O 49 nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W 18 O 49 nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near-infrared fluorescence imaging, and tumor growth inhibition experiment. These nanoparticles have a mean size around 110 nm and show a pH sensitive drug release behavior. After irradiation by the 980 nm laser, these nanoparticles show more pronounced cytotoxicity against HeLa cells than that of free doxorubicin or photothermal therapy alone. The in vivo experiments confirm that their antitumor ability is significantly improved, resulting in superior efficiency in impeding tumor growth and extension of the lifetime of mice. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

PubMed

Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

2015-01-01

Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

Chitosan Nanolayered Cisplatin-Loaded Lipid Nanoparticles for Enhanced Anticancer Efficacy in Cervical Cancer

NASA Astrophysics Data System (ADS)

Wang, Jing-yi; Wang, Yu; Meng, Xia

2016-11-01

In this study, cisplatin (CDDP)-loaded chitosan-coated solid lipid nanoparticles (SLN) was successfully formulated to treat HeLa cervical carcinoma. The formulation nanoparticles were nanosized and exhibited a controlled release of drug in physiological conditions. The blank nanoparticles exhibited an excellent biocompatibility profile indicating its suitability for cancer targeting. The incorporation of CDDP in SLN remarkably increased the cancer cell death as evident from the MTT assay. Importantly, CDDP-loaded chitosan-coated SLN (CChSLN) significantly ( P < 0.05) decreased the viability of cancer cells even at low concentration. The higher cytotoxicity potential of CChSLN was attributed to the higher cellular uptake as well as the sustained drug release manner in comparison with CSLN. Consistent with the cytotoxicity assay, CChSLN showed the lowest IC50 value of 0.6125 μg/ml while CSLN presented 1.156 μg/ml. CChSLN showed a significantly higher apoptosis in cancer cells compared to that of CSLN and CDDP, which is attributed to the better internalization of nanocarriers and controlled release of anticancer drugs in the intracellular environment. Our findings suggest that this new formulation could be a promising alternative for the treatment of cervical cancers. These findings are encouraging us to continue our research, with a more extended investigation of cellular response in real time and in animal models.

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

Preparation and antioxidant properties of selenium nanoparticles-loaded chitosan microspheres.

PubMed

Bai, Kaikai; Hong, Bihong; He, Jianlin; Hong, Zhuan; Tan, Ran

2017-01-01

Selenium nanoparticles (SeNPs), as a special form of selenium (Se) supplement, have attracted worldwide attention due to their favorable properties and unique bioactivities. Herein, an eco-friendly and economic way to prepare stable SeNPs is introduced. SeNPs were synthesized in aqueous chitosan (CTS) and then embedded into CTS microspheres by spray-drying, forming selenium nanoparticles-loaded chitosan microspheres (SeNPs-M). The physicochemical properties including morphology, elemental state, size distribution and surface potential were investigated. Institute of Cancer Research mice were used as model animal to evaluate the bioactivities of SeNPs-M. Trigonal-phase SeNPs of ~35 nm were synthesized, and SeNPs-M physically embedding those SeNPs were successfully prepared. Amazingly, acute toxicity test indicated that SeNPs-M were much safer than selenite in terms of Se dose, with a LD 50 of around 18-fold of that of selenite. In addition, SeNPs-M possessed powerful antioxidant activities, as evidenced by a dramatic increase of both Se retention and the levels of glutathione peroxidase, superoxide dismutase and catalase. The design of SeNPs-M can offer a new way for further development of SeNPs with a higher efficacy and better biosafety. Thus, SeNPs-M may be a potential candidate for further evaluation as an Se supplement with antioxidant properties and be used against Se deficiency in animals and human beings.

Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma

PubMed Central

Ahmed, Mohammed Hadi

2013-01-01

Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and 13C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and 13C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment. PMID:24222858

N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

PubMed Central

Zhang, Chun-ge; Zhu, Qiao-ling; Zhou, Yi; Liu, Yang; Chen, Wei-liang; Yuan, Zhi-Qiang; Yang, Shu-di; Zhou, Xiao-feng; Zhu, Ai-jun; Zhang, Xue-nong; Jin, Yong

2014-01-01

N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor. PMID:24966673

A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants.

PubMed

Zhao, Pengkun; Liu, Hongyu; Deng, Hongbing; Xiao, Ling; Qin, Caiqin; Du, Yumin; Shi, Xiaowen

2014-11-01

In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Alginate/Gelatin scaffolds incorporated with Silibinin-loaded Chitosan nanoparticles for bone formation in vitro.

PubMed

Leena, R S; Vairamani, M; Selvamurugan, N

2017-10-01

Silibinin is a plant derived flavonolignan known for its multiple biological properties, but its role in the promotion of bone formation has not yet been well studied. Moreover, the delivery of Silibinin is hindered by its complex hydrophobic nature, which limits its bioavailability. Hence, in this study, we fabricated a drug delivery system using chitosan nanoparticles loaded with Silibinin at different concentrations (20μM, 50μM, and 100μM). They were then incorporated into scaffolds containing Alginate and Gelatin (Alg/Gel) for the sustained and prolonged release of Silibinin. The Silibinin-loaded chitosan nanoparticles (SCN) were prepared using the ionic gelation technique, and the scaffolds (Alg/Gel-SCN) were synthesized by the conventional method of freeze drying. The scaffolds were subjected to physicochemical and material characterization studies. The addition of SCN did not affect the porosity of the scaffolds, yet increased the protein adsorption, degradation rates, and bio-mineralization. These scaffolds were biocompatible with mouse mesenchymal stem cells. The scaffolds loaded with 50μM Silibinin promoted osteoblast differentiation, which was determined at cellular and molecular levels. Recent studies indicated the role of microRNAs (miRNAs) in osteogenesis and we found that the Silibinin released from scaffolds regulated miRNAs that control the bone morphogenetic protein pathway. Hence, our results suggest the potential for sustained and prolonged release of Silibinin to promote bone formation and, thus, these Alg/Gel-SCN scaffolds may be candidates for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Facile approach to prepare drug-loading film from hemicelluloses and chitosan.

PubMed

Guan, Ying; Qi, Xian-Ming; Chen, Ge-Gu; Peng, Feng; Sun, Run-Cang

2016-11-20

This study introduces a facile and green route to fabricate film from bio-based polymers. The film has been prepared by the cross-linking reaction of quaternized hemicelluloses (QH) and chitosan (CHO) with epichlorohydrin (ECH) as crosslinker. It exhibits an excellently mechanical performance as a result of its high tensile strength (up to 37MPa). Importantly, the roughness of film was 2-5nm in the area of 400nm, and smooth surface with pores were presented on the film based on the results of scanning electron microscope (SEM) and atomic force microscope (AFM). Ciprofloxacin was utilized as a mode compound to investigate the loading behavior of the film, and the highest loading concentration was about 18%. The drug release was about 20% in film1 in comparison to only 15% in film3 within 48h. Furthermore, the results of a 293T cell viability assay indicated its good biocompatibility and non-toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Validation of the analytical methods in the LWR code BOXER for gadolinium-loaded fuel pins

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

Paratte, J.M.; Arkuszewski, J.J.; Kamboj, B.K.

1990-01-01

Due to the very high absorption occurring in gadolinium-loaded fuel pins, calculations of lattices with such pins present are a demanding test of the analysis methods in light water reactor (LWR) cell and assembly codes. Considerable effort has, therefore, been devoted to the validation of code methods for gadolinia fuel. The goal of the work reported in this paper is to check the analysis methods in the LWR cell/assembly code BOXER and its associated cross-section processing code ETOBOX, by comparison of BOXER results with those from a very accurate Monte Carlo calculation for a gadolinium benchmark problem. Initial results ofmore » such a comparison have been previously reported. However, the Monte Carlo calculations, done with the MCNP code, were performed at Los Alamos National Laboratory using ENDF/B-V data, while the BOXER calculations were performed at the Paul Scherrer Institute using JEF-1 nuclear data. This difference in the basic nuclear data used for the two calculations, caused by the restricted nature of these evaluated data files, led to associated uncertainties in a comparison of the results for methods validation. In the joint investigations at the Georgia Institute of Technology and PSI, such uncertainty in this comparison was eliminated by using ENDF/B-V data for BOXER calculations at Georgia Tech.« less

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

Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

PubMed

Park, Sohyeon; Choi, Daheui; Jeong, Hyejoong; Heo, Jiwoong; Hong, Jinkee

2017-10-02

The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

Preparation and antioxidant properties of selenium nanoparticles-loaded chitosan microspheres

PubMed Central

Bai, Kaikai; Hong, Bihong; He, Jianlin; Hong, Zhuan; Tan, Ran

2017-01-01

Selenium nanoparticles (SeNPs), as a special form of selenium (Se) supplement, have attracted worldwide attention due to their favorable properties and unique bioactivities. Herein, an eco-friendly and economic way to prepare stable SeNPs is introduced. SeNPs were synthesized in aqueous chitosan (CTS) and then embedded into CTS microspheres by spray-drying, forming selenium nanoparticles-loaded chitosan microspheres (SeNPs-M). The physicochemical properties including morphology, elemental state, size distribution and surface potential were investigated. Institute of Cancer Research mice were used as model animal to evaluate the bioactivities of SeNPs-M. Trigonal-phase SeNPs of ~35 nm were synthesized, and SeNPs-M physically embedding those SeNPs were successfully prepared. Amazingly, acute toxicity test indicated that SeNPs-M were much safer than selenite in terms of Se dose, with a LD50 of around 18-fold of that of selenite. In addition, SeNPs-M possessed powerful antioxidant activities, as evidenced by a dramatic increase of both Se retention and the levels of glutathione peroxidase, superoxide dismutase and catalase. The design of SeNPs-M can offer a new way for further development of SeNPs with a higher efficacy and better biosafety. Thus, SeNPs-M may be a potential candidate for further evaluation as an Se supplement with antioxidant properties and be used against Se deficiency in animals and human beings. PMID:28684913

Healing of skin wounds with a chitosan-gelatin sponge loaded with tannins and platelet-rich plasma.

PubMed

Lu, Bitao; Wang, Tianyou; Li, Zhiquan; Dai, Fangying; Lv, Lingmei; Tang, Fengling; Yu, Kun; Liu, Jiawei; Lan, Guangqian

2016-01-01

A chitosan-gelatin sponge (CSGT) was prepared using a chitosan/ascorbic acid solution blend containing gelatin, followed by crosslinking with tannin acid and freeze-drying, thereby combining the chitosan sponge and gelatin sponge. The structure of the CSGT was observed by scanning electron microscopy and was shown to have uniform and abundant pores measuring about 145-240μm in size. We also characterized the sponges by infrared spectroscopy, thermogravimetric analysis, mechanical property tests, swelling behavior analysis, water retention capacity tests, antibacterial property analysis, and cytotoxicity tests. Our data showed that the CSGT had good thermostability and mechanical properties as well as efficient water absorption and retention capacities. Moreover, the CSGT could effectively inhibit the growth of Escherichia coli and Staphylococcus aureus with low toxicity. In animal experiments, macroscopic observations and histological examinations showed that the wound covered by the CSGT healed quickly. Additionally, loading of the CSGT with platelet-rich plasma resulted in further acceleration of wound healing. Therefore, the CSGT and the CSGT with platelet-rich plasma were suitable for application as a wound dressing and may have potential for use in various biomedical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Strong adhesion and cohesion of chitosan in aqueous solutions

PubMed Central

Lee, Dong Woog; Lim, Chanoong; Israelachvili, Jacob N.; Hwang, Dong Soo

2014-01-01

Chitosan, a load-bearing biomacromolecule found in the exoskeletons of crustaceans and insects, is a promising biopolymer for the replacement of synthetic plastic compounds. Here, surface interactions mediated by chitosan in aqueous solutions, including the effects of pH and contact time, were investigated using a surface forces apparatus (SFA). Chitosan films showed an adhesion to mica for all tested pH ranges (3.0–8.5), achieving a maximum value at pH 3.0 after a contact time of 1 hr (Wad ~6.4 mJ/m2). We also found weak or no cohesion between two opposing chitosan layers on mica in aqueous buffer until the critical contact time for maximum adhesion (chitosan-mica) was reached. Strong cohesion (Wco ~8.5 mJ/m2) between the films was measured with increasing contact times up to 1 hr at pH 3.0, which is equivalent to ~60% of the strongest, previously reported, mussel underwater adhesion. Such time-dependent adhesion properties are most likely related to molecular or molecular group reorientations and interdigitations. At high pH (8.5), the solubility of chitosan changes drastically, causing the chitosan-chitosan (cohesion) interaction to be repulsive at all separation distances and contact times. The strong contact time and pH-dependent chitosan-chitosan cohesion and adhesion properties provide new insight into the development of chitosan based load-bearing materials. PMID:24138057

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.

Preparation of chitosan/tripolyphosphate nanoparticles with highly tunable size and low polydispersity.

PubMed

Sawtarie, Nader; Cai, Yuhang; Lapitsky, Yakov

2017-09-01

Nanoparticles prepared through the ionotropic gelation of chitosan with tripolyphosphate (TPP) have been extensively studied as vehicles for drug and gene delivery. Though a number of these works have focused on preparing particles with narrow size distributions, the monodisperse particles produced by these methods have been limited to narrow size ranges (where the average particle size was not varied by more than twofold). Here we show how, by tuning the NaCl concentration in the parent chitosan and TPP solutions, low-polydispersity particles with z-average diameters ranging between roughly 100 and 900nm can be prepared. Further, we explore how the size of these particles depends on the method by which the TPP is mixed into the chitosan solution, specifically comparing: (1) single-shot mixing; (2) dropwise addition; and (3) a dilution technique, where chitosan and TPP are codissolved at a high (gelation-inhibiting) ionic strength and then diluted to lower ionic strengths to trigger gelation. Though the particle size increases sigmoidally with the NaCl concentration for all three mixing methods, the dilution method delivers the most uniform/gradual size increase - i.e., it provides the most precise control. Also investigated are the effects of mixture composition and mixing procedure on the particle yield. These reveal the particle yield to increase with the chitosan/TPP concentration, decrease with the NaCl concentration, and vary only weakly with the mixing protocol; thus, at elevated NaCl concentrations, it may be beneficial to increase chitosan and TPP concentrations to ensure high particle yields. Finally, possible pitfalls of the salt-assisted size control strategy (and their solutions) are discussed. Taken together, these findings provide a simple and reliable method for extensively tuning chitosan/TPP particle size while maintaining narrow size distributions. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Response of gadolinium doped liquid scintillator to charged particles: measurement based on intrinsic U/Th contamination

NASA Astrophysics Data System (ADS)

Du, Q.; Lin, S. T.; He, H. T.; Liu, S. K.; Tang, C. J.; Wang, L.; Wong, H. T.; Xing, H. Y.; Yue, Q.; Zhu, J. J.

2018-04-01

A measurement is reported for the response to charged particles of a liquid scintillator named EJ-335 doped with 0.5% gadolinium by weight. This liquid scintillator was used as the detection medium in a neutron detector. The measurement is based on the in-situ α-particles from the intrinsic Uranium and Thorium contamination in the scintillator. The β–α and the α–α cascade decays from the U/Th decay chains were used to select α-particles. The contamination levels of U/Th were consequently measured to be (5.54±0.15)× 10‑11 g/g, (1.45±0.01)× 10‑10 g/g and (1.07±0.01)× 10‑11 g/g for 232Th, 238U and 235U, respectively, assuming secular equilibrium. The stopping power of α-particles in the liquid scintillator was simulated by the TRIM software. Then the Birks constant, kB, of the scintillator for α-particles was determined to be (7.28±0.23) mg/(cm2ṡMeV) by Birks' formulation. The response for protons is also presented assuming the kB constant is the same as for α-particles.

Gadolinium toxicity and treatment.

PubMed

Ramalho, Joana; Ramalho, Miguel; Jay, Michael; Burke, Lauren M; Semelka, Richard C

2016-12-01

Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known. Copyright © 2016 Elsevier Inc. All rights reserved.

Localised controlled release of simvastatin from porous chitosan-gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application.

PubMed

Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Daly, Jacqueline; Chiono, Valeria; Mattu, Clara; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

2016-02-01

Localised controlled release of simvastatin from porous freeze-dried chitosan-gelatin (CH-G) scaffolds was investigated by incorporating simvastatin loaded poly-(dl-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245±56% to 570±35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0±1.0kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH-G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Electrophoretic deposition of dexamethasone-loaded gelatin nanospheres/chitosan coating and its dual function in anti-inflammation and osteogenesis.

PubMed

Qi, Hongfei; Chen, Qiang; Ren, Hailong; Wu, Xianglong; Liu, Xianhu; Lu, Tingli

2018-05-18

Surface modification of metallic implants with bioactive and biodegradable coatings could be a promising approach for bone regeneration. The objective of this study was to prepare chitosan/gelatin nanospheres (GNs) composite coating for the delivery of dexamethasone (DEX). GNs with narrow size distribution and negative surface charge were firstly prepared by a two-step desolvation method. Homogeneous and stable gelatin nanospheres/chitosan (GNs/CTS) composite coatings were formed by electrophoretic deposition (EPD). Drug loading, encapsulation efficiency and in vitro release of DEX were estimated using high performance liquid chromatography (HPLC). The anti-inflammatory effect of DEX-loaded coatings on macrophage RAW 264.7 cells was assessed by the secretion of tumour necrosis factor (TNF) and inducible nitric oxide synthase (iNOS). Osteogenic differentiation of MC3T3-E1 osteoblasts on DEX-loaded coatings was investigated by osteogenic gene expression and mineralization. The DEX in GNs/CTS composite coating showed a two-stage release pattern could not only suppress inflammation during the burst release period, but also promote osteogenic differentiation in the sustained release period. This study might offer a feasible method for modifying the surface of metallic implants in bone regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications.

PubMed

Chai, Fujuan; Sun, Linlin; He, Xinyi; Li, Jieli; Liu, Yuanfen; Xiong, Fei; Ge, Liang; Webster, Thomas J; Zheng, Chunli

2017-01-01

Natural polyelectrolyte multilayers of chitosan (CHI) and alginate (ALG) were alternately deposited on doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with layer by layer self-assembly to control drug release for antitumor activity. Numerous factors which influenced the multilayer growth on nano-colloidal particles were studied: polyelectrolyte concentration, NaCl concentration and temperature. Then the growth regime of the CHI/ALG multilayers was elucidated. The coated NPs were characterized by transmission electron microscopy, atomic force microscopy, X-ray diffraction and a zeta potential analyzer. In vitro studies demonstrated an undesirable initial burst release of DOX-loaded PLGA NPs (DOX-PLGA NPs), which was relieved from 55.12% to 5.78% through the use of the layer by layer technique. The release of DOX increased more than 40% as the pH of media decreased from 7.4 to 5.0. More importantly, DOX-PLGA (CHI/ALG) 3 NPs had superior in vivo tumor inhibition rates at 83.17% and decreased toxicity, compared with DOX-PLGA NPs and DOX in solution. Thus, the presently formulated PLGA-polyelectrolyte NPs have strong potential applications for numerous controlled anticancer drug release applications.

Chitosan but Not Chitin Activates the Inflammasome by a Mechanism Dependent upon Phagocytosis*

PubMed Central

Bueter, Chelsea L.; Lee, Chrono K.; Rathinam, Vijay A. K.; Healy, Gloria J.; Taron, Christopher H.; Specht, Charles A.; Levitz, Stuart M.

2011-01-01

Chitin is an abundant polysaccharide found in fungal cell walls, crustacean shells, and insect exoskeletons. The immunological properties of both chitin and its deacetylated derivative chitosan are of relevance because of frequent natural exposure and their use in medical applications. Depending on the preparation studied and the end point measured, these compounds have been reported to induce allergic responses, inflammatory responses, or no response at all. We prepared highly purified chitosan and chitin and examined the capacity of these glycans to stimulate murine macrophages to release the inflammasome-associated cytokine IL-1β. We found that although chitosan was a potent NLRP3 inflammasome activator, acetylation of the chitosan to chitin resulted in a near total loss of activity. The size of the chitosan particles played an important role, with small particles eliciting the greatest activity. An inverse relationship between size and stimulatory activity was demonstrated using chitosan passed through size exclusion filters as well as with chitosan-coated beads of defined size. Partial digestion of chitosan with pepsin resulted in a larger fraction of small phagocytosable particles and more potent inflammasome activity. Inhibition of phagocytosis with cytochalasin D abolished the IL-1β stimulatory activity of chitosan, offering an explanation for why the largest particles were nearly devoid of activity. Thus, the deacetylated polysaccharide chitosan potently activates the NLRP3 inflammasome in a phagocytosis-dependent manner. In contrast, chitin is relatively inert. PMID:21862582

Chitosan but not chitin activates the inflammasome by a mechanism dependent upon phagocytosis.

PubMed

Bueter, Chelsea L; Lee, Chrono K; Rathinam, Vijay A K; Healy, Gloria J; Taron, Christopher H; Specht, Charles A; Levitz, Stuart M

2011-10-14

Chitin is an abundant polysaccharide found in fungal cell walls, crustacean shells, and insect exoskeletons. The immunological properties of both chitin and its deacetylated derivative chitosan are of relevance because of frequent natural exposure and their use in medical applications. Depending on the preparation studied and the end point measured, these compounds have been reported to induce allergic responses, inflammatory responses, or no response at all. We prepared highly purified chitosan and chitin and examined the capacity of these glycans to stimulate murine macrophages to release the inflammasome-associated cytokine IL-1β. We found that although chitosan was a potent NLRP3 inflammasome activator, acetylation of the chitosan to chitin resulted in a near total loss of activity. The size of the chitosan particles played an important role, with small particles eliciting the greatest activity. An inverse relationship between size and stimulatory activity was demonstrated using chitosan passed through size exclusion filters as well as with chitosan-coated beads of defined size. Partial digestion of chitosan with pepsin resulted in a larger fraction of small phagocytosable particles and more potent inflammasome activity. Inhibition of phagocytosis with cytochalasin D abolished the IL-1β stimulatory activity of chitosan, offering an explanation for why the largest particles were nearly devoid of activity. Thus, the deacetylated polysaccharide chitosan potently activates the NLRP3 inflammasome in a phagocytosis-dependent manner. In contrast, chitin is relatively inert.

MitoQ Loaded Chitosan-Hyaluronan Composite Membranes for Wound Healing.

PubMed

Tamer, Tamer M; Collins, Maurice N; Valachová, Katarina; Hassan, Mohamed A; Omer, Ahmed M; Mohy-Eldin, Mohamed S; Švík, Karol; Jurčík, Rastislav; Ondruška, Ľubomír; Biró, Csaba; Albadarin, Ahmad B; Šoltés, Ladislav

2018-04-07

Two self-associating biopolymers, namely chitosan (Ch) and a high-molar-mass hyaluronan (HA), were used to prepare membranes with the aim to protect and to enhance the healing of injured skin. A mitochondrially-targeted antioxidant-MitoQ-was incorporated into the mixture of biopolymers prior to their self-association. These three-component membranes were evaluated in detail utilising surface roughness measurements, contact angle measurements, hemocompatibility, and thrombogenicity analyses. Furthermore, in vivo application of Ch/HA/MitoQ membranes was assessed on injured rabbit and rat skin utilizing histological methods. The results showed that the prepared thrombogenic Ch/HA/MitoQ membranes had higher roughness, which allowed for greater surface area for tissue membrane interaction during the healing processes, and lower cytotoxicity levels than controls. MitoQ-loaded composite membranes displayed superior healing properties in these animal models compared to control membranes.

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.

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.

Sustained release effects of berberine-loaded chitosan microspheres on in vitro chondrocyte culture.

PubMed

Zhou, Yan; Liu, Shiqing; Ming, Jianghua; Li, Yaming; Deng, Ming; He, Bin

2017-10-01

The low bioavailability and short biological half-life of berberine chloride (BBR) negatively affect the protective role of this compound against osteoarthritis (OA). The present study was performed to evaluate the effectiveness of sustained BBR release system. Novel BBR-loaded chitosan microspheres (BBR-loaded CMs) were successfully synthesized using an ionic cross-linking method for sustained release. The basic characteristics of the prepared microspheres were subsequently evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) techniques, encapsulation efficiency (EE), and in vitro release experiments. BBR-loaded CMs displayed spherical forms to encapsulate a considerable quantity of BBR (100.8 ± 2.7 mg/g); these microspheres also exhibited an ideal releasing profile. The FT-IR spectra and XRD results revealed that BBR-loaded CMs were successfully synthesized via electrostatic interaction. In vitro experiments further showed that BBR-loaded CMs significantly inhibited sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, and led to increasing mitochondrial membrane potential and maintaining the nuclear morphology. BBR-loaded CMs exerted markedly higher anti-apoptotic activity in the treatment of OA, and markedly inhibited the protein expression levels of caspase-3, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)-5 and matrix metalloproteinase (MMP)-13 induced by SNP in rat articular chondrocytes, compared with free BBR at equivalent concentration. Therefore, novel BBR-loaded CMs may offer potential for application in the treatment of OA.

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.

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.

Promising biocidal activity of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) as anti-infective agents against perilous pathogens.

PubMed

Manukumar, H M; Umesha, S; Kumar, H N Naveen

2017-09-01

The advent of biodegradable polymer-encapsulated drug nanoparticles has made an exciting area of drug delivery research. The present study investigated novel and simple route for synthesis of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) using chitosan and thymol as reducing, capping agent respectively to understand the therapeutic efficacy. The UV-vis spectroscopy, DLS, FT-IR, SEM, EDS, XRD used for characterization and radical scavenging activity, anti-microbial and biocompatibility was taken to ascertain an efficacy of novel T-C@AgNPs. The T-C@AgNPs intense peak at 490nm indicates the formation of nanoparticles and had average particle size of 28.94nm with spherical shape, monodisperse state in water, also exhibited excellent biocompatibility of cubic shaped pure silver element containing T-C@AgNPs. The antibacterial activity was studied for gram positive and gram negative food-borne pathogens and effective inhibition at 100μgmL -1 to S. aureus, S. epidermidis, S. haemolyticus (10.08, 10.00, 11.23mm) and S. typhimurium, P. aeruginosa and S. flexneri (9.28, 9.33, 12.03mm) compared to antibiotic Streptomycin. This study revealed the efficacy against multiple food-borne pathogens and therapeutic efficacy of T-C@AgNPs offers a valuable contribution in the area of nanotechnology. This proved to be a first-class novel antimicrobial material for the first time in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and analytical characterization of vitamin(s)-loaded chitosan nanoparticles for potential food packaging applications

NASA Astrophysics Data System (ADS)

Aresta, Antonella; Calvano, Cosima Damiana; Trapani, Adriana; Cellamare, Saverio; Zambonin, Carlo Giorgio; De Giglio, Elvira

2013-04-01

Most vitamins are well-known natural antioxidant agents which can be usefully employed for foods preservation to increase their shelf life. In the present study, we aimed to investigate the potential of vitamin-based chitosan nanoparticles (CSNPs) for novel food packaging application. In particular, Vitamin C- and/or E-loaded CSNPs were formulated following the ionic gelation technique and using sulfobutylether-β-cyclodextrin as cross-linking agent. The obtained CSNPs were characterized in terms of size and zeta potential measurements, leading to size range of 375-503 nm and zeta range values from +16.0 to +33.8 mV. At the solid-state, the same particles were subjected to X-ray photoelectron spectroscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. Then, the antioxidant potential of the produced vitamin(s) nanoparticulate formulations has been evaluated through 1,1-diphenyl-2-picrylhydrazyl test, a rapid spectrophotometric assay. The standardized procedure was used on vitamin(s)-modified CSNPs systems to determine both the amount of active vitamin(s) loaded in CSNPs and their release performances by in vitro release studies. Of all, high vitamins association efficiency along with an improvement of their shelf life (also under light exposure up to 7 days) were achieved. Altogether, the results suggest that Vitamin E is available in a hydrophilic delivery system able to replace organic solvents usually used for the solubilization of this antioxidant agent. In conclusion, these nanocarriers represent a promising strategy for the co-administration of Vitamin E and Vitamin C in packaging materials intended for a better storage of hydrophilic and/or lipophilic food.

Gadolinium accumulation in organs of Sprague-Dawley® rats after implantation of a biodegradable magnesium-gadolinium alloy.

PubMed

Myrissa, Anastasia; Braeuer, Simone; Martinelli, Elisabeth; Willumeit-Römer, Regine; Goessler, Walter; Weinberg, Annelie Martina

2017-01-15

Biodegradable magnesium implants are under investigation because of their promising properties as medical devices. For enhancing the mechanical properties and the degradation resistance, rare earth elements are often used as alloying elements. In this study Mg10Gd pins were implanted into Sprague-Dawley® rats. The pin volume loss and a possible accumulation of magnesium and gadolinium in the rats' organs and blood were investigated in a long-term study over 36weeks. The results showed that Mg10Gd is a fast disintegrating material. Already 12weeks after implantation the alloy is fragmented to smaller particles, which can be found within the intramedullary cavity and the cortical bones. They disturbed the bone remodeling until the end of the study. The results concerning the elements' distribution in the animals' bodies were even more striking, since an accumulation of gadolinium could be observed in the investigated organs over the whole time span. The most affected tissue was the spleen, with up to 3240μgGd/kg wet mass, followed by the lung, liver and kidney (up to 1040, 685 and 207μgGd/kg). In the brain, muscle and heart, the gadolinium concentrations were much smaller (less than 20μg/kg), but an accumulation could still be detected. Interestingly, blood serum samples showed no accumulation of magnesium and gadolinium. This is the first time that an accumulation of gadolinium in animal organs was observed after the application of a gadolinium-containing degradable magnesium implant. These findings demonstrate the importance of future investigations concerning the distribution of the constituents of new biodegradable materials in the body, to ensure the patients' safety. In the last years, biodegradable Mg alloys are under investigation due to their promising properties as orthopaedic devices used for bone fracture stabilization. Gadolinium as Rare Earth Element enhances the mechanical properties of Mg-Gd alloys but its toxicity in humans is still questionable

Preparation and characterization of the Adriamycin-loaded amphiphilic chitosan nanoparticles and their application in the treatment of liver cancer

PubMed Central

Kou, Chang-Hua; Han, Jin; Han, Xi-Lin; Zhuang, Hui-Jie; Zhao, Zi-Ming

2017-01-01

In the present study, two nanoparticles including lactose myristoyl carboxymethyl chitosan (LMCC) and algal polysaccharide myristoyl carboxymethyl chitosan (AMCC), were obtained for hepatic-targeted Adriamycin (ADM) drug delivery systems. ADM was successfully loaded into the LMCC or AMCC nanoparticle by dialysis. The release function and liver targeting of the nanoparticles was explored, and it was revealed that ADM release from the nanoparticles was greatest at acidic pH 5.5. ADM-conjugated nanoparticles were readily taken up by HU7 human hepatocellular carcinoma cells, relative to HT22 mouse hippocampal neuron cells in vitro. In vivo, ADM-loaded nanoparticles had significant antitumor efficacy with a 62.7% inhibition rate, followed by ADM and ADM-AMCC (51.2 and 42.5%, respectively). The tissue distribution study confirmed that ADM-LMCC had an improved liver delivery efficacy, by comparison with ADM. Furthermore, a series of safety studies, including hemolysis, acute toxicity and organ toxicity, revealed that the ADM-loaded LMCC and AMCC nanoparticles had advantages over the commercially available injectable preparation of Adriamycin hydrochloride, in terms of low toxicity levels and increased tolerated dose. These results indicated that LMCC is a promising carrier for injectable ADM nanoparticle and ADM-conjugated nanoparticles may improve the efficacy of ADM by hepatic targeting. PMID:29344229

MitoQ Loaded Chitosan-Hyaluronan Composite Membranes for Wound Healing

PubMed Central

Tamer, Tamer M.; Collins, Maurice N.; Valachová, Katarina; Hassan, Mohamed A.; Omer, Ahmed M.; Mohy-Eldin, Mohamed S.; Švík, Karol; Jurčík, Rastislav; Ondruška, Ľubomír; Biró, Csaba; Albadarin, Ahmad B.; Šoltés, Ladislav

2018-01-01

Two self-associating biopolymers, namely chitosan (Ch) and a high-molar-mass hyaluronan (HA), were used to prepare membranes with the aim to protect and to enhance the healing of injured skin. A mitochondrially-targeted antioxidant—MitoQ—was incorporated into the mixture of biopolymers prior to their self-association. These three-component membranes were evaluated in detail utilising surface roughness measurements, contact angle measurements, hemocompatibility, and thrombogenicity analyses. Furthermore, in vivo application of Ch/HA/MitoQ membranes was assessed on injured rabbit and rat skin utilizing histological methods. The results showed that the prepared thrombogenic Ch/HA/MitoQ membranes had higher roughness, which allowed for greater surface area for tissue membrane interaction during the healing processes, and lower cytotoxicity levels than controls. MitoQ-loaded composite membranes displayed superior healing properties in these animal models compared to control membranes. PMID:29642447

Elution characteristics of teicoplanin-loaded biodegradable borate glass/chitosan composite.

PubMed

Jia, Wei-Tao; Zhang, Xin; Zhang, Chang-Qing; Liu, Xin; Huang, Wen-Hai; Rahaman, Mohamed N; Day, Delbert E

2010-03-15

Local antibiotic delivery system has an advantage over systemic antibiotic for osteomyelitis treatment due to the delivery of high local antibiotic concentration while avoiding potential systemic toxicity. Composite biomaterials with multifunctional roles, consisting of a controlled antibiotic release, a mechanical (load-bearing) function, and the ability to promote bone regeneration, gradually become the most active area of investigation and development of local antibiotic delivery vehicles. In the present study, a composite of borate glass and chitosan (designated BG/C) was developed as teicoplanin delivery vehicle. The in vitro elution kinetics and antibacterial activity of teicoplanin released from BG/C composite as a function of immersion time were determined. Moreover, the pH changes of eluents and the bioactivity of the composite were characterized using scanning electron microscopy coupled with energy-dispersive spectroscopy and X-ray diffraction analysis. 2009 Elsevier B.V. All rights reserved.

Tailorable thiolated trimethyl chitosans for covalently stabilized nanoparticles.

PubMed

Verheul, Rolf J; van der Wal, Steffen; Hennink, Wim E

2010-08-09

A novel four-step method is presented to synthesize partially thiolated trimethylated chitosan (TMC) with a tailorable degree of quaternization and thiolation. First, chitosan was partially N-carboxylated with glyoxylic acid and sodium borohydride. Next, the remaining amines were quantitatively dimethylated with formaldehyde and sodium borohydride and then quaternized with iodomethane in NMP. Subsequently, these partially carboxylated TMCs dissolved in water were reacted with cystamine at pH 5.5 using EDC as coupling agent. After addition of DTT and dialysis, thiolated TMCs were obtained, varying in degree of quaternization (25-54%) and degree of thiolation (5-7%), as determined with (1)H NMR and Ellman's assay. Gel permeation chromatography with light scattering detection indicated limited intermolecular cross-linking. All thiolated TMCs showed rapid oxidation to yield disulfide cross-linked TMC at pH 7.4, while the thiolated polymers were rather stable at pH 4.0. When Calu-3 cells were used, XTT and LDH cell viability tests showed a slight reduction in cytotoxicity for thiolated TMCs as compared to the nonthiolated polymers with similar DQs. Positively charged nanoparticles loaded with fluorescently labeled ovalbumin were made from thiolated TMCs and thiolated hyaluronic acid. The stability of these particles was confirmed in 0.8 M NaCl, in contrast to particles made from nonthiolated polymers that dissociated under these conditions, demonstrating that the particles were held together by intermolecular disulfide bonds.

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

A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

PubMed

Oliveira, Carolina R; Rezende, Cíntia M F; Silva, Marina R; Pêgo, Ana Paula; Borges, Olga; Goes, Alfredo M

2012-01-01

Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.

Supercritical fluid assisted production of chitosan oligomers micrometric powders.

PubMed

Du, Zhe; Shen, Yu-Bin; Tang, Chuan; Guan, Yi-Xin; Yao, Shan-Jing; Zhu, Zi-Qiang

2014-02-15

Chitosan oligomers (O-chitosan) micrometric particles were produced from aqueous solution using a novel process, i.e. supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer (SAA-HCM). Hydrodynamic cavitation was introduced to enhance mass transfer and facilitate the mixing between SC-CO2 and liquid solution for fine particles formation. Well defined, separated and spherical microparticles were obtained, and the particles size could be well controlled with narrow distribution ranging from 0.5 μm to 3 μm. XRD patterns showed amorphous structure of O-chitosan microparticles. FTIR, TGA and DSC analyses confirmed that no change in molecular structure and thermal stability after SAA-HCM processing, while the water content was between 5.8% and 8.4%. Finally, tap densities were determined to be below 0.45 g/cm(3) indicating hollow or porous structures of microparticles. By tuning process parameters, theoretical mass median aerodynamic sizes lied inside respirable range of 1-2 μm, which presented the potential of the O-chitosan microparticles in application as inhaled dry powders. SAA-HCM was demonstrated to be very useful in particle size engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chitosan-coated liposome dry-powder formulations loaded with ghrelin for nose-to-brain delivery.

PubMed

Salade, Laurent; Wauthoz, Nathalie; Vermeersch, Marjorie; Amighi, Karim; Goole, Jonathan

2018-06-11

The nose-to-brain delivery of ghrelin loaded in liposomes is a promising approach for the management of cachexia. It could limit the plasmatic degradation of ghrelin and provide direct access to the brain, where ghrelin's specific receptors are located. Anionic liposomes coated with chitosan in either a liquid or a dry-powder formulation were compared. The powder formulation showed stronger adhesion to mucins (89 ± 4% vs 61 ± 4%), higher ghrelin entrapment efficiency (64 ± 2% vs 55 ± 4%), higher enzymatic protection against trypsin (26 ± 2% vs 20 ± 3%) and lower ghrelin storage degradation at 25°C (2.67 ± 1.1% vs 95.64 ± 0.85% after 4 weeks). The powder formulation was also placed in unit-dose system devices that were able to generate an appropriate aerosol characterized by a Dv50 of 38 ± 6 µm, a limited percentage of particles smaller than 10 µm of 4 ± 1% and a reproducible mass delivery (CV: 1.49%). In addition, the device was able to deposit a large amount of powder (52.04% w/w) in the olfactory zone of a 3D-printed nasal cast. The evaluated combination of the powder formulation and the device could provide a promising treatment for cachexia. Copyright © 2018. Published by Elsevier B.V.

Particle loading rates for HVAC filters, heat exchangers, and ducts.

PubMed

Waring, M S; Siegel, J A

2008-06-01

The rate at which airborne particulate matter deposits onto heating, ventilation, and air-conditioning (HVAC) components is important from both indoor air quality (IAQ) and energy perspectives. This modeling study predicts size-resolved particle mass loading rates for residential and commercial filters, heat exchangers (i.e. coils), and supply and return ducts. A parametric analysis evaluated the impact of different outdoor particle distributions, indoor emission sources, HVAC airflows, filtration efficiencies, coils, and duct system complexities. The median predicted residential and commercial loading rates were 2.97 and 130 g/m(2) month for the filter loading rates, 0.756 and 4.35 g/m(2) month for the coil loading rates, 0.0051 and 1.00 g/month for the supply duct loading rates, and 0.262 g/month for the commercial return duct loading rates. Loading rates are more dependent on outdoor particle distributions, indoor sources, HVAC operation strategy, and filtration than other considered parameters. The results presented herein, once validated, can be used to estimate filter changing and coil cleaning schedules, energy implications of filter and coil loading, and IAQ impacts associated with deposited particles. The results in this paper suggest important factors that lead to particle deposition on HVAC components in residential and commercial buildings. This knowledge informs the development and comparison of control strategies to limit particle deposition. The predicted mass loading rates allow for the assessment of pressure drop and indoor air quality consequences that result from particle mass loading onto HVAC system components.

Fabrication and evaluation of SDF-1 loaded galactosylated chitosan nanoparticles for liver targeting

NASA Astrophysics Data System (ADS)

Xue-Hui, Chu; Zhang-Qi, Feng; Qian, Xu; Jiang-Qiang, Xiao; Xian-Wen, Yuan; Xi-Tai, Sun

2017-03-01

Objective. SDF-1 loaded galactosylated chitosan (GC) nanoparticles for liver targeting were synthesized by electrospraying technique, and its biocompatibility and liver targeting effect were evaluated. Method. The SDF-1 loaded GC nanoparticles were constructed and its morphology was observed by the scanning electron microscopy (SEM). Hepatocytes were harvested and cocultured with the nanoparticles, and the albumin secretion and urea synthesis were detected by enzyme-linked immunosorbent assay assay, the concentration of lactate dehydrogenase (LDH) and tumor necrosis factor-α (TNF-α) was also measured. Finally, the nanoparticles were injected intravenously through the caudal vein of rat, and its liver targeting effect was evaluated. Result. SEM showed the nanoparticles distributed uniformly, with an average diameter of 100 nm and a regular spherical shape. There was no significant difference in urea synthesis, albumin secretion, concentration of LDH and TNF-α between two groups (p > 0.05). The nanoparticles were significantly accumulated in the liver tissue after its injection, but seldom fluorescence signals were observed in the lung, spleen, heart and kidney. Conclusion. The SDF-1 loaded GC nanoparticles showed uniform distribution, good biocompatibility and liver targeting effect, and suggested its potential application as a liver targeting delivery system.

Low modulus biomimetic microgel particles with high loading of hemoglobin.

PubMed

Chen, Kai; Merkel, Timothy J; Pandya, Ashish; Napier, Mary E; Luft, J Christopher; Daniel, Will; Sheiko, Sergei; DeSimone, Joseph M

2012-09-10

We synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With similar shape and size as red blood cells (RBCs), the particles were fabricated using the PRINT (particle replication in nonwetting templates) technique. Low cross-linking of the hydrogel resulted in very low mesh density for these particles, allowing passive diffusion of hemoglobin throughout the particles. Hb was secured in the particles through covalent conjugation of the lysine groups of Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy of particles bound to fluorescent dye-labeled Hb confirmed the uniform distribution of Hb throughout the particle interior, as opposed to the surface conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer by weight, were obtained without a significant effect on particle stability and shape, though particle diameter decreased slightly with Hb conjugation. Analysis of the protein by circular dichroism (CD) spectroscopy showed that the secondary structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in the particles could be maintained at a low level and the loaded Hb could still bind oxygen, as studied by UV-vis spectroscopy. Hb-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with a Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate (1000 1/s) for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into RBC mimics, we will discuss the implications for artificial blood.

Low Modulus Biomimetic Microgel Particles with High Loading of Hemoglobin

PubMed Central

Chen, Kai; Merkel, Timothy J.; Pandya, Ashish; Napier, Mary E.; Luft, J. Christopher; Daniel, Will; Sheiko, Sergei

2012-01-01

We synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With similar shape and size as red blood cells (RBCs), the particles were fabricated using the PRINT® (Particle Replication In Non-wetting Templates) technique. Low crosslinking of the hydrogel resulted in very low mesh density for these particles, allowing passive diffusion of hemoglobin throughout the particles. Hb was secured in the particles through covalent conjugation of the lysine groups of Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy of particles bound to fluorescent dye-labeled Hb confirmed the uniform distribution of Hb throughout the particle interior, as opposed to the surface conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer by weight, were obtained, without a significant effect on particle stability, shape, though particle diameter decreased slightly with Hb conjugation. Analysis of the protein by circular dichroism (CD) spectroscopy showed that the secondary structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in the particles could be maintained at a low level and the loaded Hb could still bind oxygen as studied by UV-vis spectroscopy. Hb-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate (1,000 1/s) for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into RBC mimics, we will discuss the implications for artificial blood. PMID:22852860

Synthesis and characterization of chitosan quaternary ammonium salt and its application as drug carrier for ribavirin.

PubMed

Li, Si-Dong; Li, Pu-Wang; Yang, Zi-Ming; Peng, Zheng; Quan, Wei-Yan; Yang, Xi-Hong; Yang, Lei; Dong, Jing-Jing

2014-11-01

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is hydro-soluble chitosan (CS) derivative, which can be obtained by the reaction between epoxypropyl trimethyl ammonium chloride (ETA) and CS. The preparation parameters for the synthesis of HTCC were optimized by orthogonal experimental design. ETA was successfully grafted into the free amino group of CS. Grafting of ETA with CS had great effect on the crystal structure of HTCC, which was confirmed by the XRD results. HTCC displayed higher capability to form nanoparticles by crosslinking with negatively charged sodium tripolyphosphate (TPP). Ribavrin- (RIV-) loaded HTCC nanoparticles were positively charged and were spherical in shape with average particle size of 200 nm. More efficient drug encapsulation efficiency and loading capacity were obtained for HTCC in comparison with CS, however, HTCC nanoparticles displayed faster release rate due to its hydro-soluble properties. The results suggest that HTCC is a promising CS derivative for the encapsulation of hydrophilic drugs in obtaining sustained release of drugs.

Water soluble folate-chitosan nanogels crosslinked by genipin.

PubMed

Pujana, Maite Arteche; Pérez-Álvarez, Leyre; Iturbe, L Carlos Cesteros; Katime, Issa

2014-01-30

Folate-chitosan conjugates were prepared by a concurrent functionalization and crosslinking reaction with the natural crosslinker genipin. Genipin molecule was employed simultaneously as crosslinker agent and spacer molecule in order to allow the functionalization with folic acid for active tumor targeting. The reaction was carried out in reverse microemulsion which provided colloidal size and monodisperse particle size distribution. The water solubility of the obtained folate-genipin-chitosan nanogels was studied as function of the pH of the medium and all nanoparticles were totally dispersible at physiological pH. The enzymatic degradability of the nanogels in a lysozyme solution was evaluated at acidic and physiological pH. QELS analyses of the swelling behavior of the nanogels with the pH did not show a clear pH-sensitivity. However, the study on the loading and release capacity of 5-fluorouracil revealed an interesting pH-responsive behavior of the nanogels that makes them promising as nanodevices for targeted anticancer drug delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nano and micro mechanical properties of uncross-linked and cross-linked chitosan films

PubMed Central

Aryaei, Ashkan; Jayatissa, Ahalapitiya H.; Jayasuriya, A. Champa

2016-01-01

The aim of this study is to determine the nano and micro mechanical properties for uncross-linked and cross-linked chitosan films. Specifically, we looked at nanoindentation hardness, microhardness, and elastic modulus. It is important to study the nano and microscale mechanical properties of chitosan since chitosan has been widely used for biomedical applications. Using the solvent-cast method, the chitosan films were prepared at room temperature on the cleaned glass plates. The chitosan solution was prepared by dissolving chitosan in acetic acid 1% (v/v). Tripolyphosphate (TPP) was used to create the cross-links between amine groups in chitosan and phosphate groups in TPP. In this study, atomic force microscopy was used to measure the nanoindentation hardness and surface topography of the uncross-linked and cross-linked chitosan films. Elastic modulus was then calculated from the nanoindentation results. The effective elastic modulus was determined by microhardness with some modifications to previous theories. The microhardness of the chitosan films were measured using Vicker’s hardness meter under three different loads. Our results show that the microhardness and elastic modulus for cross-linked chitosan films are higher than the uncross-linked films. However, the cross-linked chitosan films show increased brittleness when compared to uncross-linked films. By increasing the load magnitude, the microhardness increases for both uncross-linked and cross-linked chitosan films. PMID:22100082

Functional modification of chitosan for biomedical application

NASA Astrophysics Data System (ADS)

Tang, Ruogu

focused on chitosan treatment on titanium surface. We have covalently immobilized chitosan onto titanium (Ti), a widely used implant material, to manage implant-related infection and poor osseointegration that are two of most serious orthopedic implants. The Ti surface was first treated with sulfuric acid and then covalently reacted with chitosan. Surface properties including roughness, contact angle and zeta potential of the samples were markedly increased by the sulfuric acid treatment and the subsequent chitosan immobilization. We have cooperated with the Dr. Ying Deng group's and demonstrated that the chitosan-immobilized Ti showed two novel antimicrobial roles: It prevented the invasion and internalization of bacteria into the osteoblast-like cells; on the other hand, it significantly increased the susceptibility of adherent bacteria to antibiotics. In addition, the SA-Ti and CS-Ti led to a significantly increased osteoblast-likecell attachment, enhanced cell proliferation, and better osteogenic differentiation and mineralization of cells. Chitosan based nanoparticle for drug loading and delivery is also reported in this thesis. By adopting the self-assembly approach, we have prepared alginate/chitosan nanoparticles where the chlorhexidine/cyclodextrin complex is loaded on. The nanoparticles have been proved to be antimicrobial effective and it can bind on cells.

Biodegradable chitosan nanogels crosslinked with genipin.

PubMed

Arteche Pujana, Maite; Pérez-Álvarez, Leyre; Cesteros Iturbe, Luis Carlos; Katime, Issa

2013-05-15

Chitosan nanoparticles crosslinked with genipin were prepared by reverse microemulsion that allowed to obtain highly monodisperse (3-20 nm by TEM) nanogels. The incorporation of genipin into chitosan was confirmed and quantitatively evaluated by UV-vis and (1)H NMR. Loosely crosslinked chitosan networks showed higher water solubility at neutral pHs than pure chitosan. The hydrodynamic diameter of the genipin-chitosan nanogels ranged from 270 to 390 nm and no remarkable differences were found when the crosslinking degree was varied. The hydrodynamic diameters of the nanoparticles increased slightly at acidic pH and the protonation of ionizable amino groups with the pH was confirmed by the zeta potential measurements. The biocompatible and biodegradable nature, as well as the colloidal and monodisperse particle size of the prepared nanogels, make them attractive candidates for a large variety of biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Particulate systems based on pectin/chitosan association for the delivery of manuka honey components and platelet lysate in chronic skin ulcers.

PubMed

Tenci, Marika; Rossi, Silvia; Bonferoni, Maria Cristina; Sandri, Giuseppina; Boselli, Cinzia; Di Lorenzo, Arianna; Daglia, Maria; Icaro Cornaglia, Antonia; Gioglio, Luciana; Perotti, Cesare; Caramella, Carla; Ferrari, Franca

2016-07-25

The aim of the present work was the development of a powder formulation for the delivery of manuka honey (MH) bioactive components and platelet lysate (PL) in chronic skin ulcers. In particular pectin (PEC)/chitosan (CS) particles were prepared by ionotropic gelation in the presence of calcium chloride and subsequently characterized for particle size, hydration properties and mechanical resistance. Different experimental conditions (calcium chloride and CS concentrations; rest time in the cationic solution) were considered in order to obtain particles characterized by optimal size, hydration properties and mechanical resistance. Two different fractions of MH were examined: one (Fr1), rich in methylglyoxal and the other (Fr2), rich in polyphenols. Particles were loaded with Fr1, fraction able to enhance in vitro proliferation of human fibroblasts, and with PL. The presence of CS in Fr1-loaded particles produced an improvement in cell proliferation. Moreover, PL loading into particles did not affect the biological activity of the hemoderivative. In vivo efficacy of PL- and Fr1-loaded particles was evaluated on a rat wound model. Both treatments markedly increased wound healing to the same extent. Copyright © 2016 Elsevier B.V. All rights reserved.

Cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride for superoxide dismutase delivery.

PubMed

Cheng, Ye; Cai, Huanxin; Yin, Baoru; Yao, Ping

2013-09-15

A series of novel amphiphilic chitosan derivatives, cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride (HTCC-CA) with different quaternization degrees and cholic acid substitutions were synthesized in this study. HTCC-CA is biocompatible and forms particles in aqueous solution. The binding with superoxide dismutase (SOD) at pH 6.8 destroys the original aggregates of HTCC-CA and produces smaller SOD/HTCC-CA complex nanoparticles via electrostatic and hydrophobic interactions. The SOD loading efficiency and loading capacity of HTCC-CA can reach to more than 90% and 45%, respectively. Confocal laser scanning microscopy observation and flow cytometry analysis reveal that SOD/HTCC-CA complex nanoparticles greatly enhance the cellular internalization of the loaded SOD. The SOD activities and malonaldehyde concentrations in the serum and organs of the rats, administrated intravenously with free SOD, free HTCC-CA, and SOD/HTCC-CA nanoparticles, were assayed to evaluate the antioxidant efficiency in vivo. The results demonstrate that free HTCC-CA is effective to scavenge superoxide radicals in the blood circulation and SOD/HTCC-CA nanoparticles have better antioxidant efficiency than free SOD as well as free HTCC-CA. Copyright © 2013 Elsevier B.V. All rights reserved.

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

2014-06-01

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

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.

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.

Effect of pore size of three-dimensionally ordered macroporous chitosan-silica matrix on solubility, drug release, and oral bioavailability of loaded-nimodipine.

PubMed

Gao, Yikun; Xie, Yuling; Sun, Hongrui; Zhao, Qinfu; Zheng, Xin; Wang, Siling; Jiang, Tongying

2016-01-01

To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan-silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug. 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated. With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively. Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.

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.

Lecithin/chitosan nanoparticles for transdermal delivery of melatonin.

PubMed

Hafner, Anita; Lovrić, Jasmina; Pepić, Ivan; Filipović-Grčić, Jelena

2011-01-01

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as colloidal nanosystem for transdermal melatonin delivery was investigated. Mean diameter and zeta-potential of NPs differing in lecithin type (Lipoid S45 and S100) and chitosan content ranged between 113.7 and 331.5 nm and 4.6 and 31.2 mV, respectively. Melatonin loadings were up to 7.2%. The potential of lecithin/chitosan NPs to enhance transdermal melatonin delivery was investigated by determining the drug flux across dermatomed porcine skin and its skin deposition. Lecithin/chitosan NPs provided 1.3-2.3-fold higher flux compared to melatonin solution. The highest flux, 9.0 ± 0.21 µg/cm²/h, was observed for S45 lecithin/chitosan NPs with lecithin/chitosan weight ratio of 20:1. NP possible cytotoxicity in vitro was evaluated using human skin keratinocytes and fibroblasts. It was demonstrated that lecithin/chitosan NPs can be applied to skin cells at concentrations up to 200 µg/mL without inducing plasma membrane damage or cell viability decrease.

In vitro and in vivo evaluation of curcumin loaded lauroyl sulphated chitosan for enhancing oral bioavailability.

PubMed

Shelma, R; Sharma, Chandra P

2013-06-05

Curcumin has been demonstrated as a potent anticancer agent but its clinical application has been limited by its poor aqueous solubility and bioavailability. Here we describe encapsulation of curcumin in the lauroyl sulphated chitosan with a view to improve its bioavailability. In vitro antioxidant activity of extract of curcumin loaded matrix was investigated and exhibited dose dependent radical scavenging and reducing activity. Cytotoxicity studies carried out with curcumin loaded carrier on C6 cell line and were found to be toxic. Its in vitro effects on proliferation using the C6 cell lines also studied and observed antiproliferation of C6 cell line. Plasma concentration of curcumin-time profiles from pharmacokinetic studies in rats after oral administration showed a 11.5-fold increased pharmacological availability of curcumin with encapsulated curcumin compared with native curcumin. Overall we demonstrate that the curcumin loaded matrix has shown a superior pharmacological availability in vivo over curcumin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

NASA Astrophysics Data System (ADS)

Cai, Limei; Yu, Rufen; Hao, Xi; Ding, Xiangcui

2017-08-01

In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

Endocytotic potential governs magnetic particle loading in dividing neural cells: studying modes of particle inheritance

PubMed Central

Tickle, Jacqueline A; Jenkins, Stuart I; Polyak, Boris; Pickard, Mark R; Chari, Divya M

2016-01-01

Aim: To achieve high and sustained magnetic particle loading in a proliferative and endocytotically active neural transplant population (astrocytes) through tailored magnetite content in polymeric iron oxide particles. Materials & methods: MPs of varying magnetite content were applied to primary-derived rat cortical astrocytes ± static/oscillating magnetic fields to assess labeling efficiency and safety. Results: Higher magnetite content particles display high but safe accumulation in astrocytes, with longer-term label retention versus lower/no magnetite content particles. Magnetic fields enhanced loading extent. Dynamic live cell imaging of dividing labeled astrocytes demonstrated that particle distribution into daughter cells is predominantly ‘asymmetric’. Conclusion: These findings could inform protocols to achieve efficient MP loading into neural transplant cells, with significant implications for post-transplantation tracking/localization. PMID:26785794

Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

PubMed Central

Coughlin, Andrew J.; Ananta, Jeyarama S.; Deng, Nanfu; Larina, Irina V.; Decuzzi, Paolo

2014-01-01

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, we have engineered gadolinium-conjugated gold nanoshells and demonstrated that they enhance contrast for magnetic resonance imaging, X-Ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. PMID:24115690

The effects of particle loading on turbulence structure and modelling

NASA Technical Reports Server (NTRS)

Squires, Kyle D.; Eaton, J. K.

1989-01-01

The objective of the present research was to extend the Direct Numerical Simulation (DNS) approach to particle-laden turbulent flows using a simple model of particle/flow interaction. The program addressed the simplest type of flow, homogeneous, isotropic turbulence, and examined interactions between the particles and gas phase turbulence. The specific range of problems examined include those in which the particle is much smaller than the smallest length scales of the turbulence yet heavy enough to slip relative to the flow. The particle mass loading is large enough to have a significant impact on the turbulence, while the volume loading was small enough such that particle-particle interactions could be neglected. Therefore, these simulations are relevant to practical problems involving small, dense particles conveyed by turbulent gas flows at moderate loadings. A sample of the results illustrating modifications of the particle concentration field caused by the turbulence structure is presented and attenuation of turbulence by the particle cloud is also illustrated.

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.

Effect of enzymatic degradation of chitosan in polyhydroxybutyrate/chitosan/calcium phosphate composites on in vitro osteoblast response.

PubMed

Giretova, Maria; Medvecky, Lubomir; Stulajterova, Radoslava; Sopcak, Tibor; Briancin, Jaroslav; Tatarkova, Monika

2016-12-01

Polyhydroxybutyrate/chitosan/calcium phosphate composites are interesting biomaterials for utilization in regenerative medicine and they may by applied in reconstruction of deeper subchondral defects. Insufficient informations were found in recent papers about the influence of lysozyme degradation of chitosan in calcium phosphate/chitosan based composites on in vitro cytotoxicity and proliferation activity of osteoblasts. The effect of enzymatic chitosan degradation on osteoblasts proliferation was studied on composite films in which the porosity of origin 3D scaffolds was eliminated and the surface texture was modified. The significantly enhanced proliferation activity with faster population growth of osteoblasts were found on enzymatically degraded biopolymer composite films with α-tricalcium phosphate and nanohydroxyapatite. No cytotoxicity of composite films prepared from lysozyme degraded scaffolds containing a large fraction of low molecular weight chitosans (LMWC), was revealed after 10 days of cultivation. Contrary to above in the higher cytotoxicity origin untreated nanohydroxyapatite films and porous composite scaffolds. The results showed that the synergistic effect of surface distribution, morphology of nanohydroxyapatite particles, microtopography and the presence of LMWC due to chitosan degradation in composite films were responsible for compensation of the cytotoxicity of nanohydroxyapatite composite films or porous composite scaffolds.

Enhancement of Mechanical and Thermal Properties of Polycaprolactone/Chitosan Blend by Calcium Carbonate Nanoparticles

PubMed Central

Abdolmohammadi, Sanaz; Siyamak, Samira; Ibrahim, Nor Azowa; Yunus, Wan Md Zin Wan; Rahman, Mohamad Zaki Ab; Azizi, Susan; Fatehi, Asma

2012-01-01

This study investigates the effects of calcium carbonate (CaCO3) nanoparticles on the mechanical and thermal properties and surface morphology of polycaprolactone (PCL)/chitosan nanocomposites. The nanocomposites of PCL/chitosan/CaCO3 were prepared using a melt blending technique. Transmission electron microscopy (TEM) results indicate the average size of nanoparticles to be approximately 62 nm. Tensile measurement results show an increase in the tensile modulus with CaCO3 nanoparticle loading. Tensile strength and elongation at break show gradual improvement with the addition of up to 1 wt% of nano-sized CaCO3. Decreasing performance of these properties is observed for loading of more than 1 wt% of nano-sized CaCO3. The thermal stability was best enhanced at 1 wt% of CaCO3 nanoparticle loading. The fractured surface morphology of the PCL/chitosan blend becomes more stretched and homogeneous in PCL/chitosan/CaCO3 nanocomposite. TEM micrograph displays good dispersion of CaCO3 at lower nanoparticle loading within the matrix. PMID:22605993

Chitosan-based nanocarriers for antimalarials

NASA Astrophysics Data System (ADS)

Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Bende, A.; Borodi, Gh.; Bratu, I.

2012-02-01

The objective of this research was to synthesize and characterize chitosan-based liquid and solid materials with unique absorptive and mechanical properties as carriers for quinine - one of the most used antimalarial drug. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare solid release systems as sponges is presented. The preparation by double emulsification of CTS hydrogels carrying quinine as anti-malarial drug is reported. The concentration of quinine in the CTS hydrogel was 0.08 mmol. Chitosan - drug loaded hydrogel was used to generate solid sponges by freeze-drying at -610°C and 0.09 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-VIS), spectrofluorimetry, differential scanning calorimetry (DSC) and X-ray diffractometry. The results indicated that the drug molecule is forming temporary chelates in CTS hydrogels and sponges. Electron paramagnetic resonance (EPR) demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan - drug supramolecular cross-linked assemblies.

Co-encapsulated resveratrol and quercetin in chitosan and peg modified chitosan nanoparticles: For efficient intra ocular pressure reduction.

PubMed

Natesan, Subramanian; Pandian, Saravanakumar; Ponnusamy, Chandrasekar; Palanichamy, Rajaguru; Muthusamy, Sivakumar; Kandasamy, Ruckmani

2017-11-01

Natural anti-oxidants resveratrol (RES) and quercetin (QUR) posses the ability to reduce intra ocular pressure efficiently. Concurrent administration of RES and QUR was able to enhance the bioavailability of RES. Present research work describes upsurge of QUR in RES loaded chitosan (CS) nanoparticles (NPs) and polyethylene glycol (PEG) modified CS NPs for improved delivery and synergic effects on reducing intra ocular pressure for the treatment of glaucoma. CS NPs and PEG modified CS NPs were prepared by ionic gelation of tripolyphosphate and CS. The synthesised NPs were spherical in shape and RES entrapment and loading efficiency in the formulation decreased with increasing PEG concentration. Particle size of the formulation increased while incorporating PEG and drugs. The crystalline nature of RES and QUR changed in the NPs and that was confirmed by XRD study. Free radical neutralising efficiency improved while incorporating QUR in the formulation. Ex-vivo corneal permeation of RES was higher from RES and QUR loaded formulation than RES alone containing NPs and free RES dispersion. RES and QUR loaded PEG modified CS NPs showed sustained and enhanced reduction of intra ocular pressure (5.5±0.5mmHg) in normotensive rabbits. Copyright © 2017 Elsevier B.V. All rights reserved.

Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

NASA Astrophysics Data System (ADS)

Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

2004-06-01

Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been able to image the subcellular distribution of gadolinium-157, as well as the other six naturally abundant isotopes of gadolinium, with SIMS ion microscopy. T98G human glioblastoma cells were treated for 24 h with 25 mg/ml of the metal ion complex diethylenetriaminepentaacetic acid Gd(III) dihydrogen salt hydrate (Gd-DTPA). Gd-DTPA is a contrast enhancing agent used for MRI of brain tumors, blood-brain barrier impairment, diseases of the central nervous system, etc. A highly heterogeneous subcellular distribution was observed for gadolinium-157. The nuclei in each cell were distinctly lower in gadolinium-157 than in the cytoplasm. Even within the cytoplasm the gadolinium-157 was heterogeneously distributed. The other six naturally abundant isotopes of gadolinium were imaged from the same cells and exhibited a subcellular distribution consistent with that observed for gadolinium-157. These observations indicate that SIMS ion microscopy may be a viable approach for subcellular studies of gadolinium containing neutron capture therapy drugs and may even play a major role in the development and validation of new gadolinium contrast enhancing agents for diagnostic MRI applications.

Synthesis, characterization and antibacterial activity of hybrid chitosan-cerium oxide nanoparticles: As a bionanomaterials.

PubMed

Senthilkumar, R P; Bhuvaneshwari, V; Ranjithkumar, R; Sathiyavimal, S; Malayaman, V; Chandarshekar, B

2017-11-01

The hybrid chitosan cerium oxide nanoparticles were prepared for the first time by green chemistry approach using plant leaf extract. The intense peak observed around 292nm in the UV-vis spectrum indicate the formation of cerium oxide nanoparticles. The XRD pattern revealed that the hybrid chitosan-cerium oxide nanoparticles have a polycrystalline structure with cubic fluorite phase. The FTIR spectrum of prepared samples showed the formation of Ce-O bonds and chitosan main chains COC and CO. The FESEM image of hybrid chitosan cerium oxide nanoparticles revealed that the particles are spherical in shape with grains size varying from 23.12nm to 89.91nm. EDAX analysis confirmed the presence of Ce, O, C and N elements in the prepared sample. TEM images showed that the prepared hybrid chitosan-cerium oxide nanoparticles are predominantly uniform in size and most of the particles are spherical in shape with less agglomeration and the particles size varies from 3.61nm to 24.40nm. The prepared chitosan cerium oxide nanoparticles of 50μL concentration showed good antibacterial properties against test pathogens, which was confirmed by the FESEM analysis. The prepared small particle size facilitate that these hybrid ChiCO 2 NPs could effectively be used in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Chitosan Ascorbate Nanoparticles for the Vaginal Delivery of Antibiotic Drugs in Atrophic Vaginitis

PubMed Central

Vigani, Barbara; Puccio, Antonella; Ferrari, Franca

2017-01-01

The aim of the present work was the development of chitosan ascorbate nanoparticles (CSA NPs) loaded into a fast-dissolving matrix for the delivery of antibiotic drugs in the treatment of atrophic vaginitis. CSA NPs loaded with amoxicillin trihydrate (AX) were obtained by ionotropic gelation in the presence of pentasodium tripolyphosphate (TPP). Different CSA:TPP and CSA:AX weight ratios were considered and their influence on the particle size, polydispersion index and production yield were investigated. CSA NPs were characterized for mucoadhesive, wound healing and antimicrobial properties. Subsequently, CSA NPs were loaded in polymeric matrices, whose composition was optimized using a DoE (Design of Experiments) approach (simplex centroid design). Matrices were obtained by freeze-drying aqueous solutions of three hydrophilic excipients, polyvinylpirrolidone, mannitol and glycin. They should possess a mechanical resistance suitable for the administration into the vaginal cavity and should readily dissolve in the vaginal fluid. In addition to antioxidant properties, due to the presence of ascorbic acid, CSA NPs showed in vitro mucoadhesive, wound healing and antimicrobial properties. In particular, nanoparticles were characterized by an improved antimicrobial activity with respect to a chitosan solution, prepared at the same concentration. The optimized matrix was characterized by mechanical resistance and by the fast release in simulated vaginal fluid of nanoparticles characterized by unchanged size. PMID:29048359

Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

PubMed

Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

2016-12-14

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

Development of Chitosan-based Dry Powder Inhalation System of Cisplatin for Lung Cancer

PubMed Central

Singh, D. J.; Lohade, A. A.; Parmar, J. J.; Hegde, Darshana D.; Soni, P.; Samad, A.; Menon, Mala D.

2012-01-01

Cisplatin, a platinum compound, exerts its cytotoxic effects by coordinating to DNA where it inhibits both replication and transcription, and induces programmed cell death. It is used in the treatment of non-small cell lung cancer. In the present study, an attempt was made to achieve better treatment of lung cancer by direct lung delivery of cisplatin microparticulate systems, which helps to localize the drug in the lungs, and also provide sustained action. Cisplatin-loaded chitosan microspheres were prepared by emulsification and ionotropic gelation method, and characterized for drug content, particle size, densities, flow properties, moisture content, and surface topography by SEM and in vitro drug release was evaluated in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction (FPF) was determined by using twin stage impinger (TSI). Further stability evaluation of cisplatin-loaded DPI systems was carried out at 25°/60% RH and at 40°/75% RH. PMID:23798777

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy

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

Lee, Dongkyu; Maeng, Inhee; Son, Joo-Hiuk

2009-04-19

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRImore » technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.« less

Chitosan-graphene oxide films and CO2-dried porous aerogel microspheres: Interfacial interplay and stability.

PubMed

Frindy, Sana; Primo, Ana; Ennajih, Hamid; El Kacem Qaiss, Abou; Bouhfid, Rachid; Lahcini, Mohamed; Essassi, El Mokhtar; Garcia, Hermenegildo; El Kadib, Abdelkrim

2017-07-01

The intimate interplay of chitosan (CS) and graphene oxide (GO) in aqueous acidic solution has been explored to design upon casting, nanostructured "brick-and-mortar" films (CS-GO-f) and by acidic-to-basic pH inversion, porous CO 2 -dried aerogel microspheres (CS-GO-m). Owing to the presence of oxygenated functional groups in GO, good-quality crack-free hybrid films were obtained. Mechanical properties were improved independently of the GO content and it was found that a 20wt% loading affords hybrid film characterized with a Young modulus three times superior to that reached with the same loading of layered clay. The presence of graphene oxide was found to be detrimental for the thermal stability of the polysaccharide at T <350°C, a fact attributed to the well-established decomposition of the oxygenated functional groups of the graphene sheets. Irrespective to the graphene oxide loading, chitosan-graphene oxide mixture preserves the gelation memory of the polysaccharide. Supercritical drying of the resulting soft hydrogels provides macroporous network with surface areas ranging from 226m 2 g -1 to 554m 2 g -1 . XPS and RAMAN analyses evidenced the selective reduction of GO sheets inside of these microspheres, affording the hitherto unknown macroporous chitosan-entangled-reduced graphene oxide (CS-rGO-m) aerogels. Improvement in both hydrothermal stability (under water reflux) and chemical stability (under acidic conditions) have been noticed for chitosan-graphene oxide microspheres with respect to non-modified chitosan and chitosan-clay bio-hybrids, a result rooted in the substantial hydrophobic character imparted by the addition of graphenic material to the polysaccharide skeleton. In essence, this contribution demonstrates that graphene oxide loading do not disturb neither the filmogenicity of chitosan nor its gelation ability and constitutes a promising route for novel chitosan-based functional hybrid materials. Copyright © 2017 Elsevier Ltd. All rights

Bioadhesive and biocompatible films as wound dressing materials based on a novel dendronized chitosan loaded with ciprofloxacin.

PubMed

García, Mónica C; Aldana, Ana A; Tártara, Luis I; Alovero, Fabiana; Strumia, Miriam C; Manzo, Rubén H; Martinelli, Marisa; Jimenez-Kairuz, Alvaro F

2017-11-01

The bioadhesive polymeric films as topical drug delivery systems are interesting alternatives to improve the pharmacotherapy and patient compliances. New derivate biomaterials based on weisocyanate- dendronized PVP- crosslinked chitosan and loaded with ciprofloxacin (CIP), as model drug, were used to prepare bioadhesive films. Relevant in vitro/in vivo attributes to define main physicochemical and biopharmaceutical characteristics for topical wound-healing applications were evaluated. A high proportion of CIP, uniformly dispersed along throughout the film, was loaded. An extended release of CIP and different behaviors of release profiles, depending on the presence of dendron, were observed. The films loaded with CIP were effective in inhibiting the growth of both Gram positive and Gram negative bacteria. In addition, biocompatibility and bioadhesion into conjuntival-sacs of the rabbits suggests that these films have good properties to be applied over skin wounds for topical applications, allowing a reduction of the frequency of administration and improving the residence time of the films. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules.

PubMed

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2012-05-30

Mucoadhesive chitosan based films, incorporated with insulin loaded nanoparticles (NPs) made of poly(ethylene glycol)methyl ether-block-polylactide (PEG-b-PLA) have been developed and characterised. Blank-NPs were prepared by double emulsion solvent evaporation technique with varying concentrations of the copolymer (5 and 10%, w/v). The optimised formulation was loaded with insulin (model protein) at initial loadings of 2, 5 and 10% with respect to copolymer weight. The developed NPs were analysed for size, size distribution, surface charge, morphology, encapsulation efficiency and drug release. NPs showing negative (ζ)-potential (<-6 mV) with average diameter> 300 nm and a polydispersity index (P.I.) of ≈ 0.2, irrespective of formulation process, were achieved. Insulin encapsulation efficiencies of 70% and 30% for NPs-Insulin-2 and NPs-Insulin-5 were obtained, respectively. The in vitro release behaviour of both formulations showed a classic biphasic sustained release of protein over 5 weeks which was influenced by pH of the release medium. Optimised chitosan films embedded with 3mg of insulin loaded NPs were produced by solvent casting with homogeneous distribution of NPs in the mucoadhesive matrix, which displayed excellent physico-mechanical properties. The drug delivery system has been designed as a novel platform for potential buccal delivery of macromolecules. Copyright © 2012 Elsevier B.V. All rights reserved.

Methotrexate loading in chitosan nanoparticles at a novel pH: Response surface modeling, optimization and characterization.

PubMed

Hashad, Rania A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

2016-10-01

The aim of this study was to assess the feasibility of employing a novel but critical formulation pH (6.2) to encapsulate an anionic model drug (methotrexate, MTX) into chitosan(Cs)-tripolyphosphate nanoparticles(NPs). A response surface methodology using a three-level full factorial design was applied studying the effects of two independent variables namely; Cs concentration and MTX concentration. The responses investigated were the entrapment efficiency (EE%), mean hydrodynamic particle size (PS), polydispersity index (PDI) and zeta potential (ZP). In order to simultaneously optimize the series of models obtained, the desirability function approach was applied with a goal to produce high percent of MTX encapsulated into highly charged Cs-TPP NPs of homogenous optimum PS. MTX-loaded CsNPs were successfully prepared at the novel pH applied. The suggested significant models were found quadratic for EE, PS and ZP responses, while 2-factor interaction model for PDI. The optimization overlay graph showed that the maximum global desirability, D=0.856, was reached when the conditions were set at high Cs and MTX concentration. Thus, the use of such optimized conditions, at this novel pH, achieved a maximum drug EE% (73.38%) into NPs characterized by optimum PS (232.6nm), small PDI value (0.195) and highly surface charged (+18.4mV). Copyright © 2016 Elsevier B.V. All rights reserved.

The potentiality of cross-linked fungal chitosan to control water contamination through bioactive filtration.

PubMed

Tayel, Ahmed A; El-Tras, Wael F; Elguindy, Nihal M

2016-07-01

Water contamination, with heavy metals and microbial pathogens, is among the most dangerous challenges that confront human health worldwide. Chitosan is a bioactive biopolymer that could be produced from fungal mycelia to be utilized in various applied fields. An attempt to apply fungal chitosan for heavy metals chelation and microbial pathogens inhibition, in contaminated water, was performed in current study. Chitosan was produced from the mycelia of Aspergillus niger, Cunninghamella elegans, Mucor rouxii and from shrimp shells, using unified production conditions. The FT-IR spectra of produced chitosans were closely comparable. M. rouxii chitosan had the highest deacetylation degree (91.3%) and the lowest molecular weight (33.2kDa). All chitosan types had potent antibacterial activities against Escherichia coli and Staphylococcus aureus; the most forceful type was C. elegans chitosan. Chitosan beads were cross-linked with glutaraldehyde (GLA) and ethylene-glycol-diglycidyl ether (EGDE); linked beads became insoluble in water, acidic and alkaline solutions and could effectively adsorb heavy metals ions, e.g. copper, lead and zinc, in aqueous solution. The bioactive filter, loaded with EGDE- A. niger chitosan beads, was able to reduce heavy metals' concentration with >68%, and microbial load with >81%, after 6h of continuous water flow in the experimentally designed filter. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

PubMed Central

Wang, Mengshu; Zhang, Yong; Feng, Jiao; Gu, Tiejun; Dong, Qingguang; Yang, Xu; Sun, Yanan; Wu, Yongge; Chen, Yan; Kong, Wei

2013-01-01

Background Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results Nanoparticles were prepared using a modified water–oil–water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9- and 16.5-fold, respectively

Fabrication of Apigenin loaded gellan gum-chitosan hydrogels (GGCH-HGs) for effective diabetic wound healing.

PubMed

Shukla, Rajesh; Kashaw, Sushil K; Jain, Alok Pal; Lodhi, Santram

2016-10-01

The Apigenin (APN) was isolated from ethanolic extract of M. alba leaves and screened by in-vivo wound models (Diabetic and Dead space) in rats. Apigenin loaded hydrogel (HGs) was prepared using gellan gum-chitosan (GGCH) with PEG as a cross linker and characterized for various parameter like AFM, swelling property, entrapment efficiency and drug release. Further performance of hydrogel was evaluated by wound healing activity tested against wound contraction, collagen content, dried granuloma weights and antioxidant activity. The percent entrapment efficiency of optimized hydrogel found to be 87.15±1.20. APN loaded GGCH-HGs were able to release 96.11% APN in 24h. The level of superoxide dismutase (SOD) and catalase were found increased significantly in granuloma tissue of APN treated group. APN GGCH-HGs found higher wound healing effect in diabetic as well as normal wound tissues with significant antioxidant activity. Results proven the utility of prepared hydrogel (APN loaded GGCH-HGs) seems to be highly suitable for wound healing due to its unique properties of biocompatibility, biodegradability, moist nature and antioxidant effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of chitosan/PLA nano-fibers by emulsion eletrospinning for periodontal tissue engineering.

PubMed

Shen, Renze; Xu, Weihong; Xue, Yanxiang; Chen, Luyuan; Ye, Haicheng; Zhong, Enyi; Ye, Zhanchao; Gao, Jie; Yan, Yurong

2018-04-16

In this study, nanofibrous scaffolds base on pure polylactic acid (PLA) and chitosan/PLA blends were fabricated by emulsion eletrospinning. By modulating their mechanical and biological properties, cell-compatible and biodegradable scaffolds were developed for periodontal bone regeneration. Pure PLA and different weight ratios of chitosan nano-particle/PLA nano-fibers were fabricated by emulsion eletrospinning. Scanning electron microscope (SEM) was performed to observe the morphology of nano-fibers. Mechanical properties of nano-fibers were tested by single fiber strength tester. Hydrophilic/hydrophobic nature of the nano-fibers was observed by stereomicroscope. In vitro degradation was also tested. Cells were seeded on nano-fibers scaffolds. Changes in cell adhesion, proliferation and osteogenic differentiation were tested by MTT assay and Alizarin Red S staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to evaluate the expression of (Toll-like receptor 4) TLR4, IL-6, IL-8, IL-1β, OPG, RUNX2 mRNA. It is shown that the mean diameter of nano-fibers is about 200 nm. The mean diameter of chitosan nano-particles is about 50 nm. The combination of chitosan nano-particles enhanced the mechanical properties of pure PLA nano-fibers. By adding a certain amount of chitosan nano-particles, it promoted cell adhesion. It also promoted the osteogenic differentiation of bone marrow stem cells (BMSCs) by elevating the expression of osteogenic marker genes such as BSP, Ocn, collagen I, and OPN and enhanced ECM mineralization. Nonetheless, it caused higher expression of inflammatory mediators and TLR4 of human periodontal ligament cells (hPDLCs). The combination of chitosan nano-particles enhanced the mechanical properties of pure PLA nano-fibers and increased its hydrophilicity. Pure PLA nano-fibers scaffold facilitated BMSCs proliferation. Adding an appropriate amount of chitosan nano-particles may promote its properties of cell proliferation

Chitosan Loaded into a Hydrogel Delivery System as a Strategy to Treat Vaginal Co-Infection

PubMed Central

Perinelli, Diego R.; Bonacucina, Giulia; Cespi, Marco; Mastrotto, Francesca; Baffone, Wally; Casettari, Luca

2018-01-01

Polymeric hydrogels are common dosage forms designed for the topical administration of antimicrobial drugs to treat vaginal infections. One of the major advantages of using chitosan in these formulations is related to the intrinsic and broad antimicrobial activity exerted on bacteria and fungi by this natural polymer. Most vaginal yeast infections are caused by the pathogenic fungus Candida albicans. However, despite the anti-Candida activity towards and strains susceptibility to low molecular weight chitosan being documented, no information is available regarding the antimicrobial efficacy of mixed hydrogels in which chitosan is dispersed in a polymeric matrix. Therefore, the aim of the study is to evaluate the anti-Candida activity against eight different albicans and non-albicans strains of a mixed hydroxypropyl methylcellulose (HPMC)/chitosan hydrogel. Importantly, chitosan was dispersed in HPMC matrix either assembled in nanoparticles or in a monomolecular state to eventually correlate any variation in terms of rheological and mucoadhesive properties, as well as anti-Candida activity, with the chitosan form. Hydrogels containing 1% w/w chitosan, either as free polymer chain or assembled in nanoparticles, showed an improved mucoadhesiveness and an anti-Candida effect against all tested albicans and non-albicans strains. Overall, the results demonstrate the feasibility of preparing HPMC/CS mixed hydrogels intended for the prevention and treatment of Candida infections after vaginal administration. PMID:29401648

Design, synthesis, fabrication and in vitro evalution of mucoadhesive 5-amino-2-mercaptobenzimidazole chitosan as low water soluble drug carriers.

PubMed

Kongsong, Mullika; Songsurang, Kultida; Sangvanich, Polkit; Siralertmukul, Krisana; Muangsin, Nongnuj

2014-11-01

Mucoadhesive thiolated chitosan suitable as a carrier for low water soluble drugs was designed and synthesized by conjugating 5-amino-2-mercaptobenzimidazole (MBI) using methylacrylate (MA) as the linking agent. A 14.4% degree of substitution of MA, as determined by (1)H NMR analysis, and 11.86±0.01μmol thiol groups/g of polymer, as determined by Ellman's method, was obtained. The MBI-MA-chitosan had an 11-fold stronger mucoadhesive property compared to unmodified chitosan at pH 1.2, as determined by the periodic acid: Schiff colorimetric method. Chitosan, MA-chitosan and MBI-MA-chitosan were fabricated as well-formed microspheres using electrospray ionization, including an entrapment efficiency of simvastatin (SV) of over 80% for the MBI-MA-chitosan. The mucoadhesiveness of the SV-loaded MBI-MA-CS microspheres was still higher than that for SV-loaded chitosan at pH 1.2 and 6.4. The SV-loaded MBI-MA-CS microspheres revealed a reduced burst effect and an increased release rate (more than fivefold higher than pure SV) of SV over 12h. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.

PubMed

Ding, Yi; Qiao, Youbei; Wang, Min; Zhang, Huinan; Li, Liang; Zhang, Yikai; Ge, Jie; Song, Ying; Li, Yuwen; Wen, Aidong

2016-08-01

Acetyl-11-keto-β-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia-reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA-NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 ± 18 nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy.

Sorption kinetics of zinc and nickel on modified chitosan.

PubMed

Tripathi, Nimisha; Choppala, Girish; Singh, Raj S; Srivastava, Prashant; Seshadri, Balaji

2016-09-01

This study was conducted to evaluate the effect of equilibration time on adsorption of zinc [Zn(II)] and nickel [Ni(II)] on pure and modified chitosan beads. The initial adsorption of Zn(II) was high on molybdenum (Mo)-impregnated chitosan beads (MoCB) during the initial 60 min. However, after 240 min, Zn(II) adsorption occurred more on single super phosphate chitosan beads (SSPCB), followed by monocalcium phosphate chitosan beads (MCPCB), untreated pure chitosan beads (UCB), and MoCB. Similarly, Ni(II) adsorption was greatest on MoCB during the initial 60 min. At the conclusion of the experiment (at 240 min), the greatest adsorption was occurred on MCPCB, followed by MoCB, UCB, and SSPCB. Chemical sorption and intra-particle diffusion were probably the dominant processes responsible for Zn(II) and Ni(II) sorption onto chitosan beads. The results demonstrated that modified chitosan beads were effective in adsorbing Zn and Ni and hence, could be used for the removal of these toxic metals from soil.

Chitosan-coated boron nitride nanospheres enhance delivery of CpG oligodeoxynucleotides and induction of cytokines

PubMed Central

Zhang, Huijie; Chen, Song; Zhi, Chunyi; Yamazaki, Tomohiko; Hanagata, Nobutaka

2013-01-01

Background Cytosine-phosphate-guanine (CpG) oligodeoxynucleotides activate Toll-like receptor 9, leading to induction of proinflammatory cytokines, which play an important role in induction and maintenance of innate and adaptive immune responses. Previously, we have used boron nitride nanospheres (BNNS) as a carrier for delivery of unmodified CpG oligodeoxynucleotides to activate Toll-like receptor 9. However, because CpG oligodeoxynucleotides and BNNS are both negatively charged, electrostatic repulsion between them is likely to reduce the loading of CpG oligodeoxynucleotides onto BNNS. Therefore, the efficiency of uptake of CpG oligodeoxynucleotides is also limited and does not result in induction of a robust cytokine response. To ameliorate these problems, we developed a CpG oligodeoxynucleotide delivery system using chitosan-coated BNNS as a carrier. Methods To facilitate attachment of CpG oligodeoxynucleotides onto the BNNS and improve their loading capacity, we prepared positively charged BNNS by coating them with chitosan preparations of three different molecular weights and used them as carriers for delivery of CpG oligodeoxynucleotides. Results The zeta potentials of the BNNS-CS complexes were positive, and chitosan coating improved their dispersity and stability in aqueous solution compared with BNNS. The positive charge of the BNNS-CS complexes greatly improved the loading capacity and cellular uptake efficiency of CpG oligodeoxynucleotides. The loading capacity of the CpG oligodeoxynucleotides depended on the molecular weight of chitosan, which affected the positive charge density on the surface of the BNNS. CpG oligodeoxynucleotides loaded onto BNNS-CS complexes significantly enhanced production of interleukin-6 and tumor necrosis factor-α by peripheral blood mononuclear cells compared with CpG oligodeoxynucleotides directly loaded onto BNNS, or when Lipofectamine™ 2000 was used as the carrier. The molecular weight of the chitosan used to coat the

The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

NASA Astrophysics Data System (ADS)

Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2016-07-01

We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.

Electrophoretic Deposition of Chitosan/h-BN and Chitosan/h-BN/TiO₂ Composite Coatings on Stainless Steel (316L) Substrates.

PubMed

Raddaha, Namir S; Cordero-Arias, Luis; Cabanas-Polo, Sandra; Virtanen, Sannakaisa; Roether, Judith A; Boccaccini, Aldo R

2014-03-04

This article presents the results of an experimental investigation designed to deposit chitosan/hexagonal boron nitride (h-BN) and chitosan/h-BN/titania (TiO₂) composites on SS316L substrates using electrophoretic deposition (EPD) for potential antibacterial applications. The influence of EPD parameters (voltage and deposition time) and relative concentrations of chitosan, h-BN and TiO₂ in suspension on deposition yield was studied. The composition and structure of deposited coatings were investigated by FTIR, XRD and SEM. It was observed that h-BN and TiO₂ particles were dispersed in the chitosan matrix through simultaneous deposition. The adhesion between the electrophoretic coatings and the stainless steel substrates was tested by using tape test technique, and the results showed that the adhesion strength corresponded to 3B and 4B classes. Corrosion resistance was evaluated by electrochemical polarization curves, indicating enhanced corrosion resistance of the chitosan/h-BN/TiO₂ and chitosan/h-BN coatings compared to the bare stainless steel substrate. In order to investigate the in-vitro inorganic bioactivity, coatings were immersed in simulated body fluid (SBF) for 28 days. FTIR and XRD results showed no formation of hydroxyapatite on the surface of chitosan/h-BN/TiO₂ and chitosan/h-BN coatings, which are therefore non bioactive but potentially useful as antibacterial coatings.

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

2017-02-01

Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

PubMed

Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

2010-06-01

Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications.

Development of hydroxyapatite-chitosan gel sunscreen combating clinical multidrug-resistant bacteria

NASA Astrophysics Data System (ADS)

Morsy, Reda; Ali, Sameh S.; El-Shetehy, Mohamed

2017-09-01

The several harmful effects on infected human skin resulting from exposure to the sun's UV radiation generate an interest in the development of a multifunctional hydroxyapatite-chitosan (HAp-chitosan) gel that works as an antibacterial sunscreen agent for skin care. In this work, HAp-chitosan gel was synthesized via coprecipitation method by dissolving chitosan in phosphoric acid and adding HAp. The characteristics of HAp-chitosan composite were investigated by conventional techniques, such as XRD, FTIR, and SEM techniques, while its sunscreen property was investigated by UV-spectroscopy. In addition to the influence of the gel on bacterial cell morphology, the antibacterial activity of HAp-chitosan gel against clinical multidrug resistant skin pathogens, such as Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa has been studied. The results revealed the formation of HAp-chitosan gel having nanosized particles, which confers protection against UV-radiation. The antibacterial activity records showed that chitosan-HAp gel exhibits a significant effect on the growth and ultrastructure of multi-drug resistant bacterial activities. Therefore, the chitosan-HAp gel is promising for skin health care as an antibacterial sunscreen.

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.

Fabrication and application of coaxial polyvinyl alcohol/chitosan nanofiber membranes

NASA Astrophysics Data System (ADS)

Kuo, Ting-Yun; Jhang, Cuei-Fang; Lin, Che-Min; Hsien, Tzu-Yang; Hsieh, Hsyue-Jen

2017-12-01

It is difficult to fabricate chitosan-wrapped coaxial nanofibers, because highly viscous chitosan solutions might hinder the manufacturing process. To overcome this difficulty, our newly developed method, which included the addition of a small amount of gum arabic, was utilized to prepare much less viscous chitosan solutions. In this way, coaxial polyvinyl alcohol (PVA)/chitosan (as core/shell) nanofiber membranes were fabricated successfully by coaxial electrospinning. The core/shell structures were confirmed by TEM, and the existence of PVA and chitosan was also verified using FT-IR and TGA. The tensile strength of the nanofiber membranes was increased from 0.6-0.7 MPa to 0.8-0.9 MPa after being crosslinked with glutaraldehyde. The application potential of the PVA/chitosan nanofiber membranes was tested in drug release experiments by loading the core (PVA) with theophylline as a model drug. The use of the coaxial PVA/chitosan nanofiber membranes in drug release extended the release time of theophylline from 5 minutes to 24 hours. Further, the release mechanisms could be described by the Korsmeyer-Peppas model. In summary, by combining the advantages of PVA and chitosan (good mechanical strength and good biocompatibility respectively), the coaxial PVA/chitosan nanofiber membranes are potential biomaterials for various biomedical applications.

Universal shape evolution of particles by bed-load

NASA Astrophysics Data System (ADS)

Jerolmack, D. J.; Domokos, G.; Shaw, S.; Sipos, A.; Szabo, T.

2016-12-01

River currents, wind and waves drive bed-load transport, in which sediment particles collide with each other and the Earth's surface. A generic consequence is erosion and rounding of particles as a result of chipping, often referred to in geological literature as abrasion. Recent studies have shown that the erosion of river pebbles can be modeled as diffusion of surface curvature, indicating that geometric aspects of chipping erosion are insensitive to details of collisions and material properties. Here we present data from fluvial, aeolian and coastal environments that suggest a universal relation between particle circularity and mass lost due to bed-load chipping. Simulations and experiments support the diffusion model and demonstrate that three constraints are required to produce this universal curve: (i) initial particles are fragments; (ii) erosion is dominated by collisions among like-sized particles; and (iii) collision energy is small enough that chipping dominates over fragmentation. We show that the mechanics of bedrock weathering and bed-load transport select these constraints, providing the foundation to estimate a particle's erosion rate from its shape alone in most sedimentary environments. These findings may be used to determine the contribution of chipping to downstream fining in rivers and deserts, and to infer transport conditions using only images of sediment grains.

Recent advances of chitosan nanoparticles as drug carriers

PubMed Central

Wang, Jun Jie; Zeng, Zhao Wu; Xiao, Ren Zhong; Xie, Tian; Zhou, Guang Lin; Zhan, Xiao Ri; Wang, Shu Ling

2011-01-01

Chitosan nanoparticles are good drug carriers because of their good biocompatibility and biodegradability, and can be readily modified. As a new drug delivery system, they have attracted increasing attention for their wide applications in, for example, loading protein drugs, gene drugs, and anticancer chemical drugs, and via various routes of administration including oral, nasal, intravenous, and ocular. This paper reviews published research on chitosan nanoparticles, including its preparation methods, characteristics, modification, in vivo metabolic processes, and applications. PMID:21589644

Removal of gadolinium by peritoneal dialysis.

PubMed

Murashima, M; Drott, H R; Carlow, D; Shaw, L M; Milone, M; Bachman, M; Tsai, D E; Yang, S-L; Bloom, R D

2008-05-01

An association between gadolinium-containing contrast and the development of nephrogenic systemic fibrosis (NSF) has been increasingly recognized. For patients receiving hemodialysis (HD) who are exposed to gadolinium, the Federal Drug Administration (FDA) recommends HD to remove this contrast agent in order to minimize the risk of NSF. This study examines if gadolinium can be removed by frequent exchanges by peritoneal dialysis (PD). Following administration of 0.1 mmol/kg of gadodiamide to a patient with end-stage renal disease, the serum clearance of this contrast agent by automated PD was examined. 10 and 15 exchanges of PD using an automated cycler were respectively performed during the first and second 24-hour periods after gadolinium exposure. Serum gadolinium levels were measured 1 hour after the gadolinium administration, then at 24 and 48 hours after PD was initiated. 90% of the gadolinium was removed from the circulation in 2 days with a regimen of 10-15 exchanges per day of PD. For patients on chronic maintenance PD who receive gadolinium, our case suggests that a temporary intensive automated PD regimen, aimed at maximizing clearance of this contrast agent immediately after exposure, could be an effective alternative when institution of HD is problematic.

Impact of pectin esterification on the antimicrobial activity of nisin-loaded pectin particles.

PubMed

Krivorotova, Tatjana; Staneviciene, Ramune; Luksa, Juliana; Serviene, Elena; Sereikaite, Jolanta

2017-01-01

The relationship between pectin structure and the antimicrobial activity of nisin-loaded pectin particles was examined. The antimicrobial activity of five different nisin-loaded pectin particles, i.e., nisin-loaded high methoxyl pectin, low methoxyl pectin, pectic acid, dodecyl pectin with 5.4 and 25% degree of substitution were tested in the pH range of 4.0-7.0 by agar-diffusion assay and agar plate count methods. It was found that the degree of esterification of carboxyl group of galacturonic acid in pectin molecule is important for the antimicrobial activity of nisin-loaded pectin particles. Nisin-loaded particles prepared using pectic acid or the pectin with low degree of esterification exhibit higher antimicrobial activity than nisin-loaded high methoxyl pectin particles. Pectins with free carboxyl groups or of low degree of esterification are the most suitable for particles preparation. Moreover, nisin-loaded pectin particles were active at close to neutral or neutral pH values. Therefore, they could be effectively applied for food preservation. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:245-251, 2017. © 2016 American Institute of Chemical Engineers.

Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy (abstract)

NASA Astrophysics Data System (ADS)

Lee, Dongkyu; Maeng, Inhee; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol; Son, Joo-Hiuk

2009-04-01

The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd2O3) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

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.

Electrophoretic Deposition of Chitosan/h-BN and Chitosan/h-BN/TiO2 Composite Coatings on Stainless Steel (316L) Substrates

PubMed Central

Raddaha, Namir S.; Cordero-Arias, Luis; Cabanas-Polo, Sandra; Virtanen, Sannakaisa; Roether, Judith A.; Boccaccini, Aldo R.

2014-01-01

This article presents the results of an experimental investigation designed to deposit chitosan/hexagonal boron nitride (h-BN) and chitosan/h-BN/titania (TiO2) composites on SS316L substrates using electrophoretic deposition (EPD) for potential antibacterial applications. The influence of EPD parameters (voltage and deposition time) and relative concentrations of chitosan, h-BN and TiO2 in suspension on deposition yield was studied. The composition and structure of deposited coatings were investigated by FTIR, XRD and SEM. It was observed that h-BN and TiO2 particles were dispersed in the chitosan matrix through simultaneous deposition. The adhesion between the electrophoretic coatings and the stainless steel substrates was tested by using tape test technique, and the results showed that the adhesion strength corresponded to 3B and 4B classes. Corrosion resistance was evaluated by electrochemical polarization curves, indicating enhanced corrosion resistance of the chitosan/h-BN/TiO2 and chitosan/h-BN coatings compared to the bare stainless steel substrate. In order to investigate the in-vitro inorganic bioactivity, coatings were immersed in simulated body fluid (SBF) for 28 days. FTIR and XRD results showed no formation of hydroxyapatite on the surface of chitosan/h-BN/TiO2 and chitosan/h-BN coatings, which are therefore non bioactive but potentially useful as antibacterial coatings. PMID:28788541

In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™.

PubMed

Praveen, Radhakrishnan; Prasad Verma, Priya Ranjan; Venkatesan, Jayachandran; Yoon, Dong-Han; Kim, Se-Kwon; Singh, Sandeep Kumar

2017-09-01

The objective of present investigation was to develop gastro-retentive controlled release system of carvedilol using biological macromolecule, chitosan. 3 2 full factorial design was adopted for optimization of tripolyphosphate (X 1 ) and curing time (X 2 ). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading, dissolution efficiency and cumulative percentage release at 8th hour were evaluated as dependent variables. The levels of X 1 and X 2 of optimized formulation having maximum desirability was found to 2.0% w/v and 62.66min, respectively. The in silico predicted responses and observed response were found to be in good agreement (percent bias error: -13.295 to +13.269). SEM images showed numerous pores in the cross sectional image that renders buoyancy. AUC 0-∞ of optimized formulation was 1.47 times higher as compared to suspension corroborating enhanced extent of absorption. T max and mean residence time were significantly higher from optimized formulation vis a vis suspension. In silico study indicated maximum regional absorption from the duodenum (94.1%) followed by jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred deconvolution approach over numerical deconvolution to establish IVIVC. In conclusion, the study showed that gastro-retentive controlled release system prepared using chitosan could be a potential drug carrier of carvedilol with improved bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

pH-controlled doxorubicin anticancer loading and release from carbon nanotube noncovalently modified by chitosan: MD simulations.

PubMed

Rungnim, Chompoonut; Rungrotmongkol, Thanyada; Poo-Arporn, Rungtiva P

2016-11-01

In the present study, we describe here the pH condition activating doxorubicin (DOX) anticancer drugs loading and release over single-wall carbon nanotube (SWNT) non-covalently wrapped with chitosan (CS). The possibility of drug displacement on DOX/CS/SWNT nanocarrier was investigated using molecular dynamics simulations. The drug loading and release were monitored via displacement analysis and binding energy calculations. The simulated results clearly showed that the drugs well interacted with the CS/SWNT at physiological pH (pH 7.4), where CS was in the deprotonated form. Contrastingly, in weakly acidic environments (pH 5.0-6.5) which is a pH characteristics of certain cancer environments, the protonated CS became loosen wrapped around the SWNT and triggered drugs release as a result of charge-charge repulsion between CS and drug molecules. The obtained data fulfil the understanding at atomic level of drug loading and release controlled by pH-sensitive polymer, which might be useful for further cancer therapy researches. Copyright © 2016 Elsevier Inc. All rights reserved.

Formulation and Characterization of a Plasma Sterilized, Pharmaceutical Grade Chitosan Powder

PubMed Central

Crofton, Andrew R; Hudson, Samuel M; Howard, Kristy; Pender, Tyler; Abdelgawad, Abdelrahman; Wolski, Daniel; Kirsch, Wolff M

2016-01-01

Chitosan has great potential as a pharmaceutical excipient. In this study, chitosan flake was micronized using cryo-ball and cryo-jet milling and subsequently sterilized with nitrogen plasma. Micronized chitosan was characterized by laser diffraction, scanning electron microscopy (SEM), conductometric titration, viscometry, loss on drying, FTIR, and limulus amebocyte lysate (LAL) assays. Cryo-jet milling produced mean particle size of 16.05 μm, 44% smaller than cryo-ball milling. Cryomilled chitosan demonstrated increased hygroscopicity, but reduced molecular weight and degree of deacetylation (DD). SEM imaging showed highly irregular shapes. FTIR showed changes consistent with reduced DD and an unexplained shift at 1100 cm−1. Plasma treated chitosan was sterile with <2.5 EU/g after low-pressure plasma and <1.3 EU/g after atmospheric pressure plasma treatment. Plasma treatment decreased the reduced viscosity of chitosan flake and powder, with a greater effect on powder. In conclusion, pharmaceutical grade, sterile chitosan powder was produced with cryo-jet milling and plasma sterilization. PMID:27112892

Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging.

PubMed

Alric, Christophe; Taleb, Jacqueline; Le Duc, Géraldine; Mandon, Céline; Billotey, Claire; Le Meur-Herland, Alice; Brochard, Thierry; Vocanson, Francis; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2008-05-07

Functionalized gold nanoparticles were applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. These particles were obtained by encapsulating gold cores within a multilayered organic shell which is composed of gadolinium chelates bound to each other through disulfide bonds. The contrast enhancement in MRI stems from the presence of gadolinium ions which are entrapped in the organic shell, whereas the gold core provides a strong X-ray absorption. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in the lungs, spleen, and liver.

Microscopic Examination of Chitosan Polyphosphate Beads with Entrapped Spores of the Biocontrol Agent, Streptomyces melanosporofaciens EF-76

NASA Astrophysics Data System (ADS)

Jobin, Guy; Grondin, Gilles; Couture, Geneviève; Beaulieu, Carole

2005-04-01

Spores of the biocontrol agent, Streptomyces melanosporofaciens EF-76, were entrapped by complex coacervation in beads composed of a macromolecular complex (MC) of chitosan and polyphosphate. A proportion of spores entrapped in beads survived the entrapment procedure as shown by treating spores from chitosan beads with a dye allowing the differentiation of live and dead cells. The spore-loaded chitosan beads could be digested by a chitosanase, suggesting that, once introduced in soil, the beads would be degraded to release the biocontrol agent. Spore-loaded beads were examined by optical and scanning electron microscopy because the release of the biological agent depends on the spore distribution in the chitosan beads. The microscopic examination revealed that the beads had a porous surface and contained a network of inner microfibrils. Spores were entrapped in both the chitosan microfibrils and the bead lacuna.

Hexavalent chromium removal by chitosan modified-bioreduced nontronite

NASA Astrophysics Data System (ADS)

Singh, Rajesh; Dong, Hailiang; Zeng, Qiang; Zhang, Li; Rengasamy, Karthikeyan

2017-08-01

Recent efforts have focused on structural Fe(II) in chemically or biologically reduced clay minerals to immobilize Cr(VI) from aqueous solution, but the coulombic repulsion between the negatively charged clay surface and the polyanionic form of Cr(VI), e.g., dichromate, can hinder the effectiveness of this process. The purpose of this study was to investigate the efficiency and mechanism of Cr(VI) removal by a charge-reversed nontronite (NAu-2), an Fe-rich smectite. Chitosan, a linear polysaccharide derived from chitin found in soil and groundwater, was used to reverse the charge of NAu-2. Intercalation of chitosan into NAu-2 interlayer increased the basal d-spacing of NAu-2 from 1.23 nm to 1.83 nm and zeta potential from -27.17 to +34.13 mV, with the amount of increase depending on chitosan/NAu-2 ratio. Structural Fe(III) in chitosan-exchanged NAu-2 was then biologically reduced by an iron-reducing bacterium Shewanella putrefaciens CN32 in bicarbonate buffer with lactate as the sole electron donor, with and without electron shuttle, AQDS. Without AQDS, the extent of Fe(III) reduction increased from the lowest (∼9%) for the chitosan-free NAu-2 to the highest (∼12%) for the highest chitosan loaded NAu-2 (3:1 ratio). This enhancement of Fe(III) reduction was likely due to the attachment of negatively charged bacterial cells to charge-reversed (e.g., positively charged) NAu-2 surfaces, facilitating the electron transfer between cells and structural Fe(III). With AQDS, Fe(III) reduction extent doubled relative to those without AQDS, but the enhancement effect was similar across all chitosan loadings, suggesting that AQDS was more important than chitosan in enhancing Fe(III) bioreduction. Chitosan-exchanged, biologically reduced NAu-2 was then utilized for removing Cr(VI) in batch experiments with three consecutive spikes of 50 μM Cr. With the first Cr spike, the rate of Cr(VI) removal by charged-reversed NAu-2 that was bioreduced without and with AQDS was ∼1

Electrodeposition to construct free-standing chitosan/layered double hydroxides hydro-membrane for electrically triggered protein release.

PubMed

Zhao, Pengkun; Zhao, Yanan; Xiao, Ling; Deng, Hongbing; Du, Yumin; Chen, Yun; Shi, Xiaowen

2017-10-01

In this study, we report the electrodeposition of a chitosan/layered double hydroxides (LDHs) hydro-membrane for protein release triggered by an electrical signal. The electrodeposition was performed in a chitosan and insulin loaded LDHs suspension in the absence of salt. A free-standing chitosan/LDHs hydro-membrane was generated on the electrode with improved mechanical properties, which is dramatically different from the weak hydrogel deposited in the presence of salt. The amount of LDHs in the hydro-membrane affects the optical transmittance and multilayered structure of the hybrid membrane. Compared to the weak chitosan/LDHs hydrogel, the hydro-membrane has a higher insulin loading capacity and the release of insulin is relatively slow. By biasing electrical potentials to the hydro-membrane, the release behavior of insulin can be adjusted accordingly. In addition, the chitosan/LDHs hydro-membrane showed no toxicity to cells. Our results provide a facile method to construct a chitosan/LDHs hybrid multilayered hydro-membrane and suggest the great potential of the hydro-membrane in controlled protein release. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan–thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers

PubMed Central

Ay Şenyiğit, Zeynep; Karavana, Sinem Yaprak; İlem-Özdemir, Derya; Çalışkan, Çağrı; Waldner, Claudia; Şen, Sait; Bernkop-Schnürch, Andreas; Baloğlu, Esra

2015-01-01

This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan–thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosanthioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles. PMID:26508855

Structural investigation of chitosan-based microspheres with some anti-inflammatory drugs

NASA Astrophysics Data System (ADS)

Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Dragan, Felicia; Bende, A.; Borodi, Gh.; Bratu, I.

2011-06-01

The use of chitosan as an excipient in oral formulations, as a drug delivery vehicle for ulcerogenic anti-inflammatory drugs and as base in polyelectrolyte complex systems, to prepare solid release systems as sponges was investigated. The preparation by double emulsification of chitosan hydrogels carrying diclofenac, acetyl-salycilic acid and hydrocortisone acetate as anti-inflammatory drugs is reported. The concentration of anti-inflammatory drug in the chitosan hydrogel generating the sponges was 0.08 mmol. Chitosan-drug loaded sponges with anti-inflammatory drugs were prepared by freeze-drying at -60 °C and 0.009 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared and ultraviolet-visible spectroscopy, spectrofluorimetry, differential scanning calorimetry and X-ray diffractometry. The results indicated that the drug molecules are forming temporary chelates in chitosan hydrogels and sponges. Electron paramagnetic resonance demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan-drug supramolecular cross-linked assemblies.

Pathophysiology of gadolinium-associated systemic fibrosis

PubMed Central

Drel, Viktor; Gorin, Yves

2016-01-01

Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis. PMID:27147669

Structure, apatite inducing ability, and corrosion behavior of chitosan/halloysite nanotube coatings prepared by electrophoretic deposition on titanium substrate.

PubMed

Molaei, A; Amadeh, A; Yari, M; Reza Afshar, M

2016-02-01

In this study chitosan/halloysite nanotube composite (CS/HNT) coatings were deposited by electrophoretic deposition (EPD) on titanium substrate. Using HNT particles were investigated as new substituents for carbon nanotubes (CNTs) in chitosan matrix coatings. The ability of chitosan as a stabilizing, charging, and blending agent for HNT particles was exploited. Furthermore, the effects of pH, electrophoretic bath, and sonicating duration were studied on the deposition of suspensions containing HNT particles. Microstructure properties of coatings showed uniform distribution of HNT particles in chitosan matrix to form smooth nanocomposite coatings. The zeta potential results revealed that at pH around 3 there is an isoelectric point for HNT and it would have cathodic and anionic states at pH values less and more than 3, respectively. Therefore, CS/HNT composite deposits were produced in the pH range of 2.5 to 3. The apatite inducing ability of chitosan-HNT composite coating assigned that HNT particles were biocompatible because they formed carbonated hydroxyapatite particles on CS/HNT coating in corrected simulated body fluid (C-SBF). Finally, electrochemical corrosion characterizations determined that corrosion resistance in CS/HNT coating has been improved compared to bare titanium substrate. Copyright © 2015 Elsevier B.V. All rights reserved.

Universal characteristics of particle shape evolution by bed-load chipping.

PubMed

Novák-Szabó, Tímea; Sipos, András Árpád; Shaw, Sam; Bertoni, Duccio; Pozzebon, Alessandro; Grottoli, Edoardo; Sarti, Giovanni; Ciavola, Paolo; Domokos, Gábor; Jerolmack, Douglas J

2018-03-01

River currents, wind, and waves drive bed-load transport, in which sediment particles collide with each other and Earth's surface. A generic consequence is impact attrition and rounding of particles as a result of chipping, often referred to in geological literature as abrasion. Recent studies have shown that the rounding of river pebbles can be modeled as diffusion of surface curvature, indicating that geometric aspects of impact attrition are insensitive to details of collisions and material properties. We present data from fluvial, aeolian, and coastal environments and laboratory experiments that suggest a common relation between circularity and mass attrition for particles transported as bed load. Theory and simulations demonstrate that universal characteristics of shape evolution arise because of three constraints: (i) Initial particles are mildly elongated fragments, (ii) particles collide with similarly-sized particles or the bed, and (iii) collision energy is small enough that chipping dominates over fragmentation but large enough that sliding friction is negligible. We show that bed-load transport selects these constraints, providing the foundation to estimate a particle's attrition rate from its shape alone in most sedimentary environments. These findings may be used to determine the contribution of attrition to downstream fining in rivers and deserts and to infer transport conditions using only images of sediment grains.

Chitosan derivatives with antimicrobial, antitumour and antioxidant activities--a review.

PubMed

Jarmila, Vinsová; Vavríková, Eva

2011-01-01

Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film that protects cells against nutrient transport through the microbial cell membrane. Low molecular weight chitosan derivatives are water soluble and can better incorporate the active molecule into the cell. Gram-negative bacteria, often represented by Escherichia coli, have an anionic bacterial surface on which cationic chitosan derivatives interact electrostatically. Thus, many chitosan conjugates have cationic components such as ammonium, pyridinium or piperazinium substituents introduced into their molecules to increase their positive charge. Gram-positive bacteria like Staphylococcus aureus are inhibited by the binding of lower molecular weight chitosan derivatives to DNA or RNA. Chitosan nanoparticles exhibit an increase in loading capacity and efficacy. Antitumour active compounds such as doxorubicin, paclitaxel, docetaxel and norcantharidin are used as drug carriers. It is evident that chitosan, with its low molecular weight, is a useful carrier for molecular drugs requiring targeted delivery. The antioxidant scavenging activity of chitosan has been established by the strong hydrogen-donating ability of chitosan. The low molecular weight and greater degree of quarternization have a positive influence on the antioxidant activity

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

Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

PubMed Central

Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

2015-01-01

Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

Preparation and characterization of chitosan membranes by using a combined freeze gelation and mild crosslinking method.

PubMed

Orrego, Carlos E; Valencia, Jesús S

2009-02-01

When gelification is performed by freezing-thawing repeated cycles, the resultant gel-like polymer systems are called cryogels. This work aims to assess the effect of the addition of glutaraldehyde and 18 Crown Ether-6 on surface properties and protein loading of dried chitosan cryogel films. Residual water content of treated chitosan membranes ranged between 11.93 and 13.86%, while their water activities vary from 0.5 to 0.7 (measured from 4 to 60 degrees C). Based on thermal data, water evaporation peak and degradation temperatures of chitosan membranes shifted to a higher temperature for crosslinked samples. X-ray diffractograms provide high values of crystallinity for all the samples (70.67-92.86%), the highest value being for the glutaraldehyde-treated membrane. Candida rugosa lipase can be immobilized successfully on chitosan membranes. Lipase immobilized on glutaraldehyde-crosslinked chitosan yielded the highest efficiency in terms of total coupled protein and protein loading efficiency.

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

Fabrication of graphene oxide-modified chitosan for controlled release of dexamethasone phosphate

NASA Astrophysics Data System (ADS)

Sun, Huanghui; Zhang, Lingfan; Xia, Wei; Chen, Linxiao; Xu, Zhizhen; Zhang, Wenqing

2016-07-01

Functionalized graphene oxide with its unique physical and chemical properties is widely applied in biomaterials, especially in drug carrier materials. In the past few years, a number of different drugs have been loaded on functionalized graphene oxide via π-π stacking and hydrophobic interactions. The present report described a new approach, dexamethasone phosphate successfully loaded onto graphene oxide-chitosan nanocomposites as drug carrier materials by covalent bonding of phosphate ester linkage. Compared with the graphene oxide-chitosan nanocomposites that dexamethasone phosphate was loaded on via simple physical attachment, covalently linked composites as drug carrier materials were more biocompatible which effectively reduced the burst release of drug, and controlled the release of drug in different pH conditions.

An in vitro study of the anti-biofilm properties of proanthocyanidin and chitosan in Pseudomonas syringae pv. papulans

NASA Astrophysics Data System (ADS)

Song, Kai

Biofilm-forming bacteria are a form of planktonic microorganisms that can become resistant against conventional antibiotics. Because they are difficult to eradicate, biofilm-forming bacteria are extremely problematic for the medical industry areas. Thus, materials that can distort biofilm structure would be helpful for eliminating chronic infection and decreasing bacterial resistance. The primary objective of this study is to evaluate the anti-biofilm effect of two bio-derived substances, proanthocyanidin and chitosan. Proanthocyanidins are secondary plant metabolites that are reported to have antibiotic and antioxidant functions. Chitosan (poly [beta-(1, 4)-amino-2-deoxy-beta-D-glucose]) is a deacetylated derivative of chitin, which is abundant in the exoskeleton of crustaceans and insects. It is reported to be a suitable substitute for conventional fungicides and can enhance the proanthocyanidin content in plants when used as an agrochemical. Chitosan-tripolyphosphate (TPP) nanoparticles, which have good neutral water solubility and are nanoscale in size, can be used as carriers for gene and drug therapy and are thus favorable to be tested as a treatment method against bacterial biofilms. In this study, the anti-biofilm and antibacterial properties of proanthocyanidin, chitosan-TPP nanoparticles and proanthocyanidins-loaded chitosan-TPP nanoparticles were tested using the model plant bacterium, Pseudomonas syringae pv. papulans (Psp), a pathogen isolated from infected apples. At a lower concentration (1 mg/mL and 2.5 mg/mL), both chitosan nanoparticles and proanthocyanidins can postpone the formation of biofilms and eventually disrupted part of the biofilm. While higher concentration (above 5 mg/mL) of chitosan nanoparticles or proanthocyanidins can eliminate most of the biofilm in this study. PAC-loaded chitosan nanoparticles also can also distort biofilms. Both proanthocyanidins and chitosan-TPP nanoparticle showed a mild antibacterial property. PAC-loaded

In vivo experimental study on laser welded ICG-loaded chitosan patches for vessel repair

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Matteini, Paolo; Esposito, Giuseppe; Albanese, Alessio; Puca, Alfredo; Maira, Giulio; Rossi, Giacomo; Pini, Roberto

2011-03-01

Laser welding of microvessels provides several advantages over conventional suturing techniques: surgical times reduction, vascular healing process improvement, tissue damage reduction. We present the first application of biopolymeric patches in an in vivo laser assisted procedure for vessel repair. The study was performed in 20 New Zealand rabbits. After anesthesia, a 3-cm segment of the right common carotid artery was exposed and clamped proximally and distally. A linear lesion 3 mm in length was carried out. We used a diode laser emitting at 810 nm and equipped with a 300 μm diameter optical fiber. To close the cut, ICG-loaded chitosan films were prepared: chitosan is characterized by biodegradability, biocompatibility, antimicrobial, haemostatic and wound healing-promoting activity. ICG is an organic chromophore commonly used in the laser welding procedures to mediate the photothermal conversion at the basis of the welding effect. The membranes were used to wrap the whole length of the cut, and then they were welded in the correct position by delivering single laser spots to induce local patch/tissue adhesion. The result is an immediate closure of the wound, with no bleeding at clamps release. The animals were observed during follow-up and sacrificed after 2, 7, 30 and 90 days. All the repaired vessels were patent, no bleeding signs were documented. The carotid samples underwent histological examinations. The advantages of the proposed technique are: simplification of the surgical procedure and shortening of the operative time; good strength of the vessel repair; decreased foreign-body reaction, reduced inflammatory response and improved vascular healing process.

Microencapsulation of oleoresin from red ginger (Zingiber officinale var. Rubrum) in chitosan and alginate for fresh milk preservatives

NASA Astrophysics Data System (ADS)

Krisanti, Elsa; Astuty, Rizka Margi; Mulia, Kamarza

2017-02-01

The usage of red ginger rhizome (Zingiber officinale var. Rubrum) oleoresin extract as the preservative for fresh milk has not been studied yet. The aim of this research was to compare the inhibition effect of oleoresin extract-loaded chitosan-alginate microparticles, and various ginger-based preservatives added into fresh milk, on the growth of bacteria. The total count plate growth of bacteria after addition of the oleoresin-loaded chitosan-alginate microparticles was the lowest. In addition, the organoleptic test showed that this formulation had no significant effect on the color, taste, and flavor of fresh milk. The experimental results indicated that the oleoresin-loaded chitosan-alginate microparticles may effectively be used as a preservative for fresh milk.

Chitosan nanocomposite films: enhanced electrical conductivity, thermal stability, and mechanical properties.

PubMed

Marroquin, Jason B; Rhee, K Y; Park, S J

2013-02-15

A novel, high-performance Fe(3)O(4)/MWNT/Chitosan nanocomposite has been prepared by a simple solution evaporation method. A significant synergistic effect of Fe(3)O(4) and MWNT provided enhanced electrical conductivity, mechanical properties, and thermal stability on the nanocomposites. A 5% (wt) loading of Fe(3)O(4)/MWNT in the nanocomposite increased conductivity from 5.34×10(-5) S/m to 1.49×10(-2) S/m compared to 5% (wt) MWNT loadings. The Fe(3)O(4)/MWNT/Chitosan films also exhibited increases in tensile strength and modulus of 70% and 155%, respectively. The integral procedure decomposition temperature (IPDT) was enhanced from 501 °C to 568 °C. These effects resulted from a number of factors: generation of a greater number of conductive channels through interactions between MWNT and Fe(3)O(4) surfaces, a higher relative crystallinity, the antiplasticizing effects of Fe(3)O(4), a restricted mobility and hindrance of depolymerization of the Chitosan chain segments, as well as uniform distribution, improved dispersion, and strong interfacial adhesion between the MWNT and Chitosan matrix. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lagrangian and Eulerian description of bed-load particle kinematics

NASA Astrophysics Data System (ADS)

Ballio, Francesco; Sadabadi, Seyed Abbas Hosseini; Pokrajac, Dubravka; Radice, Alessio

2016-04-01

The motion of bed-load sediment particles transported by a flow can be analyzed within a Lagrangian or an Eulerian framework. In the former case, we consider the particles as individual objects in motion and we study their kinematic properties. The latter approach is instead referred to suitably chosen control volumes. Quantities describing sediment motion in the two frameworks are different, and the relationships among the two approaches are not straightforward. In this work, we intend to discuss the kinematic properties of sediment transport: first, a set of quantities is univocally defined; then, relationships among different representations are explored. Proof-of-concept results presented in the study are from a recent experiment involving weak bed-load sediment transport, where the moving particles were released over a fixed rough bed. The bulk flow velocity was 1.4 times the critical value for incipient particle motion, and particles were mostly moving by rolling and sliding, with limited saltation. The particle motion was filmed from the top and the measurements were conducted by image-based methods, obtaining extensive samples of virtually-instantaneous quantities.

Mucoadhesive films containing chitosan-coated nanoparticles: a new strategy for buccal curcumin release.

PubMed

Mazzarino, Letícia; Borsali, Redouane; Lemos-Senna, Elenara

2014-11-01

Mucoadhesive films containing curcumin-loaded nanoparticles were developed, aiming to prolong the residence time of the dosage form in the oral cavity and to increase drug absorption through the buccal mucosa. Films were prepared by the casting method after incorporation of curcumin-loaded chitosan-coated polycaprolactone nanoparticles into plasticized chitosan solutions. Different molar masses of mucoadhesive polysaccharide chitosan and concentrations of plasticizer glycerol were used to optimize the preparation conditions. Films obtained using medium and high molar mass chitosan were found to be homogeneous and flexible. Curcumin-loaded nanoparticles were uniformly distributed on the film surface, as evidenced by atomic force microscopy and high-resolution field-emission gun scanning electron microscopy (FEG-SEM) images. Analyses of film cross sections using FEG-SEM demonstrate the presence of nanoparticles inside the films. In addition, films proved to have a good rate of hydration in simulated saliva solution, displaying a maximum swelling of around 80% and in vitro prolonged-controlled delivery of curcumin. These results indicate that the mucoadhesive films containing nanoparticles offer a promising approach for buccal delivery of curcumin, which may be particularly useful in the treatment of periodontal diseases that require a sustained drug delivery. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

Study of the controlled assembly of DNA gated PEI/Chitosan/SiO2 fluorescent sensor.

PubMed

Chang, Zheng; Mi, Yinghao; Zheng, Xingwang

2018-03-01

In this paper, polyethylenimine (PEI) and Chitosan were simultaneously one-step doped into silicon dioxide (SiO 2 ) nanoparticles to synthesize PEI/Chitosan/SiO 2 composite nanoparticles. The polymer PEI contained a large amount of amino groups, which can realize the amino functionalized SiO 2 nanoparticles. And, the good pore forming effect of Chitosan was introduced into SiO 2 nanoparticles, and the resulting composite nanoparticles also had a porous structure. In pH 7.4 phosphate buffer solution (PBS), the amino groups of PEI had positive charges, and therefore the fluorescein sodium dye molecule can be loaded into the channels of PEI/Chitosan/SiO 2 composite nanoparticles by electrostatic adsorption. Furthermore, utilizing the diversity of DNA molecular conformation, we designed a high sensitive controllable assembly of DNA gated fluorescent sensor based on PEI/Chitosan/SiO 2 composite nanoparticles as loading materials. The factors affecting the sensing performance of the sensor were investigated, and the sensing mechanism was also further studied. Copyright © 2017 John Wiley & Sons, Ltd.

Loading relativistic Maxwell distributions in particle simulations

NASA Astrophysics Data System (ADS)

Zenitani, Seiji

2015-04-01

Numerical algorithms to load relativistic Maxwell distributions in particle-in-cell (PIC) and Monte-Carlo simulations are presented. For stationary relativistic Maxwellian, the inverse transform method and the Sobol algorithm are reviewed. To boost particles to obtain relativistic shifted-Maxwellian, two rejection methods are proposed in a physically transparent manner. Their acceptance efficiencies are ≈50 % for generic cases and 100% for symmetric distributions. They can be combined with arbitrary base algorithms.

Formation and cleaning function of physically cross-linked dual strengthened water-soluble chitosan-based core-shell particles.

PubMed

Dong, Yanrui; Xiao, Congming

2017-09-01

Facile and mild ionic cross-linking and freezing/thawing technologies were applied to prepare double strengthened core-shell particles by using water-soluble chitosan (WSC), sodium alginate (SA) and poly(vinyl alcohol) (PVA) as starting materials. The aqueous solution contained WSC and PVA was dropped in ethanol to form beads. The beads were converted into WSC/PVA hydrogel particles by being subjected to three freeze/thaw cycles. Subsequently, ionic cross-linked hydrogel layer was formed around each WSC/PVA particle to generate core-shell particulates. Fourier transform infrared spectra confirmed the combination among various components. Dynamic mechanical thermal analysis indicated that the storage modulus of the core-shell hydrogel was improved obviously. Thermogravimetric analysis exhibited the thermal stability of the particles was also enhanced by incorporation of PVA. It was found that the particles were able to adsorb carbon dioxide, lead ion and copper ion. The adsorption capacities of dry particles toward carbon dioxide, Pb(II) and Cu(II) could reach 199.62, 39.28 and 26.03mg/g, respectively. The rates of the particles for binding Pb(II) and Cu(II) at initial stage were 26.57 and 4.30%/min, respectively. These experimental results suggested that the particles were an efficient sorbent for removing hazardous substances such as carbon dioxide and heavy-metal ions. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and biosorption evaluation of Bacillus subtilis/alginate–chitosan microcapsule

PubMed Central

Tong, Ke

2017-01-01

The aim of this study was to assess the effect of alginate–chitosan microcapsule on viability characteristics of Bacillus subtilis and the ability of B. subtilis/alginate–chitosan microcapsule to remove uranium ion from aqueous solution. The effects of particle size, chitosan molecular weight and inoculum density on viability characteristics were studied using alginate–chitosan microcapsule-immobilized B. subtilis experiments. In addition, the effects of pH, immobilized spherule dosage, temperature, initial uranium ion concentration and contact time on removal of uranium ion were studied using batch adsorption experiments. The results showed that alginate–chitosan microcapsule significantly improved the viability characteristics of B. subtilis and that B. subtilis/alginate–chitosan microcapsule strongly promoted uranium ion absorption. Moreover, the optimum values of pH was 6; immobilized spherule dosage was 3.5; temperature was 20°C; initial uranium ion concentration was 150 mg/L; contact time was 3 h of uranium ion absorption and the maximum adsorption capacity of uranium ion was 376.64 mg/g. PMID:28223783

Exploration of hydrophobic modification degree of chitosan-based nanocomplexes on the oral delivery of enoxaparin.

PubMed

Wang, Linlin; Li, Liang; Sun, Yujiao; Tian, Ye; Li, Ying; Li, Conghao; Junyaprasert, Varaporn B; Mao, Shirui

2013-11-20

The objective of this paper is to elucidate the influence of lipophilic modification degree of chitosan on the peroral absorption of enoxaparin. A series of novel chitosan grafted glyceryl monostearate (GM) copolymers with different GM substitution degree were synthesized and the successful synthesis was confirmed by (1)H NMR, FTIR and X-ray diffraction. Enoxaparin loaded nanocomplexes with different carriers were prepared by self-assembly process. Influence of GM substitution degree and chitosan molecular weight in the copolymer on the properties of the nanocomplexes was investigated. Morphology of the nanocomplexes was observed by atomic force microscopy. Mucoadhesive properties of the nanocomplexes were characterized using mucin particle method. Initially, mucoadhesion of the nanocomplexes increased with the increase of GM substitution degree and it started to decrease when the substitution degree was up to 18.6%. A good linear relationship between GM substitution degree and in vivo absorption of enoxaparin in fasted rats was established in the substitution degree range of 0-11.1%. In agreement with mucoadhesion data, further increasing GM substitution degree to 18.6% caused a decrease in oral absorption. In conclusion, oral bioavailability of enoxaparin can be enhanced by structure modification of the carriers and the bioavailability is hydrophobic modification degree dependent. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Repetitive heterocoagulation of oppositely charged particles for enhancement of magnetic nanoparticle loading into monodisperse silica particles.

PubMed

Matsumoto, Hideki; Nagao, Daisuke; Konno, Mikio

2010-03-16

Oppositely charged particles were repetitively heterocoagulated to fabricate highly monodisperse magnetic silica particles with high loading of magnetic nanoparticles. Positively charged magnetic nanoparticles prepared by surface modification with N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TSA) were used to heterocoagulate with silica particles under basic conditions to give rise to negative silica surface charge and prevent the oxidation of the magnetic nanoparticles. The resultant particles of silica core homogeneously coated with the magnetic nanoparticles were further coated with thin silica layer with sodium silicate in order to enhance colloidal stability and avoid desorption of the magnetic nanoparticles from the silica cores. Five repetitions of the heterocoagulation and the silica coating could increase saturation magnetization of the magnetic silica particles to 27.7 emu/g, keeping the coefficient of variation of particle sizes (C(V)) less than 6.5%. Highly homogeneous loading of the magnetic component was confirmed by measuring Fe-to-Si atomic ratios of individual particles with energy dispersive X-ray spectroscopy.

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.

Chitosan Microspheres in Novel Drug Delivery Systems

PubMed Central

Mitra, Analava; Dey, Baishakhi

2011-01-01

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

Hexavalent chromium removal in contaminated water using reticulated chitosan micro/nanoparticles from seafood processing wastes.

PubMed

Dima, Jimena Bernadette; Sequeiros, Cynthia; Zaritzky, Noemi E

2015-12-01

Chitosan particles (CH) were obtained from seafood processing wastes (shrimp shells) and physicochemically characterized; deacetylation degree of CH was measured by Infrared Spectroscopy (FTIR) and potentiometric titration; polymer molecular weight was determined by intrinsic viscosity measurements. Reticulated micro/nanoparticles of chitosan (MCH) with an average diameter close to 100nm were synthesized by ionic gelation of chitosan using tripolyphosphate (TPP), and characterized by SEM, size distribution and Zeta-potential. Detoxification capacities of CH and MCH were tested analyzing the removal of hexavalent chromium Cr(VI) from contaminated water, at different initial chromium concentrations. The effect of pH on adsorption capacity of CH and MCH was experimentally determined and analyzed considering the Cr(VI) stable complexes (anions) formed, the presence of protonated groups in chitosan particles and the addition of the reticulating agent (TPP). Chitosan crosslinking was necessary to adsorb Cr(VI) at pH<2 due to the instability of CH particles in acid media. Langmuir isotherm described better than Freundlich and Temkin equations the equilibrium adsorption data. Pseudo-second order rate provided the best fitting to the kinetic data in comparison to pseudo-first order and Elovich equations. Chemical analysis to determine the oxidation state of the adsorbed Cr, showed that Cr(VI) was adsorbed on CH particles without further reduction; in contrast Cr(VI) removed from the solution was reduced and bound to the MCH as Cr(III). The reduction of toxic Cr(VI) to the less or nontoxic Cr(III) by the reticulated chitosan micro/nanoparticles can be considered a very efficient detoxification technique for the treatment of Cr(VI) contaminated water. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relaxivity enhancement of aquated Tris(β-diketonate)gadolinium(III) chelates by confinement within ultrashort single-walled carbon nanotubes.

PubMed

Law, Justin J; Guven, Adem; Wilson, Lon J

2014-01-01

Ultrashort single-walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1 -weighted relaxivities (>100 mm(-1) s(-1) ). To further examine the effect of nanoconfinement on the relaxivity of gadolinium-based contrast agents for magnetic resonance imaging, a series of ultrashort single-walled carbon nanotube (US-tube) materials internally loaded with gadolinium chelates have been prepared and studied. US-tubes were loaded with Gd(acac)3  · 2H2 O, Gd(hfac)3  · 2H2 O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm(-1) s(-1) for Gd(acac)3  · 2H2 O@US-tubes, 105 mm(-1) s(-1) for Gd(hfac)3  · 2H2 O@US-tubes and 26 mm(-1) s(-1) for Gd(thd)3 @US-tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm(-1) s(-1) ) as well as accounting for the T1 reduction observed for the empty US-tubes, the boost in relaxivity for chelate-loaded US-tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.

Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice.

PubMed

Moreno, Esther; Schwartz, Juana; Larrea, Esther; Conde, Iosune; Font, Maria; Sanmartín, Carmen; Irache, Juan Manuel; Espuelas, Socorro

2015-11-01

Patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. Lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. In this study, we proposed the loading of β-lapachone (β-LP) in lecithin-chitosan nanoparticles (NP) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. Although the loading of β-LP in NP did not influence the drug antileishmanial activity it was critical to achieve important drug accumulation in the dermis and permeation through the skin. When topically applied in Leishmania major infected BALB/c mice, β-LP NP achieved no parasite reduction but they stopped the lesion progression. Immuno-histopathological assays in CL lesions and quantitative mRNA studies in draining lymph nodes confirmed that β-LP exhibited anti-inflammatory activity leading to the down-regulation of IL-1β and COX-2 expression and a decrease of neutrophils infiltrate. Cutaneous leishmaniasis often leaves patients with unsightly scars due to the body's inflammatory response to the infection. The authors in this paper described topical treatment using β-lapachone (β- LP) loaded in lecithin-chitosan nanoparticles (NP) in an animal model. Results confirmed the reduction of inflammatory response without affecting the parasite killing efficacy. These findings would pave way for further clinical testing in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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.

Tuning effect of polysaccharide Chitosan on structural, morphological, optical and photoluminescence properties of ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Magesh, G.; Bhoopathi, G.; Nithya, N.; Arun, A. P.; Ranjith Kumar, E.

2018-05-01

Chitosan/ZnO nanocomposites was synthesized by in-situ chemical precipitation method. The effect of polysaccharide Chitosan concentration (0.1 g, 0.5 g, 1 g and 3 g) was investigated by X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM) with Energy dispersive spectroscopy (EDX), High Resolution Transmission Electron Microscopy (HRTEM), UV-visible (UV), Fourier Transform Infrared (FTIR) and Photoluminescence Spectroscopy (PL). XRD pattern confirms the hexagonal wurtzite structure of the Chitosan/ZnO nanocomposites. The structural morphology and the elemental composition of the samples were analysed by FESEM and EDX respectively. From TEM analysis, it is observed that the particles in spindle shape morphology with average particle size ranges 10-20 nm. UV-Vis analysis reveals that the Chitosan concentration affect the absorption band edge and shift towards lower wavelength. The oxygen vacancy induced photoluminescence of ZnO nanoparticles was observed and its intensity decreases by tuning the Chitosan concentration.

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

PubMed Central

Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

2014-01-01

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America.

PubMed

Mithal, Leena B; Patel, Payal S; Mithal, Divakar; Palac, Hannah L; Rozenfeld, Michael N

2017-05-01

Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P<0.0001). Radiologists and referring providers expressed similar levels of concern (95% and 89%). Twelve percent of radiologists and 2% of referring providers reported patients asking about brain gadolinium deposition. Radiologists were significantly more comfortable addressing patient inquiries than referring pediatric physicians (48% vs. 6%; P<0.0001). The number of MRIs requested by referring pediatric physicians correlated with their knowledge of brain gadolinium deposition, contrast agent used by their hospital, and comfort discussing brain gadolinium deposition with patients (P<0.0001). Since the discovery of brain gadolinium deposition, many pediatric hospitals have switched to or plan to switch to a more stable macrocyclic MR contrast agent, most commonly gadoterate meglumine. Despite this, there is need for substantial further education of radiologists and

Universal characteristics of particle shape evolution by bed-load chipping

PubMed Central

Sipos, András Árpád; Shaw, Sam; Sarti, Giovanni; Domokos, Gábor

2018-01-01

River currents, wind, and waves drive bed-load transport, in which sediment particles collide with each other and Earth’s surface. A generic consequence is impact attrition and rounding of particles as a result of chipping, often referred to in geological literature as abrasion. Recent studies have shown that the rounding of river pebbles can be modeled as diffusion of surface curvature, indicating that geometric aspects of impact attrition are insensitive to details of collisions and material properties. We present data from fluvial, aeolian, and coastal environments and laboratory experiments that suggest a common relation between circularity and mass attrition for particles transported as bed load. Theory and simulations demonstrate that universal characteristics of shape evolution arise because of three constraints: (i) Initial particles are mildly elongated fragments, (ii) particles collide with similarly-sized particles or the bed, and (iii) collision energy is small enough that chipping dominates over fragmentation but large enough that sliding friction is negligible. We show that bed-load transport selects these constraints, providing the foundation to estimate a particle’s attrition rate from its shape alone in most sedimentary environments. These findings may be used to determine the contribution of attrition to downstream fining in rivers and deserts and to infer transport conditions using only images of sediment grains. PMID:29670937

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.

Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability

PubMed Central

Severino, Patrícia; de Oliveira, George G.G.; Ferraz, Humberto G.; Souto, Eliana B.; Santana, Maria H.A.

2012-01-01

The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration, aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile. Chitosan microspheres were produced under fluidized bed, followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm. The pellets were then coated with Kollidon® VA64 and Kollicoat® MAE100P in water dispersion to depict a sustained release profile. Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine. Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine. PMID:29403741

Construction of METHFR shRNA/5-fluorouracil co-loaded folate-targeted chitosan polymeric nanoparticles and its anti-carcinoma effect on gastric cells growth

NASA Astrophysics Data System (ADS)

Xin, Lin; Fan, Ji-Chang; Le, Yi-Guan; Zeng, Fei; Cheng, Hua; Hu, Xiao-yun; Cao, Jia-Qing

2016-05-01

PEGylated and folate-targeted chitosan polymeric nanoparticles (FPNs) for the treatment of gastric carcinoma were prepared successfully. OQC-anchored folate conjugates were synthesized and used in assembling FPNs nano-system for enhancing intracellular uptake against folate receptor overexpressing cancer cells. The results indicated that folate-targeted chitosan polymeric nanoparticles (CPNs) can reverse drug-resistant SGC-7901 cells of 5-fluorouracil (5-FU) compared with non-targeted CPNs. Increased therapeutic efficiency of 5-FU/METHFR shRNA co-loaded PNs were also tested in SGC-7901 cells and compaed with 5-FU or METHFR shRNA in solution, which was associated with increased cell inhibition function for single drug group and synergistic effects of 5-FU and METHFR shRNA at 2.0 µg/mL FPNs concentration. In addition, the cell accumulation levels of 5-FU in SGC-7901 cells was time dependent for these nanoparticles. FPNs (effective diameter: 83.2 ± 1.1 nm; polydispersity index: 0.193) could significantly boost cellular accumulation of 5-FU and overcome the drug efflux mechanism of MDR than 5-FU-loaded NPNs and 5-FU in solution. In conclusion, ligand-targeted PNs can be used as a potentially effective drug delivery system.

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.

Superhydrophobic surfaces generated by one-pot spray-coating of chitosan-based nanoparticles.

PubMed

Wang, Shuangfei; Sha, Jiulong; Wang, Wei; Qin, Chengrong; Li, Wei; Qin, Caiqin

2018-09-01

Superhydrophobic surfaces have attracted great attention due to their attractive properties. Biopolymer-based low-cost and environmentally-friendly superhydrophobic coatings with easy-to-perform fabrication methods are always desirable. Herein, we report superhydrophobic surfaces using a one-step spray-coating of chitosan-based nanoparticles. The particles were easily prepared by a nanoprecipitation strategy using synthesized organosoluble chitosan stearoyl ester (CSSE). The resulting particles had an average size of 165 ∼ 235 nm depending on the applied concentration. Subsequently, spray-coating of such particles onto silicon wafer generated a surface with a water contact angle of 155 ± 1°. SEM and AFM images exhibited a nano/microscaled roughness appeared on the coated surface. The superhydrophobic surfaces showed a stable superhydrophobic performance even after storage for 15 days, pH stability between pH 1 to pH 11 and thermal stability until a temperature no more than 50 °C. These properties would broaden the application fields of superhydrophobic surfaces as well as the chitosan itself. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optimization, in vitro release and bioavailability of gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan.

PubMed

Kim, Jong Soo; Lee, Ji-Soo; Chang, Pahn-Shick; Lee, Hyeon Gyu

2010-09-30

Response surface methodology was used to optimize coating conditions, including chitosan concentration (X(1)) and coating time (X(2)), for sustained release of chitosan-coated Ca-pectinate (CP) microparticles containing oryzanol (OZ). The optimized values of X(1) and X(2) were found to be 1.48% and 69.92 min, respectively. These optimized values agreed favorably with the predicted results, indicating the utility of predictive models for the release of OZ in simulated intestinal fluid. In vitro release studies revealed that the chitosan-coated CP microparticles were quite stable under acidic conditions, but swell and disintegrate under alkaline conditions. In vivo release study of OZ, physically entrapped within chitosan-coated CP microcapsules, demonstrated the sustained release of OZ and could be used to improve the bioavailability of OZ following oral administration. Copyright 2010 Elsevier B.V. All rights reserved.

Synthesis and in vitro antifungal efficacy of oleoyl-chitosan nanoparticles against plant pathogenic fungi.

PubMed

Xing, Ke; Shen, Xiaoqiang; Zhu, Xiao; Ju, Xiuyun; Miao, Xiangmin; Tian, Jun; Feng, Zhaozhong; Peng, Xue; Jiang, Jihong; Qin, Sheng

2016-01-01

An antifungal dispersion system was prepared by oleoyl-chitosan (O-chitosan) nanoparticles, and the antifungal activity against several plant pathogenic fungi was investigated. Under scanning electron microscopy, the nanoparticles formulation appeared to be uniform with almost spherical shape. The particle size of nanoparticles was around 296.962 nm. Transmission electron microscopy observation showed that nanoparticles could be well distributed in potato dextrose agar medium. Mycelium growth experiment demonstrated that Nigrospora sphaerica, Botryosphaeria dothidea, Nigrospora oryzae and Alternaria tenuissima were chitosan-sensitive, while Gibberella zeae and Fusarium culmorum were chitosan-resistant. The antifungal index was increased as the concentration of nanoparticles increased for chitosan-sensitive fungi. Fatty acid analyses revealed that plasma membranes of chitosan-sensitive fungi were shown to have lower levels of unsaturated fatty acid than chitosan-resistant fungi. Phylogenetic analysis based on ITS gene sequences indicated that two chitosan-resistant fungi had a near phylogenetic relationship. Results showed that O-chitosan nanoparticles could be a useful alternative for controlling pathogenic fungi in agriculture. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization of chitosan treatments for managing microflora in lettuce seeds without affecting germination.

PubMed

Goñi, M G; Moreira, M R; Viacava, G E; Roura, S I

2013-01-30

Many studies have focused on seed decontamination but no one has been capable of eliminating all pathogenic bacteria. Two objectives were followed. First, to assess the in vitro antimicrobial activity of chitosan against: (a) Escherichia coli O157:H7, (b) native microflora of lettuce and (c) native microflora of lettuce seeds. Second, to evaluate the efficiency of chitosan on reducing microflora on lettuce seeds. The overall goal was to find a combination of contact time and chitosan concentration that reduces the microflora of lettuce seeds, without affecting germination. After treatment lettuce seeds presented no detectable microbial counts (<10(2)CFU/50 seeds) for all populations. Moreover, chitosan eliminated E. coli. Regardless of the reduction in the microbial load, a 90% reduction on germination makes imbibition with chitosan, uneconomical. Subsequent treatments identified the optimal treatment as 10 min contact with a 10 g/L chitosan solution, which maintained the highest germination percentage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Use of Artificial Neural Networks to Examine Parameters Affecting the Immobilization of Streptokinase in Chitosan

PubMed Central

Modaresi, Seyed Mohamad Sadegh; Faramarzi, Mohammad Ali; Soltani, Arash; Baharifar, Hadi; Amani, Amir

2014-01-01

Streptokinase is a potent fibrinolytic agent which is widely used in treatment of deep vein thrombosis (DVT), pulmonary embolism (PE) and acute myocardial infarction (MI). Major limitation of this enzyme is its short biological half-life in the blood stream. Our previous report showed that complexing streptokinase with chitosan could be a solution to overcome this limitation. The aim of this research was to establish an artificial neural networks (ANNs) model for identifying main factors influencing the loading efficiency of streptokinase, as an essential parameter determining efficacy of the enzyme. Three variables, namely, chitosan concentration, buffer pH and enzyme concentration were considered as input values and the loading efficiency was used as output. Subsequently, the experimental data were modeled and the model was validated against a set of unseen data. The developed model indicated chitosan concentration as probably the most important factor, having reverse effect on the loading efficiency. PMID:25587327

Controlled and extended drug release behavior of chitosan-based nanoparticle carrier.

PubMed

Yuan, Q; Shah, J; Hein, S; Misra, R D K

2010-03-01

Controlled drug release is presently gaining significant attention. In this regard, we describe here the synthesis (based on the understanding of chemical structure), structural morphology, swelling behavior and drug release response of chitosan intercalated in an expandable layered aluminosilicate. In contrast to pure chitosan, for which there is a continuous increase in drug release with time, the chitosan-aluminosilicate nanocomposite carrier was characterized by controlled and extended release. Drug release from the nanocomposite particle carrier occurred by degradation of the carrier to its individual components or nanostructures with a different composition. In both the layered aluminosilicate-based mineral and chitosan-aluminosilicate nanocomposite carriers the positively charged chemotherapeutic drug strongly bound to the negatively charged aluminosilicate and release of the drug was slow. Furthermore, the pattern of drug release from the chitosan-aluminosilicate nanocomposite carrier was affected by pH and the chitosan/aluminosilicate ratio. The study points to the potential application of this hybrid nanocomposite carrier in biomedical applications, including tissue engineering and controlled drug delivery. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Direct compression of chitosan: process and formulation factors to improve powder flow and tablet performance.

PubMed

Buys, Gerhard M; du Plessis, Lissinda H; Marais, Andries F; Kotze, Awie F; Hamman, Josias H

2013-06-01

Chitosan is a polymer derived from chitin that is widely available at relatively low cost, but due to compression challenges it has limited application for the production of direct compression tablets. The aim of this study was to use certain process and formulation variables to improve manufacturing of tablets containing chitosan as bulking agent. Chitosan particle size and flow properties were determined, which included bulk density, tapped density, compressibility and moisture uptake. The effect of process variables (i.e. compression force, punch depth, percentage compaction in a novel double fill compression process) and formulation variables (i.e. type of glidant, citric acid, pectin, coating with Eudragit S®) on chitosan tablet performance (i.e. mass variation, tensile strength, dissolution) was investigated. Moisture content of the chitosan powder, particle size and the inclusion of glidants had a pronounced effect on its flow ability. Varying the percentage compaction during the first cycle of a double fill compression process produced chitosan tablets with more acceptable tensile strength and dissolution rate properties. The inclusion of citric acid and pectin into the formulation significantly decreased the dissolution rate of isoniazid from the tablets due to gel formation. Direct compression of chitosan powder into tablets can be significantly improved by the investigated process and formulation variables as well as applying a double fill compression process.

Functional characterisation and permeation studies of lyophilised thiolated chitosan xerogels for buccal delivery of insulin.

PubMed

Boateng, Joshua S; Mitchell, John C; Pawar, Harshavardhan; Ayensu, Isaac

2014-01-01

Stable and mucoadhesive, lyophilised, thiolated chitosan xerogels, loaded with insulin for buccal mucosa deliv- ery, in place of the currently used parenteral route have been developed. The xerogels were backed with impervious ethyl- cellulose laminate to ensure unidirectional release and also loaded with enzyme inhibitor to enhance insulin permeability across the buccal mucosa. Characterisation of xerogels using(1) HNMR confirmed the degree of deacetylation of the syn- thesised thiolated chitosan. The amount of thiol groups immobilised on the modified chitosan was quantified by Ellman's reaction and molecular weight monitored by gel permeation chromatography. The stability of the secondary structure of insulin was examined by attenuated total reflectance Fourier transform infra-red spectroscopy and circular dichroism. In vitro and ex vivo permeation studies were undertaken by using EpiOral ™ and sheep buccal membrane respectively. Insu- lin released from thiolated chitosan xerogels, loaded with aprotinin (enzyme inhibitor and permeation enhancer) showed a 1.7-fold increase in permeation through EpiOral ™ buccal tissue construct compared to the pure drug. However, permea- tion was decreased for xerogels containing the enzyme inhibitor glutathione. Further, aprotinin containing xerogels en- hanced insulin permeation through sheep buccal membrane and demonstrated good linear correlation with the permeation data from the EpiOral ™ study. The results show the potential application of lyoph ilised thiolated chitosan xerogels con- taining aprotinin with improved mucoadhesion, penetration enhancing and enzyme inhibition characteristics for buccal mucosa delivery of macromolecules such as insulin.

Spray-dried chitosan as a direct compression tableting excipient.

PubMed

Chinta, Dakshinamurthy Devanga; Graves, Richard A; Pamujula, Sarala; Praetorius, Natalie; Bostanian, Levon A; Mandal, Tarun K

2009-01-01

The objective of this study was to prepare and evaluate a novel spray-dried tableting excipient using a mixture of chitosan and lactose. Three different grades of chitosan (low-, medium-, and high-molecular-weight) were used for this study. Propranolol hydrochloride was used as a model drug. A specific amount of chitosan (1, 1.9, and 2.5 g, respectively) was dissolved in 50 mL of an aqueous solution of citric acid (1%) and later mixed with 50 mL of an aqueous solution containing lactose (20, 19.1, and 18.5 g, respectively) and propanolol (2.2 g). The resultant solution was sprayed through a laboratory spray drier at 1.4 mL/min. The granules were evaluated for bulk density, tap density, Carr index, particle size distribution, surface morphology, thermal properties, and tableting properties. Bulk density of the granules decreased from 0.16 to 0.13 g/mL when the granules were prepared using medium- or high-molecular-weight chitosan compared with the low-molecular-weight chitosan. The relative proportion of chitosan also showed a significant effect on the bulk density. The granules prepared with 1 g of low-molecular-weight chitosan showed the minimum Carr index (11.1%) indicating the best flow properties among all five formulations. All three granules prepared with 1 g chitosan, irrespective of their molecular weight, showed excellent flow properties. Floating tablets prepared by direct compression of these granules with sodium bicarbonate showed 50% drug release between 30 and 35 min. In conclusion, the spray-dried granules prepared with chitosan and lactose showed excellent flow properties and were suitable for tableting.

Synthesis and optimization of chitosan nanoparticles: Potential applications in nanomedicine and biomedical engineering.

PubMed

Ghadi, Arezou; Mahjoub, Soleiman; Tabandeh, Fatemeh; Talebnia, Farid

2014-01-01

Chitosan nanoparticles have become of great interest for nanomedicine, biomedical engineering and development of new therapeutic drug release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity. The aim of the present study was to synthesis and optimize of the chitosan nanoparticles for industrial and biomedical applications. Fe3O4 was synthesized and optimized as magnetic core nanoparticles and then chitosan covered this magnetic core. The size and morphology of the nano-magnetic chitosan was analyzed by scanning electron microscope (SEM). Topography and size distribution of the nanoparticles were shown with two-dimensional and three-dimensional images of atomic force microscopy (AFM). The nanoparticles were analyzed using transmission electron microscopy (TEM). The chitosan nanoparticles prepared in the experiment exhibited white powder shape. The SEM micrographs of the nano-magnetic chitosan showed that they were approximately uniform spheres. The unmodified chitosan nanoparticles composed of clusters of nanoparticles with sizes ranging from 10 nm to 80 nm. AFM provides a three-dimensional surface profile. The TEM image showed physical aggregation of the chitosan nanoparticles. The results show that a novel chitosan nanoparticle was successfully synthesized and characterized. It seems that this nanoparticle like the other chitosan nano particles has potential applications for nanomedicine, biomedical engineering, industrial and pharmaceutical fields.

Image-based Lagrangian Particle Tracking in Bed-load Experiments.

PubMed

Radice, Alessio; Sarkar, Sankar; Ballio, Francesco

2017-07-20

Image analysis has been increasingly used for the measurement of river flows due to its capabilities to furnish detailed quantitative depictions at a relatively low cost. This manuscript describes an application of particle tracking velocimetry (PTV) to a bed-load experiment with lightweight sediment. The key characteristics of the investigated sediment transport conditions were the presence of a covered flow and of a fixed rough bed above which particles were released in limited number at the flume inlet. Under the applied flow conditions, the motion of the individual bed-load particles was intermittent, with alternating movement and stillness terms. The flow pattern was preliminarily characterized by acoustic measurements of vertical profiles of the stream-wise velocity. During process visualization, a large field of view was obtained using two action-cameras placed at different locations along the flume. The experimental protocol is described in terms of channel calibration, experiment realization, image pre-processing, automatic particle tracking, and post-processing of particle track data from the two cameras. The presented proof-of-concept results include probability distributions of the particle hop length and duration. The achievements of this work are compared to those of existing literature to demonstrate the validity of the protocol.

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

Enzyme immobilization in novel alginate-chitosan core-shell microcapsules.

PubMed

Taqieddin, Ehab; Amiji, Mansoor

2004-05-01

Alginate-chitosan core-shell microcapsules were prepared in order to develop a biocompatible matrix for enzyme immobilization, where the protein is retained either in a liquid or solid core and the shell allows permeability control over substrates and products. The permeability coefficients of different molecular weight compounds (vitamin B2, vitamin B12, and myoglobin) were determined through sodium tripolyphosphate (Na-TPP)-crosslinked chitosan membrane. The microcapsule core was formed by crosslinking sodium alginate with either calcium or barium ions. The crosslinked alginate core was uniformly coated with a chitosan layer and crosslinked with Na-TPP. In the case of calcium alginate, the phosphate ions of Na-TPP were able to extract the calcium ions from alginate and liquefy the core. A model enzyme, beta-galactosidase, was immobilized in the alginate core and the catalytic activity was measured with o-nitrophenyl-beta-D-galactopyranoside (ONPG). Change in the activity of free and immobilized enzyme was determined at three different temperatures. Na-TPP crosslinked chitosan membranes were found to be permeable to solutes of up to 17,000Da molecular weight. The enzyme loading efficiency was higher in the barium alginate core (100%) as compared to the calcium alginate core (60%). The rate of ONPG conversion to o-nitrophenol was faster in the case of calcium alginate-chitosan microcapsules as compared to barium alginate-chitosan microcapsules. Barium alginate-chitosan microcapsules, however, did improve the stability of the enzyme at 37 degrees C relative to calcium alginate-chitosan microcapsules or free enzyme. This study illustrates a new method of enzyme immobilization for biotechnology applications using liquid or solid core and shell microcapsule technology.

Elaboration of chitosan/activated carbon composites for the removal of organic micropollutants from waters.

PubMed

Venault, A; Vachoud, L; Pochat, C; Bouyer, D; Faur, C

2008-12-01

Composite hydrogels were prepared by a wet-casting process by blending a biopolymer, chitosan, with activated carbon (AC) for use in water treatment. Adsorption properties of the composite gels for an organic micro-pollutant (phenol) which may be encountered in wastewaters was studied with an experimental design approach as a function of: - the concentration of raw materials and thus the AC weight within the chitosan matrix. - the accessibility of AC in the polymeric matrix, which is assumed to be related to the coating and thus to the pH of the immersion bath. ESEM observations showed that at a higher pH of gelation (pH = 14), AC particles were entrapped at the surface of the polymer matrix because of a faster gelation kinetic than at a lower pH (13.3). Adsorption kinetic tests showed that phenol adsorption occurred according to two mechanisms. During the first step, phenol molecules were adsorbed by the AC particles located at the surface. The second step corresponded to a slow diffusion through chitosan chains leading to an adsorption by AC particles entrapped within the polymeric matrix coupled to an adsorption on to the chitosan. A mass transfer model was used to describe this two-step adsorption phenomenon. However, due to a heterogeneous coating of AC by chitosan, this phenomenon was not supported by experimental design results: the initial kinetic coefficients were associated with a high experimental error which didn't allow for an analysis of the influence of elaboration parameters on kinetic coefficients. Regardling equilibrium adsorption properties, it was shown that composite gels were good adsorbents for phenol with removal ranging from 94% to 98% corresponding to adsorption capacities from 30 to 41 mg g(-1). The pH of the immersion bath had no influence on equilibrium adsorption properties, contrary to the AC weight within the chitosan matrix which wasdemonstrated to influence significantly adsorption capacities. Because carbon particles may improve

Synthesis of gadolinium carbonate-conjugated-poly(ethylene)glycol (Gd{sub 2}(CO{sub 3}){sub 3}@PEG) particles via a modified solvothermal method

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

Nasution, Erika L. Y.; Ahab, Atika; Nuryadin, Bebeh W.

2016-02-08

PEGylated gadolinium carbonate ((Gd{sub 2}(CO{sub 3}){sub 3})@PEG) powder was successfully synthesized by a modified solvothermal method. The synthesized products were characterized by means of X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Spectroscopy (EDS). A systematic change in the chemical surface composition, crystallinity and size properties of the Gd{sub 2}(CO{sub 3}){sub 3}@PEG particles was observed by increasing the reaction time at 5 hours, 7 hours, and 8 hours. The corresponding XRD patterns showed that the Gd{sub 2}(CO{sub 3}){sub 3} particles had hexagonal symmetry (JCPDS No. 37-0559) with a crystallite size of 3.5,more » 2.9, and 4.6 nm. FTIR spectra showed that the Gd{sub 2}(CO{sub 3}){sub 3})@PEG particles were formed with the PEG as carbonyl and hydroxyl group attached to the surface. SEM analysis showed that the Gd{sub 2}(CO{sub 3}){sub 3})@PEG particles had a flake-like morphology of homogeneous sized particles and agglomerates. EDS analysis confirmed the presence of constituent Gd{sub 2}(CO{sub 3}){sub 3} elements.« less

ASME AG-1 Section FC Qualified HEPA Filters; a Particle Loading Comparison - 13435

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

Stillo, Andrew; Ricketts, Craig I.

High Efficiency Particulate Air (HEPA) Filters used to protect personnel, the public and the environment from airborne radioactive materials are designed, manufactured and qualified in accordance with ASME AG-1 Code section FC (HEPA Filters) [1]. The qualification process requires that filters manufactured in accordance with this ASME AG-1 code section must meet several performance requirements. These requirements include performance specifications for resistance to airflow, aerosol penetration, resistance to rough handling, resistance to pressure (includes high humidity and water droplet exposure), resistance to heated air, spot flame resistance and a visual/dimensional inspection. None of these requirements evaluate the particle loading capacitymore » of a HEPA filter design. Concerns, over the particle loading capacity, of the different designs included within the ASME AG-1 section FC code[1], have been voiced in the recent past. Additionally, the ability of a filter to maintain its integrity, if subjected to severe operating conditions such as elevated relative humidity, fog conditions or elevated temperature, after loading in use over long service intervals is also a major concern. Although currently qualified HEPA filter media are likely to have similar loading characteristics when evaluated independently, filter pleat geometry can have a significant impact on the in-situ particle loading capacity of filter packs. Aerosol particle characteristics, such as size and composition, may also have a significant impact on filter loading capacity. Test results comparing filter loading capacities for three different aerosol particles and three different filter pack configurations are reviewed. The information presented represents an empirical performance comparison among the filter designs tested. The results may serve as a basis for further discussion toward the possible development of a particle loading test to be included in the qualification requirements of ASME

Preparation and evaluation of a chitosan-coated antioxidant liposome containing vitamin C and folic acid.

PubMed

Jiao, Zhen; Wang, Xiudong; Yin, Yuting; Xia, Jingxin; Mei, Yanan

2018-05-03

Vitamin C (VC) and folic acid (FA) are the important nutrient and antioxidant in human body. In order to improve their stability, their co-loaded liposomes (VCFA-Lip) and chitosan-coated liposomes (CS-VCFA-Lip) are prepared and characterised. The mean particle size of VCFA-Lip and CS-VCFA-Lip is 138 nm and 249 nm, respectively. The encapsulation efficiencies of both drugs for CS-VCFA-Lip are much higher than those for VCFA-Lip. Furthermore, the experimental results show that the antioxidant activity of CS-VCFA-Lip is higher than that of VCFA-Lip. Moreover, the storage stability study reveals that the chitosan coating can efficiently improve the physical stability of VCFA-Lip. These results indicate that stability of VC and FA can be greatly improved after being wrapped by liposomes. In addition, the performance of CS-VCFA-Lip is better than VCFA-Lip, indicating CS-VCFA-Lip can be applied as a promising delivery system for the antioxidant defence system to the food industry and cosmetic industry.

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.

Polymicrobial Biofilm Inhibition Effects of Acetate-Buffered Chitosan Sponge Delivery Device.

PubMed

Jennings, Jessica Amber; Beenken, Karen E; Parker, Ashley C; Smith, James Keaton; Courtney, Harry S; Smeltzer, Mark S; Haggard, Warren O

2016-04-01

Polymicrobial biofilm-associated implant infections present a challenging clinical problem. Through modifications of lyophilized chitosan sponges, degradable drug delivery devices for antibiotic solution have been fabricated for prevention and treatment of contaminated musculoskeletal wounds. Elution of amikacin, vancomycin, or a combination of both follows a burst release pattern with vancomycin released above minimum inhibitory concentration for Staphylococcus aureus for 72 h and amikacin released above inhibitory concentrations for Pseudomonas aeruginosa for 3 h. Delivery of a vancomycin, amikacin, or a combination of both reduces biofilm formation on polytetrafluoroethylene catheters in an in vivo model of contamination. Release of dual antibiotics from sponges is more effective at preventing biofilm formation than single-loaded chitosan sponges. Treatment of pre-formed biofilm with high-dose antibiotic release from chitosan sponges shows minimal reduction after 48 h. These results demonstrate infection-preventive efficacy for antibiotic-loaded sponges, as well as the need for modifications in the development of advanced materials to enhance treatment efficacy in removing established biofilm. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

NASA Astrophysics Data System (ADS)

Ordikhani, F.; Simchi, A.

2014-10-01

Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery.

PubMed

Almeida, Andreia; Silva, Daniella; Gonçalves, Virginia; Sarmento, Bruno

2018-04-01

In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis ( 1 H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents.

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.

Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells

NASA Astrophysics Data System (ADS)

Li, Jing; Ma, Fang-Kui; Dang, Qi-Feng; Liang, Xing-Guo; Chen, Xi-Guang

2014-12-01

A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles (GCNPs), was developed for specific recognition and interaction with glucose transporters (Gluts) over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan (CS), and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of (187.9 ± 3.8) nm and a zeta potential of (- 15.43 ± 0.31) mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin (DOX) could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-loaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline (pH 7.4). In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.

Development of chitosan-nanoparticle film based materials for controlled quality of minced beef during refrigerated storage

NASA Astrophysics Data System (ADS)

Erdawati

2010-10-01

Chitosan nanoparticles were prepared based on the ionic gelation of chitosan with tripolyphosphate anions. The physicochemical properties of the chitosan nanoparticles were determined by FTIR analysis, XRD pattern and TEM. The effects of chitosan nanoparticles treatment on the shelf-life extension of minced beef stored at 20±1° C were studied, including chemical and microbiological,. Results indicated that chitosan nanoparticle treatment reduced the total microbial load of fresh minced beef about 10-fold (from 3.2×104 CFU/g to 5.4×102 CFU/g) before storage and the microbial flora was different with that of raw samples. The wide-spectrum antibacterial property of chitosan against bacteria isolated from minced beef was confirmed, and chitosan concentration of 400 ppm was eventually determined for application in minced beef. Based on microbiological analysis, biochemical indices determination and sensory evaluation, shelf-lives of 2-3 days for control, 4-5 days for nanoparticle chitosan treatment samples, were observed, indicating that chitosan nanoparticle have a great potential for minced beef preservation.

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.

Chitosan-silica complex membranes from sulfonic acid functionalized silica nanoparticles for pervaporation dehydration of ethanol-water solutions.

PubMed

Liu, Ying-Ling; Hsu, Chih-Yuan; Su, Yu-Huei; Lai, Juin-Yih

2005-01-01

Nanosized silica particles with sulfonic acid groups (ST-GPE-S) were utilized as a cross-linker for chitosan to form a chitosan-silica complex membranes, which were applied to pervaporation dehydration of ethanol-water solutions. ST-GPE-S was obtained from reacting nanoscale silica particles with glycidyl phenyl ether, and subsequent sulfonation onto the attached phenyl groups. The chemical structure of the functionalized silica was characterized with FTIR, (1)H NMR, and energy-dispersive X-ray. Homogeneous dispersion of the silica particles in chitosan was observed with electronic microscopies, and the membranes obtained were considered as nanocomposites. The silica nanoparticles in the membranes served as spacers for polymer chains to provide extra space for water permeation, so as to bring high permeation rates to the complex membranes. With addition of 5 parts per hundred of functionalized silica into chitosan, the resulting membrane exhibited a separation factor of 919 and permeation flux of 410 g/(m(2) h) in pervaporation dehydration of 90 wt % ethanol aqueous solution at 70 degrees C.

Study of glycol chitosan-carboxymethyl β-cyclodextrins as anticancer drugs carrier.

PubMed

Tan, Haina; Qin, Fei; Chen, Dongfeng; Han, Songbai; Lu, Wu; Yao, Xin

2013-04-02

Efficient target delivery system for insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. Herein, glycol chitosan-carboxymethyl β-cyclodextrins (G-chitosan-CM-dextrins) was synthesized for delivering different hydrophobic anticancer drugs. Surface plasmon resonance and UV-vis spectroscopy results showed that all the three anticancer drugs (5-fluorouracil, doxorubicin, and vinblastine) could be successfully loaded into the cavities of the covalently linked CM-dextrins. Moreover, the free carboxymethyl groups could enhance the binding interactions between the covalently linked CM-dextrins and anticancer drugs. Release behaviors with pH changes of the three drugs were also explored, result showed different drugs would be released by different ways, as for doxorubicin, pH sensitive release has been realized. The obtained G-chitosan-CM-dextrins carrier has both mucoadhesive property of G-chitosan and hydrophobic cavities of β-cyclodextrins. Therefore, the new synthesized G-chitosan-CM-dextrins carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Induction of apoptosis in HeLa cancer cells by an ultrasonic-mediated synthesis of curcumin-loaded chitosan-alginate-STPP nanoparticles.

PubMed

Ahmadi, Fatemeh; Ghasemi-Kasman, Maryam; Ghasemi, Shahram; Gholamitabar Tabari, Maryam; Pourbagher, Roghayeh; Kazemi, Sohrab; Alinejad-Mir, Ali

2017-01-01

Natural herbal compounds have been widely introduced as an alternative therapeutic approach in cancer therapy. Despite potent anticancer activity of curcumin, its clinical application has been limited because of low water solubility and resulting poor bioavailability. In this study, we designed a novel ultrasonic-assisted method for the synthesis of curcumin-loaded chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). Furthermore, antitumor effect of curcumin-loaded NPs was evaluated in vitro. Field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) were used to characterize the properties of NPs. Antitumor activity of curcumin-loaded NPs was assessed by using MTT and quantitative real-time polymerase chain reaction (qRT-PCR). FE-SEM and AFM data revealed the spherical morphology, and the average size of NPs was <50 nm. In vitro cytotoxicity assay suggested that curcumin-loaded CS-ALG-STPP NPs displayed significant antitumor activity compared with the free curcumin. Gene expression level analyses showed that curcumin NPs significantly increased the apoptotic gene expression. Collectively, our results suggest that curcumin-loaded NPs significantly suppressed proliferation and promoted the induction of apoptosis in human cervical epithelioid carcinoma cancer cells, which might be regarded as an effective alternative strategy for cancer therapy.

In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages.

PubMed

Chachuli, Siti Haziyah Mohd; Nawaz, Asif; Shah, Kifayatullah; Naharudin, Idanawati; Wong, Tin Wui

2016-06-01

Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages. Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques. The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary. Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.

New chitosan nanobubbles for ultrasound-mediated gene delivery: preparation and in vitro characterization.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Trotta, Michele; Argenziano, Monica; Civra, Andrea; Donalisio, Manuela; Lembo, David

2012-01-01

The development of nonviral gene delivery systems is one of the most intriguing topics in nanomedicine. However, despite the advances made in recent years, several key issues remain unsettled. One of the main problems relates to the difficulty in designing nanodevices for targeted delivery of genes and other drugs to specific anatomic sites. In this study, we describe the development of a novel chitosan nanobubble-based gene delivery system for ultrasound-triggered release. Chitosan was selected for the nanobubble shell because of its low toxicity, low immunogenicity, and excellent biocompatibility, while the core consisted of perfluoropentane. DNA-loaded chitosan nanobubbles were formed with a mean diameter of less than 300 nm and a positive surface charge. Transmission electron microscopic analysis confirmed composition of the core-shell structure. The ability of the chitosan nanobubbles to complex with and protect DNA was confirmed by agarose gel assay. Chitosan nanobubbles were found to be stable following insonation (2.5 MHz) for up to 3 minutes at 37°C. DNA release was evaluated in vitro in both the presence and absence of ultrasound. The release of chitosan nanobubble-bound plasmid DNA occurred after just one minute of insonation. In vitro transfection experiments were performed by exposing adherent COS7 cells to ultrasound in the presence of different concentrations of plasmid DNA-loaded nanobubbles. In the absence of ultrasound, nanobubbles failed to trigger transfection at all concentrations tested. In contrast, 30 seconds of ultrasound promoted a moderate degree of transfection. Cell viability experiments demonstrated that neither ultrasound nor the nanobubbles affected cell viability under these experimental conditions. Based on these results, chitosan nanobubbles have the potential to be promising tools for ultrasound-mediated DNA delivery.

New chitosan nanobubbles for ultrasound-mediated gene delivery: preparation and in vitro characterization

PubMed Central

Cavalli, Roberta; Bisazza, Agnese; Trotta, Michele; Argenziano, Monica; Civra, Andrea; Donalisio, Manuela; Lembo, David

2012-01-01

Background The development of nonviral gene delivery systems is one of the most intriguing topics in nanomedicine. However, despite the advances made in recent years, several key issues remain unsettled. One of the main problems relates to the difficulty in designing nanodevices for targeted delivery of genes and other drugs to specific anatomic sites. In this study, we describe the development of a novel chitosan nanobubble-based gene delivery system for ultrasound-triggered release. Methods and results Chitosan was selected for the nanobubble shell because of its low toxicity, low immunogenicity, and excellent biocompatibility, while the core consisted of perfluoropentane. DNA-loaded chitosan nanobubbles were formed with a mean diameter of less than 300 nm and a positive surface charge. Transmission electron microscopic analysis confirmed composition of the core-shell structure. The ability of the chitosan nanobubbles to complex with and protect DNA was confirmed by agarose gel assay. Chitosan nanobubbles were found to be stable following insonation (2.5 MHz) for up to 3 minutes at 37°C. DNA release was evaluated in vitro in both the presence and absence of ultrasound. The release of chitosan nanobubble-bound plasmid DNA occurred after just one minute of insonation. In vitro transfection experiments were performed by exposing adherent COS7 cells to ultrasound in the presence of different concentrations of plasmid DNA-loaded nanobubbles. In the absence of ultrasound, nanobubbles failed to trigger transfection at all concentrations tested. In contrast, 30 seconds of ultrasound promoted a moderate degree of transfection. Cell viability experiments demonstrated that neither ultrasound nor the nanobubbles affected cell viability under these experimental conditions. Conclusion Based on these results, chitosan nanobubbles have the potential to be promising tools for ultrasound-mediated DNA delivery. PMID:22802689

Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery.

PubMed

Antoniraj, M Gover; Ayyavu, Mahesh; Henry, Linda Jeeva Kumari; Nageshwar Rao, Goutham; Natesan, Subramanian; Sundar, D Sathish; Kandasamy, Ruckmani

2018-03-01

Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and 1 H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p < .01) reduction (1.5-fold) of reactive oxygen species (ROS) accumulation was observed in lipopolysaccharides-stimulated RAW264.7 macrophages, revealing its potent antioxidant property. From the obtained results, it is concluded that folic acid functionalization of 5-FU-PNPs is an ideal approach for sustained and targeted drug delivery, thereby influencing better therapeutic effect.

Self-replicating Replicon-RNA Delivery to Dendritic Cells by Chitosan-nanoparticles for Translation In Vitro and In Vivo

PubMed Central

McCullough, Kenneth C; Bassi, Isabelle; Milona, Panagiota; Suter, Rolf; Thomann-Harwood, Lisa; Englezou, Pavlos; Démoulins, Thomas; Ruggli, Nicolas

2014-01-01

Self-amplifying replicon RNA (RepRNA) possesses high potential for increasing antigen load within dendritic cells (DCs). The major aim of the present work was to define how RepRNA delivered by biodegradable, chitosan-based nanoparticulate delivery vehicles (nanogel-alginate (NGA)) interacts with DCs, and whether this could lead to translation of the RepRNA in the DCs. Although studies employed virus replicon particles (VRPs), there are no reports on biodegradable, nanoparticulate vehicle delivery of RepRNA. VRP studies employed cytopathogenic agents, contrary to DC requirements—slow processing and antigen retention. We employed noncytopathogenic RepRNA with NGA, demonstrating for the first time the efficiency of RepRNA association with nanoparticles, NGA delivery to DCs, and RepRNA internalization by DCs. RepRNA accumulated in vesicular structures, with patterns typifying cytosolic release. This promoted RepRNA translation, in vitro and in vivo. Delivery and translation were RepRNA concentration-dependent, occurring in a kinetic manner. Including cationic lipids with chitosan during nanoparticle formation enhanced delivery and translation kinetics, but was not required for translation of immunogenic levels in vivo. This work describes for the first time the characteristics associated with chitosan-nanoparticle delivery of self-amplifying RepRNA to DCs, leading to translation of encoded foreign genes, namely influenza virus hemagglutinin and nucleoprotein. PMID:25004099

Self-Assembled Coacervates of Chitosan and an Insect Cuticle Protein Containing a Rebers-Riddiford Motif.

PubMed

Vaclaw, M Coleman; Sprouse, Patricia A; Dittmer, Neal T; Ghazvini, Saba; Middaugh, C Russell; Kanost, Michael R; Gehrke, Stevin H; Dhar, Prajnaparamita

2018-05-09

The interactions among biomacromolecules within insect cuticle may offer new motifs for biomimetic material design. CPR27 is an abundant protein in the rigid cuticle of the elytron from Tribolium castaneum. CPR27 contains the Rebers-Riddiford (RR) motif, which is hypothesized to bind chitin. In this study, active magnetic microrheology coupled with microscopy and protein particle analysis techniques were used to correlate alterations in the viscosity of chitosan solutions with changes in solution microstructure. Addition of CPR27 to chitosan solutions led to a 3-fold drop in viscosity. This change was accompanied by the presence of micrometer-sized coacervate particles in solution. Coacervate formation had a strong dependence on chitosan concentration. Analysis showed the existence of a critical CPR27 concentration beyond which a significant increase in particle count was observed. These effects were not observed when a non-RR cuticular protein, CP30, was tested, providing evidence of a structure-function relationship related to the RR motif.

Three-dimensional boron particle loaded thermal neutron detector

DOEpatents

Nikolic, Rebecca J.; Conway, Adam M.; Graff, Robert T.; Kuntz, Joshua D.; Reinhardt, Catherine; Voss, Lars F.; Cheung, Chin Li; Heineck, Daniel

2014-09-09

Three-dimensional boron particle loaded thermal neutron detectors utilize neutron sensitive conversion materials in the form of nano-powders and micro-sized particles, as opposed to thin films, suspensions, paraffin, etc. More specifically, methods to infiltrate, intersperse and embed the neutron nano-powders to form two-dimensional and/or three-dimensional charge sensitive platforms are specified. The use of nano-powders enables conformal contact with the entire charge-collecting structure regardless of its shape or configuration.

Composite particles formed by complexation of poly(methacrylic acid) - stabilized magnetic fluid with chitosan: Magnetic material for bioapplications.

PubMed

Safarik, Ivo; Stepanek, Miroslav; Uchman, Mariusz; Slouf, Miroslav; Baldikova, Eva; Nydlova, Leona; Pospiskova, Kristyna; Safarikova, Mirka

2016-10-01

A simple procedure for the synthesis of magnetic fluid (ferrofluid) stabilized by poly(methacrylic acid) has been developed. This ferrofluid was used to prepare a novel type of magnetically responsive chitosan-based composite material. Both ferrofluid and magnetic chitosan composite were characterized by a combination of microscopy (optical microscopy, TEM, SEM), scattering (static and dynamic light scattering, SANS) and spectroscopy (FTIR) techniques. Magnetic chitosan was found to be a perspective material for various bioapplications, especially as a magnetic carrier for immobilization of enzymes and cells. Lipase from Candida rugosa was covalently attached after cross-linking and activation of chitosan using glutaraldehyde. Baker's yeast cells (Saccharomyces cerevisiae) were incorporated into the chitosan composite during its preparation; both biocatalysts were active after reaction with appropriate substrates. 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

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.

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve.

PubMed

Sarabia-Estrada, Rachel; Bañuelos-Pineda, Jacinto; Osuna Carrasco, Laura P; Jiménez-Vallejo, Salvador; Jiménez-Estrada, Ismael; Rivas-Celis, Efrain; Dueñas-Jiménez, Judith M; Dueñas-Jiménez, Sergio H

2015-07-01

Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes

Wheat germ agglutinin-conjugated chitosan-Ca-alginate microparticles for local colon delivery of 5-FU: development and in vitro characterization.

PubMed

Glavas Dodov, M; Calis, S; Crcarevska, M S; Geskovski, N; Petrovska, V; Goracinova, K

2009-11-03

The aim of this work was to prepare lectin-conjugated chitosan-Ca-alginate microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU) for efficient local treatment of colon cancer. MPs were prepared by a novel one-step spray-drying technique and after wheat germ agglutinin (WGA) conjugation, they were characterized for size, swelling behavior, surface charge, entrapment efficiency and in vitro drug release. Prepared particles were spherical, with 6.73 microg/mg of WGA conjugated onto their surface. The size and zeta potential increased after conjugation, from 6.6 to 14.7 microm and from 9.6 to 15.3 mV, while drug encapsulation was 75.6 and 72.8%, respectively after conjugation. The swelling behavior of beads was mainly determined by properties of the cross-linked chitosan-alginate network. In vitro drug release studies carried out in simulated in vivo conditions with respect to pH, confirmed the potential of the particles to release the drug in a controlled manner. Also, the drug release was not significantly affected by WGA conjugation. The retention of biorecognitive activity of WGA after covalent coupling to MPs was confirmed by haemagglutination test. Functionalized MPs showed excessive mucoadhesiveness in vitro, due to the positive surface charge, pH-dependent swelling of the matrix and lectin-sugar recognition.

Ultrasound-mediated oxygen delivery from chitosan nanobubbles.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Rolfo, Alessandro; Balbis, Sonia; Madonnaripa, Daniele; Caniggia, Isabella; Guiot, Caterina

2009-08-13

Ultrasound (US) energy combined with gas-filled microbubbles has been used for several years in medical imaging. This study investigated the ability of oxygen-loaded chitosan bubbles to exchange oxygen in the presence or in the absence of US. Oxygen delivery is enhanced by sonication and both frequency and time duration of US affected the exchange kinetics.

Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

PubMed

Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

2016-08-01

The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes

PubMed Central

Ye, Ya-Jing; Wang, Yun; Lou, Kai-Yan; Chen, Yan-Zuo; Chen, Rongjun; Gao, Feng

2015-01-01

A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol®), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC0→24h (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects. PMID:26170666

Efficacy, pharmacokinetics, and biodistribution of thermosensitive chitosan/β-glycerophosphate hydrogel loaded with docetaxel.

PubMed

Li, Cuiyun; Ren, Shuangxia; Dai, Yu; Tian, Fengjie; Wang, Xin; Zhou, Sufeng; Deng, Shuhua; Liu, Qi; Zhao, Jie; Chen, Xijing

2014-04-01

Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.

Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer

PubMed Central

Dai, Dejian; Hou, Yiming

2017-01-01

The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo. PMID:28938619

The significance of relative density for particle damage in loaded and sheared gravels

NASA Astrophysics Data System (ADS)

Fityus, Stephen; Imre, Emőke

2017-06-01

For granular assemblages of strong particles, an increase in the relative density usually leads to a significant increase in shear strength, which is evident as a peak strength, accompanied by significant dilation as the peak strength is attained. This paper describes an experimental study of shearing in assemblages of weak particles, where particle breakage offsets dilation for all but the lowest of confining stresses. In such materials, prone to particle breakage, the shear strengths of loose and dense assemblages rapidly converge to similar values as confining stress increases, and any benefit of greater relative density is lost. This is attributed to the densification effect associated with the loading under a high stress prior to shearing, which is characterised by widespread particle breakage and the formation of smaller particles to occupy space between coarser ones. Interestingly, under both low and high stresses, there was a tendency for greater particle breakage in the loose samples, as a result of both shearing and compression. This result suggests that, despite the denser assemblage having its particles more rigidly constrained and less able to rearrange to avoid direct loading, the influence of greater load-spreading capacity afforded by an increased number of particle contacts in a denser sample, is more dominant in controlling breakage.

Development of drug-loaded chitosan hollow nanoparticles for delivery of paclitaxel to human lung cancer A549 cells.

PubMed

Jiang, Jie; Liu, Ying; Wu, Chao; Qiu, Yang; Xu, Xiaoyan; Lv, Huiling; Bai, Andi; Liu, Xuan

2017-08-01

In this study, biodegradable chitosan hollow nanospheres (CHN) were fabricated using polystyrene nanospheres (PS) as templates. CHN were applied to increase the solubility of poorly water-soluble drugs. The lung cancer drug paclitaxel (PTX), which is used as a model drug, was loaded into CHN by the adsorption equilibrium method. The drug-loaded sample (PTX-CHN) offered sustained PTX release and good bioavailability. The state characterization of PTX by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that the PTX absorbed into CHN existed in an amorphous state. An in vitro toxicity experiment indicated that CHN were nontoxic as carriers of poorly water-soluble drugs. The PTX-CHN produced a marked inhibition of lung cancer A549 cells proliferation and encouraged apoptosis. A cell uptake experiment indicated that PTX-CHN was successfully taken up by lung cancer A549 cells. Furthermore, a degradation experiment revealed that CHN were readily biodegradable. These findings state clearly that CHN can be regarded as promising biomaterials for lung cancer treatment.

Ethyl acetate Salix alba leaves extract-loaded chitosan-based hydrogel film for wound dressing applications.

PubMed

Qureshi, Mohammad A; Khatoon, Fehmeeda; Rizvi, Moshahid A; Zafaryab, Md

2015-01-01

High toxicity and multidrug resistance associated with various standard antimicrobial drugs have necessitated search for safer alternatives in plant-derived materials. In this study, we performed biological examination of chitosan-based hydrogel film loaded with ethyl acetate Salix alba leaves extract against 11 standard laboratory strains. FTIR showed regeneration of saccharide peak in CP1A at 1047 cm(-1) and increased in height of other peaks. DSC exothermic decomposition peaks at 112 °C, 175 °C and 251 °C reveal the effect of extract on hydrogel film. From FESEM images, three-dimensional cross-linking and extract easily seen in the globular form from the surface. MTT assay on HEK 293 cells showed that CP1A was non-toxic. Minimum inhibitory concentration ranges from 4000 μg/ml to 125 μg/ml. Enterococcus faecium, Candida glabrata and Candida tropicalis were the most resistant, while Salmonella typhi and Candida guilliermondii were the most susceptible micro-organisms.

Ascorbic acid prevents cellular uptake and improves biocompatibility of chitosan nanoparticles.

PubMed

Elshoky, Hisham A; Salaheldin, Taher A; Ali, Maha A; Gaber, Mohamed H

2018-04-11

Chitosan nanoparticles have many applications, such as gene and drug delivery, due to their biocompatibility. Chitosan nanoparticles are currently produced by dissolution in acetic acid that affects the biocompatibility at acidic pH. Here, we synthesized and characterized chitosan (CS) and ascorbate chitosan (AsCS) nanoparticles and investigated their cytotoxic effects, internalization, and distribution in the human colon carcinoma cell line using confocal laser scanning microscopy (CLSM). The CS and AsCS nanoparticles were spherical with average particle sizes of 44±8.4nm and 87±13.6nm, respectively. CS nanoparticles were taken up by the cells and showed dose-dependent cytotoxicity. By contrast, AsCS nanoparticles were not internalized and showed no cytotoxicity. Therefore, AsCS nanoparticles are more biocompatible than CS nanoparticles and may be more suitable for extracellular drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Bio-clarification of water from heavy metals and microbial effluence using fungal chitosan.

PubMed

Tayel, Ahmed A; Gharieb, Mohamed M; Zaki, Hanaa R; Elguindy, Nihal M

2016-02-01

Water pollution is among the most hazardous problems that threaten human health worldwide. Chitosan is a marvelous bioactive polymer that could be produced from fungal mycelia. This study was conducted to produce chitosan from Cunninghamella elegans and to use it for water pollutants elimination, e.g. heavy metals and waterborne microorganisms, and to investigate its antibacterial mode of action against Escherichia coli. The produced fungal chitosan had a deacetylation degree of 81%, a molecular weight of 92.73 kDa and a matched FT-IR spectrum with standard shrimp chitosan. Fungal chitosan exhibited remarkable antimicrobial activity against E. coli, Staphylococcus aureus and Candida albicans. Chitosan was proved as an effective metal adsorbent, toward the examined metal ions, Cu2+, Zn2+ and Pb2+, and its adsorption capacity greatly increased with the increasing of metal concentration, especially for Cu and Zn. The scanning electron micrographs, of treated E. coli cells with fungal chitosan, indicated that the cells began to lyse and combine after 3h of exposure and chitosan particles attached to the combined cells and, after 12 h from exposure, the entire bacterial cell walls were fully disrupted and lysed. Therefore, fungal chitosan could be recommended, as a bioactive, renewable, ecofriendly and cost effective material, for overcoming water pollution problems, from chemical and microbial origins. Copyright © 2015 Elsevier B.V. All rights reserved.

Loading of chitosan - Nano metal oxide hybrids onto cotton/polyester fabrics to impart permanent and effective multifunctions.

PubMed

Ibrahim, Nabil A; Eid, Basma M; El-Aziz, Eman Abd; Elmaaty, Tarek M Abou; Ramadan, Shaimaa M

2017-12-01

New and durable multifunctional properties of cotton/polyester blended fabrics were developed through loading of chitosan (Cs) and various metal oxide nanoparticles (MONPs) namely ZnO, TiO 2 , and SiO 2 onto fabric surface using citric acid/Sodium hypophosphite for ester-crosslinking and creating new anchoring and binding sites, COOH groups, onto the ester-crosslinked fabrics surface. The surface morphology and the presence of active ingredients (Cs & MONPs) onto selected - coated fabric samples were analyzed by SEM images and confirmed by EDS spectrums. The influence of various finishing formulations on some performance and functional properties such as wettability, antibacterial activity, UV-protection, self-cleaning, resiliency and durability to wash were studied. The obtained results revealed that the extent of improvement in the imparted functional properties is governed by type of loaded-hybrid and follows the decreasing order: Cs-TiO 2 NPs>Cs-ZnONPs>SiO 2 NP s >Cs alone, as well as kind of substrate cotton/polyester (65/35)>cotton/polyester (50/50). Moreover, after 15 washing cycles, the durability of the imparted functional properties of Cs/TiO 2 NP s - loaded substrates marginally decreased indicating the strong fixation of the hybrid components onto the ester-crosslinked substrates. The obtained bioactive multifunctional textiles can be used for producing eco-friendly protective textile materials for numerous applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

NASA Astrophysics Data System (ADS)

Ni, Kaiyuan; Zhao, Zhenghuan; Zhang, Zongjun; Zhou, Zijian; Yang, Li; Wang, Lirong; Ai, Hua; Gao, Jinhao

2016-02-01

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy

Gadolinium Distribution in Cerebrospinal Fluid after Administration of a Gadolinium-based MR Contrast Agent in Humans.

PubMed

Berger, Florian; Kubik-Huch, Rahel A; Niemann, Tilo; Schmid, Hans Ruedi; Poetzsch, Michael; Froehlich, Johannes M; Beer, Jürg H; Thali, Michael J; Kraemer, Thomas

2018-05-08

Purpose To evaluate whether gadolinium penetrates human cerebrospinal fluid (CSF) after MR imaging (MRI) with a gadolinium-based contrast agent (GBCA). Materials and Methods For this retrospective study, the authors analyzed 60 CSF samples from 57 patients (median age, 50 years; range, 3-92 years) who underwent one contrast material-enhanced MRI examination with gadoterate meglumine within 60 days of CSF extraction between January and December 2016. CSF samples from patients who underwent MRI without contrast material administration (n = 22) or those who underwent contrast-enhanced MRI at least 1 year before extraction (n = 2) were analyzed and used as control samples. CSF measurements were performed with inductively coupled plasma mass spectrometry by monitoring the gadolinium 158 isotope. Statistical analyses were performed by using a preliminary Kruskal-Wallis test. Results Higher CSF gadolinium concentrations were detected within the first 8 hours after GBCA administration (mean concentration, 1152 ng/mL ± 734.6). Concentrations were lower between 8 and 48 hours (872 ng/mL ± 586). After 48 hours, gadolinium was almost completely cleared from CSF (121 ng/mL ± 296.3). All but two samples from the 24 control patients (median age, 60.5 years; range, 19-79 years) were negative for the presence of gadolinium. Those samples were from patients who had undergone GBCA-enhanced MRI examination more than a year before CSF extraction (0.1 and 0.2 ng/mL after 1 and 3 years, respectively). The concentrations in patients with chronic renal insufficiency (n = 3), cerebral toxoplasmosis (n = 1), and liver cirrhosis (n = 1) were higher than the mean concentrations. Conclusion Gadoterate meglumine can be detected in human CSF after intravenous administration. © RSNA, 2018.

Characterization of the paclitaxel loaded chitosan graft Pluronic F127 copolymer micelles conjugate with a DNA aptamer targeting HER-2 overexpressing breast cancer cells

NASA Astrophysics Data System (ADS)

Thach Nguyen, Kim; Nguyen, Thu Ha; Do, Dinh Ho; Huan Le, Quang

2017-03-01

In this work we report the isolation of DNA aptamer that is specifically bound to a HER-2 overexpressing SK-BR-3 human breast cancer cell line, using SELEX strategy. Paclitaxel (PTX) loaded chitosan graft Pluronic F127 copolymer micelles conjugate with a DNA aptamer was synthesized and its structure was confirmed by TEM image. This binary mixed system consisting of DNA aptamer modified Pluronic F127 and chitosan could enhance PTX loading capacity and increase micelle stability. Morphology images confirmed the existence of PTX micelles, with an average size of approximately 86.22 ± 1.45 nm diameters. Drug release profile showed that the PTX conjugate maintained a sustained PTX release. From in vitro cell experiment it was shown that 89%-93%, 50%-58%, 55%-62%, 24%-28% and 2%-7% of the SK-BR-3, NS-VN-67, LH-VN-48, HT-VN-26 and NV-VN-31, respectively, were dead after 6-48 h. These results demonstrated a novel DNA aptamer-micelle assembly for efficient detection and a system for the delivery of PTX targeting specific HER-2 overexpressing. We have also successfully cultivated cancer tissues of explants from Vietnamese patients on a type I collagen substrate. The NS-VN-67, LH-VN-48, HT-VN-26 and NV-VN-31cell lines were used as cellular model sources for the study of chemotherapy drug in cancer.

Characterization, Cytotoxicity, and Genotoxicity of TiO2 and Folate-Coupled Chitosan Nanoparticles Loading Polyprenol-Based Nanoemulsion.

PubMed

Tao, Ran; Wang, Chengzhang; Zhang, Changwei; Li, WenJun; Zhou, Hao; Chen, Hongxia; Ye, Jianzhong

2018-07-01

The structure and bioactivity of Ginkgo biloba leaves polyprenol (GBP) are similar to that of dolichol which widely exists in human and mammalian organs. GBP possesses potential pharmacological activities against cancer. This study involved oil-in-water type nanoemulsion (NE) loading GBP was prepared by dissolving polyprenol in nanoemulsion of sodium tripolyphosphate (TPP)/TiO 2 solution, Triton X-100, and 1-octanol by inversed-phase emulsification (EIP) and ultrasonic emulsification (UE) method. Folic acid (FA)-coupled chitosan (CS) nanoparticles (NPs), GBP-FA-CS-NPs and GBP-TiO 2 -FA-CS-NPs, were fabricated by ionic cross-linking of positively charged FA-CS conjugates and negatively charged nanoemulsion with TPP/TiO 2 . And characterizations of them were investigated by TEM, SEM, FTIR, particle size, and zeta potential. The cytotoxic and genotoxic effects of GBP-TiO 2 -FA-CS-NP treatment were higher than GBP-NE, GBP-FA-CS-NPs, TiO 2 -NE, GBP-TiO 2 -NE, TiO 2 -FA-CS-NPs, and GBP-TiO 2 -FA-CS-NP treatment at the same tested concentrations in HepG2 cells. GBP-TiO 2 -FA-CS-NPs at low TiO 2 concentration (from 1 to 2.5 μg/ml) showed good inhibition capacity on HepG2 cells and low cytotoxic and genotoxic effects on HL-7702 cells. The possible mechanism of cytotoxicity on GBP-TiO 2 -FA-CS-NPs against HepG2 cells is by preventing excessive intracellular Ca 2+ into extracellular spaces via inhibiting Ca 2+ -ATPase and Ca 2+ /Mg 2+ -ATPase.

The effect of loading carbon nanotubes onto chitosan films on electrochemical dopamine sensing in the presence of biological interference.

PubMed

Shukla, Sudheesh K; Lavon, Avia; Shmulevich, Offir; Ben-Yoav, Hadar

2018-05-01

In vivo monitoring of the neurotransmitter dopamine can potentially improve the diagnosis of neurological disorders and elucidate their underlying biochemical mechanisms. While electrochemical sensors can detect unlabeled dopamine molecules, their sensing performance is dramatically reduced by electrochemical currents generated by other, interfering molecules (e.g., uric acid) in the biological environment. To overcome this caveat, the surface of the sensor is often modified with electrocatalytic materials, which are encapsulated inside a polymeric film; however, the effect of the encapsulating film on the sensing performance of the electrode has not been systematically studied. This study characterizes the effect of loading carbon nanotubes (CNTs) onto a chitosan film on the electrochemical sensing performance of dopamine in the presence of uric acid. Higher CNT loading increases the diffusion and electron transfer rate coefficients of the sensor and, in the presence of uric acid, provides better sensitivity (3.00µALµmol -1 for 1.75% CNT loading, vs 0.01µALµmol -1 for 1% loading) but a poorer limit-of-detection (2.00µmolL -1 vs 1.00, respectively), as reported here for the first time. These findings can help optimize the sensitivity and the limit-of-detection of electrochemical sensors in complex biofluids to enable an in vivo monitoring of dopamine and other redox-active molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimization of Enzyme Co-Immobilization with Sodium Alginate and Glutaraldehyde-Activated Chitosan Beads.

PubMed

Gür, Sinem Diken; İdil, Neslihan; Aksöz, Nilüfer

2018-02-01

In this study, two different materials-alginate and glutaraldehyde-activated chitosan beads-were used for the co-immobilization of α-amylase, protease, and pectinase. Firstly, optimization of multienzyme immobilization with Na alginate beads was carried out. Optimum Na alginate and CaCl 2 concentration were found to be 2.5% and 0.1 M, respectively, and optimal enzyme loading ratio was determined as 2:1:0.02 for pectinase, protease, and α-amylase, respectively. Next, the immobilization of multiple enzymes on glutaraldehyde-activated chitosan beads was optimized (3% chitosan concentration, 0.25% glutaraldehyde with 3 h of activation and 3 h of coupling time). While co-immobilization was successfully performed with both materials, the specific activities of enzymes were found to be higher for the enzymes co-immobilized with glutaraldehyde-activated chitosan beads. In this process, glutaraldehyde was acting as a spacer arm. SEM and FTIR were used for the characterization of activated chitosan beads. Moreover, pectinase and α-amylase enzymes immobilized with chitosan beads were also found to have higher activity than their free forms. Three different enzymes were co-immobilized with these two materials for the first time in this study.

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.

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.

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.

Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells

PubMed Central

Cheng, Mingrong; Xu, Hongzhi; Wang, Yong; Chen, Houxiang; He, Bing; Gao, Xiaoyan; Li, Yingchun; Han, Jiang; Zhang, Zhiping

2013-01-01

Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma. PMID:24187487

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

Removal of hexavalent chromium from wastewater using a new composite chitosan biosorbent.

PubMed

Boddu, Veera M; Abburi, Krishnaiah; Talbott, Jonathan L; Smith, Edgar D

2003-10-01

A new composite chitosan biosorbent was prepared by coating chitosan, a glucosamine biopolymer, onto ceramic alumina. The composite bioadsorbent was characterized by high-temperature pyrolysis, porosimetry, scanning electron microscopy, and X-ray photoelectron spectroscopy. Batch isothermal equilibrium and continuous column adsorption experiments were conducted at 25 degrees C to evaluate the biosorbent for the removal of hexavalent chromium from synthetic as well as field samples obtained from chrome plating facilities. The effect of pH, sulfate, and chloride ion on adsorption was also investigated. The biosorbent loaded with Cr(VI) was regenerated using 0.1 M sodium hydroxide solution. A comparison of the results of the present investigation with those reported in the literature showed that chitosan coated on alumina exhibits greater adsorption capacity for chromium(VI). Further, experimental equilibrium data were fitted to Langmuir and Freundlich adsorption isotherms, and values of the parameters of the isotherms are reported. The ultimate capacity obtained from the Langmuir model is 153.85 mg/g chitosan.

Loading relativistic Maxwell distributions in particle simulations

NASA Astrophysics Data System (ADS)

Zenitani, S.

2015-12-01

In order to study energetic plasma phenomena by using particle-in-cell (PIC) and Monte-Carlo simulations, we need to deal with relativistic velocity distributions in these simulations. However, numerical algorithms to deal with relativistic distributions are not well known. In this contribution, we overview basic algorithms to load relativistic Maxwell distributions in PIC and Monte-Carlo simulations. For stationary relativistic Maxwellian, the inverse transform method and the Sobol algorithm are reviewed. To boost particles to obtain relativistic shifted-Maxwellian, two rejection methods are newly proposed in a physically transparent manner. Their acceptance efficiencies are 􏰅50% for generic cases and 100% for symmetric distributions. They can be combined with arbitrary base algorithms.

Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration.

PubMed

Busilacchi, Alberto; Gigante, Antonio; Mattioli-Belmonte, Monica; Manzotti, Sandra; Muzzarelli, Riccardo A A

2013-10-15

The idea of using chitosan as a functional delivery aid to support simultaneously PRP, stem cells and growth factors (GF) is associated with the intention to use morphogenic biomaterials to modulate the natural healing sequence in bone and other tissues. For example, chitosan-chondroitin sulfate loaded with platelet lysate was included in a poly(D,L-lactate) foam that was then seeded with human adipose-derived stem cells and cultured in vitro under osteogenic stimulus: the platelet lysate provided to the bone tissue the most suitable assortment of GF which induces the osteogenic differentiation of the mesenchymal stem cells. PDGF, FGF, IGF and TGF-β were protagonists in the repair of callus fractures. The release of GF from the composites of chitosan-PRP and either nano-hydroxyapatite or tricalcium phosphate was highly beneficial for enhancing MSC proliferation and differentiation, thus qualifying chitosan as an excellent vehicle. A number of biochemical characteristics of chitosan exert synergism with stem cells in the regeneration of soft tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preparation of crosslinked chitosan magnetic membrane for cations sorption from aqueous solution.

PubMed

Khan, Adnan; Begum, Samina; Ali, Nauman; Khan, Sabir; Hussain, Sajjad; Sotomayor, Maria Del Pilar Taboada

2017-05-01

A chitosan magnetic membrane was prepared in order to confer magnetic properties to the membrane, which could be used for the removal of cations from aqueous solution. The crosslinked magnetic membrane was compared with pristine chitosan membrane in term of stability, morphology and cation adsorption capacity. The fabricated magnetic materials are thermally stable as shown by thermogravimetric curves. The membrane containing nickel magnetic particles (CHNiF-G) shows high thermal stability compared to the other membranes. The Fourier transform infrared spectroscopy showed successful preparation of chitosan magnetic membrane. Scanning electron microscopy micrographs showed the rough surface of the membrane with increased porosity. The prepared chitosan membranes were applied to cations of copper, nickel and lead in dilute aqueous solution. The chitosan membrane showed the following adsorption order for metallic cations: Cu 2+ > Ni 2+ > Pb 2+ , while CHNiF-G showed higher capacity, 3.51 mmol g -1 for copper, reflecting the improvement in adsorption capacity, since the amount of copper on pristine chitosan gave 1.40 mmol g -1 . The time required for adsorption to reach to the equilibrium was 6 h for the selected cations using different chitosan membranes. The kinetic study showed that adsorption followed pseudo-second order kinetics. The most commonly used isotherm models, Freundlich, Langmuir and Temkin, were applied to experimental data using linear regression technique. However, The Temkin model fits better to experimental data.

Smart release of doxorubicin loaded on polyetheretherketone (PEEK) surface with 3D porous structure.

PubMed

Ouyang, Liping; Sun, Zhenjie; Wang, Donghui; Qiao, Yuqin; Zhu, Hongqin; Ma, Xiaohan; Liu, Xuanyong

2018-03-01

It is important to fabricate an implant possessing environment sensitive drug delivery. In this work, the construction of 3D porous structure on polyetheretherketone (PEEK) surface and pH sensitive polymer, chitosan, was introduced. The smart release of doxorubicin can be realized on the 3D porous surface of PEEK loading chitosan. We give a feasible explanation for the effect of chitosan on smart drug release according to Henderson-Hasselbalch equation. Furthermore, the intracellular drug content of the cell cultured on the samples with highest chitosan is significantly higher at pH 4.0, whereas lower at pH 7.4 than other samples. The smart release of doxorubicin via modification with chitosan onto 3D porous PEEK surface paves the way for the application of PEEK in drug loading platform for recovering bone defect caused by malignant bone tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Li, Lele; Tong, Rong; Li, Mengyuan; Kohane, Daniel S

2016-03-01

Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB-231 tumor growth in mice. Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities. Published by Elsevier Ltd.

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

In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan.

PubMed

Krauland, Alexander H; Leitner, Verena M; Grabovac, Vjera; Bernkop-Schnürch, Andreas

2006-11-01

The aim of this study was the preparation and in vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. 2-Iminothiolane was covalently attached to chitosan. The resulting conjugate (chitosan-TBA) exhibited 304.9 +/- 63.5 micromol thiol groups per gram polymer. Microparticles were prepared via a new precipitation-micronization technique. The microparticulate delivery system comprised insulin, reduced glutathione and chitosan-TBA (Chito-TBA/Ins) or unmodified chitosan (Chito/Ins) and control microparticles were composed of insulin and mannitol (Mannitol/Ins). Due to a hydration process the size of Chito-TBA/Ins and Chito/Ins microparticles increased in phosphate buffer pH 6.8 2.6- and 2.2-fold, respectively. Fluorescent-labeled insulin-loaded chitosan-TBA microparticles showed a controlled release over 4 h. Chito-TBA/Ins administered nasally to rats led to an absolute bioavailability of 6.9 +/- 1.5%. The blood glucose level decreased for more than 2 h and the calculated absolute pharmacological efficacy was 4.9 +/- 1.4%. Chito/Ins, in comparison, displayed a bioavailability of 4.2 +/- 1.8% and a pharmacological efficacy of 0.7 +/- 0.6%. Mannitol/Ins showed a bioavailability of 1.6 +/- 0.4% and no reduction of the blood glucose level at all. According to these findings microparticles comprising chitosan-TBA seem to have substantial higher potential for nasal insulin administration than unmodified chitosan. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association

In Vitro Analysis of Nanoparticulate Hydroxyapatite/Chitosan Composites as Potential Drug Delivery Platforms for the Sustained Release of Antibiotics in the Treatment of Osteomyelitis

PubMed Central

USKOKOVIĆ, VUK; DESAI, TEJAL A.

2014-01-01

Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, and promoted sustained-release kinetics throughout the 3 weeks of release time. The addition of chitosan to the particulate drug carrier formulation, however, reduced the antibacterial efficacy against S aureus. Excellent cell spreading and proliferation of osteoblastic MC3T3-E1 cells evidenced on microscopic conglomerates of HAp nanoparticles in vitro also markedly diminished on HAp/chitosan composites. Mitochondrial dehydrogenase activity exhibited normal values only for HAp/chitosan particle concentrations of up to 2 mg/cm2 and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm2). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor Runx2 was downregulated in cells incubated in the presence of 3 mg/cm2 HAp/chitosan composite particles, whereas the expression of osteopontin, a potent mineralization inhibitor, was upregulated, further demonstrating the partially unfavorable osteoblastic cell response to the given particles. The peak in the expression of osteogenic markers paralleling the osteoblastic differentiation was also delayed most for the cell population incubated with HAp/chitosan particles

pH-triggered chitosan nanogels via an ortho ester-based linkage for efficient chemotherapy.

PubMed

Yang, Guanqing; Wang, Xin; Fu, Shengxiang; Tang, Rupei; Wang, Jun

2017-09-15

We report on new types of chitosan-based nanogels via an ortho ester-based linkage, used as drug carriers for efficient chemotherapy. First, we synthesized a novel diacrylamide containing ortho ester (OEAM) as an acid-labile cross-linker. Subsequently, methacrylated succinyl-chitosan (MASCS) was prepared and polymerized with OEAM at different molar ratios to give a series of pH-triggered MASCS nanogels. Doxorubicin (DOX) as a model anticancer drug was loaded into MASCS nanogels with a loading content of 16.5%. As expected, with the incorporation of ortho ester linkages, these nanogels showed pH-triggered degradation and drug release at acidic pH values. In vitro cellular uptake shows that the DOX-loaded nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs), resulting in higher inhibition of the proliferation of tumor cells. In vivo biodistribution and anti-tumor effect were determined in H22 tumor-bearing mice, and the results demonstrate that the acid-labile MASCS nanogels can significantly prolong the blood circulation time of DOX and improve the accumulation in tumor areas, leading to higher therapeutic efficacy. We designed new pH-triggered chitosan nanogels via an ortho ester-based cross-linker for efficient drug-loading and chemotherapy. These drug-loaded nanogels exhibit excellent pH-triggered drug release behavior due to the degradation of ortho ester linkages in mildly acidic environments. In vitro and in vivo results demonstrate that the nanogels could be efficiently internalized by 2D cells and 3D-MCs, improve drug concentration in solid tumors, and lead to higher therapeutic efficacy. To the best of our knowledge, this is the first report on using an ortho ester-based cross-linker to prepare pH-triggered chitosan nanogels as tumor carriers, which may provide a potential route for improved safety and to increase the therapeutic efficacy of anticancer therapy. Copyright © 2017

Effect of the addition CNTs on performance of CaP/chitosan/coating deposited on magnesium alloy by electrophoretic deposition.

PubMed

Zhang, Jie; Wen, Zhaohui; Zhao, Meng; Li, Guozhong; Dai, Changsong

2016-01-01

CaP/chitosan/carbon nanotubes (CNTs) coating on AZ91D magnesium alloy was prepared via electrophoretic deposition (EPD) followed by conversion in a phosphate buffer solution (PBS). The bonding between the layer and the substrate was studied by an automatic scratch instrument. The phase compositions and microstructures of the composite coatings were determined by using X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR), Raman spectroscopy and scanning electron microscope (SEM). The element concentration and gentamicin concentration were respectively determined by inductively coupled plasma optical emission spectrometer (ICP-OES) test and ultraviolet spectrophotometer (UV). The cell counting kit (CCK) assay was used to evaluate the cytotoxicity of samples to SaOS-2 cells. The results showed that a few CNTs with their original tubular morphology could be found in the CaP/chitosan coating and they were beneficial for the crystal growth of phosphate and improvement of the coating bonding when the addition amount of CNTs in 500 ml of electrophoretic solution was from 0.05 g to 0.125 g. The loading amount of gentamicin increased and the releasing speed of gentamicin decreased after CNTs was added into the CaP/chitosan coating for immersion loading and EPD loading. The cell viability of Mg based CaP/chitosan/CNTs was higher than that of Mg based CaP/chitosan from 16 days to 90 days. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro BMP-2 peptide release from thiolated chitosan based hydrogel.

PubMed

Liu, Xujie; Yu, Bo; Huang, Qianli; Liu, Rui; Feng, Qingling; Cai, Qiang; Mi, Shengli

2016-12-01

Thiolated chitosan based thermo-sensitive hydrogel is a water soluble system and the existing thiol groups are beneficial for the delivery of cysteine-rich peptides. In the present study, a kind of thiolated chitosan, i.e. chitosan-4-thio-butylamidine (CS-TBA) conjugate was characterized and used to prepare CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP) thermo-sensitive hydrogel. The cysteine terminated peptide 24 (P24) containing residues 73-92 of the knuckle epitope of BMP-2 (N→C: KIPKASSVPTELSAISTLYLSGGC) was synthesized and characterized. The release behavior of P24 from CS-TBA based hydrogel was investigated in vitro. The thiol groups in CS-TBA may react with thiol groups in P24, thus decreases the P24 release rate and maintains the peptide release for a longer time compared with unmodified chitosan based hydrogel. Moreover, the bioactivity of P24 is preserved during release process. These results indicate that P24 loaded CS-TBA based thermosensitive hydrogel is a potential material for minimally invasive surgery of bone repair. Copyright © 2016 Elsevier B.V. All rights reserved.

Kanamycin Sulphate Loaded PLGA-Vitamin-E-TPGS Long Circulating Nanoparticles Using Combined Coating of PEG and Water-Soluble Chitosan

PubMed Central

Mustafa, Sanaul

2017-01-01

Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. Due to its intense hydrophilicity, KS is cleared from the body within 8 h. KS has a very short plasma half-life (2.5 h). KS is used in high concentrations to reach the therapeutic levels in plasma, which results in serious nephrotoxicity/ototoxicity. To overcome aforementioned limitations, the current study aimed to develop KS loaded PLGA-Vitamin-E-TPGS nanoparticles (KS-PLGA-TPGS NPs), to act as an efficient carrier for controlled delivery of KS. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to KS-PLGA-TPGS NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was raised for surface modification of NPs. Surface modified NPs (KS-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetics and in vivo biodistribution following intramuscular administration were investigated. NPs surface charge was close to neutral +3.61 mV and significantly affected by the WSC coating. KS-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long drew-out the blood circulation half-life with resultant reduced kidney sequestration vis-à-vis KS-PLGA-TPGS NPs. The studies, therefore, indicate the successful formulation development of KS-PEG-WSC NPs with reduced frequency of dosing of KS indicating low incidence of nephrotoxicity/ototoxicity. PMID:28352475

Nephrogenic Systemic Fibrosis Manifesting a Decade After Exposure to Gadolinium.

PubMed

Larson, Krista N; Gagnon, Amy L; Darling, Melissa D; Patterson, James W; Cropley, Thomas G

2015-10-01

Nephrogenic systemic fibrosis (NSF) is a fibrosing skin disorder that develops in patients with kidney failure and has been linked to exposure to gadolinium-containing contrast agents. The time between exposure to gadolinium and the initial presentation of NSF is typically weeks to months but has been documented to be as long as 3½ years. We report a case of NSF developing 10 years after exposure to gadolinium. A long-term hemodialysis patient was exposed to gadolinium several times between 1998 and 2004 during magnetic resonance angiography of his abdominal vessels and arteriovenous fistula. In 2014, he was seen at our clinic with new dermal papules and plaques. Biopsy of affected skin showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis, supporting the diagnosis of NSF. The clinical history and histopathological features of this case support the diagnosis of NSF 10 years after exposure to gadolinium. Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease.

Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity.

PubMed

Bollimpelli, V Satish; Kumar, Prashant; Kumari, Sonali; Kondapi, Anand K

2016-05-01

Curcumin is known to have neuroprotective role and possess antioxidant, anti-inflammatory activities. Rotenone, a flavonoid induced neurotoxicity in dopaminergic cells is being widely studied in Parkinson's Disease (PD) research. In the present study, curcumin loaded lactoferrin nano particles prepared by sol-oil chemistry were used to protect dopaminergic cell line SK-N-SH against rotenone induced neurotoxicity. These curcumin loaded nano particles were of 43-60 nm diameter size and around 100 nm hydrodynamic size as assessed by transmission electron microscopy, atomic force microscopy and dynamic light scattering analysis respectively. The encapsulation efficiency was 61.3% ± 2.4%. Cellular uptake of curcumin through these nano particles was confirmed by confocal imaging and spectrofluorimetric analysis. The curcumin loaded lactoferrin nanoparticles showed greater intracellular drug uptake, sustained retention and greater neuroprotection than soluble counterpart. Neuroprotective activity was characterized through viability assays and by estimating ROS levels. Furthermore rotenone induced PD like features were characterized by decrease in tyrosine hydroxylase expression and increase in α-synuclein expression. Taken together curcumin loaded lactoferrin nanoparticles could be a promising drug delivery strategy against neurotoxicity in dopaminergic neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Chitosan and Liposome Nanoparticles as Adjuvant Codelivery on the Immunoglobulin G Subclass Distribution in a Mouse Model.

PubMed

Haryono, Agus; Salsabila, Korrie; Restu, Witta Kartika; Harmami, Sri Budi; Safari, Dodi

2017-01-01

We investigate the immunogenic properties of chitosan and liposome nanoparticles as adjuvant codelivery against a commercial pneumococcal conjugate vaccine (PCV) in an animal model. The chitosan and liposome nanoparticles were prepared by ionic gelation and dry methods, respectively. The PCV immunization was performed intradermally in the presence of adjuvants and booster injections which were given without an adjuvant. The Quil-A® was used as a control adjuvant. The ELISA was performed to measure the antibodies against pneumococcal type 14 polysaccharide (Pn14PS). The level of total antibodies against Pn14PS antigen was no different between the mouse groups with or without adjuvant codelivery. Codelivery of the PCV with chitosan nanoparticles as well as the Quil-A adjuvant elicited IgG1, IgG2a, IgG2b, and IgG3 antibodies. Meanwhile, codelivery of liposome nanoparticles elicited mainly IgG1 antibodies against the Pn14PS. The chitosan and liposome nanoparticles as adjuvant codelivery were successfully synthesized. These nanoparticles have different shapes in particle formation, liposome nanoparticle with their unilamellar shape and chitosan nanoparticles in large shape due to the aggregation of small-size particles. Codelivery of chitosan nanoparticles has more effect on the IgG subclass antibody production than that of liposome nanoparticles in a mouse model.

Amphotericin-B entrapped lecithin/chitosan nanoparticles for prolonged ocular application.

PubMed

Chhonker, Yashpal S; Prasad, Yarra Durga; Chandasana, Hardik; Vishvkarma, Akhilesh; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

2015-01-01

Fungal keratitis is the major cause of vision loss worldwide. Amphotericin-B is considered as the drug of choice for fungal infections. However, its use in ophthalmic drug delivery is limited by the low precorneal residence at ocular surface as a result of blinking reflex, tear turnover and nasopharyngeal drainage. We report Amphotericin-B loaded lecithin/chitosan nanoparticles for prolonged ocular application. The prepared nanoparticles were in the size range of 161.9-230.5 nm, entrapment efficiency of 70-75%, theoretical drug loading of 5.71% with positive zeta potential of 26.6-38.3 mV. As demonstrated by antifungal susceptibility against Candida albicans and Aspergillus fumigatus, nanoparticles were more effective than marketed formulation. They exhibited pronounced mucoadhesive properties. In-vivo pharmacokinetic studies in New Zealand albino rabbit eyes indicated improved bioavailablity (∼ 2.04 fold) and precorneal residence time (∼ 3.36 fold) by nanoparticles prepared from low molecular weight chitosan as compared with marketed formulation. Copyright © 2014. Published by Elsevier B.V.

Fluoride loaded polymeric nanoparticles for dental delivery.

PubMed

Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

2017-06-15

The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation, characterization and stability of curcumin-loaded zein-shellac composite colloidal particles.

PubMed

Sun, Cuixia; Xu, Chenqi; Mao, Like; Wang, Di; Yang, Jie; Gao, Yanxiang

2017-08-01

Curcumin-loaded zein-shellac composite particles were prepared by the antisolvent co-precipitation method. The encapsulation efficiency of curcumin was significantly improved from 82.7% in zein particles to 93.2% in zein-shellac complex particles. The result of differential scanning calorimetry suggested that curcumin in the polymeric matrix was in an amorphous state. Fourier transform infrared spectroscopy analysis revealed that curcumin had non-covalently interacted with zein and shellac, mainly through hydrogen bonding and hydrophobic interaction. Aggregates in irregular shapes, with large sizes, were found by atomic force microscopy, and conglutination, integration or fusion of different entities into network structures occurred at a high level of shellac. At the mass ratio of zein to shellac of 1:1, curcumin in the complex particles exhibited improved photochemical and thermal stability. Curcumin-loaded zein-shellac complex particles allowed the controlled release of curcumin in both PBS medium and simulated gastrointestinal fluids. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Biomolecule-loaded chitosan nanoparticles induce apoptosis and molecular changes in cancer cell line (SiHa).

PubMed

Sujima Anbu, Anbu; Velmurugan, Palanivel; Lee, Jeong-Ho; Oh, Byung-Taek; Venkatachalam, Perumal

2016-07-01

The present study reports on the synthesis of chitosan nanoparticles (CNPs) using methanol extracts of Gymnema sylvestre (GS) leaves and Cinnamomum zeylanicum (CZ) bark. Biomolecule-loaded nanoparticles induced apoptosis in a human cervical cancer (SiHa) cell line, and experiments were carried out to elucidate the underlying molecular mechanisms. FT-IR and XRD showed possible functional groups of the biomolecules and the crystalline nature of CNPs, respectively. Transmission electron microscopy images revealed that synthesized GSCNPs and CZCNPs had a smooth spherical shape with average sizes of about 58-80 and 60-120nm, respectively. Dynamic light scattering studies indicated that both GSCNPs and CZCNs were structurally stable with homogenous and heterogeneous natures, respectively. Furthermore, synthesized GSCNPs and CZCNPs exhibited dose-dependent cytotoxicity against the SiHa cancer cell line, with inhibitory concentration (IC50) values of 102.17μg/ml, 87.75μg/ml, 132.74μg/ml and 90.35μg/ml for GS leaf extract, GSCNPs, CZBE and CZCNPs, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and evaluation of chitosan-based nanogels/gels for oral delivery of myricetin.

PubMed

Yao, Yashu; Xia, Mengxin; Wang, Huizhen; Li, Guowen; Shen, Hongyi; Ji, Guang; Meng, Qianchao; Xie, Yan

2016-08-25

A novel nanogel/gel based on chitosan (CS) for the oral delivery of myricetin (Myr) was developed and evaluated comprehensively. The particle size of the obtained Myr-loaded CS/β-glycerol phosphate (β-GP) nanogels was in the range of 100-300nm. The rheological tests showed that the sol-gel transition happened when the nanogels were exposed to physiological temperatures, and 3D network structures of the gelatinized nanogels (gels) were confirmed by Scanning Electron Microscopy. Myr was released from CS/β-GP nanogel/gel in acidic buffers via a Fickian mechanism, and this release was simultaneously accompanied by swelling and erosion. Moreover, the nanogel/gel exhibited no cytotoxicity by MTT assay, and the oral bioavailability of Myr in rats was improved with an accelerated absorption rate after Myr was loaded into CS/β-GP nanogel/gel. In summary, all of the above showed that CS/β-GP nanogel/gel was an excellent system for orally delivering Myr. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Utilization of chitosan as an antimicrobial agent for pasteurized palm sap (Borassus flabellifer Linn.) during storage.

PubMed

Naknean, Phisut; Jutasukosol, Keawta; Mankit, Theerarat

2015-02-01

The objective of this research was to assess the potential of chitosan for improvement the quality of pasteurized palm sap during storage. First, the effect of chitosan content on sensory attributes was investigated to select suitable concentration of chitosan for further study. Fresh palm sap was enriched with chitosan at various concentrations (0-2 g/L) and pasteurized at 80 °C for 10 min, consequently evaluated by consumers. It was found that samples added chitosan in the range of 0-1.00 g/L were considered acceptable. Thus, the addition chitosan in the concentration of 0-1.00 g/L was chosen for further study. The sample without chitosan addition was used as a control sample. Each selected sample was determined for their qualities during storage at 1 week interval. It was found that lightness and transmittance values of all samples tended to increase during storage. Lower PPO and invertase activity were observed in all chitosan-treated samples compared to control sample. Chitosan could minimize the loss of sucrose and the increase in glucose and fructose content during storage. In addition, an increase in chitosan concentration resulted in the increase in DPPH radical scavenging activity. Furthermore, the addition of chitosan could retard the development of microorganism during storage as demonstrated by lower microbial loads compared to control sample. It can be concluded that a combination of pasteurization with chitosan addition (0.50 g/L) and low temperature storage could preserve palm sap for approximately 6 weeks. Thus, the incorporation of chitosan in palm sap could be used as an alternative way to extend shelf life of pasteurized palm sap.

Investigation of Self-Assembly Processes for Chitosan-Based Coagulant-Flocculant Systems: A Mini-Review

PubMed Central

Bhalkaran, Savi; Wilson, Lee D.

2016-01-01

The presence of contaminants in wastewater poses significant challenges to water treatment processes and environmental remediation. The use of coagulation-flocculation represents a facile and efficient way of removing charged particles from water. The formation of stable colloidal flocs is necessary for floc aggregation and, hence, their subsequent removal. Aggregation occurs when these flocs form extended networks through the self-assembly of polyelectrolytes, such as the amine-based polysaccharide (chitosan), which form polymer “bridges” in a floc network. The aim of this overview is to evaluate how the self-assembly process of chitosan and its derivatives is influenced by factors related to the morphology of chitosan (flocculant) and the role of the solution conditions in the flocculation properties of chitosan and its modified forms. Chitosan has been used alone or in conjunction with a salt, such as aluminum sulphate, as an aid for the removal of various waterborne contaminants. Modified chitosan relates to grafted anionic or cationic groups onto the C-6 hydroxyl group or the amine group at C-2 on the glucosamine monomer of chitosan. By varying the parameters, such as molecular weight and the degree of deacetylation of chitosan, pH, reaction and settling time, dosage and temperature, self-assembly can be further investigated. This mini-review places an emphasis on the molecular-level details of the flocculation and the self-assembly processes for the marine-based biopolymer, chitosan. PMID:27706052

In Situ Sampling of Relative Dust Devil Particle Loads and Their Vertical Grain Size Distributions.

PubMed

Raack, Jan; Reiss, Dennis; Balme, Matthew R; Taj-Eddine, Kamal; Ori, Gian Gabriele

2017-04-19

During a field campaign in the Sahara Desert in southern Morocco, spring 2012, we sampled the vertical grain size distribution of two active dust devils that exhibited different dimensions and intensities. With these in situ samples of grains in the vortices, it was possible to derive detailed vertical grain size distributions and measurements of the lifted relative particle load. Measurements of the two dust devils show that the majority of all lifted particles were only lifted within the first meter (∼46.5% and ∼61% of all particles; ∼76.5 wt % and ∼89 wt % of the relative particle load). Furthermore, ∼69% and ∼82% of all lifted sand grains occurred in the first meter of the dust devils, indicating the occurrence of "sand skirts." Both sampled dust devils were relatively small (∼15 m and ∼4-5 m in diameter) compared to dust devils in surrounding regions; nevertheless, measurements show that ∼58.5% to 73.5% of all lifted particles were small enough to go into suspension (<31 μm, depending on the used grain size classification). This relatively high amount represents only ∼0.05 to 0.15 wt % of the lifted particle load. Larger dust devils probably entrain larger amounts of fine-grained material into the atmosphere, which can have an influence on the climate. Furthermore, our results indicate that the composition of the surface, on which the dust devils evolved, also had an influence on the particle load composition of the dust devil vortices. The internal particle load structure of both sampled dust devils was comparable related to their vertical grain size distribution and relative particle load, although both dust devils differed in their dimensions and intensities. A general trend of decreasing grain sizes with height was also detected. Key Words: Mars-Dust devils-Planetary science-Desert soils-Atmosphere-Grain sizes. Astrobiology 17, xxx-xxx.

Particle size variations between bed load and bed material in natural gravel bed channels

Treesearch

Thomas E. Lisle

1995-01-01

Abstract - Particle sizes of bed load and bed material that represent materials transported and stored over a period of years are used to investigate selective transport in 13 previously sampled, natural gravel bed channels. The ratio (D*) of median particle size of bed material to the transport- and frequency-weighted mean of median bed load size decreases to unity...

Characterization of PAH matrix with monazite stream containing uranium, gadolinium and iron

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

Pal, Sangita, E-mail: sangpal@barc.gov.in; Goswami, D.; Meena, Sher Singh

2016-05-23

Uranium (U) gadolinium (Gd) and iron (Fe) containing alkaline waste simulated effluent (relevant to alkaline effluent of monazite ore) has been treated with a novel amphoteric resin viz, Polyamidehydroxamate (PAH) containing amide and hydroxamic acid groups. The resin has been synthesized in an eco-friendly manner by polymerization nad conversion to functional groups characterized by FT-IR spectra and architectural overview by SEM. Coloration of the loaded matrix and de-coloration after extraction of uranium is the special characteristic of the matrix. Effluent streams have been analyzed by ICP-AES, U loaded PAH has been characterized by FT-IR, EXAFS, Gd and Fe by X-raymore » energy values of EDXRF at 6.053 KeVand 6.405 KeV respectively. The remarkable change has been observed in Mössbauer spectrum of Fe-loaded PAH samples.« less

NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.

PubMed

Rao, Jia-Sheng; Zhao, Can; Zhang, Aifeng; Duan, Hongmei; Hao, Peng; Wei, Rui-Han; Shang, Junkui; Zhao, Wen; Liu, Zuxiang; Yu, Juehua; Fan, Kevin S; Tian, Zhaolong; He, Qihua; Song, Wei; Yang, Zhaoyang; Sun, Yi Eve; Li, Xiaoguang

2018-06-12

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

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.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

PubMed

Farace, Cristiano; Sánchez-Moreno, Paola; Orecchioni, Marco; Manetti, Roberto; Sgarrella, Francesco; Asara, Yolande; Peula-García, José M; Marchal, Juan A; Madeddu, Roberto; Delogu, Lucia G

2016-01-05

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol

PubMed Central

Farace, Cristiano; Sánchez-Moreno, Paola; Orecchioni, Marco; Manetti, Roberto; Sgarrella, Francesco; Asara, Yolande; Peula-García, José M.; Marchal, Juan A.; Madeddu, Roberto; Delogu, Lucia G.

2016-01-01

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications. PMID:26728491

Synthesis of bulk-size transparent gadolinium oxide–polymer nanocomposites for gamma ray spectroscopy

PubMed Central

Cai, Wen; Chen, Qi; Cherepy, Nerine; Dooraghi, Alex; Kishpaugh, David; Chatziioannou, Arion; Payne, Stephen; Xiang, Weidong

2015-01-01

Heavy element loaded polymer composites have long been proposed to detect high energy X- and γ-rays upon scintillation. The previously reported bulk composite scintillators have achieved limited success because of the diminished light output resulting from fluorescence quenching and opacity. We demonstrate the synthesis of a transparent nanocomposite comprising gadolinium oxide nanocrystals uniformly dispersed in bulk-size samples at a high loading content. The strategy to avoid luminescence quenching and opacity in the nanocomposite was successfully deployed, which led to the radioluminescence light yield of up to 27 000/MeV, about twice as much as standard commercial plastic scintillators. Nanocomposites monoliths (14 mm diameter by 3 mm thickness) with 31 wt% loading of nanocrystals generated a photoelectric peak for Cs-137 gamma (662 keV) with 11.4% energy resolution. PMID:26478816

Enhanced oral delivery of docetaxel using thiolated chitosan nanoparticles: preparation, in vitro and in vivo studies.

PubMed

Saremi, Shahrooz; Dinarvand, Rassoul; Kebriaeezadeh, Abbas; Ostad, Seyed Nasser; Atyabi, Fatemeh

2013-01-01

The aim of this study was to evaluate a nanoparticulate system with mucoadhesion properties composed of a core of polymethyl methacrylate surrounded by a shell of thiolated chitosan (Ch-GSH-pMMA) for enhancing oral bioavailability of docetaxel (DTX), an anticancer drug. DTX-loaded nanoparticles were prepared by emulsion polymerization method using cerium ammonium nitrate as an initiator. Physicochemical properties of the nanoparticles such as particle size, size distribution, morphology, drug loading, and entrapment efficiency were characterized. The pharmacokinetic study was carried out in vivo using wistar rats. The half-life of DTX-loaded NPs was about 9 times longer than oral DTX used as positive control. The oral bioavailability of DTX was increased to 68.9% for DTX-loaded nanoparticles compared to 6.5% for positive control. The nanoparticles showed stronger effect on the reduction of the transepithelial electrical resistance (TEER) of Caco-2 cell monolayer by opening the tight junctions. According to apparent permeability coefficient (P(app)) results, the DTX-loaded NPs showed more specific permeation across the Caco-2 cell monolayer in comparison to the DTX. In conclusion, the nanoparticles prepared in this study showed promising results for the development of an oral drug delivery system for anticancer drugs.

Enhanced Oral Delivery of Docetaxel Using Thiolated Chitosan Nanoparticles: Preparation, In Vitro and In Vivo Studies

PubMed Central

Saremi, Shahrooz; Kebriaeezadeh, Abbas; Ostad, Seyed Nasser; Atyabi, Fatemeh

2013-01-01

The aim of this study was to evaluate a nanoparticulate system with mucoadhesion properties composed of a core of polymethyl methacrylate surrounded by a shell of thiolated chitosan (Ch-GSH-pMMA) for enhancing oral bioavailability of docetaxel (DTX), an anticancer drug. DTX-loaded nanoparticles were prepared by emulsion polymerization method using cerium ammonium nitrate as an initiator. Physicochemical properties of the nanoparticles such as particle size, size distribution, morphology, drug loading, and entrapment efficiency were characterized. The pharmacokinetic study was carried out in vivo using wistar rats. The half-life of DTX-loaded NPs was about 9 times longer than oral DTX used as positive control. The oral bioavailability of DTX was increased to 68.9% for DTX-loaded nanoparticles compared to 6.5% for positive control. The nanoparticles showed stronger effect on the reduction of the transepithelial electrical resistance (TEER) of Caco-2 cell monolayer by opening the tight junctions. According to apparent permeability coefficient (P app) results, the DTX-loaded NPs showed more specific permeation across the Caco-2 cell monolayer in comparison to the DTX. In conclusion, the nanoparticles prepared in this study showed promising results for the development of an oral drug delivery system for anticancer drugs. PMID:23971023

Gadolinium photoionization process

DOEpatents

Paisner, J.A.; Comaskey, B.J.; Haynam, C.A.; Eggert, J.H.

1993-04-13

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

Gadolinium photoionization process

DOEpatents

Paisner, Jeffrey A.; Comaskey, Brian J.; Haynam, Christopher A.; Eggert, Jon H.

1993-01-01

A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing.

PubMed

Khadjavi, Amina; Magnetto, Chiara; Panariti, Alice; Argenziano, Monica; Gulino, Giulia Rossana; Rivolta, Ilaria; Cavalli, Roberta; Giribaldi, Giuliana; Guiot, Caterina; Prato, Mauro

2015-08-01

In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. HaCaT cells were treated for 24h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and Characterization of Chitosan Cross-Linked With Tripolyphosphate as a Sustained Release Agent in Tablets, Part I: Design of Experiments and Optimization.

PubMed

Pinto, Colin A; Saripella, Kalyan K; Loka, Nikhil C; Neau, Steven H

2018-04-01

Certain issues with the use of particles of chitosan (Ch) cross-linked with tripolyphosphate (TPP) in sustained release formulations include inefficient drug loading, burst drug release, and incomplete drug release. Acetaminophen was added to Ch:TPP particles to test for advantages of drug addition extragranularly over drug addition made during cross-linking. The influences of Ch concentration, Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of experiments allowed identification of factors and 2-factor interactions that have significant effects on average particle size and size distribution, yield, zeta potential, and true density of the particles, as well as drug release from the directly compressed tablets. Statistical model equations directed production of a control batch that minimized span, maximized yield, and targeted a t 50 of 90 min (sample A); sample B that differed by targeting a t 50 of 240-300 min to provide sustained release; and sample C that differed from sample B by maximizing span. Sample B maximized yield and provided its targeted t 50 and the smallest average particle size, with the higher zeta potential and the lower span of samples B and C. Extragranular addition of a drug to Ch:TPP particles achieved 100% drug loading, eliminated a burst drug release, and can accomplish complete drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.