Science.gov

Sample records for targeted gadolinium-loaded chitosan

  1. 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

  2. Gadolinium-loaded chitosan nanoparticles for neutron-capture therapy: Influence of micrometric properties of the nanoparticles on tumor-killing effect.

    PubMed

    Ichikawa, Hideki; Uneme, Takeshi; Andoh, Tooru; Arita, Yuya; Fujimoto, Takuya; Suzuki, Minoru; Sakurai, Yoshinori; Shinto, Hiroyuki; Fukasawa, Tomonori; Fujii, Fumihiko; Fukumori, Yoshinobu

    2014-06-01

    As a nanoparticulate device for controlled delivery of Gd in NCT, the authors have developed gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs). In the present study, influence of micrometric properties such as particle size, particle-surface charge and Gd content of Gd-nanoCPs on tumor-killing effect by Gd-NCT was investigated with Gd-nanoCPs. Two types of Gd-nanoCPs with different mean particle size, zeta potential and Gd-content (Gd-nanoCP-400; 391nm, 28mV, 9wt% and Gd-nanoCP-200; 214nm, 19mV, 24wt%) could be prepared by using chitosans with different molecular weights. Gd-nanoCPs incorporating 1.2mg of natural Gd were injected intratumorally once or twice to mice subcutaneously-bearing B16F10 melanoma. Eight hours after the last administration, thermal neutron was irradiated to tumor region of the mice. Remarkable tumor-growth was observed in both hot and cold control groups. In contrast, Gd-NCT groups showed significant tumor-growth suppression effect, though their efficacy was found to depend on the micrometric properties of Gd-nanoCPs. In particular, the Gd-nanoCP-200 exhibited stronger tumor-killing effect than the Gd-nanoCP-400 at the same Gd dose and it was still similar to Gd-nanoCP-400 in tumor-growth suppressing effect even at the half of Gd dose of Gd-nanoCP-400. This significance in tumor-killing effect would be ascribed from a higher Gd retention in the tumor tissue and an improved distribution of Gd with intratumorally administered Gd-nanoCP-200. Indeed, the Gd concentration in tumor tissue at the time corresponding to the onset of thermal neutron irradiation was determined to be significantly higher in Gd-nanoCP-200, compared with Gd-nanoCP-400. These results demonstrated that appropriate modification of Gd-nanoCPs in micrometric properties would be an effective way to improve the retention of Gd in the tumor tissue after intratumoral injection, leading to the enhanced tumor-killing effect in Gd-NCT. PMID:24462286

  3. Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles.

    PubMed

    Rudzinski, Walter E; Palacios, Adriana; Ahmed, Abuzar; Lane, Michelle A; Aminabhavi, Tejraj M

    2016-08-20

    Small interfering RNA (siRNA) molecules specifically target messenger RNA species, decreasing intracellular protein levels. β-Catenin protein concentrations are increased in 70-80% of colon tumors, promoting tumor progression. Chitosan exhibits low levels of toxicity and can be transported across mucosal membranes; therefore, our objective was to develop chitosan and poly(ethylene glycol)-grafted (PEGylated) chitosan nanoparticles, 100-150nm in diameter, encapsulating anti-β-catenin siRNA for transfection into colon cancer cells. Encapsulation efficiencies up to 97% were observed. Confocal microscopy visualized the entry of fluorescently-tagged siRNA into cells. Western blot analysis showed that both chitosan and PEGylated chitosan nanoparticles containing anti-β-catenin siRNA decreased β-catenin protein levels in cultured colon cancer cells. These results indicate that nanoparticles made with chitosan and PEGylated chitosan can successfully enter colon cancer cells and decrease the level of a protein that promotes tumor progression. These or similar nanoparticles may prove beneficial for the treatment of colon cancer in humans. PMID:27178938

  4. Advances in the targeting molecules modified chitosan-based nanoformulations.

    PubMed

    Du, Hongliang; Cai, Xiaoqing; Zhai, Guangxi

    2013-08-01

    Chitosan, a cationic polysaccharide, has prompted the continuous impetus for the development of safe and effective drug delivery systems due to its unique properties such as mucoadhesive feature, absorption enhancement and active functional groups for chemical modifications. By using chitosan-based nanoformulations, many studies have attempted to improve the dispersion of loaded hydrophobic drugs in aqueous environment, protect the encapsulated proteins and genes against enzymatic degradation, and increase their absorption by target tissues. It's noteworthy that the derivatization of chitosan-based carriers with a ligand leads to the selective targeting of the nanoformulations to selected cells, thereby facilitating far more sensitive internalization and localization of nanoformulations for diseases' diagnosis and treatment. As such, this review focuses on some of the most poignant reports of the utility of targeting molecules such as carbohydrates, antibodies, peptides and some small molecules in chitosan-based nanoformulations for targeted delivery. Additionally, the affinity mechanism of different targeting molecules and the pros and cons of their conjugation strategies will be illustrated summarily. PMID:23469876

  5. Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles

    PubMed Central

    Wang, Xin; Tang, Huang; Wang, Chongzhi; Zhang, Jialiang; Wu, Wei; Jiang, Xiqun

    2016-01-01

    The phenylboronic acid-conjugated chitosan nanoparticles were prepared by particle surface modification. The size, zeta potential and morphology of the nanoparticles were characterized by dynamic light scattering, zeta potential measurement and transmission electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using monolayer cell model, 3-D multicellular spheroid model and H22 tumor-bearing mice. The incorporation of phenylboronic acid group into chitosan nanoparticles impart a surface charge-reversible characteristic to the nanoparticles. In vitro evaluation using 2-D and 3-D cell models showed that phenylboronic acid-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated chitosan nanoparticles, and could deliver more drug into tumor cells due to the active targeting effect of boronic acid group. Furthermore, the phenylboronic acid-decorated nanoparticles displayed a deeper penetration and persistent accumulation in the multicellular spheroids, resulting in better inhibition growth to multicellular spheroids than non-decorated nanoparticles. Tumor penetration, drug distribution and near infrared fluorescence imaging revealed that phenylboronic acid-decorated nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. In vivo antitumor examination demonstrated that the phenylboronic acid-decorated nanoparticles have superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles. PMID:27375786

  6. Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles.

    PubMed

    Wang, Xin; Tang, Huang; Wang, Chongzhi; Zhang, Jialiang; Wu, Wei; Jiang, Xiqun

    2016-01-01

    The phenylboronic acid-conjugated chitosan nanoparticles were prepared by particle surface modification. The size, zeta potential and morphology of the nanoparticles were characterized by dynamic light scattering, zeta potential measurement and transmission electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using monolayer cell model, 3-D multicellular spheroid model and H22 tumor-bearing mice. The incorporation of phenylboronic acid group into chitosan nanoparticles impart a surface charge-reversible characteristic to the nanoparticles. In vitro evaluation using 2-D and 3-D cell models showed that phenylboronic acid-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated chitosan nanoparticles, and could deliver more drug into tumor cells due to the active targeting effect of boronic acid group. Furthermore, the phenylboronic acid-decorated nanoparticles displayed a deeper penetration and persistent accumulation in the multicellular spheroids, resulting in better inhibition growth to multicellular spheroids than non-decorated nanoparticles. Tumor penetration, drug distribution and near infrared fluorescence imaging revealed that phenylboronic acid-decorated nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. In vivo antitumor examination demonstrated that the phenylboronic acid-decorated nanoparticles have superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles. PMID:27375786

  7. Chitosan coatings to control release and target tissues for therapeutic delivery.

    PubMed

    Jennings, Jessica Amber; Wells, Carlos Montez; McGraw, Gregory S; Velasquez Pulgarin, Diego A; Whitaker, Marsalas D; Pruitt, Reginald L; Bumgardner, Joel David

    2015-07-01

    The natural biopolymer chitosan has versatile applications in therapeutic delivery. Coating drug delivery matrices or biomaterials with chitosan offers several advantages in drug delivery, including control of drug release, slowing degradation rate and improving biocompatibility. Advanced uses of chitosan in coating form include targeting drug delivery vehicles to specific tissue as well as providing a stimulus-controlled release response. The present review summarizes the current applications of chitosan coatings in the context of different biomaterial delivery technologies, as well as future directions of chitosan coatings for drug delivery technologies under development. PMID:26228776

  8. Biocompatible and target specific hydrophobically modified glycol chitosan nanoparticles.

    PubMed

    Yin, Wei; Li, Weiyi; Rubenstein, David A; Meng, Yizhi

    2016-01-01

    Cardiovascular disease is the leading cause of death in the United States. Atherosclerosis is a major cause for cardiovascular diseases. Drugs that treat atherosclerosis usually act nonspecifically. To enhance drug delivery specificity, the authors developed a hydrophobically modified glycol chitosan (HGC) nanoparticle that can specifically target activated endothelial cells. The biocompatibility of these nanoparticles toward red blood cells and platelets was evaluated through hemolysis, platelet activation, platelet thrombogenicity, and platelet aggregation assays. The biocompatibility of these nanoparticles toward vascular endothelial cells was evaluated by their effects on endothelial cell growth, metabolic activity, and activation. The results demonstrated that HGC nanoparticles did not cause hemolysis, or affect platelet activation, thrombogenicity, and aggregation capability in vitro. The nanoparticles did not impair vascular endothelial cell growth or metabolic activities in vitro, and did not cause cell activation either. When conjugated with intercellular adhesion molecular 1 antibodies, HGC nanoparticles showed a significantly increased targeting specificity toward activated endothelial cells. These results suggested that HGC nanoparticles are likely compatible toward red blood cells, platelets, and endothelial cells, and they can be potentially used to identify activated endothelial cells at atherosclerotic lesion areas within the vasculature, and deliver therapeutic drugs. PMID:27126597

  9. 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

  10. Neurospora crassa transcriptomics reveals oxidative stress and plasma membrane homeostasis biology genes as key targets in response to chitosan.

    PubMed

    Lopez-Moya, Federico; Kowbel, David; Nueda, Maria José; Palma-Guerrero, Javier; Glass, N Louise; Lopez-Llorca, Luis Vicente

    2016-02-01

    Chitosan is a natural polymer with antimicrobial activity. Chitosan causes plasma membrane permeabilization and induction of intracellular reactive oxygen species (ROS) in Neurospora crassa. We have determined the transcriptional profile of N. crassa to chitosan and identified the main gene targets involved in the cellular response to this compound. Global network analyses showed membrane, transport and oxidoreductase activity as key nodes affected by chitosan. Activation of oxidative metabolism indicates the importance of ROS and cell energy together with plasma membrane homeostasis in N. crassa response to chitosan. Deletion strain analysis of chitosan susceptibility pointed NCU03639 encoding a class 3 lipase, involved in plasma membrane repair by lipid replacement, and NCU04537 a MFS monosaccharide transporter related to assimilation of simple sugars, as main gene targets of chitosan. NCU10521, a glutathione S-transferase-4 involved in the generation of reducing power for scavenging intracellular ROS is also a determinant chitosan gene target. Ca(2+) increased tolerance to chitosan in N. crassa. Growth of NCU10610 (fig 1 domain) and SYT1 (a synaptotagmin) deletion strains was significantly increased by Ca(2+) in the presence of chitosan. Both genes play a determinant role in N. crassa membrane homeostasis. Our results are of paramount importance for developing chitosan as an antifungal. PMID:26694141

  11. Neurospora crassa transcriptomics reveals oxidative stress and plasma membrane homeostasis biology genes as key targets in response to chitosan

    PubMed Central

    Lopez-Moya, Federico; Kowbel, David; Nueda, Ma José; Palma-Guerrero, Javier; Glass, N. Louise; Lopez-Llorca, Luis Vicente

    2016-01-01

    Chitosan is a natural polymer with antimicrobial activity. Chitosan causes plasma membrane permeabilization and induction of intracellular reactive oxygen species (ROS) in Neurospora crassa. We have determined the transcriptional profile of N. crassa to chitosan and identified the main gene targets involved in the cellular response to this compound. Global network analyses showed membrane, transport and oxidoreductase activity as key nodes affected by chitosan. Activation of oxidative metabolism indicates the importance of ROS and cell energy together with plasma membrane homeostasis in N. crassa response to chitosan. Deletion strain analysis of chitosan susceptibility pointed, NCU03639 encoding a class 3 lipase, involved in plasma membrane repair by lipid replacement and NCU04537 a MFS monosaccharide transporter related with assimilation of simple sugars, as main gene targets of chitosan. NCU10521, a glutathione S-transferase-4 involved in the generation of reducing power for scavenging intracellular ROS is also a determinant chitosan gene target. Ca2+ increased tolerance to chitosan in N. crassa. Growth of NCU10610 (fig 1 domain) and SYT1 (a synaptotagmin) deletion strains was significantly increased by Ca2+ in presence of chitosan. Both genes play a determinant role in N. crassa membrane homeostasis. Our results are of paramount importance for developing chitosan as antifungal. PMID:26694141

  12. Hierarchical targeted hepatocyte mitochondrial multifunctional chitosan nanoparticles for anticancer drug delivery.

    PubMed

    Chen, Zhipeng; Zhang, Liujie; Song, Yang; He, Jiayu; Wu, Li; Zhao, Can; Xiao, Yanyu; Li, Wei; Cai, Baochang; Cheng, Haibo; Li, Weidong

    2015-06-01

    The overwhelming majority of drugs exert their pharmacological effects after reaching their target sites of action, however, these target sites are mainly located in the cytosol or intracellular organelles. Consequently, delivering drugs to the specific organelle is the key to achieve maximum therapeutic effects and minimum side-effects. In the work reported here, we designed, synthesized, and evaluated a novel mitochondrial-targeted multifunctional nanoparticles (MNPs) based on chitosan derivatives according to the physiological environment of the tumor and the requirement of mitochondrial targeting drug delivery. The intelligent chitosan nanoparticles possess various functions such as stealth, hepatocyte targeting, multistage pH-response, lysosomal escape and mitochondrial targeting, which lead to targeted drug release after the progressively shedding of functional groups, thus realize the efficient intracellular delivery and mitochondrial localization, inhibit the growth of tumor, elevate the antitumor efficacy, and reduce the toxicity of anticancer drugs. It provides a safe and efficient nanocarrier platform for mitochondria targeting anticancer drug delivery. PMID:25818430

  13. Functional single-walled carbon nanotubes/chitosan conjugate for tumor cells targeting

    NASA Astrophysics Data System (ADS)

    Wu, Baoyan; Ou, Zhongmin; Xing, Da

    2009-08-01

    The application of single-walled carbon nanotubes (SWCNTs) in the field of biomedicine is becoming an exciting topic because of their flexible structure and propensity for chemical functionalization. In this assay, a novel noncovalently functional SWCNTs based on a natural biocompatible polymer chitosan has been developed for tumor cells targeting. First, SWCNTs were modified by chitosan (CHIT-SWCNT). Second, CHIT-SWCNT was coupled with fluorescein isothiocyanate (FITC), based on the reaction between the isothiocyanate group of FITC and the primary amino group of chitosan. Third, the FITC functionalized CHIT-SWCNT was conjugated with folic acid (FA) after activation with EDC/NHS, based on the reaction between the NHS group of FA and the primary free amino group of chitosan to construct the functional SWCNT/CHIT conjugate, CHIT-SWCNT-FA. The fluorescence CHIT-SWCNT-FA has been used to detect tumor cells with confocal microscopy imaging technology. Our experimental results indicate that the novel CHIT-SWCNT-FA is soluble and stable in PBS, and it can be readily transported inside tumor cells. Combining the intrinsic properties of carbon nanotubes and the versatility of chitosan, CHIT-SWCNT can be used as potential devices for targeted drug delivery and tumor cell sensing. The proposed assay could provide a feasible alternative to presently available functional SWCNTs in biological applications.

  14. Target gene delivery from targeting ligand conjugated chitosan-PEI copolymer for cancer therapy.

    PubMed

    Nam, Joung-Pyo; Nah, Jae-Woon

    2016-01-01

    In this study, we designed a novel carrier which was having low cytotoxicity, site-specific target function, and high transfection efficiency using low molecular weight water soluble O-carboxymethyl chitosan (OCMCh), branched low molecular weight poly(ethyleneimine) (bPEI), and targeting ligand (epitope type, HER-2/neu). OCMCh/bPEI/targeting ligand, HPOCP copolymer, and targeting ligand-modified polyamphoteric polymer, and were prepared by chemical reaction and characterized by (1)H NMR and FT-IR. The binding affinity, protecting efficiency, and releasing ability of gene/HPOCP polyplex were confirmed by gel retardation assay. The pDNA(pEGFP)/HPOCP polyplexes showed high gene transfection efficiency in HCT 119 cell. In addition, siRNA/HPOCP polyplexes formed spherical shape and have particle sizes from 100 to 300nm. The siRNA/HPOCP polyplexes have lower cytotoxicity than PEI in the all of siRNA concentrations ranging from 0 to 2μg/μL in HEK 293 cells. The cell viability of siRNA/HPOCP polyplexes was performed in SK-Br3 cells with VEGF siRNA or BCL2 siRNA. In addition, confocal laser-scanning microscopy and flow cytometry assay were performed for cellular localization and cellular uptake efficiency of siRNA/HPOCP polyplexes. The results of the present study demonstrate that HPOCP copolymer is a good candidate as gene delivery carriers for gene delivery system or gene therapy. PMID:26453863

  15. 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. PMID:21130904

  16. 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.

  17. Development and evaluation of chitosan and chitosan/Kollicoat® Smartseal 30 D film-coated tablets for colon targeting.

    PubMed

    Drechsler, Michael; Garbacz, Grzegorz; Thomann, Ralf; Schubert, Rolf

    2014-11-01

    The aim of the present study was to develop film-coated tablets which release a minor amount of the active pharmaceutical ingredient (API) into the stomach and small intestine, yet show a sharp increase of drug release in the colon. Tablets containing the model drug Diclofenac-Na, microcrystalline cellulose as a filler (MT), as well as tablets consisting of Ludiflash® (LT), both were used as tablet cores, respectively. Either chitosan (CHI) alone or different ratios of chitosan and Kollicoat® Smartseal 30 D (KCSS) were applied onto these cores. The resulting film-coated tablets were analyzed for swelling, drug dissolution and stability. In order to clarify whether the colon release is mainly enzyme-driven or pressure-controlled, the coated tablets were both tested in the colon microflora test (CMT), which simulates the enzyme environment within the colon, and using a bio-relevant dissolution apparatus mimicking the intraluminal pressures and stress conditions present in the gastrointestinal tract (GIT). CHI/KCSS (25:75) coated LTs showed a pressure-controlled site-specific drug release in the large intestine, while remaining intact in the upper GIT. CHI as well as CHI/KCSS (25:75) applied onto MTs, remained stable during the entire simulated bio-relevant dissolution transit of the GIT, but showed enzymatically controlled colon targeting in the CMT. These results could be confirmed for CHI/KCSS (25:75) film-coated MTs top-coated with an additional hydroxypropylmethylcellulose (HPMC) layer and an Eudragit L 30 D-55 (EUL) layer to avoid the dissolution in the fasting stomach. PMID:25301294

  18. Cellular uptake and imaging studies of gadolinium-loaded single-walled carbon nanotubes as MRI contrast agents.

    PubMed

    Tang, Annie M; Ananta, Jeyarama S; Zhao, Hong; Cisneros, Brandon T; Lam, Edmund Y; Wong, Stephen T; Wilson, Lon J; Wong, Kelvin K

    2011-01-01

    We quantify here, for the first time, the intracellular uptake (J774A.1 murine macrophage cells) of gadolinium-loaded ultra-short single-walled carbon nanotubes (gadonanotubes or GNTs) in a 3 T MRI scanner using R(2) and R(2)* mapping in vitro. GNT-labeled cells exhibited high and linear changes in net transverse relaxations (ΔR(2) and ΔR 2*) with increasing cell concentration. The measured ΔR(2)* were about three to four times greater than the respective ΔR(2) for each cell concentration. The intracellular uptake of GNTs was validated with inductively coupled plasma optical emission spectrometry (ICP-OES), indicating an average cellular uptake of 0.44 ± 0.09 pg Gd per cell or 1.69 × 10(9) Gd(3+) ions per cell. Cell proliferation MTS assays demonstrated that the cells were effectively labeled, without cytotoxicity, for GNTs concentrations ≤28 µM Gd. In vivo relaxometry of a subcutaneously-injected GNT-labeled cell pellet in a mouse was also demonstrated at 3 T. Finally, the pronounced R(2)* effect of GNT-labeled cells enabled successful in vitro visualization of labeled cells at 9.4 T. PMID:21504063

  19. Folate mediated in vitro targeting of depolymerised trimethylated chitosan having arginine functionality.

    PubMed

    Morris, Viola B; Sharma, Chandra P

    2010-08-15

    Delivery vectors having targeting ligands provide an impending impact on cancer gene therapy. Our work focuses on folate mediated targeting induced by conjugating poly(ethylene glycol)-folate (PEG-FA) with arginine modified chitosan polymer having low molecular weight of 15 kDa and high degree of quaternization (ATFP15H). The ATFP15H derivative on condensation with plasmid DNA formed nanoparticles with core shell nanostructure. It also affirmed good buffering capacity. The derivative was found to protect DNA from DNase I degradation and also from disassembly in presence of negatively charged plasma proteins. It exhibited blood compatibility in terms of percentage hemolysis, erythrocyte aggregation and also by platelet activation. At a concentration of 10 microg, the capability of the derivative to enhance cell growth at normal cell growing conditions was observed. The transfection efficiency was also found to be comparable to PEI when transfected in KB cell line, which over expressed the folate receptor (FR) in presence of 10% fetal bovine serum (FBS). On comparison with native chitosan and trimethylated chitosan, ATFP15H derivative exhibited high cellular uptake and nuclear localization due to the superior colloidal stability attained on conjugation with polyethylene glycol. This has been ascertained by flow cytometry and YOYO labeling of plasmid DNA. PMID:20580766

  20. Bioengineered quantum dot/chitosan-tripeptide nanoconjugates for targeting the receptors of cancer cells.

    PubMed

    Mansur, Alexandra A P; de Carvalho, Sandhra M; Mansur, Herman S

    2016-01-01

    Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular level for diagnostic and therapeutic purposes. In this work, we report the synthesis of novel multifunctional nanoconjugates composed of fluorescent inorganic semiconductor quantum dot (QD) cores and tripeptide-modified polysaccharide organic shells. These structures were designed for targeting and imaging the αvβ3 integrin receptors of cancer cells. Initially, chitosan was covalently bound with the RGD peptide using a crosslinker to form bioconjugates (RGD-chitosan), which were later utilized as capping ligands for the production of surface-functionalized CdS QDs via a single-step process in aqueous media at room temperature. These core-shell nanostructures were extensively characterized by UV-vis spectroscopy, photoluminescence (PL) spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), zeta potential (ZP) and dynamic light scattering (DLS). The TEM images and the UV-vis absorption results indicated the formation of ultra-small CdS QD nanocrystals with average diameters between 2.0 and 3.0 nm. In addition, the PL results demonstrated that the nanobioconjugates exhibited intense green fluorescence under excitation. The CdS-RGD-chitosan systems were effective at specific targeting integrin when assayed in vitro using two model cell cultures, HEK 293 (non-cancerous human embryonic kidney cell) and SAOS (cancerous sarcoma osteogenic-derived cells) imaged using fluorescence microscopy. PMID:26499085

  1. Development of (153) Sm-folate-polyethyleneimine-conjugated chitosan nanoparticles for targeted therapy.

    PubMed

    Mollarazi, Esmail; Jalilian, Amir R; Johari-Daha, Fariba; Atyabi, Fatemeh

    2015-06-30

    The aim of this study was to develop biocompatible, water-soluble (153) Sm-labeled chitosan nanoparticles (NPs) containing folate and polyethyleneimine functionalities i.e. chitosan-graft-PEI-folate (CHI-DTPA-g-PEI-FA), suitable for targeted therapy. The physicochemical properties of the obtained NPs were characterized by dynamic light-scattering analysis for their mean size, size distribution, and zeta potential; scanning electron microscopy for surface morphology; and (1) H-NMR, FT-IR analyses for molecular dispersity of folate in the NPs. NPs were spherical with mean diameter below 250 nm, polydispersity of below 0.15, and positive zeta potential values. The NP complex ((153) Sm-CHI-DTPA-g-PEI-FA) was stable at 25 °C (6-8 h, >90% radiochemical purity, instant thin layer chromatography (ITLC)). Binding studies using fluorescent NPs for internalization also demonstrated significant uptake in MCF-7 cells. MCF-7 cell internalization was significantly greater for 4T1. In blocking studies, both MCF-7 and 4T1 cell lines demonstrated specific folate receptor (FR) binding (decreasing 45%). In vivo biodistribution studies indicated major excretion of NPs metabolites and/or free (153) Sm through the kidneys. The preliminary imaging studies in 4T1 tumor-bearing mice showed minor uptake up to 96 h. The present folic acid that functionalized chitosan NP is a candidate material for folate receptor therapy. PMID:26036233

  2. Hydrosoluble 50% N-acetylation-thiolated chitosan complex with cobalt as a pH-responsive renal fibrosis targeting drugs.

    PubMed

    Li, Min; Tan, Lishan; Tang, Liangfeng; Li, Aiqing; Hu, Jianqiang

    2016-07-01

    About 50% N-acetylation-thiolated chitosan possessing good water solubility was modified from commercial low-molecular-weight chitosan. Chitosan performed obvious target toward renal tubular epithelial cells, and bivalent cobalt ions improved the renal fibrosis inflammation significantly. There were many complexation sites on chitosan after being modified with sulfydryl. So sulfydryl played a role of connecting bridge between chitosan and cobalt ions. Then, this N-acetylation-thiolated chitosan cobalt (NTCC) nanocomplex was designed. The nanocomplex showed excellent stability under normal physiological conditions, and cobalt would be released from the biomaterials in acidic environment. As it was affected by inflammation, the pH in renal fibrosis lesion region was acidic. So there was a specific drug release process happening in lesion region. And drug release efficiency was determined by acidity, which demonstrated that lower the acidity, the faster and more the cobalt ion release. When this nanocomplex was intraperitoneally injected into ureter-obstructed mice, obvious attenuation of fibrotic progression was shown. It was demonstrated that NTCC exhibited special renal-targeting capacity and could be chosen as drug for treating renal fibrosis. PMID:27115330

  3. Design and synthesis of dual-ligand modified chitosan as a liver targeting vector.

    PubMed

    Chen, Houxiang; Li, Min; Wan, Tao; Zheng, Qichang; Cheng, Mingrong; Huang, Shiqi; Wang, Yong

    2012-02-01

    Vector plays an important role in hepatic targeted drug delivery system. In this study, a novel material as a liver targeting vector, dual-ligand modified chitosan (GCGA) composed of chitosan (CTS), glycyrrhetinic acid (GA) and lactobionic acid (LA), was designed and synthesized by an orthogonal experiment with two-step synthesis under mild conditions. The synthesized final product was characterized and confirmed by FTIR and (1)H-NMR spectroscopy, and DS of GA and LA in CTS were measured to be 13.77 and 16.74 mol% using (1)H-NMR, respectively. The cytotoxicity of CTS and GCGA was concentration dependent which was inverse proportion to the cell viability by MTT assay using L929 cell line, and inhibitory concentration 50% (IC50) was 0.2 mg/ml for GCGA. The in vitro targeting efficiency and the in vitro cellular uptake were investigated. Compared with CTS NPs and GA-CTS NPs, GCGA NPs showed good cell specificity to BEL-7402 cells via the dual-ligand-receptor-mediated recognition, leading to a higher affinity to BEL-7402 cells. The results suggested that GCGA described here has the potential to be used as an effective vector for hepatic targeted drug therapy. PMID:22105225

  4. 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

  5. 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. PMID:26903771

  6. Effective method of chitosan-coated alginate nanoparticles for target drug delivery applications.

    PubMed

    Wang, Fang; Yang, Siqian; Yuan, Jian; Gao, Qinwei; Huang, Chaobo

    2016-07-01

    In the present study, alginate nanoparticles were firstly prepared for paclitaxel (PTX) delivery with an average size of 200 ± 21 nm. To improve the stability and targeting effect, the chitosan (CS) and folate-chitosan (FA-CS) were introduced to form PTX-loaded CS/ALG NPs and FA-CS/ALG NPs by a new double emulsion cross-linking electrostatic attraction method. The optimization chitosan concentration was 0.5% obtained from the experiment results. The CS/ALG-PTX NPs and FA-CS/ALG-PTX NPs had the average particle size of 306.9 ± 12.9 nm and 283.6 ± 19.2 nm with the zeta potential of 31.1 ± 1.3 mV and -2.98 ± 0.7 mV, and had higher drug loading and entrapment efficiencies than ALG-PTX NPs. The in vitro drug release profile along with release kinetics and mechanism from PTX-loaded NPs were studied under two simulated physiological conditions. Further, the in vitro anti-cancer activity of nanoparticles and the cellular uptake of nanoparticles on HepG2 cells were investigated. The results demonstrated that alginate, CS/ALG and FA-CS/ALG can be used as nanoformulation drug carriers by our new method, and FA-CS/ALG was a promising vehicle for anticancer drug targeted delivery system. PMID:27164869

  7. Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles.

    PubMed

    Matos, Breno Noronha; Reis, Thaiene Avila; Gratieri, Taís; Gelfuso, Guilherme Martins

    2015-04-01

    This work developed minoxidil sulphate-loaded chitosan nanoparticles (MXS-NP) for targeted delivery to hair follicles, which could sustain drug release and improve the topical treatment of alopecia. Chitosan nanoparticles were obtained using low-molecular weight chitosan and tripolyphosphate as crosslink agent. MXS-NP presented a monomodal distribution with hydrodynamic diameter of 235.5 ± 99.9 nm (PDI of 0.31 ± 0.01) and positive zeta potential (+38.6 ± 6.0 mV). SEM analysis confirmed nanoparticles average size and spherical shape. A drug loading efficiency of 73.0 ± 0.3% was obtained with polymer:drug ratio of 1:1 (w/w). Drug release through cellulose acetate membranes from MXS-NP was sustained in about 5 times in comparison to the diffusion rate of MXS from the solution (188.9 ± 6.0 μg/cm(2)/h and 35.4 ± 1.8 μg/cm(2)/h). Drug permeation studies through the skin in vitro, followed by selective recovery of MXS from the hair follicles, showed that MXS-NP application resulted in a two-fold MXS increase into hair follicles after 6h in comparison to the control solution (5.9 ± 0.6 μg/cm(2) and 2.9 ± 0.8 μg/cm(2)). MXS-loading in nanoparticles appears as a promising and easy strategy to target and sustain drug delivery to hair follicles, which may improve the topical treatment of alopecia. PMID:25647618

  8. The liver-targeting study of the N-galactosylated chitosan in vivo and in vitro.

    PubMed

    Liang, Meihao; Zheng, Xiaoliang; Tu, Linglan; Ma, Zhen; Wang, Zunyuan; Yan, Dongmei; Shen, Zhengrong

    2014-12-01

    In order to study the liver targeting of the N-galactosylated chitosan (GC) polymer in liver, we first conjugated the lactobionic acid with chitosan (CS) to obtain the carrier of GC with different degree of substitution of lactosyl group. Western blot was performed to detect the expression levels of the asialoglycoprotein receptors (ASGPR) in the cell lines of HepG2, SMMC-7721, and HL-7702. The protein level of ASGPR was lower in HepG2 compared to HL-7702 and SMMC-7721. Although all treated by CS, viabilities of HL-7702 and HepG2 did not experience any significant drop, while viability of SMMC-7721 decreased 15% on average from control. It was the first data about the inhibitory effect of GC on the liver cells. Fluorescein isothiocyanate (FITC) labeled GC (GC-FITC) was injected intravenously into mice at a dose of 0.02 μmol/mouse. GC-FITC showed maximum liver localization at 5 min and even detectable at 48 h after injection. Further, the accumulation of GC in liver was about 5.4-fold higher than that of CS. In conclusion, GC demonstrated its higher efficacy in drug liver targeting and thus could be a more promising drug or gene carrier in future therapies. PMID:24066968

  9. 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.

  10. Tumor targeting chitosan nanoparticles for dual-modality optical/MR cancer imaging.

    PubMed

    Nam, Taehwan; Park, Sangjin; Lee, Seung-Young; Park, Kyeongsoon; Choi, Kuiwon; Song, In Chan; Han, Moon Hee; Leary, James J; Yuk, Simseok Andrew; Kwon, Ick Chan; Kim, Kwangmeyung; Jeong, Seo Young

    2010-04-21

    We report tumor targeting nanoparticles for optical/MR dual imaging based on self-assembled glycol chitosan to be a potential multimodal imaging probe. To develop an optical/MR dual imaging probe, biocompatible and water-soluble glycol chitosan (M(w) = 50 kDa) were chemically modified with 5beta-cholanic acid (CA), resulting in amphiphilic glycol chitosan-5beta-cholanic acid conjugates (GC-CA). For optical imaging near-infrared fluorescence (NIRF) dye, Cy5.5, was conjugated to GC-CA resulting in Cy5-labeled GC-CA conjugates (Cy5.5-GC-CA). Moreover, in order to chelate gadolinium (Gd(III)) in the Cy5.5-GC-CA conjugates, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was directly conjugated in Cy5.5-GC-CA. Finally, the excess GdCl(3) was added to DOTA modified Cy5.5-GC-CA conjugates in distilled water (pH 5.5). The freshly prepared Gd(III) encapsulated Cy5.5-GC-CA conjugates were spontaneously self-assembled into stable Cy5.5 labeled and Gd(III) encapsulated chitosan nanoparticles (Cy5.5-CNP-Gd(III)). The Cy5.5-CNP-Gd(III) was spherical in shape and approximately 350 nm in size. From the cellular experiment, it was demonstrated that Cy5.5-CNP-Gd(III) were efficiently taken up and distributed in cytoplasm (NIRF filter; red). When the Cy5.5-GC-Gd(III) were systemically administrated into the tail vein of tumor-bearing mice, large amounts of nanoparticles were successfully localized within the tumor, which was confirmed by noninvasive near-infrared fluorescence and MR imaging system simultaneously. These results revealed that the dual-modal imaging probe of Cy5.5-CNP-Gd(III) has the potential to be used as an optical/MR dual imaging agent for cancer treatment. PMID:20201550

  11. PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier.

    PubMed

    Kim, You-Kyoung; Zhang, Mei; Lu, Jin-Jian; Xu, Fengguo; Chen, Bao-An; Xing, Lei; Jiang, Hu-Lin

    2016-06-01

    Superparamagnetic iron oxide nanoparticle (SPION) holds great potential as a gene delivery system due to its unique properties, such as good biocompatibility and non-invasive targeting ability. In this study, we modified SPION with chitosan-graft-PEI (CHI-g-PEI) and PK11195, to fabricate a mitochondria-targeting gene carrier, PK-CP-SPION. PK-CP-SPION manifested prominent physicochemical properties for magnetic guided gene delivery, and it could effectively condense and protect DNA at proper weight ratios. The in vitro cytotoxicity of PK-CP-SPIONs was mild. Under an external magnetic field, the transfection efficiency of PK-CP-SPIONs was comparable to PEI 25 K with shorter transfection time. PK11195 facilitated the specific accumulation of PK-CP-SPIONs in mitochondria, leading to the leakage of cytochrome c, the dissipation of mitochondrial membrane potential and subsequently the activation of mitochondria apoptosis pathway. These results indicated that with further development, PK-CP-SPIONs could serve as a multifunctional nanoplatform for magnetic targeting gene delivery and mitochondria-targeting therapy, leading enhanced therapeutic effect towards tumor cells. PMID:26390926

  12. Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles.

    PubMed

    Hwang, Ho-Young; Kim, In-San; Kwon, Ick Chan; Kim, Yong-Hee

    2008-05-22

    Hydrophobically modified glycol chitosan (HGC) nanoparticles, a new nano-sized drug carrier, were prepared by introducing a hydrophobic molecule, cholanic acid, to water soluble glycol chitosan. The HGC nanoparticles were easily loaded with the anticancer drug docetaxel (DTX) using a dialysis method, and the resulting docetaxel-loaded HGC (DTX-HGC) nanoparticles formed spontaneously self-assembled aggregates with a mean diameter of 350 nm in aqueous condition. The DTX-HGC nanoparticles were well dispersed and stable for 2 weeks under physiological conditions (pH 7.4 and 37 degrees C) and a sustained drug release profile, in vitro. In addition, the DTX-HGC nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the DTX-HGC nanoparticles might also be stable in the blood stream. The DTX-HGC nanoparticles exhibited a distinctive deformability in aqueous conditions, in that they could easily pass through a filter membrane with 200 nm pores despite their mean diameter of 350 nm. We also evaluated the time-dependent excretion profile, in vivo biodistribution, prolonged circulation time, and tumor targeting ability of DTX-HGC nanoparticles by using a non-invasive live animal imaging technology. Finally, under optimal conditions for cancer therapy, the DTX-HGC nanoparticles showed higher antitumor efficacy such as reduced tumor volume and increased survival rate in A549 lung cancer cells-bearing mice and strongly reduced the anticancer drug toxicity compared to that of free DTX in tumor-bearing mice. Together our results showed that the anticancer loaded nano-sized drug carriers are a promising nano-sized drug formulation for cancer therapy. PMID:18374444

  13. Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells.

    PubMed

    Maya, S; Sarmento, Bruno; Lakshmanan, Vinoth-Kumar; Menon, Deepthy; Seabra, Vitor; Jayakumar, R

    2014-08-01

    Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds. PMID:24950310

  14. Folatereceptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Dipsikha; Das, Manasmita; Mishra, Debashis; Banerjee, Indranil; Sahu, Sumanta K.; Maiti, Tapas K.; Pramanik, Panchanan

    2011-04-01

    This article delineates the design and synthesis of a novel, bio-functionalized, magneto-fluorescent multifunctional nanoparticles suitable for cancer-specific targeting, detection and imaging. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl and aldehyde groups were designed using o-carboxymethyl chitosan (OCMC). The free aminegroups of OCMC stabilized magnetite nanoparticles on the surface allow for the covalent attachment of a fluorescent dye such as rhodamine isothiocyanate (RITC) with the aim to develop a magneto-fluorescent nanoprobe for optical imaging. In order to impart specific cancer cell targeting properties, folic acid and its aminated derivative was conjugated onto these magneto-fluorescent nanoparticles using different pendant groups (-NH2, -COOH, -CHO). These newly synthesized iron-oxide folate nanoconjugates (FA-RITC-OCMC-SPIONs) showed excellent dispersibility, biocompatibility and good hydrodynamic sizes under physiological conditions which were extensively studied by a variety of complementary techniques. The cellular internalization efficacy of these folate-targeted and its non-targeted counterparts were studied using a folate-overexpressed (HeLa) and a normal (L929fibroblast) cells by fluorescence microscopy and magnetically activated cell sorting (MACS). Cell-uptake behaviors of nanoparticles clearly demonstrate that cancer cells over-expressing the human folatereceptor internalized a higher level of these nanoparticle-folate conjugates than normal cells. These folate targeted nanoparticles possess specific magnetic properties in the presence of an external magnetic field and the potential of these nanoconjugates as T2-weighted negative contrast MR imaging agent were evaluated in folate-overexpressed HeLa and normal L929fibroblastcells.

  15. Galactosyl conjugated N-succinyl-chitosan-graft-polyethylenimine for targeting gene transfer.

    PubMed

    Lu, Bo; Wu, De-Qun; Zheng, Hua; Quan, Chang-Yun; Zhang, Xian-Zheng; Zhuo, Ren-Xi

    2010-12-01

    Through incorporating lactobionic acid (LA) bearing a galactose group to N-succinyl-chitosan-graft-polyethylenimine (NSC-g-PEI), NSC-g-PEI-LA copolymers were synthesized as gene vectors with hepatocyte targeting properties. The molecular weight and composition of NSC-g-PEI-LA copolymers were characterized using gel permeation chromatography (GPC) and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) respectively. Agarose gel electrophoresis assays showed good DNA binding ability of NSC-g-PEI-LA, and the particle size of the NSC-g-PEI-LA/DNA complexes were between 150 and 400 nm as determined by a Zeta sizer. The NSC-g-PEI-LA/DNA complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The zeta potentials of these complexes were increased with the weight ratio of NSC-g-PEI-LA/DNA. NSC-g-PEI-LA has a lower cytotoxicity than PEI (25 kDa) and the toxicity decreased with increasing substitution of LA. The transfection efficiency of different complexes was evaluated by luciferase assay. Compared with PEI (25 kDa) and NSC-g-PEI/DNA, NSC-g-PEI-LA showed good transfection activity and cell specificity to HepG2 cells. The results suggested that NSC-g-PEI-LA has the potential to be used as a safe and effective targeting gene vector. PMID:20957247

  16. Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems.

    PubMed

    Pan, Qixia; Lv, Yao; Williams, Gareth R; Tao, Lei; Yang, Huihui; Li, Heyu; Zhu, Limin

    2016-10-20

    In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems. PMID:27474628

  17. Carboxymethyl chitosan-mediated synthesis of hyaluronic acid-targeted graphene oxide for cancer drug delivery.

    PubMed

    Yang, Huihui; Bremner, David H; Tao, Lei; Li, Heyu; Hu, Juan; Zhu, Limin

    2016-01-01

    In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release, a new drug carrier was developed. Graphene oxide (GO) was first modified with carboxymethyl chitosan (CMC), followed by conjugation of hyaluronic acid (HA) and fluorescein isothiocyanate (FI). The resulting GO-CMC-FI-HA conjugate was characterized and used as a carrier to encapsulate the anticancer drug doxorubicin (DOX) to study in vitro release behavior. The drug loading capacity is as high as 95% and the drug release rate under tumor cell microenvironment of pH 5.8 is significantly higher than that under physiological conditions of pH 7.4. Cell uptake studies show that the GO-CMC-FI-HA/DOX complex can specifically target cancer cells, which are over-expressing CD44 receptors and effectively inhibit their growth. The above results suggest that the functionalized graphene-based material has potential applications for targeted delivery and controlled release of anticancer drugs. PMID:26453853

  18. Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution

    PubMed Central

    2011-01-01

    Both folic acid (FA)- and methoxypoly(ethylene glycol) (mPEG)-conjugated chitosan nanoparticles (NPs) had been designed for targeted and prolong anticancer drug delivery system. The chitosan NPs were prepared with combination of ionic gelation and chemical cross-linking method, followed by conjugation with both FA and mPEG, respectively. FA-mPEG-NPs were compared with either NPs or mPEG-/FA-NPs in terms of their size, targeting cellular efficiency and tumor tissue distribution. The specificity of the mPEG-FA-NPs targeting cancerous cells was demonstrated by comparative intracellular uptake of NPs and mPEG-/FA-NPs by human adenocarcinoma HeLa cells. Mitomycin C (MMC), as a model drug, was loaded to the mPEG-FA-NPs. Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group. In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release. Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that an increased amount of mPEG-FA-NPs or FA-NPs were accumulated in the tumor tissue relative to the mPEG-NPs or NPs alone. These results suggest that both FA- and mPEG-conjugated chitosan NPs are potentially prolonged drug delivery system for tumor cell-selective targeting treatments. PMID:22027239

  19. Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

    PubMed Central

    Xie, Yi-Ting; Du, Yong-Zhong; Yuan, Hong; Hu, Fu-Qiang

    2012-01-01

    Purpose Therapy for central nervous system disease is mainly restricted by the blood–brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied. Methods Stearic acid–grafted chitosan (CS-SA) was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX), as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells. Results The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 μg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC50 of which was 237.6 ± 6.61 μg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 μg/mL, compared with 0.181 ± 0.066 μg/mL of DOX · HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood–brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour. Meanwhile, free DOX · HCl was not detected in brain. In other major tissues, DOX-loaded micelles were mainly distributed into lung, liver, and

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

    PubMed Central

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

    2015-01-01

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

  1. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

    PubMed Central

    Yousefpour, Parisa; Atyabi, Fatemeh; Vasheghani-Farahani, Ebrahim; Movahedi, Ali-Akbar Mousavi; Dinarvand, Rassoul

    2011-01-01

    Background Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action. Methods Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX) nanoparticles (particle size, 200 nm) via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles. Results CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb) contained 47 μg/mg doxorubicin and 33.5 μg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and selective uptake of CS-DOX-mAb by Her2+ cancer cells compared with nontargeted CS-DOX nanoparticles and free drug. Conclusion Antibody-conjugated nanoparticles were shown to discriminate between Her2+ and Her2− cells, and thus have the potential to be used in active targeted drug delivery, with reduction of drug side effects in Her2+ breast and ovarian cancers. PMID:21976974

  2. Galactosylated Chitosan Oligosaccharide Nanoparticles for Hepatocellular Carcinoma Cell-Targeted Delivery of Adenosine Triphosphate

    PubMed Central

    Zhu, Xiu Liang; Du, Yong Zhong; Yu, Ri Sheng; Liu, Ping; Shi, Dan; Chen, Ying; Wang, Ying; Huang, Fang Fang

    2013-01-01

    Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were 51.03 ± 3.26 nm and 30.50 ± 1.25 mV, respectively, suggesting suitable properties for a drug delivery system. Subsequently, the cytotoxicity of Gal-CSO/ATP nanoparticles were examined by the methyl tetrazolium (MTT) assay, and the half maximal inhibitory concentration (IC50) values were calculated with HepG2 (human hepatocellular carcinoma cell line) cells. The results showed that the cytotoxic effect of nanoparticles on HepG2 cells was low. In the meantime, it was also found that the Gal-CSO/ATP nanoparticles could be uptaken by HepG2 cells, due to expression of the asialoglycoprotein receptor (ASGP-R) on their surfaces. The presented results indicate that the Gal-CSO nanoparticles might be very attractive to be used as an intracellular drug delivery carrier for hepatocellular carcinoma cell targeting, thus warranting further in vivo or clinical investigations. PMID:23899789

  3. Efficient pH Dependent Drug Delivery to Target Cancer Cells by Gold Nanoparticles Capped with Carboxymethyl Chitosan

    PubMed Central

    Madhusudhan, Alle; Reddy, Gangapuram Bhagavanth; Venkatesham, Maragoni; Veerabhadram, Guttena; Kumar, Dudde Anil; Natarajan, Sumathi; Yang, Ming-Yeh; Hu, Anren; Singh, Surya S.

    2014-01-01

    Doxorubicin (DOX) was immobilized on gold nanoparticles (AuNPs) capped with carboxymethyl chitosan (CMC) for effective delivery to cancer cells. The carboxylic group of carboxymethyl chitosan interacts with the amino group of the doxorubicin (DOX) forming stable, non-covalent interactions on the surface of AuNPs. The carboxylic group ionizes at acidic pH, thereby releasing the drug effectively at acidic pH suitable to target cancer cells. The DOX loaded gold nanoparticles were effectively absorbed by cervical cancer cells compared to free DOX and their uptake was further increased at acidic conditions induced by nigericin, an ionophore that causes intracellular acidification. These results suggest that DOX loaded AuNPs with pH-triggered drug releasing properties is a novel nanotheraputic approach to overcome drug resistance in cancer. PMID:24821542

  4. Bufalin loaded biotinylated chitosan nanoparticles: an efficient drug delivery system for targeted chemotherapy against breast carcinoma.

    PubMed

    Tian, Xin; Yin, Hongzhuan; Zhang, Shichen; Luo, Ying; Xu, Kai; Ma, Ping; Sui, Chengguang; Meng, Fandong; Liu, Yunpeng; Jiang, Youhong; Fang, Jun

    2014-08-01

    Bufalin is a traditional oriental medicine which is known to induce apoptosis in many tumor cells, and it is thus considered as a new anticancer therapeutic. By now, most of the studies of bufalin are in vitro, however in vivo evaluations of its therapeutic efficacy are less and are in great demand for its development toward anticancer drug. One of the problems probably hampering the development of bufalin is the lack of tumor selectivity, which may reduce the therapeutic effect as well as showing side effects. To overcome this drawback, in this study, we designed a tumor-targeted drug delivery system of bufalin based on enhanced permeability and retention (EPR) effect, by using biotinylated chitosan, resulting in bufalin encapsulating nanoparticles (Bu-BCS-NPs) with mean hydrodynamic size of 171.6 nm, as evidenced by dynamic light scattering and transmission electron microscope. Bu-BCS-NPs showed a relative slow and almost linear release of bufalin, and about 36.8% of bufalin was released in 24 h when dissolved in sodium phosphate buffer. Compared to native bufalin, Bu-BCS-NPs exhibited a stronger cytotoxicity against breast cancer MCF-7 cells (IC50 of 0.582 μg/ml vs 1.896 μg/ml of native bufalin). Similar results were also obtained in intracellular reactive oxygen species production, apoptosis induction, and decrease in mitochondria membrane potential. These results may contribute to the rapid intracellular uptake of nanoparticles, partly benefiting from the highly expressed biotin receptors in tumor cells. In vivo studies using MCF-7 tumor models in nude mice confirmed the remarkable therapeutic effect of Bu-BCS-NPs. These findings suggest the potential of Bu-BCS-NPs as an anticancer drug with tumor targeting property. PMID:24846793

  5. Carboxymethyl Chitosan-Modified Polyamidoamine Dendrimer Enables Progressive Drug Targeting of Tumors via pH-Sensitive Charge Inversion.

    PubMed

    Qi, Xiaole; Qin, Jiayi; Fan, Yuchao; Qin, Xiaoxue; Jiang, Yujie; Wu, Zhenghong

    2016-04-01

    Polyamidoamine dendrimers are potential candidates for drug delivery systems due to their remarkable cell-penetrating power that results from their strong positive surface charge. However, the positively charged surfaces always lead to serious cytotoxicity and the rapid clearance of polyamidoamine in vivo, which limit the application of these dendrimers. To overcome these drawbacks, we developed a carboxymethyl chitosan-modified polyamidoamine dendrimer to achieve progressive drug targeting of tumors via pH-sensitive charge inversion. With the shielding of carboxymethyl chitosan, the complex was negatively charged at physiological conditions (pH 7.4) and prone to enrich at tumor sites due to the enhanced permeation and retention effect; however, it regained a positive charge via the removal of the carboxymethyl chitosan coating under tumor-acidic conditions (pH 6.5) and achieved high intracellular uptake in tumor cells through electrostatic adsorptive endocytosis. In this study, these dendrimers exhibited 1.99- and 1.76-times higher cellular uptake efficiencies at pH 7.4 in MCF-7 or A549 cells, respectively, compared with efficiencies at pH 6.5, indicating an effective pH-dependent accumulation; the fluorescence intensities of these cells exposed to the dendrimers at pH 6.5 were also 16.45- and 9.27-fold greater, respectively, than those of free doxorubicin. After intravenous administration in mice bearing H22 tumors, doxorubicin-loaded dendrimers exhibited a 1.50-fold greater antitumor activity and presented no obvious systematic toxicity based on histological analysis compared with free drugs. Overall, a simple decoration of carboxymethyl chitosan demonstrated to be a promising way for cationic nanocarriers to achieve pH-sensitive drug release and charge conversion response to tumor microenvironment pH and enhance the antitumor therapy efficiency of anticancer drugs. PMID:27301193

  6. The targeted behavior of folate-decorated N-succinyl-N'-octyl chitosan evaluated by NIR system in mouse model

    NASA Astrophysics Data System (ADS)

    Zhu, Hongyan; Deng, Dawei; Chen, Haiyan; Qian, Zhiyu; Gu, Yueqing

    2010-11-01

    The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to construct and evaluate the folate-decorated, self-assembled nanoparticles as candidates to deliver near infrared fluorescent dyes into tumors and to investigate the mechanisms underlying the tumor targeting with folate-decorated, self-assembled nanoparticles. Folate-decorated N-succinyl-N'-octyl chitosan (folate-SOC) were synthesized. The chemical modification chitosan could self-assemble into stable micelles in aqueous medium. Micelle size determined by size analysis was around 140 nm in a phosphate-buffered saline (PBS, PH 7.4). Folate-SOC could maintain their structure for up to 15 days in PBS. Near infrared dye ICG-Der-01 as a mode drug was loaded in the micelles, and the entrapment efficiency (EE) and drug loading (DL) were investigated. The targeted behavior of folate-SOC was evaluated by near-infrared fluorescence imaging in vivo on different groups of denuded mice, with A549 or Bel-7402 tumors. The optical imaging results indicated that folated-decorated SOC showed an excellent tumor specificity in Bel-7402 tumor-bearing mice, and weak tumor specificity in A549 tumor bearing mice. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

  7. Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging.

    PubMed

    Key, Jaehong; Dhawan, Deepika; Cooper, Christy L; Knapp, Deborah W; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Park, Kinam; Decuzzi, Paolo; Leary, James F

    2016-01-01

    While current imaging modalities, such as magnetic resonance imaging (MRI), computed tomography, and positron emission tomography, play an important role in detecting tumors in the body, no single-modality imaging possesses all the functions needed for a complete diagnostic imaging, such as spatial resolution, signal sensitivity, and tissue penetration depth. For this reason, multimodal imaging strategies have become promising tools for advanced biomedical research and cancer diagnostics and therapeutics. In designing multimodal nanoparticles, the physicochemical properties of the nanoparticles should be engineered so that they successfully accumulate at the tumor site and minimize nonspecific uptake by other organs. Finely altering the nano-scale properties can dramatically change the biodistribution and tumor accumulation of nanoparticles in the body. In this study, we engineered multimodal nanoparticles for both MRI, by using ferrimagnetic nanocubes (NCs), and near infrared fluorescence imaging, by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging. PMID:27621615

  8. Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

    PubMed Central

    Key, Jaehong; Dhawan, Deepika; Cooper, Christy L; Knapp, Deborah W; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Park, Kinam; Decuzzi, Paolo; Leary, James F

    2016-01-01

    While current imaging modalities, such as magnetic resonance imaging (MRI), computed tomography, and positron emission tomography, play an important role in detecting tumors in the body, no single-modality imaging possesses all the functions needed for a complete diagnostic imaging, such as spatial resolution, signal sensitivity, and tissue penetration depth. For this reason, multimodal imaging strategies have become promising tools for advanced biomedical research and cancer diagnostics and therapeutics. In designing multimodal nanoparticles, the physicochemical properties of the nanoparticles should be engineered so that they successfully accumulate at the tumor site and minimize nonspecific uptake by other organs. Finely altering the nano-scale properties can dramatically change the biodistribution and tumor accumulation of nanoparticles in the body. In this study, we engineered multimodal nanoparticles for both MRI, by using ferrimagnetic nanocubes (NCs), and near infrared fluorescence imaging, by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging. PMID:27621615

  9. Targeted chitosan-based bionanocomposites for controlled oral mucosal delivery of chlorhexidine.

    PubMed

    Onnainty, Renée; Onida, Barbara; Páez, Paulina; Longhi, Marcela; Barresi, Antonello; Granero, Gladys

    2016-07-25

    The purpose of this study was to develop sustained release systems based on chitosan (CS) and montmorillonite (MMT) for chlorhexidine (CLX). Nanocomposites were prepared by ion-exchange. CLX systems were characterized by X-ray powder diffraction (XRD), thermal analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray fluorescence analysis (XRF). The mucoadhesion properties of CLX nanocomposites were evaluated by SEM. The release behavior of these systems was also studied by the dialysis technique. The antibacterial activity was investigated in vitro by the disk diffusion test. Results showed long-term sustained release of CLX from the hybrid carriers without initial burst release. The release profiles of CLX from the carriers suggested the diffusion through a swollen matrix and water filled pores as the controlled drug release mechanism. The CLX hybrid nanosystem containing the positively-charged chitosan exhibited good mucoadhesion properties maintaining the CLX antimicrobial properties. PMID:27282538

  10. Disruption of Aedes aegypti Olfactory System Development through Chitosan/siRNA Nanoparticle Targeting of semaphorin-1a

    PubMed Central

    Mysore, Keshava; Flannery, Ellen M.; Tomchaney, Michael; Severson, David W.; Duman-Scheel, Molly

    2013-01-01

    Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a) during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention. PMID:23696908

  11. An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles.

    PubMed

    Pramanik, Arindam; Laha, Dipranjan; Dash, Sandeep Kumar; Chattopadhyay, Sourav; Roy, Somenath; Das, Dipak Kumar; Pramanik, Panchanan; Karmakar, Parimal

    2016-11-01

    We have developed a strategy for targeted delivery of metal-diketo complex, "bis(2,4-pentanedionato) copper(II)" to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex "bis(2,4-pentanedionato)copper(II)". This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+ /her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes. PMID:27524027

  12. Enhanced tumor targeting and antitumor efficacy via hydroxycamptothecin-encapsulated folate-modified N-succinyl-N'-octyl chitosan micelles.

    PubMed

    Zhu, Hongyan; Cao, Jie; Cui, Sisi; Qian, Zhiyu; Gu, Yueqing

    2013-04-01

    10-Hydroxycamptothecin (HCPT) is an effective anticancer drug against various types of solid tumors. But the antitumor efficacy of HCPT is far from satisfactory because of its poor physicochemical properties, short circulating half-life, low stability, and nonspecific toxicity to normal tissues. Therefore, a targeted delivery strategy for HCPT to pathological sites is eagerly needed to overcome these limitations. The folate-modified N-succinyl-N'-octyl chitosan (folate-SOC) micelle was chosen in this study and served as the targeted delivery system for HCPT to improve the antitumor efficacy. The water-insoluble anticancer drug HCPT was encapsulated into the folate-SOC micelles by the dialysis method. The near-spherical HCPT-loaded folate-SOC (HCPT/folate-SOC) micelles were formed in aqueous media with diameter of about 100-200 nm. The HCPT/folate-SOC micelles displayed a good stability, reasonable drug-loading content (about 10%), and sustained release behavior for the water-insoluble HCPT. Compared with free HCPT, HCPT/folate-SOC micelles exhibited a significant enhancement of cellular uptake, higher cytotoxicity against folate receptor positive tumor cell (Bel-7402), excellent tumor-targeting capability and substantially better antitumor efficacy on the nude mice bearing Bel-7402 xenografts. These results demonstrate the potential of folate-SOC micelles as long-term stable and effective drug delivery systems in cancer therapy. PMID:23400693

  13. Targeted delivery of microRNA-126 to vascular endothelial cells via REDV peptide modified PEG-trimethyl chitosan.

    PubMed

    Zhou, Fang; Jia, Xiaoling; Yang, Qingmao; Yang, Yang; Zhao, Yunhui; Fan, Yubo; Yuan, Xiaoyan

    2016-05-26

    Manipulation of gene expression by means of microRNAs (miRNAs) is one of the emerging strategies to treat cardiovascular and cancer diseases. Nevertheless, efficient delivery of miRNAs to a specific vascular tissue is limited. In this work, a short peptide Arg-Glu-Asp-Val (REDV) was linked to trimethyl chitosan (TMC) via a bifunctional poly(ethylene glycol) (PEG) linker for the targeted delivery of microRNA-126 (miRNA-126) to vascular endothelial cells (VECs). The morphology, serum stability and cytotoxicity of the polyplex/miRNA complexes, namely, TMC/miRNA, TMC-g-PEG/miRNA and TMC-g-PEG-REDV/miRNA, were investigated along with the cellular uptake, proliferation and in vitro miRNA transfection efficiency. By REDV modification, the TMC-g-PEG-REDV/miRNA complex showed negligible cytotoxicity, increased expression of miRNA-126 and enhanced VEC proliferation compared with the TMC/miRNA and TMC-g-PEG/miRNA complexes. In particular, the approaches adopted for the miRNA delivery and targeted peptide REDV modification promote the selective uptake and the growth of VECs over vascular smooth muscle cells. It was suggested that the REDV peptide-modified TMC-g-PEG polyplex could be potentially used as a miRNA carrier in artificial blood vessels for rapid endothelialization. PMID:27055482

  14. Octreotide-modified N-octyl-O, N-carboxymethyl chitosan micelles as potential carriers for targeted antitumor drug delivery.

    PubMed

    Zou, Aifeng; Huo, Meirong; Zhang, Yong; Zhou, Jianping; Yin, Xiaoqiang; Yao, Chengli; Zhu, Qinnv; Zhang, Min; Ren, Jinshan; Zhang, Qiang

    2012-02-01

    Octreotide (OCT) was recently found to have high binding affinity to the positive tumor cells of somatostatin receptors (SSTRs). In this study, octreotide-Phe-polyethylene glycol-stearic acid was first successfully synthesized and used as a targeting molecule for N-octyl-O, N-carboxymethyl chitosan (OCC). Doxorubicin (DOX) was loaded into OCT-modified OCC micelles (DOX-OCC-OCT). The drug-loaded micelles obtained exhibited spherical shape, small particle sizes, and negative zeta potentials. The cytotoxicity of DOX-OCC-OCT micelles against MCF-7 cells (SSTRs expressing) was found to significantly increase with the increased amount of OCT modification, whereas no significant difference was observed against WI-38 cells (no SSTRs expressing). Results of flow cytometry, fluorescence microscopy, and confocal laser scanning microscopy confirmed that DOX-OCC-OCT micelles could remarkably increase the uptake of DOX in MCF-7 cells. All the results indicated that OCC-OCT micelles may be a promising intracellular targeting carrier for efficient delivery of antitumor drugs into tumor cells. PMID:22083725

  15. Galactosylation of chitosan-graft-spermine as a gene carrier for hepatocyte targeting in vitro and in vivo.

    PubMed

    Kim, Ji-Hye; Kim, You-Kyoung; Arash, Minai-Tehrani; Hong, Seong-Ho; Lee, Jae-Ho; Kang, Bit Na; Bang, Yong-Bin; Cho, Chong-Su; Yu, Dae-Yeul; Jiang, Hu-Lin; Cho, Myung-Haing

    2012-07-01

    Polyethyleneimine (PEI) has been described as a highly efficient gene carrier due to its efficient proton sponge effect within endosomes. However, many studies have demonstrated that PEI is toxic and associated with a lack of cell specificity despite high transfection efficiency. In order to minimize the toxicity of PEI, we prepared chitosan-graft-spermine (CHI-g-SPE) in a previous study. CHI-g-SPE showed low toxicity and high transfection efficiency. However, this compound also had limited target cell specificity. In the present study, we synthesized galactosylated CHI-g-SPE (GCS) because this modified GCS could be delivered specifically into the liver due to hepatocyte-specific galactose receptors. The DNA-binding properties of GCS at various copolymer/DNA weight ratios were evaluated by a gel retardation assay. The GCS copolymer exhibited significant DNA-binding ability and efficiently protected DNA from nuclease attack. Using energy-filtered transmission electron microscopy (EF-TEM), we observed dense spherical, nano-sized GCS/DNA complexes with a homogenous distribution. Most importantly, GCS was associated with remarkably low cytotoxicity compared to PEI in HepG2, HeLa, and A549 cells. Moreover, GCS carriers specifically delivered the gene-of-interest into hepatocytes in vitro as well as in vivo. Our results suggest that the novel GCS described here is a safe and highly efficient carrier for hepatocyte-targeted gene delivery. PMID:22966542

  16. Low molecular weight hydroxyethyl chitosan-prednisolone conjugate for renal targeting therapy: synthesis, characterization and in vivo studies.

    PubMed

    He, Xia-kai; Yuan, Zhi-xiang; Wu, Xiao-juan; Xu, Chao-qun; Li, Wan-yu

    2012-01-01

    To further evaluate the potential renal targeting profile of low molecular weight hydroxyethyl chitosan (LMWHC) we developed before, prednisolone (Pre) was conjugated with LMWHC by EDC/NHS chemistry to improve the therapeutic effect of glucocorticoids in vivo. The conjugate was denoted as LMWHC-Pre. The prednisolone content of the conjugate was determined by reversed-phase high-performance liquid chromatography (HPLC) with Kromasil C18 column. The results showed that the average coupling degree of prednisolone to LMWHC was 76.7±3.2 μg·mg(-1). The stability and physicochemical characterization of LMWHC-Pre under various conditions were also investigated. To study the fate of LMWHC-Pre after intravenous (i.v.) administration, fluorescein isothiocyanate (FITC) was coupled to the conjugate to explore the renal targeting efficacy. The in vivo results showed that significant amount of the conjugate was accumulated into the kidneys while negligible signal could be detected when the mixture of FITC-LMWHC and prednisolone was co-administered. The preliminary pharmacodynamics study of LMWHC-Pre showed that the conjugate could effectively alleviate the nephrotic syndrome of rats induced by minimal change nephrosis (MCN) model. Toxicity study also revealed that there was little glucocorticoid-induced osteoporosis by LMWHC-Pre upon 20 days of treatment. From this study, LMWHC-Pre may be employed as an effective potential drug candidate for the treatment of chronic renal disease. PMID:23227122

  17. Chitosan-Decorated Doxorubicin-Encapsulated Nanoparticle Targets and Eliminates Tumor Reinitiating Cancer Stem-like Cells.

    PubMed

    Rao, Wei; Wang, Hai; Han, Jianfeng; Zhao, Shuting; Dumbleton, Jenna; Agarwal, Pranay; Zhang, Wujie; Zhao, Gang; Yu, Jianhua; Zynger, Debra L; Lu, Xiongbin; He, Xiaoming

    2015-06-23

    Tumor reinitiating cancer stem-like cells are responsible for cancer recurrence associated with conventional chemotherapy. We developed a doxorubicin-encapsulated polymeric nanoparticle surface-decorated with chitosan that can specifically target the CD44 receptors of these cells. This nanoparticle system was engineered to release the doxorubicin in acidic environments, which occurs when the nanoparticles are localized in the acidic tumor microenvironment and when they are internalized and localized in the cellular endosomes/lysosomes. This nanoparticle design strategy increases the cytotoxicity of the doxorubicin by six times in comparison to the use of free doxorubicin for eliminating CD44(+) cancer stem-like cells residing in 3D mammary tumor spheroids (i.e., mammospheres). We further show these nanoparticles reduced the size of tumors in an orthotopic xenograft tumor model with no evident systemic toxicity. The development of nanoparticle system to target cancer stem-like cells with low systemic toxicity provides a new treatment arsenal for improving the survival of cancer patients. PMID:26004286

  18. Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration.

    PubMed

    Van Woensel, Matthias; Wauthoz, Nathalie; Rosière, Rémi; Mathieu, Véronique; Kiss, Robert; Lefranc, Florence; Steelant, Brecht; Dilissen, Ellen; Van Gool, Stefaan W; Mathivet, Thomas; Gerhardt, Holger; Amighi, Karim; De Vleeschouwer, Steven

    2016-04-10

    Galectin-1 (Gal-1) is a naturally occurring galactose-binding lectin, which is overexpressed in glioblastoma multiforme (GBM). Gal-1 is associated with tumor progression, and is a potent immune suppressor in the tumor micro-environment. To inhibit Gal-1 in GBM, an effective therapy is required that reaches the central nervous system tumor, with limited systemic effects. In this study, we report for the first time that concentrated chitosan nanoparticle suspensions can deliver small interfering RNA (siRNA) into the central nervous system tumor within hours after intranasal administration. These nanoparticles are able to complex siRNA targeting Gal-1 to a high percentage, and protect them from RNAse degradation. Moreover, a successful intracellular delivery of anti-Gal-1 siRNA resulted in a decreased expression of Gal-1 in both murine and human GBM cells. Sequence specific RNAinterference, resulted in more than 50% Gal-1 reduction in tumor bearing mice. This study indicates that the intranasal pathway is an underexplored transport route for delivering siRNA-based therapies targeting Gal-1 in the treatment of GBM. PMID:26902800

  19. Low Molecular Weight Hydroxyethyl Chitosan-Prednisolone Conjugate for Renal Targeting Therapy: Synthesis, Characterization and In Vivo Studies

    PubMed Central

    He, Xia-kai; Yuan, Zhi-xiang; Wu, Xiao-juan; Xu, Chao-qun; Li, Wan-yu

    2012-01-01

    To further evaluate the potential renal targeting profile of low molecular weight hydroxyethyl chitosan (LMWHC) we developed before, prednisolone (Pre) was conjugated with LMWHC by EDC/NHS chemistry to improve the therapeutic effect of glucocorticoids in vivo. The conjugate was denoted as LMWHC-Pre. The prednisolone content of the conjugate was determined by reversed-phase high-performance liquid chromatography (HPLC) with Kromasil C18 column. The results showed that the average coupling degree of prednisolone to LMWHC was 76.7±3.2 μg·mg-1. The stability and physicochemical characterization of LMWHC-Pre under various conditions were also investigated. To study the fate of LMWHC-Pre after intravenous (i.v.) administration, fluorescein isothiocyanate (FITC) was coupled to the conjugate to explore the renal targeting efficacy. The in vivo results showed that significant amount of the conjugate was accumulated into the kidneys while negligible signal could be detected when the mixture of FITC-LMWHC and prednisolone was co-administered. The preliminary pharmacodynamics study of LMWHC-Pre showed that the conjugate could effectively alleviate the nephrotic syndrome of rats induced by minimal change nephrosis (MCN) model. Toxicity study also revealed that there was little glucocorticoid-induced osteoporosis by LMWHC-Pre upon 20 days of treatment. From this study, LMWHC-Pre may be employed as an effective potential drug candidate for the treatment of chronic renal disease. PMID:23227122

  20. Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries.

    PubMed

    Dalpiaz, Alessandro; Fogagnolo, Marco; Ferraro, Luca; Capuzzo, Antonio; Pavan, Barbara; Rassu, Giovanna; Salis, Andrea; Giunchedi, Paolo; Gavini, Elisabetta

    2015-11-01

    Zidovudine (AZT) is an antiretroviral drug that is a substrate of active efflux transporters (AETs) that extrude the drug from the central nervous system (CNS) and macrophages, which are considered to be sanctuaries of HIV. The conjugation of AZT to ursodeoxycholic acid is known to produce a prodrug (UDCA-AZT) that is able to elude the AET systems, indicating the potential ability of this prodrug to act as a carrier of AZT in the CNS and in macrophages. Here, we demonstrate that UDCA-AZT is able to permeate and remain in murine macrophages with an efficiency twenty times higher than that of AZT. Moreover, we propose the nasal administration of this prodrug in order to induce its uptake into the CNS. Chitosan chloride-based microparticles (CP) were prepared by spray-drying and were characterized with respect to size, morphology, density, water uptake and the dissolution profile of UDCA-AZT. The CP sample was then nasally administered to rats. All in vitro and in vivo measurements were also performed for a CP parent physical mixture. The CP sample was able to increase the dissolution rate of UDCA-AZT and to reduce water uptake with respect to its parent physical mixture, inducing better uptake of UDCA-AZT into the cerebrospinal fluid of rats, where the prodrug can act as an AZT carrier in macrophages. PMID:26427553

  1. Novel albendazole-chitosan nanoparticles for intestinal absorption enhancement and hepatic targeting improvement in rats.

    PubMed

    Liu, Yang; Wang, Xiao-qing; Ren, Wei-xin; Chen, Yuan-lan; Yu, Yang; Zhang, Jian-kang; Bawudong, Dilimulati; Gu, Jun-peng; Xu, Xiao-dong; Zhang, Xue-nong

    2013-08-01

    To improve the treatment of helminthiasis, filariasis, and colorectal cancer, albendazole-associated chitosan nanoparticles (ABZ-CS-NPs) were prepared using the emulsion crosslinking volatile technique with contained sodium tripolyphosphate as the crosslinking agent and Poloxamer 188 as the auxiliary solvent. The structural characteristics of the NPs were determined using X-ray diffraction to analyze the interaction between CS and the drug. The NPs were then evaluated in terms of their physicochemical characteristics, drug release behavior, in vivo pharmacokinetic parameters, and biodistribution in animal studies. ABZ-loaded NPs with a uniformly spherical particle sizes (157.8 ± 2.82 nm) showed efficient drug loading, encapsulated efficiency, and high physical stability. The drug release from ABZ-CS-NPs was extended over several periods. Kinetic models were then fitted to determine the release mechanisms. ABZ and its metabolite albendazole sulfoxide (ABZSX) were analyzed in rats with mebendazole as the internal standard using reversed-phase high-performance liquid chromatography. Compared with the ABZ suspension groups, the relative bioavailability values of ABZ and ABZSX were 146.05 and 222.15%, respectively. In addition, the plasma concentration versus time curve is consistent with that of the two compartment models in the plasma concentration versus time curve. The results indicate that the ABZ-loaded NPs are promising novel ABZ candidates for passive diffusion in the treatment of hydatid cysts in the liver via oral administration. PMID:23529958

  2. An inhalable β₂-adrenoceptor ligand-directed guanidinylated chitosan carrier for targeted delivery of siRNA to lung.

    PubMed

    Luo, Yongfeng; Zhai, Xinyun; Ma, Chaonan; Sun, Peng; Fu, Zhiping; Liu, Wenguang; Xu, Jun

    2012-08-20

    SiRNA-based strategies appear to be an exciting new approach for the treatment of respiratory diseases. To extrapolate siRNA-mediated interventions from bench to bedside in this area, several aspects have to be jointly considered, including a safe and efficient gene carrier with pulmonary deposition efficiency, as well as in vivo method for siRNA/nanoparticles delivery. Accordingly, in this work, (i) a non-viral DNA vector, guanidinylated chitosan (GCS) that has been developed in our previous study [X.Y. Zhai, P. Sun, Y.F. Luo, C.N. Ma, J. Xu, W.G. Liu, 2011], was tested for siRNA delivery. We demonstrated that GCS was able to completely condense siRNA at weight ratio 40:1, forming nanosize particles of diameter ~100 nm, 15 mV in surface potential. Guanidinylation of chitosan not only decreased the cytotoxicity but also facilitated cellular internalization of siRNA nanoparticles, leading to an enhanced gene-silencing efficiency compared to the pristine chitosan (CS). (ii) We chemically coupled salbutamol, a β(2)-adrenoceptor agonist, to GCS (SGCS), which successfully improved targeting specificity of the green fluorescent protein (GFP)-siRNA carrier to lung cells harbored with β(2)-adrenergic receptor, and remarkably enhanced the efficacy of gene silence in vitro and in the lung of enhanced green fluorescent protein (EGFP)-transgenic mice in vivo. (iii) It was proved that this chitosan-based polymer was able to provide both the pDNA and siRNA with the protection against destructive shear forces generated by the mesh-based nebulizers. Aerosol treatment improved the nanoparticle size distribution, which should be in favor of enhancing the transfection efficiency. We suggest a potential application of the chitosan-derived nanodelivery vehicle (SGCS) in RNA interference therapy for lung diseases via aerosol inhalation. PMID:22698944

  3. Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell-targeting molecular transporter.

    PubMed

    El-Sayed, Naglaa S; Shirazi, Amir N; El-Meligy, Magda G; El-Ziaty, Ahmed K; Nagieb, Zenat A; Parang, Keykavous; Tiwari, Rakesh K

    2016-06-01

    Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using sulfo-SMCC as a bifunctional linker to afford COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, (1)H NMR, (13)C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of a cell-impermeable cargo (e.g., F'-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338nm, and zeta potential of 12.2-18.3mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs. PMID:26976071

  4. Intranasal Piperine-Loaded Chitosan Nanoparticles as Brain-Targeted Therapy in Alzheimer's Disease: Optimization, Biological Efficacy, and Potential Toxicity.

    PubMed

    Elnaggar, Yosra S R; Etman, Samar M; Abdelmonsif, Doaa A; Abdallah, Ossama Y

    2015-10-01

    Piperine (PIP) is a phytopharmaceutical with reported neuroprotective potential in Alzheimer's disease (AD). Oral PIP delivery suffers from its hydrophobicity and pre-systemic metabolism. In this article, mono-disperse intranasal chitosan nanoparticles (CS-NPs) were elaborated for brain targeting of PIP. Formula optimization was based on particle size (PS), zeta potential (ZP), polydispersity index (PDI), % entrapment efficiency (% EE), release studies, and transmission electron microscopy. AD was induced in 48 male Wistar rats on which full behavioral and biochemical testing was conducted. Brain toxicity was assessed based on Caspase-3 assay for apoptosis and tumor necrosis factor for inflammation. Spherical NPs with optimum % EE (81.70), PS (248.50 nm), PDI (0.24), and ZP (+56.30 mV) were elaborated. PIP-NPs could significantly improve cognitive functions as efficient as standard drug (donpezil injection) with additional advantages of dual mechanism (Ach esterase inhibition and antioxidant effect). CS-NPs could significantly alleviate PIP nasal irritation and showed no brain toxicity. This work was the first to report additional mechanism of PIP in AD via anti-apoptosis and anti-inflammatory effects. To conclude, mucoadhesive CS-NPs were successfully tailored for effective, safe, and non-invasive PIP delivery with 20-folds decrease in oral dose, opening a gate for a future with lower AD morbidity. PMID:26147711

  5. Heparin modification enhances the delivery and tumor targeting of paclitaxel-loaded N-octyl-N-trimethyl chitosan micelles.

    PubMed

    Zhang, Feiran; Fei, Jia; Sun, Minjie; Ping, Qineng

    2016-09-10

    Polycations have been widely used as efficient drug and gene carriers. However, the further application of polycation nanocarriers is greatly hampered by the serious cytotoxicity caused by exposed positive charges. Despite recent progress towards the therapeutic delivery of nucleic acids, there remains a compelling need for development of novel delivery systems for various types of drug. Here, we created mixed micelles based on N-octyl-N-trimethyl chitosan (OTMC) and coated them with an anionic polymer for delivery of paclitaxel (PTX). OTMC/PEG-100 stearate (S-100) micelles (PTX-SN) were firstly prepared by a dialysis method with a high drug loading efficiency and positive charge. PTX-SN micelles were then coated with two anionic polymers, heparin sodium (PTX-HSN) and sodium carboxymethyl cellulose (PTX-CSN) to shield positive charges. Both PTX-HSN and PTX-CSN micelles showed decreased cytotoxicity and hemolysis while retaining high uptake efficiency. PTX-HSN micelles were taken up more effectively than PTX-CSN by HeLa cells, which over-express heparanase. PTX-HSN micelles persisted longer in the circulation of rats than free drug in pharmacokinetic studies. DIR-HSN micelles accumulated strongly in tumors, and PTX-HSN micelles significantly inhibited tumor growth in tumor-bearing mice. Overall, the results validate heparin-coated OTMC micelles as safe and effective tumor-targeting carriers that are suitable for anti-tumor drug delivery. PMID:27426109

  6. Delivery of siRNA targeting tumor metabolism using non-covalent PEGylated chitosan nanoparticles: Identification of an optimal combination of ligand structure, linker and grafting method.

    PubMed

    Corbet, Cyril; Ragelle, Héloïse; Pourcelle, Vincent; Vanvarenberg, Kévin; Marchand-Brynaert, Jacqueline; Préat, Véronique; Feron, Olivier

    2016-02-10

    PEGylated chitosan-based nanoparticles offer attractive platforms for siRNA cocktail delivery into tumors. Still, therapeutic efficacy requires us to select a rational combination of siRNAs and an efficient tumor delivery after systemic administration. Here, we showed that non-covalent PEGylation of chitosan-based nanoparticles loaded with siRNA targeting two key transporters of energy fuels for cancer cells, namely the lactate transporter MCT1 and the glutamine transporter ASCT2, could lead to significant antitumor effects. As a ligand, we tested variations of the prototypical RGD peptidomimetic (RGDp). A higher siRNA delivery was obtained with naphthyridine-containing RGDp randomly conjugated on the PEG chain by clip photochemistry and the use of a lipophilic linker than when using traditional chain-end grafting and RGDp with a hydrophilic linker. The antiproliferative effects resulting from ASCT2 and MCT1 silencing were validated separately in vitro in conditions mimicking specific metabolic profiles of cancer cells and in vivo upon concomitant delivery. The combination of those siRNA and the selected components of targeted RGDp nanoparticles led to a dramatic tumor growth inhibition upon peri-tumoral but also systemic administration in mice. Altogether these data emphasize the convenience of using non-covalent PEGylated chitosan particles to produce sheddable stealth protection compatible with an efficient siRNA delivery in tumors. PMID:26699426

  7. Fabrication of nano-mosquitocides using chitosan from crab shells: Impact on non-target organisms in the aquatic environment.

    PubMed

    Murugan, Kadarkarai; Anitha, Jaganathan; Dinesh, Devakumar; Suresh, Udaiyan; Rajaganesh, Rajapandian; Chandramohan, Balamurugan; Subramaniam, Jayapal; Paulpandi, Manickam; Vadivalagan, Chitravel; Amuthavalli, Pandiyan; Wang, Lan; Hwang, Jiang-Shiou; Wei, Hui; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Kumar, Suresh; Pugazhendy, Kannaiyan; Higuchi, Akon; Nicoletti, Marcello; Benelli, Giovanni

    2016-10-01

    Mosquitoes are arthropods of huge medical and veterinary relevance, since they vector pathogens and parasites of public health importance, including malaria, dengue and Zika virus. Currently, nanotechnology is considered a potential eco-friendly approach in mosquito control research. We proposed a novel method of biofabrication of silver nanoparticles (AgNP) using chitosan (Ch) from crab shells. Ch-AgNP nanocomposite was characterized by UV-vis spectroscopy, FTIR, SEM, EDX and XRD. Ch-AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi obtaining LC50 ranging from 3.18 ppm (I) to 6.54 ppm (pupae). The antibacterial properties of Ch-AgNP were proved against Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi, while no growth inhibition was reported in assays conducted on Proteus vulgaris. Concerning non-target effects, in standard laboratory considtions the predation efficiency of Danio rerio zebrafishes was 68.8% and 61.6% against I and II instar larvae of A. stephensi, respectively. In a Ch-AgNP-contaminated environment, fish predation was boosted to 89.5% and 77.3%, respectively. Quantitative analysis of antioxidant enzymes SOD, CAT and LPO from hepatopancreas of fresh water crabs Paratelphusa hydrodromous exposed for 16 days to a Ch-AgNP-contaminated aquatic environment were conducted. Notably, deleterious effects of Ch-AgNP contaminating aquatic enviroment on the non-target crab P. hydrodromous were observed, particularly when doses higher than 8-10ppm are tested. Overall, this research highlights the potential of Ch-AGNP for the development of newer control tools against young instar populations of malaria mosquitoes, also highlighting some risks concerned the employ of nanoparticles in aquatic environments. PMID:27344400

  8. Carbon Dots Embedded Magnetic Nanoparticles @Chitosan @Metal Organic Framework as a Nanoprobe for pH Sensitive Targeted Anticancer Drug Delivery.

    PubMed

    Chowdhuri, Angshuman Ray; Singh, Tanya; Ghosh, Sudip Kumar; Sahu, Sumanta Kumar

    2016-07-01

    Recently, nanoscale metal organic frameworks (NMOFs) have been demonstrated as a promising carrier for drug delivery, as they possess many advantages like large surface area, high porosity, and tunable functionality. However, there are no reports about the functionalization of NMOFs, which combines cancer-targeted drug delivery/imaging, magnetic property, high drug loading content, and pH-sensitive drug release into one system. Existing formulations for integrating target molecules into NMOF are based on multistep synthetic processes. However, in this study, we report an approach that combines NMOF (IRMOF-3) synthesis and target molecule (Folic acid) encapsulation on the surface of chitosan modified magnetic nanoparticles in a single step. A noticeable feature of chitosan is control and pH responsive drug release for several days. More importantly, doxorubicin (DOX) was incorporated into magnetic NMOF formulation and showed high drug loading (1.63 g DOX g(-1) magnetic NMOFs). To demonstrate the optical imaging, carbon dots (CDs) are encapsulated into the synthesized magnetic NMOF, thereby endowing fluorescence features to the nanoparticles. These folate targeted magnetic NMOF possess more specific cellular internalization toward folate-overexpressed cancer (HeLa) cells in comparison to normal (L929) cells. PMID:27305490

  9. Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.

    PubMed

    Abdelghany, Sharif M; Schmid, Daniela; Deacon, Jill; Jaworski, Jakub; Fay, Francois; McLaughlin, Kirsty M; Gormley, Julie A; Burrows, James F; Longley, Daniel B; Donnelly, Ryan F; Scott, Christopher J

    2013-02-11

    meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles of 560 nm in diameter entrapping 9.1 μg of TMP per mg of formulation were produced and examined in cell-based assays. These particles were endocytosed into human colorectal carcinoma HCT116 cells and elicited a more potent photocytotoxic effect than free drug. Antibodies targeting death receptor 5 (DR5), a cell surface apoptosis-inducing receptor up-regulated in various types of cancer and found on HCT116 cells, were then conjugated onto the particles. The conjugated antibodies further enhanced uptake and cytotoxic potency of the nanoparticle. Taken together, these results show that antibody-conjugated chitosan/alginate nanoparticles significantly enhanced the therapeutic effectiveness of entrapped TMP. This novel approach provides a strategy for providing targeted site-specific delivery of TMP and other photosensitizer drugs to treat colorectal tumors using PDT. PMID:23327610

  10. Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles: A mechanistic insight.

    PubMed

    Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent; Vanvarenberg, Kevin; Vandermeulen, Gaëlle; Bouzin, Caroline; Marchand-Brynaert, Jacqueline; Feron, Olivier; Foged, Camilla; Préat, Véronique

    2015-08-10

    Integrin-targeted nanoparticles are promising for the delivery of small interfering RNA (siRNA) to tumor cells or tumor endothelium in cancer therapy aiming at silencing genes essential for tumor growth. However, during the process of optimizing and realizing their full potential, it is pertinent to gain a basic mechanistic understanding of the bottlenecks existing for nanoparticle-mediated intracellular delivery. We designed αvβ3 integrin-targeted nanoparticles by coupling arginine-glycine-aspartate (RGD) or RGD peptidomimetic (RGDp) ligands to the surface of poly(ethylene glycol) (PEG) grafted chitosan-poly(ethylene imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by αvβ3-targeted versus non-targeted nanoparticles was quantified in the human non-small cell lung carcinoma cell line H1299 expressing enhanced green fluorescent protein (EGFP) using a stem-loop reverse transcription quantitative polymerase chain reaction (RT-qPCR) approach. Data demonstrated that the internalization of αvβ3-targeted nanoparticles was highly dependent on the surface concentration of the ligand. Above a certain threshold concentration, the use of targeted nanoparticles provided a two-fold increase in the number of siRNA copies/cell, subsequently resulting in as much as 90% silencing of EGFP at well-tolerated carrier concentrations. In contrast, non-targeted nanoparticles mediated low levels of gene silencing, despite relatively high intracellular siRNA concentrations, indicating that these nanoparticles might end up in late endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus, the silencing efficiency of the chitosan-based nanoparticles is strongly dependent on the uptake and the intracellular trafficking in H1299 EGFP cells, which is critical information towards a more complete understanding of the delivery mechanism that can facilitate the future design of efficient siRNA delivery systems. PMID:25989603

  11. In vivo pharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle.

    PubMed

    Rezazadeh, Mahboubeh; Emami, Jaber; Hasanzadeh, Farshid; Sadeghi, Hojjat; Minaiyan, Mohsen; Mostafavi, Abolfazl; Rostami, Mahboubeh; Lavasanifar, Afsaneh

    2016-06-01

    A water-insoluble anti-tumor agent, paclitaxel (PTX) was successfully incorporated into novel-targeted polymeric micelles based on tocopherol succinate-chitosan-polyethylene glycol-folic acid (PTX/TS-CS-PEG-FA). The aim of the present study was to evaluate the pharmacokinetics, tissue distribution and efficacy of PTX/TS-CS-PEG-FA in comparison to Anzatax® in tumor bearing mice. The micellar formulation showed higher in vitro cytotoxicity against mice breast cancer cell line, 4T1, due to the folate receptor-mediated endocytosis. The IC50 value of PTX, a concentration at which 50% cells are killed, was 1.17 and 0.93 µM for Anzatax® and PTX/TS-CS-PEG-FA micelles, respectively. The in vivo anti-tumor efficacy of PTX/TS-CS-PEG-FA, as measured by reduction in tumor volume of 4T1 mouse breast cancer injected in Balb/c mice was significantly greater than that of Anzatax®. Pharmacokinetic study in tumor bearing mice revealed that the micellar formulation prolonged the systemic circulation time of PTX and the AUC of PTX/TS-CS-PEG-FA was obtained 0.83-fold lower than Anzatax®. Compared with Anzatax®, the Vd, T1/2ß and MRT of PTX/TS-CS-PEG-FA was increased by 2.76, 2.05 and 1.68-fold, respectively. As demonstrated by tissue distribution, the PTX/TS-CS-PEG-FA micelles increased accumulation of PTX in tumor, therefore, resulted in anti-tumor effects enhancement and drug concentration in the normal tissues reduction. Taken together, our evaluations show that PTX/TS-CS-PEG-FA micelle is a potential drug delivery system of PTX for the effective treatment of the tumor and systematic toxicity reduction, thus, the micellar formulation can provide a useful alternative dosage form for intravenous administration of PTX. PMID:25188785

  12. 3D Porous Chitosan-Alginate Scaffolds as an In Vitro Model for Evaluating Nanoparticle-Mediated Tumor Targeting and Gene Delivery to Prostate Cancer.

    PubMed

    Wang, Kui; Kievit, Forrest M; Florczyk, Stephen J; Stephen, Zachary R; Zhang, Miqin

    2015-10-12

    Cationic nanoparticles (NPs) for targeted gene delivery are conventionally evaluated using 2D in vitro cultures. However, this does not translate well to corresponding in vivo studies because of the marked difference in NP behavior in the presence of the tumor microenvironment. In this study, we investigated whether prostate cancer (PCa) cells cultured in three-dimensional (3D) chitosan-alginate (CA) porous scaffolds could model cationic NP-mediated gene targeted delivery to tumors in vitro. We assessed in vitro tumor cell proliferation, formation of tumor spheroids, and expression of marker genes that promote tumor malignancy in CA scaffolds. The efficacy of NP-targeted gene delivery was evaluated in PCa cells in 2D cultures, PCa tumor spheroids grown in CA scaffolds, and PCa tumors in a mouse TRAMP-C2 flank tumor model. PCa cells cultured in CA scaffolds grew into tumor spheroids and displayed characteristics of higher malignancy as compared to those in 2D cultures. Significantly, targeted gene delivery was only observed in cells cultured in CA scaffolds, whereas cells cultured on 2D plates showed no difference in gene delivery between targeted and nontarget control NPs. In vivo NP evaluation confirmed targeted gene delivery, indicating that only CA scaffolds correctly modeled NP-mediated targeted delivery in vivo. These findings suggest that CA scaffolds serve as a better in vitro platform than 2D cultures for evaluation of NP-mediated targeted gene delivery to PCa. PMID:26347946

  13. Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

    PubMed Central

    Yu, Xiwei; Yang, Guang; Shi, Yijie; Su, Chang; Liu, Ming; Feng, Bo; Zhao, Liang

    2015-01-01

    Nowadays, multidrug resistance and side effects of drugs limit the effectiveness of chemotherapies in clinics. P-glycoprotein (P-gp) (MDR1), as a member of the ATP-binding cassette family, acts on transporting drugs into cell plasma across the membrane of cancer cells and leads to the occurrence of multidrug resistance, thus resulting in the failure of chemotherapy in cancer. The main aims of this research were to design a nanodelivery system for accomplishing the effective co-delivery of gene and antitumor drug and overcoming multidrug resistance effect. In this study, shMDR1 and gefitinib-encapsulating chitosan nanoparticles with sustained release, small particle size, and high encapsulation efficiency were prepared. The serum stability, protection from nuclease, and transfection efficiency of gene in vitro were investigated. The effects of co-delivery of shMDR1 and gefitinib in nanoparticles on reversing multidrug resistance were also evaluated by investigating the cytotoxicity, cellular uptake mechanism, and cell apoptosis on established gefitinib-resistant cells. The results demonstrated that chitosan nanoparticles entrapping gefitinib and shMDR1 had the potential to overcome the multidrug resistance and improve cancer treatment efficacy, especially toward resistant cells. PMID:26648717

  14. Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery.

    PubMed

    Nam, Joung-Pyo; Park, Seong-Cheol; Kim, Tae-Hun; Jang, Jae-Yeang; Choi, Changyong; Jang, Mi-Kyeong; Nah, Jae-Woon

    2013-11-30

    Transferrin/PEG/O-carboxymethyl chitosan/fatty acid/paclitaxel (TPOCFP) micelles were tested for suitability as a drug carrier characterized by low cytotoxicity, sustained release, high cellular uptake, and site-specific targeted delivery of hydrophobic drugs. Characterization, drug content, encapsulation efficiency, and in vitro drug release were investigated. When the feeding amount of paclitaxel (PTX) was increased, the drug content increased, but loading efficiency decreased. TPOCFP micelles had a spherical shape, with a particle size of approximately 140-649 nm. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the micelles. Anticancer activity and confocal laser scanning microscopy (CLSM) were used to confirm the targeting efficiency of target ligand-modified TPOCFP micelles. Anticancer activity and CLSM results clearly demonstrated that transferrin-modified TPOCFP micelles were quickly taken up by the cell. The endocytic pathway of TPOCFP micelles was analyzed by flow cytometry, revealing transfection via receptor-mediated endocytosis. These results suggest that PTX-encapsulated TPOCFP micelles may be used as an effective cancer-targeting drug delivery system for chemotherapy. PMID:24076228

  15. Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro

    PubMed Central

    2014-01-01

    A synthetic method to prepare a core-shell-structured Fe3O4@SiO2 as a safe nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron oxide is encapsulated inside nonporous silica as the core to provide magnetic targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell and renders new and improved functions because of the original biocompatible properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the nanovehicle was assayed by confocal laser scanning microscope using rhodamine B (RB) as a fluorescent marker in HeLa cells. The results show that the surface modification of the core-shell silica nanovehicle with OCMCS-FA enhances the internalization of nanovehicle to HeLa cells which over-express the folate receptor. The cell viability assay demonstrated that Fe3O4@SiO2-OCMCS-FA nanovehicle has low toxicity and can be used as an eligible candidate for drug delivery system. These unique advantages make the prepared core-shell nanovehicle promising for cancer-specific targeting and therapy. PMID:24667013

  16. Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain.

    PubMed

    Saito, Ryuta; Krauze, Michal T; Bringas, John R; Noble, Charles; McKnight, Tracy R; Jackson, Pamela; Wendland, Michael F; Mamot, Christoph; Drummond, Daryl C; Kirpotin, Dimitri B; Hong, Keelung; Berger, Mitchel S; Park, John W; Bankiewicz, Krystof S

    2005-12-01

    Drug delivery to brain tumors has long posed a major challenge. Convection-enhanced delivery (CED) has been developed as a drug delivery strategy to overcome this difficulty. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain. We previously developed a magnetic resonance imaging (MRI)-based method to visualize the distribution of liposomal agents after CED in rodent brains. In the present study, CED of liposomes was further examined in the non-human primate brain (n = 6). Liposomes containing Gadoteridol, DiI-DS, and rhodamine were infused in corona radiata, putamen nucleus, and brain stem. Volume of distribution was analyzed for all delivery locations by histology and MR imaging. Real-time MRI monitoring of liposomes containing gadolinium allowed direct visualization of a robust distribution. MRI of liposomal gadolinium was highly accurate at determining tissue distribution, as confirmed by comparison with histological results from concomitant administration of fluorescent liposomes. Linear correlation for liposomal infusions between infusion volume and distribution volume was established in all targeted locations. We conclude that an integrated strategy combining liposome/nanoparticle technology, CED, and MRI may provide new opportunities for the treatment of brain tumors. Our ability to directly monitor and to control local delivery of liposomal drugs will most likely result in greater clinical efficacy when using CED in management of patients. PMID:16197944

  17. Characterization of a Conjugate between Rose Bengal and Chitosan for Targeted Antibiofilm and Tissue Stabilization Effects as a Potential Treatment of Infected Dentin

    PubMed Central

    Shrestha, Annie; Hamblin, Michael R.

    2012-01-01

    Bacterial biofilms and dentin structural changes are some of the major challenges in the management of infected dentin tissue. This study characterized a photosensitizer-conjugated chitosan with enhanced photodynamic efficacy against dental biofilms, as well as the ability to reinforce the postinfected dentin matrix in order to improve its mechanical and chemical stability. Rose Bengal-conjugated chitosan (CSRB) was synthesized using a chemical cross-linking method and characterized for photophysical, photobiological, and cytotoxicity properties. Its potential as an antibacterial and matrix-reinforcing agent on dentin collagen was also evaluated. Enterococcus faecalis as planktonic and in vitro biofilms was treated with CSRB and photodynamically activated with 5 to 60 J/cm2 green light. Dentin collagen was used for the CSRB cross-linking experiments and evaluated for chemical changes, resistance to enzymatic degradation, and mechanical properties. CSRB was a photosensitizer with efficient singlet oxygen yield. In vitro photoactivation gave higher fibroblast cell survival than did RB alone. CSRB showed significant antibiofilm photoinactivation (P < 0.01). The CSRB-cross-linked dentin collagen showed higher resistance to collagenase degradation and superior mechanical properties (P < 0.05). In summary, the photoactivated CSRB particles synthesized in this study may be a synergistic multifunctional treatment approach with lower cytotoxicity and effective antibiofilm activity as well as the ability to reinforce the dentin collagen to enhance resistance to degradation and improve mechanical properties. This may be a targeted treatment strategy to deal with infected dentin hard tissues in a clinical scenario, where both disinfection and structural integrity need to be addressed concomitantly. PMID:22777042

  18. 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

  19. Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes

    PubMed Central

    Ofokansi, Kenneth Chibuzor; Kenechukwu, Franklin Chimaobi

    2013-01-01

    Colon-targeted drug delivery systems (CTDDSs) could be useful for local treatment of inflammatory bowel diseases (IBDs). In this study, various interpolyelectrolyte complexes (IPECs), formed between Eudragit RL100 (EL) and chitosan (CS), by nonstoichiometric method, and tablets based on the IPECs, prepared by wet granulation, were evaluated as potential oral CTDDSs for ibuprofen (IBF). Results obtained showed that the tablets conformed to compendial requirements for acceptance and that CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of IBF from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (–CO–) group of EL and amino (–NH3+) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released IBF in a zero-order manner. IPECs based on CS and EL could be exploited successfully for colon-targeted delivery of IBF in the treatment of IBDs. PMID:23986877

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

    PubMed

    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

  1. 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 Central

    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. PMID:22267927

  2. Redox targeting of DNA anchored to MWCNTs and TiO2 nanoparticles dispersed in poly dialyldimethylammonium chloride and chitosan.

    PubMed

    Ensafi, Ali A; Nasr-Esfahani, Parisa; Heydari-Bafrooei, Esmaeil; Rezaei, B

    2014-09-01

    A key issue associated with electrochemical DNA-based biosensors is how to enhance DNA immobilization on the substrates. In order to improve the immobilization of DNA and to optimize DNA interaction efficiency, different kinds of strategies have been developed. In this regard, nanomaterials have attracted a great deal of attention in electrode surface modification for DNA biosensor fabrication. In this study, nanostructured films were deposited at the surface of a pencil graphite electrode (PGE) as a working electrode. For the present purpose, common polyelectrolytes are used for surface modification with double-stranded DNA. Two positively charged polyelectrolyte, namely poly dialyldimethylammonium chloride (PDDA) and chitosan, are initially compared for DNA immobilization at the surface of MWCNTs and TiO2 nanoparticles (TiO2NPs). In a second step, the basic electrochemical properties of the sensors are investigated using voltammetric methods. The modified electrodes are also characterized by scanning electron microscopy and electrochemical impedance measurements. It will be shown that electrode modification with DNA and the nanostructure that disperses in PDDA leads to an enhanced sensitivity of the DNA voltammetric detection mechanism. In a previous study, a comparison was done between MWCNTs and TiO2NPs for determining the effect of nanoparticle effect on DNA immobilization on the electrode surface. In order to compare the efficiency of the prepared DNA-based biosensors, methylene blue is chosen as an electroactive probe. It will be shown that the stability of the immobilized DNA within several days will be much higher when MWCNTs rather than TiO2NPs are used. PMID:24952239

  3. Transient aggregation of chitosan-modified poly(d,l-lactic-co-glycolic) acid nanoparticles in the blood stream and improved lung targeting efficiency.

    PubMed

    Lee, Song Yi; Jung, Eunjae; Park, Ju-Hwan; Park, Jin Woo; Shim, Chang-Koo; Kim, Dae-Duk; Yoon, In-Soo; Cho, Hyun-Jong

    2016-10-15

    Chitosan (CS)-modified poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were prepared and their lung targetability after intravenous administration was elucidated. PLGA NPs (mean diameter: 225nm; polydispersity index: 0.11; zeta potential: -15mV), 0.2% (w/v) CS-coated PLGA NPs (CS02-PLGA NPs, mean diameter: 264nm; polydispersity index: 0.17; zeta potential: -7mV), and 0.5% (w/v) CS-coated PLGA NPs (CS05-PLGA NPs, mean diameter: 338nm; polydispersity index: 0.23; zeta potential: 12mV) were fabricated by a modified solvent evaporation method. PLGA NPs maintained their initial particle size in different media, such as human serum albumin (HSA) solution, rat plasma, and distilled water (DW), while CS05-PLGA NPs exhibited the formation of aggregates in early incubation time and disassembly of those into the NPs in late incubation time (at 24h). According to the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the binding affinity of CS05-PLGA NPs with HSA and rat plasma was higher than that of PLGA NPs. By a near-infrared fluorescence (NIRF) imaging test in the mouse, the selective accumulation of CS05-PLGA NPs, rather than PLGA NPs, in lung tissue was demonstrated. These findings suggest that CS05-PLGA NPs can form transient aggregates in the blood stream after intravenous administration and markedly improve lung targeting efficiency, compared with PLGA NPs. PMID:27421112

  4. Chronotherapeutic drug delivery of Tamarind gum, Chitosan and Okra gum controlled release colon targeted directly compressed Propranolol HCl matrix tablets and in-vitro evaluation.

    PubMed

    Newton, A M J; Indana, V L; Kumar, Jatinder

    2015-08-01

    The main objective of this investigation is to develop a chronotherapeutic drug delivery of various natural polymers based colon targeted drug delivery systems to treat early morning sign in BP. The polymers such as Tamarind gum, Okra gum and Chitosan were used in the formulation design. A model drug Propranolol HCl was incorporated in the formulation in order to assess the controlled release and time dependent release potential of various natural polymers. A novel polymer Tamarind gum was extracted and used as a prime polymer in this study to prove the superiority of this polymer over other leading natural polymer. Propranolol HCl was used as a model drug which undergoes hepatic metabolism and witnesses the poor bioavailability. The matrix tablets of Propranolol HCl were prepared by direct compression. The tablets were evaluated for various quality control parameters and found to be within the limits. Carbopol 940 was used as an auxiliary polymer to modify the drug release and physicochemical characteristics of the tablets. The in vitro release studies were performed in 0.1N HCl for 1.5h, followed by pH 6.8 phosphate buffer for 2h and pH 7.4 phosphate buffer till maximum amount of drug release. The in vitro release profile of the formulations were fitted with various pharmacokinetic mathematical models and analyzed for release profile. The formulations prepared with Tamarind gum prolonged the release for an extended period of time compared to other polymer based formulation and showed an excellent compression characteristic. PMID:25936283

  5. Bioinspired Titanium Drug Eluting Platforms Based on a Poly-β-cyclodextrin-Chitosan Layer-by-Layer Self-Assembly Targeting Infections.

    PubMed

    Pérez-Anes, Alexandra; Gargouri, Myriem; Laure, William; Van Den Berghe, Hélène; Courcot, Elisabeth; Sobocinski, Jonathan; Tabary, Nicolas; Chai, Feng; Blach, Jean-François; Addad, Ahmed; Woisel, Patrice; Douroumis, Dennis; Martel, Bernard; Blanchemain, Nicolas; Lyskawa, Joël

    2015-06-17

    In the field of implantable titanium-based biomaterials, infections and inflammations are the most common forms of postoperative complications. The controlled local delivery of therapeutics from implants through polyelectrolyte multilayers (PEMs) has recently emerged as a versatile technique that has shown great promise in the transformation of a classical medical implant into a drug delivery system. Herein, we report the design and the elaboration of new biodegradable multidrug-eluting titanium platforms based on a polyelectrolyte multilayer bioactive coating that target infections. These systems were built up in mild conditions according to the layer-by-layer (L-b-L) assembly and incorporate two biocompatible polysaccharides held together through electrostatic interactions. A synthetic, negatively charged β-cyclodextrin-based polymer (PCD), well-known for forming stable and reversible complexes with hydrophobic therapeutic agents, was exploited as a multidrug reservoir, and chitosan (CHT), a naturally occurring, positively charged polyelectrolyte, was used as a barrier for controlling the drug delivery rate. These polyelectrolyte multilayer films were strongly attached to the titanium surface through a bioinspired polydopamine (PDA) film acting as an adhesive first layer and promoting the robust anchorage of PEMs onto the biomaterials. Prior to the multilayer film deposition, the interactions between both oppositely charged polyelectrolytes, as well the multilayer growth, were monitored by employing surface plasmon resonance (SPR). Several PEMs integrating 5, 10, and 15 bilayers were engineered using the dip coating strategy, and the polyelectrolyte surface densities were estimated by colorimetric titrations and gravimetric analyses. The morphologies of these multilayer systems, as well as their naturally occurring degradation in a physiological medium, were investigated by scanning electron microscopy (SEM), and their thicknesses were measured by means of

  6. Chitosan/siRNA nanoparticle targeting demonstrates a requirement for single-minded during larval and pupal olfactory system development of the vector mosquito Aedes aegypti

    PubMed Central

    2014-01-01

    Background Essentially nothing is known about the genetic regulation of olfactory system development in vector mosquitoes, which use olfactory cues to detect blood meal hosts. Studies in Drosophila melanogaster have identified a regulatory matrix of transcription factors that controls pupal/adult odorant receptor (OR) gene expression in olfactory receptor neurons (ORNs). However, it is unclear if transcription factors that function in the D. melanogaster regulatory matrix are required for OR expression in mosquitoes. Furthermore, the regulation of OR expression during development of the larval olfactory system, which is far less complex than that of pupae/adults, is not well understood in any insect, including D. melanogaster. Here, we examine the regulation of OR expression in the developing larval olfactory system of Aedes aegypti, the dengue vector mosquito. Results A. aegypti bears orthologs of eight transcription factors that regulate OR expression in D. melanogaster pupae/adults. These transcription factors are expressed in A. aegypti larval antennal sensory neurons, and consensus binding sites for these transcription factors reside in the 5’ flanking regions of A. aegypti OR genes. Consensus binding sites for Single-minded (Sim) are located adjacent to over half the A. aegypti OR genes, suggesting that this transcription factor functions as a major regulator of mosquito OR expression. To functionally test this hypothesis, chitosan/siRNA nanoparticles were used to target sim during larval olfactory development. These experiments demonstrated that Sim positively regulates expression of a large subset of OR genes, including orco, the obligate co-receptor in the assembly and function of heteromeric OR/Orco complexes. Decreased innervation of the antennal lobe was also noted in sim knockdown larvae. These OR expression and antennal lobe defects correlated with a larval odorant tracking behavioral defect. OR expression and antennal lobe defects were also

  7. Data on synthesis and characterization of chitosan nanoparticles for in vivo delivery of siRNA-Npr3: Targeting NPR-C expression in the heart.

    PubMed

    Venkatesan, Balaji; Tumala, Anusha; Subramanian, Vimala; Vellaichamy, Elangovan

    2016-09-01

    This data article contains the data related to the research article 'Transient silencing of Npr3 gene expression improved the circulatory levels of atrial natriuretic peptides and attenuated β-adrenoceptor activation-induced cardiac hypertrophic growth in experimental rats' (Venkatesan et al., 2016 [1]). The siRNA-Npr3 loaded chitosan nanoparticles were synthesized using ionotropic gelation method, where the positive charge of the chitosan interacts with the negative charge of STPP and siRNA-Npr3. The physicochemical properties of the synthesized siRNA-Npr3 loaded chitosan nanoparticles were studied by dynamic light scattering, FE-SEM and HR-TEM analysis. In addition, the loading efficiency and stability of the nanoparticles were also studied. Further, the gene silencing efficacy, hemocompatibility and biocompatibility were studied using Wistar rats (in vivo), isolated red blood cells and H9c2 cardiomyoblast cells, respectively. PMID:27366782

  8. Chitosan: a propitious biopolymer for drug delivery.

    PubMed

    Duttagupta, Dibyangana S; Jadhav, Varsha M; Kadam, Vilasrao J

    2015-01-01

    Scientists have always been interested in the use of natural polymers for drug delivery. Chitosan, being a natural cationic polysaccharide has received a great deal of attention in the past few years. It is obtained by deacetylation of chitin and is regarded as the second most ubiquitous polymer subsequent to cellulose on earth. Unlike other natural polymers, the cationic charge possessed by chitosan is accountable for imparting interesting physical and chemical properties. Chitosan has been widely exploited for its mucoadhesive character, permeation enhancing properties and controlled release of drugs. Moreover it's non-toxic, biocompatible and biodegradable properties make it a good candidate for novel drug delivery system. This review provides an insight on various chitosan based formulations for drug delivery. Some of the current applications of chitosan in areas like ophthalmic, nasal, buccal, sublingual, gastro-retentive, pulmonary, transdermal, colon-specific and vaginal drug delivery have been discussed. In addition, active targeting of drugs to tumor cells using chitosan has been described. Lastly a brief section covering the safety aspects of chitosan has also been reviewed. PMID:25761010

  9. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

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

  10. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery.

    PubMed

    Islam, Nazrul; Ferro, Vito

    2016-08-14

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed. PMID:27439116

  11. Spray Freeze-Drying as an Alternative to the Ionic Gelation Method to Produce Chitosan and Alginate Nano-Particles Targeted to the Colon.

    PubMed

    Gamboa, Alexander; Araujo, Valeria; Caro, Nelson; Gotteland, Martin; Abugoch, Lilian; Tapia, Cristian

    2015-12-01

    Chitosan and alginate nano-composite (NP) carriers intended for colonic delivery containing prednisolone and inulin were obtained by two processes. Spray freeze-drying using chitosan (SFDC) or alginate (SFDA) was proposed as an alternative to the traditional chitosan-tripolyphosphate platform (CTPP). NPs were fully characterised and assessed for their yield of particles; level of prednisolone and inulin release in phosphate and Krebs buffers; and sensitivity to degradation by lysozyme, bacteria and faecal slurry. NPs based on chitosan showed similar properties (size, structure, viscoelastic behaviour), but those based on SFDC showed a higher mean release of both active ingredients, with similar efficiency of encapsulation and loading capacity for prednisolone but lower for inulin. SFDC was less degraded in the presence of lysozyme and E. coli and was degraded by B. thetaiotaomicron but not by faecal slurry. The results obtained with SFDA were promising because this NP showed good encapsulation parameters for both active ingredients and biological degradability by E. coli and faecal slurry. However, it will be necessary to use alginate derivatives to reduce its solubility and improve its mechanical behaviour. PMID:26305273

  12. Immunoadjuvant properties of chitosan.

    PubMed

    Marcinkiewicz, J; Polewska, A; Knapczyk, J

    1991-01-01

    Adjuvant activity of water insoluble chitosan suspension was examined in CBA mice. Among different types of immune reaction only T-dependent humoral response against SRBC was enhanced by injection of chitosan. The optimal conditions of administration of both agents (antigen-SRBC, adjuvant-chitosan) was established. PMID:1804042

  13. Chitosan and radiation chemistry

    NASA Astrophysics Data System (ADS)

    Chmielewski, Andrzej G.

    2010-03-01

    Chitosan as a raw material with special properties has drawn attention of scientists working in the field of radiation processing and natural polymer products development, and also of specialists working in the field of radiation protection and oncologists. Especially the applications concern reduced molecular weight chitosan which still retain its chemical structure; such form of the compound is fostering biological, physical and chemical reactivity of the product. Chitosan degrades into fragments under γ-ray or electron beam irradiation. Antibacterial properties of the product are applied in manufacturing hydrogel for wound dressing and additional healing properties can be achieved by incorporating in the hydrogel matrix chitosan bonded silver clusters. Another possible application of chitosan is in reducing radiation damage to the radiation workers or radiation cured patients. In the case of radioisotopes oral or respiratory chitosan-based materials can be applied as chelators. Applications of chitosan in oncology are also reported.

  14. 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

  15. Preparation of chitosan gel

    NASA Astrophysics Data System (ADS)

    Moussaoui, Y.; Mnasri, N.; Elaloui, E.; Ben Salem, R.; Lagerge, S.; de Menorval, L. C.

    2012-06-01

    Aerogel conditioning of the chitosan makes it possible to prepare porous solids of significant specific surface. The increase in the chitosan concentration or the degree of acetylation decreases the specific surface of the synthesized chitosan gel. Whereas drying with supercritical CO2 more effectively makes it possible to preserve the volume of the spheres of gel and to have a more significant specific surface in comparison with evaporative drying.

  16. Preparation of magnetite-chitosan/methylcellulose nanospheres by entrapment and adsorption techniques for targeting the anti-cancer drug 5-fluorouracil.

    PubMed

    Şanlı, Oya; Kahraman, Aslı; Kondolot Solak, Ebru; Olukman, Merve

    2016-05-01

    In this work, we have formulated novel nanospheres that could be used in the controlled release of the anticancer drug, 5-fluorouracil (5-FU). The nanospheres are composed of magnetite, containing chitosan (CS) and methylcellulose (MC). The drug entrapment was achieved through the encapsulation and adsorption processes. The effects of the preparation conditions, such as magnetite content, CS/MC ratio, crosslinking concentration, exposure time to glutaraldehyde (GA), and the drug/polymer ratio were investigated for both processes. The 5-FU release was found to follow the Fickian mechanism, and the Langmuir isotherm for the nanospheres was achieved through encapsulation and adsorption processes, respectively. PMID:25677468

  17. Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells.

    PubMed

    Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Xu, Ronald X; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2015-12-01

    Dual responsive nanoparticles are developed for co-delivery of multiple anticancer drugs to target the drug resistance mechanisms of cancer stem-like cells (CSCs). The nanoparticles consist of four polymers approved by the Food and Drug Administration (FDA) for medical use: Poly(d,l-lactide-co-glycolide) (PLGA), Pluronic F127 (PF127), chitosan, and hyaluronic acid (HA). By combining PLGA and PF127 together, more stable and uniform-sized nanoparticles can be obtained than using PLGA or PF127 alone. The HA is used for not only actively targeting CSCs to reduce their drug resistance due to dormancy (i.e., slow metabolism), but also replacing the commonly used poly(vinyl alcohol) as a stabilizing agent to synthesize the nanoparticles using the double-emulsion approach and to allow for acidic pH-triggered drug release and thermal responsiveness. Besides minimizing drug efflux from CSCs, the nanoparticles encapsulated with doxorubicin hydrochloride (DOX, hydrophilic) and irinotecan (CPT, hydrophobic) to inhibit the activity of topoisomerases II and I, respectively, can fight against the CSC drug resistance associated with their enhanced DNA repair and anti-apoptosis. Ultimately, the two drugs-laden nanoparticles can be used to efficiently destroy the CSCs both in vitro and in vivo with up to ∼500 times of enhancement compared to the simple mixture of the two drugs. PMID:26344365

  18. A review on chitosan-based adsorptive membranes.

    PubMed

    Salehi, Ehsan; Daraei, Parisa; Arabi Shamsabadi, Ahmad

    2016-11-01

    Membrane adsorbents have emerged as powerful and attractive tools for the removal of hazardous materials such as dyes and heavy metal ions, mainly in trace amounts, from water resources. Among membrane adsorbents, those prepared from or modified with chitosan biopolymer and its derivatives are cases of interest because of chitosan advantages including biocompatibility, biodegradability, nontoxicity, reactivity, film and fiber forming capacity and favorable hydrophilicity. This review is oriented to provide a framework for better insight into fabrication methods and applications of chitosan-based adsorptive membranes. Critical aspects including thermokinetic analyses of adsorption and regeneration capacity of the membrane adsorbents have been also overviewed. Future of chitosan-based adsorptive membranes might include efforts for the improvement of mechanical stability and reusability and also most targeted application of appropriate copolymers as well as nanostructures in preparing high performance adsorptive membranes. PMID:27516289

  19. Chitosan-transition metal ions complexes for selective arsenic(V) preconcentration.

    PubMed

    Shinde, Rakesh N; Pandey, A K; Acharya, R; Guin, R; Das, S K; Rajurkar, N S; Pujari, P K

    2013-06-15

    Chitosan is naturally occurring bio-polymer having strong affinity towards transition metal ions. Chitosan complexed with transition metal ions takes up inorganic arsenic anions from aqueous medium. In present work, As(V) sorption in the chitosan complexed with different metal ions like Cu(II), Fe(III), La(III), Mo(VI) and Zr(IV) were studied. Sorptions of As(V) in CuS embedded chitosan, (3-aminopropyl) triethoxysilane (APTS) embedded chitosan, epichlorohydrin (ECH) crosslinked chitosan and pristine chitosan were also studied. (74)As radiotracer was prepared specifically for As(V) sorption studies by irradiation of natural germanium target with 18 MeV proton beam. The sorption studies indicated that Fe(III) and La(III) complexed with chitosan sorbed 95 ± 2% As(V) from aqueous samples in the pH range of 3-9. However, Fe(III)-chitosan showed better sorption efficiency (91 ± 2%) for As(V) from seawater than La(III)-chitosan (80 ± 2%). Therefore, Fe(III)-chitosan was selected to prepare the self-supported membrane and poly(propylene) fibrous matrix supported sorbent. The experimental As(V) sorption capacities of the fibrous and self-supported Fe(III)-chitosan sorbents were found to be 51 and 109 mg g(-1), respectively. These materials were characterized by XRD, SEM and EDXRF, and used for preconcentration of As(V) in aqueous media like tap water, ground water and seawater. To quantify the As(V) preconcentrated in Fe(III)-chitosan, the samples were subjected to instrumental neutron activation analysis (INAA) using reactor neutrons. As(V) separations were carried out using a two compartments permeation cell for the self-supported membrane and flow cell using the fibrous sorbent. The total preconcentration of arsenic content was also explored by converting As(III) to As(V). PMID:23622983

  20. Applications of chitosan nanoparticles in drug delivery.

    PubMed

    Tajmir-Riahi, H A; Nafisi, Sh; Sanyakamdhorn, S; Agudelo, D; Chanphai, P

    2014-01-01

    We have reviewed the binding affinities of several antitumor drugs doxorubicin (Dox), N-(trifluoroacetyl) doxorubicin (FDox), tamoxifen (Tam), 4-hydroxytamoxifen (4-Hydroxytam), and endoxifen (Endox) with chitosan nanoparticles of different sizes (chitosan-15, chitosan-100, and chitosan-200 KD) in order to evaluate the efficacy of chitosan nanocarriers in drug delivery systems. Spectroscopic and molecular modeling studies showed the binding sites and the stability of drug-polymer complexes. Drug-chitosan complexation occurred via hydrophobic and hydrophilic contacts as well as H-bonding network. Chitosan-100 KD was the more effective drug carrier than the chitosan-15 and chitosan-200 KD. PMID:24567139

  1. DNA/chitosan electrostatic complex.

    PubMed

    Bravo-Anaya, Lourdes Mónica; Soltero, J F Armando; Rinaudo, Marguerite

    2016-07-01

    Up to now, chitosan and DNA have been investigated for gene delivery due to chitosan advantages. It is recognized that chitosan is a biocompatible and biodegradable non-viral vector that does not produce immunological reactions, contrary to viral vectors. Chitosan has also been used and studied for its ability to protect DNA against nuclease degradation and to transfect DNA into several kinds of cells. In this work, high molecular weight DNA is compacted with chitosan. DNA-chitosan complex stoichiometry, net charge, dimensions, conformation and thermal stability are determined and discussed. The influence of external salt and chitosan molecular weight on the stoichiometry is also discussed. The isoelectric point of the complexes was found to be directly related to the protonation degree of chitosan. It is clearly demonstrated that the net charge of DNA-chitosan complex can be expressed in terms of the ratio [NH3(+)]/[P(-)], showing that the electrostatic interactions between DNA and chitosan are the main phenomena taking place in the solution. Compaction of DNA long chain complexed with low molar mass chitosan gives nanoparticles with an average radius around 150nm. Stable nanoparticles are obtained for a partial neutralization of phosphate ionic sites (i.e.: [NH3(+)]/[P(-)] fraction between 0.35 and 0.80). PMID:27050113

  2. Chitosan in Plant Protection

    PubMed Central

    El Hadrami, Abdelbasset; Adam, Lorne R.; El Hadrami, Ismail; Daayf, Fouad

    2010-01-01

    Chitin and chitosan are naturally-occurring compounds that have potential in agriculture with regard to controlling plant diseases. These molecules were shown to display toxicity and inhibit fungal growth and development. They were reported to be active against viruses, bacteria and other pests. Fragments from chitin and chitosan are known to have eliciting activities leading to a variety of defense responses in host plants in response to microbial infections, including the accumulation of phytoalexins, pathogen-related (PR) proteins and proteinase inhibitors, lignin synthesis, and callose formation. Based on these and other proprieties that help strengthen host plant defenses, interest has been growing in using them in agricultural systems to reduce the negative impact of diseases on yield and quality of crops. This review recapitulates the properties and uses of chitin, chitosan, and their derivatives, and will focus on their applications and mechanisms of action during plant-pathogen interactions. PMID:20479963

  3. Tight junction modulation by chitosan nanoparticles: comparison with chitosan solution.

    PubMed

    Vllasaliu, Driton; Exposito-Harris, Ruth; Heras, Angeles; Casettari, Luca; Garnett, Martin; Illum, Lisbeth; Stolnik, Snow

    2010-11-15

    Present work investigates the potential of chitosan nanoparticles, formulated by the ionic gelation with tripolyphosphate (TPP), to open the cellular tight junctions and in doing so, improve the permeability of model macromolecules. A comparison is made with chitosan solution at equivalent concentrations. Initial work assessed cytotoxicity (through MTS and LDH assays) of chitosan nanoparticles and solutions on Calu-3 cells. Subsequently, a concentration of chitosan nanoparticles and solution exhibiting minimal toxicity was used to investigate the effect on TEER and macromolecular permeability across filter-cultured Calu-3 monolayer. Chitosan nanoparticles and solution were also tested for their effect on the distribution of the tight junction protein, zonnula occludens-1 (ZO-1). Chitosan nanoparticles produced a sharp and reversible decrease in TEER and increased the permeability of two FITC-dextrans (FDs), FD4 (MW 4 kDa) and FD10 (MW 10 kDa), with effects of a similar magnitude to chitosan solution. Chitosan nanoparticles produced changes in ZO-1 distribution similar to chitosan solution, indicating a tight junction effect. While there was no improvement in permeability with chitosan nanoparticles compared to solution, nanoparticles provide the potential for drug incorporation, and hence the possibility for providing controlled drug release and protection from enzymatic degradation. PMID:20727955

  4. Influence of cross-linking agent type and chitosan content on the performance of pectinate-chitosan beads aimed for colon-specific drug delivery.

    PubMed

    Maestrelli, F; Cirri, M; Mennini, N; Bragagni, M; Zerrouk, N; Mura, P

    2012-09-01

    Pectinate-chitosan-beads aimed for colon theophylline delivery have been developed. The effect of zinc or calcium ions as cross-linking agent, and of chitosan concentration on the properties and colon-targeting performance of beads was investigated. Beads were characterized for morphology, entrapment efficiency and mucoadhesion properties. Zn-pectinate-chitosan beads formed a stronger gel network than the Ca-containing ones, enabling a greater entrapment efficiency, which further increased with chitosan content, probably due to polyelectrolyte complexes formation. Transport studies across Caco-2 cells evidenced a significant (p > 0.05) drug permeation increase from all beads with respect to drug alone, attributable to the enhancer and/or mucoadhesion properties of the polymers, and Ca-pectinate-chitosan beads were more effective than the Zn-containing ones. Beads formulated as enteric-coated tablets demonstrated good colon-targeting properties, and no differences were observed in drug-release profiles from Zn- or Ca-pectinate-chitosan beads. Therefore, Ca-pectinate-chitosan beads emerged as the choice formulation, joining colon-targeting specificity with better permeation enhancer power. PMID:22191551

  5. Chitosan and chemically modified chitosan beads for acid dyes sorption.

    PubMed

    Azlan, Kamari; Wan Saime, Wan Ngah; Lai Ken, Liew

    2009-01-01

    The capabilities of chitosan and chitosan-EGDE (ethylene glycol diglycidyl ether) beads for removing Acid Red 37 (AR 37) and Acid Blue 25 (AB 25) from aqueous solution were examined. Chitosan beads were cross-linked with EGDE to enhance its chemical resistance and mechanical strength. Experiments were performed as a function of pH, agitation period and concentration of AR 37 and AB 25. It was shown that the adsorption capacities of chitosan for both acid dyes were comparatively higher than those of chitosan-EGDE. This is mainly because cross-linking using EGDE reduces the major adsorption sites -NH3+ on chitosan. Langmuir isotherm model showed the best conformity compared to Freundlich and BET. The kinetic experimental data agreed very well to the pseudo second-order kinetic model. The desorption study revealed that after three cycles of adsorption and desorption by NaOH and HCl, both adsorbents retained their promising adsorption abilities. FT-IR analysis proved that the adsorption of acid dyes onto chitosan-based adsorbents was a physical adsorption. Results also showed that chitosan and chitosan-EGDE beads were favourable adsorbers and could be employed as low-cost alternatives for the removal of acid dyes in wastewater treatment. PMID:19634439

  6. Insights into the Mode of Action of Chitosan as an Antibacterial Compound▿ †

    PubMed Central

    Raafat, Dina; von Bargen, Kristine; Haas, Albert; Sahl, Hans-Georg

    2008-01-01

    Chitosan is a polysaccharide biopolymer that combines a unique set of versatile physicochemical and biological characteristics which allow for a wide range of applications. Although its antimicrobial activity is well documented, its mode of action has hitherto remained only vaguely defined. In this work we investigated the antimicrobial mode of action of chitosan using a combination of approaches, including in vitro assays, killing kinetics, cellular leakage measurements, membrane potential estimations, and electron microscopy, in addition to transcriptional response analysis. Chitosan, whose antimicrobial activity was influenced by several factors, exhibited a dose-dependent growth-inhibitory effect. A simultaneous permeabilization of the cell membrane to small cellular components, coupled to a significant membrane depolarization, was detected. A concomitant interference with cell wall biosynthesis was not observed. Chitosan treatment of Staphylococcus simulans 22 cells did not give rise to cell wall lysis; the cell membrane also remained intact. Analysis of transcriptional response data revealed that chitosan treatment leads to multiple changes in the expression profiles of Staphylococcus aureus SG511 genes involved in the regulation of stress and autolysis, as well as genes associated with energy metabolism. Finally, a possible mechanism for chitosan's activity is postulated. Although we contend that there might not be a single classical target that would explain chitosan's antimicrobial action, we speculate that binding of chitosan to teichoic acids, coupled with a potential extraction of membrane lipids (predominantly lipoteichoic acid) results in a sequence of events, ultimately leading to bacterial death. PMID:18456858

  7. Chitosan composite films. Biomedical applications.

    PubMed

    Cárdenas, Galo; Anaya, Paola; von Plessing, Carlos; Rojas, Carlos; Sepúlveda, Jackeline

    2008-06-01

    Chitosan acetate films have been prepared using chitosans from shrimps (Pleuroncodes monodon) of low and high molecular weight (LMv = 68,000 g/mol and HMv = 232,000 g/mol) and deacetylation degree of 80 and 100%, respectively. The chitosan films were obtained by addition of several additives to acetic acid chitosan solutions, such as: glycerol, oleic acid and linoleic acid in different proportions. The pH of the solutions before casting ranged from 5.0 to 6.0. The composite film thickness are reported. The films have been analyzed by FTIR showing characteristic bands corresponding to the additives. The scanning electron microscopy (SEM) studies reveals the different morphology of the composite films. The films exhibit different physical properties depending upon the additives and/or mixture of them. The addition of glycerol to composite improves the elasticity of the films. The swelling in glucose and saline solutions for several films was evaluated, being higher in the glucose solution. The bactericide test against Staphylococcus aureus, Pseudomona aeruginosa and Acinetobacter baumanii in plates with either blood and or agar tripticase showed that the molecular weight influences on the bactericidal properties of the chitosan composite films and over its effect against gram positive and gram negative bacteria. Medical applications of the composite films were done in patients with burns, ulcers and injuries, the films containing glycerol showed good adhesion in comparison with those without it. The composite films tested were mainly three (1) chitosan acetate with glycerol, (2) chitosan acetate with oleic acid and (3) chitosan acetate with glycerol and oleic acid. Excellent results in the skin recovery were obtained after 7-10 days. Since the chitosan is biodegradable by the body enzymes it does not need to be removed and increases the gradual grows of the damage tissues. PMID:18165888

  8. 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. PMID:21824068

  9. Preparation and characterization of magnetic Fe3O4-chitosan nanoparticles loaded with isoniazid

    NASA Astrophysics Data System (ADS)

    Qin, H.; Wang, C. M.; Dong, Q. Q.; Zhang, L.; Zhang, X.; Ma, Z. Y.; Han, Q. R.

    2015-05-01

    A novel and simple method has been proposed to prepare magnetic Fe3O4-chitosan nanoparticles loaded with isoniazid (Fe3O4/CS/INH nanocomposites). Efforts have been made to develop isoniazid (INH) loaded chitosan (CS) nanoparticles by ionic gelation of chitosan with tripolyphosphate (TPP). The factors that influence the preparation of chitosan nanoparticles, including the TPP concentration, the chitosan/TPP weight ratio and the chitosan concentration on loading capacity and encapsulation efficiency of chitosan nanoparticles were studied. The magnetic Fe3O4 nanoparticles were prepared by co-precipitation method of Fe2+ and Fe3+. Then the magnetic Fe3O4/CS/INH nanocomposites were prepared by ionic gelation method. The magnetic Fe3O4 nanoparticles and magnetic Fe3O4/CS/INH nanocomposites were characterized by XRD, TEM, FTIR and SQUID magnetometry. The in vitro release of Fe3O4/CS/INH nanocomposites showed an initial burst release in the first 10 h, followed by a more gradual and sustained release for 48 h. It is suggested that the magnetic Fe3O4/CS/INH nanocomposites may be exploited as potential drug carriers for controlled-release applications in magnetic targeted drugs delivery system.

  10. Combinatorial MAPLE deposition of antimicrobial orthopedic maps fabricated from chitosan and biomimetic apatite powders.

    PubMed

    Visan, A; Stan, G E; Ristoscu, C; Popescu-Pelin, G; Sopronyi, M; Besleaga, C; Luculescu, C; Chifiriuc, M C; Hussien, M D; Marsan, O; Kergourlay, E; Grossin, D; Brouillet, F; Mihailescu, I N

    2016-09-10

    Chitosan/biomimetic apatite thin films were grown in mild conditions of temperature and pressure by Combinatorial Matrix-Assisted Pulsed Laser Evaporation on Ti, Si or glass substrates. Compositional gradients were obtained by simultaneous laser vaporization of the two distinct material targets. A KrF* excimer (λ=248nm, τFWHM=25ns) laser source was used in all experiments. The nature and surface composition of deposited materials and the spatial distribution of constituents were studied by SEM, EDS, AFM, GIXRD, FTIR, micro-Raman, and XPS. The antimicrobial efficiency of the chitosan/biomimetic apatite layers against Staphylococcus aureus and Escherichia coli strains was interrogated by viable cell count assay. The obtained thin films were XRD amorphous and exhibited a morphology characteristic to the laser deposited structures composed of nanometric round shaped grains. The surface roughness has progressively increased with chitosan concentration. FTIR, EDS and XPS analyses indicated that the composition of the BmAp-CHT C-MAPLE composite films gradually modified from pure apatite to chitosan. The bioevaluation tests indicated that S. aureus biofilm is more susceptible to the action of chitosan-rich areas of the films, whilst the E. coli biofilm proved more sensible to areas containing less chitosan. The best compromise should therefore go, in our opinion, to zones with intermediate-to-high chitosan concentration which can assure a large spectrum of antimicrobial protection concomitantly with a significant enhancement of osseointegration, favored by the presence of biomimetic hydroxyapatite. PMID:27418570

  11. The coagulation characteristics of humic acid by using acid-soluble chitosan, water-soluble chitosan, and chitosan coagulant mixtures.

    PubMed

    Chen, Chih-Yu; Wu, Chung-Yu; Chung, Ying-Chien

    2015-01-01

    Chitosan is a potential substitute for traditional aluminium salts in water treatment systems. This study compared the characteristics of humic acid (HA) removal by using acid-soluble chitosan, water-soluble chitosan, and coagulant mixtures of chitosan with aluminium sulphate (alum) or polyaluminium chloride (PACl). In addition, we evaluated their respective coagulation efficiencies at various coagulant concentrations, pH values, turbidities, and hardness levels. Furthermore, we determined the size and settling velocity of flocs formed by these coagulants to identify the major factors affecting HA coagulation. The coagulation efficiency of acid- and water-soluble chitosan for 15 mg/l of HA was 74.4% and 87.5%, respectively. The optimal coagulation range of water-soluble chitosan (9-20 mg/l) was broader than that of acid-soluble chitosan (4-8 mg/l). Notably, acid-soluble chitosan/PACl and water-soluble chitosan/alum coagulant mixtures exhibited a higher coagulation efficiency for HA than for PACl or alum alone. Furthermore, these coagulant mixtures yielded an acceptable floc settling velocity and savings in both installation and operational expenses. Based on these results, we confidently assert that coagulant mixtures with a 1:1 mass ratio of acid-soluble chitosan/PACl and water-soluble chitosan/alum provide a substantially more cost-effective alternative to using chitosan alone for removing HA from water. PMID:25362971

  12. 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. PMID:23687952

  13. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    PubMed Central

    Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

    2014-01-01

    Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

  14. Versatile carboxymethyl chitin and chitosan nanomaterials: a review.

    PubMed

    Narayanan, Deepa; Jayakumar, R; Chennazhi, K P

    2014-01-01

    Biocompatibility, biodegradability, and low cost of chitin and chitosan have drawn immense attention in many fields including medicine, bioinspired material science, pharmaceuticals, and agriculture. Their handling and processing are difficult owing to its insolubility in neutral aqueous solution or organic solvents. One of the methods used to improve the solubility characteristics of chitin and chitosan is chemical modification. Introducing a carboxymethyl group is the most advantageous method of increasing the solubility of chitosan at neutral and alkaline pH. Carboxymethyl chitin (CMC) and carboxymethyl chitosan (CMCS) are water soluble derivatives formed by introducing CH₂COOH function into the polymer which endows it with better biological properties. The functional group makes CMC/CMCS nanoparticles (NPs) efficient vehicles for the delivery of DNA, proteins, and drugs. This review provides an overview of the characteristics of CMC/CMCS NPs as well as fulfills the task of describing and discussing its important roles primarily in cancer nanomedicine detailing the targeted drug delivery aspect. The application of these NPs in imaging, agriculture, and textiles has also been highlighted. The review also elaborates the advantages of using the CMC and CMCS NPs for drug and gene delivery. PMID:25266740

  15. Mucoadhesive Chitosan Derivatives as Novel Drug Carriers.

    PubMed

    Islam, Mohammad Ariful; Park, Tae-Eun; Reesor, Emma; Cherukula, Kondareddy; Hasan, Anwarul; Firdous, Jannatul; Singh, Bijay; Kang, Sang-Kee; Choi, Yun-Jaie; Park, In-Kyu; Cho, Chong-Su

    2015-01-01

    Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles. PMID:26323422

  16. A comparative study on non-covalent functionalization of carbon nanotubes by chitosan and its derivatives for delivery of doxorubicin

    NASA Astrophysics Data System (ADS)

    Ali Mohammadi, Zahra; Aghamiri, Seyed Foad; Zarrabi, Ali; Talaie, Mohammad Reza

    2015-12-01

    Three targeting drug delivery systems were formulated by functionalization of single-walled carbon nanotubes using chitosan and its derivatives (Palmitoyl Chitosan and Carboxymethyl Chitosan) for delivery of doxorubicin, an anti-cancer drug. Loading efficiency was higher than 75% for all carriers. The systems were stable under neutral pH, while effectively released drug at reduced pH. The drug loading efficiency and the release rate were revealed to be dependent on the type of applied polymer and could be adjusted to a desired rate by changing the hydrophobic/hydrophilic substitution degree. Folic acid was attached and cytotoxicity of system was compared with free drug.

  17. Spinning of hydroalcoholic chitosan solutions.

    PubMed

    Desorme, Mylène; Montembault, Alexandra; Lucas, Jean-Michel; Rochas, Cyrille; Bouet, Thierry; David, Laurent

    2013-10-15

    We investigated the spinning of hydroalcoholic chitosan solutions. The dope composition was optimized in order to obtain a continuous alcogel fiber by water evaporation on heating the extruded hydroalcoholic solution. This alcogel fiber was then neutralized in aqueous alkali baths and washed in water to eliminate the residual alcohol and salts before final drying. Depending on the alcohol content in the filament at the neutralization step, on specific alcohol-chitosan interactions and on the nature and concentration of the coagulation base, the process yielded semicrystalline chitosan fibers with different proportions of anhydrous and hydrated allomorphs. Contrarily to the classical annealing method, the formation of mainly anhydrous crystals was obtained without significant molecular weight decrease by neutralizing the polymer in hydrophobic conditions. The control of allomorph content was shown to be related to the hydrophobicity of the solvent (alcohol fraction) at the neutralization step. PMID:23987316

  18. Fine-tuned PEGylation of chitosan to maintain optimal siRNA-nanoplex bioactivity.

    PubMed

    Guţoaia, Andra; Schuster, Liane; Margutti, Simona; Laufer, Stefan; Schlosshauer, Burkhard; Krastev, Rumen; Stoll, Dieter; Hartmann, Hanna

    2016-06-01

    Polyethylene glycol (PEG) is a widely used modification for drug delivery systems. It reduces undesired interaction with biological components, aggregation of complexes and serves as a hydrophilic linker of ligands for targeted drug delivery. However, PEGylation can also lead to undesired changes in physicochemical characteristics of chitosan/siRNA nanoplexes and hamper gene silencing. To address this conflicting issue, PEG-chitosan copolymers were synthesized with stepwise increasing degrees of PEG substitution (1.5% to 8.0%). Subsequently formed PEG-chitosan/siRNA nanoplexes were characterized physicochemically and biologically. The results showed that small ratios of chitosan PEGylation did not affect nanoplex stability and density. However, higher PEGylation ratios reduced nanoplex size and charge, as well as cell uptake and final siRNA knockdown efficiency. Therefore, we recommend fine-tuning of PEGylation ratios to generate PEG-chitosan/siRNA delivery systems with maximum bioactivity. The degree of PEGylation for chitosan/siRNA nanoplexes should be kept low in order to maintain optimal nanoplex efficiency. PMID:27083340

  19. Design, synthesis and antimicrobial activity of 6-N-substituted chitosan derivatives.

    PubMed

    Hu, Linfeng; Meng, Xiangtao; Xing, Ronge; Liu, Song; Chen, Xiaolin; Qin, Yukun; Yu, Huahua; Li, Pengcheng

    2016-09-15

    Three novel 6-N-substituted chitosan derivatives were designed and synthesised and characterized by FTIR and NMR. The degree of substitution was calculated by elemental analysis results. The antimicrobial activities of the target compounds were evaluated by twofold serial broth dilution method and poisoned food technique. The antifungal activities of 6-aminoethylamino-6-deoxy chitosan (3), 6-butylamino-6-deoxy chitosan (4) and 6-pyridyl-6-deoxy chitosan (5) were significantly increased against Rhizoctonia cerealis, Fusarium oxysporum and Botrytis cinerea, and the inhibition rate ranged from 22.48% to 63.56% at the concentration of 0.2mg/mL. The compound 3 had better antibacterial activities than chitosan, and the minimum inhibition concentration of which ranged between 6.25 and 25mg/L against gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Bacillus anthracis) and gram-negative bacteria (Escherichia coli, Salmonella typhi). The antibacterial activities of 6-N-substituted chitosan tended to increase with the increase of the number of -NH2 group. PMID:27506558

  20. Chitosan based hydrogels: characteristics and pharmaceutical applications

    PubMed Central

    Ahmadi, F.; Oveisi, Z.; Samani, S. Mohammadi; Amoozgar, Z.

    2015-01-01

    Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to provide an amenable environment for cellular adherence and cellular remodeling in three dimensional structures mimicking that of natural cellular environment. Additionally, hydrogels have the capacity to carry small molecule drugs and/or proteins, growth factors and other necessary components for cell growth and differentiation. In the context of drug delivery, hydrogels can be utilized to localize drugs, increase drugs concentration at the site of action and consequently reduce off-targeted side effects. The current review aims to describe and classify hydrogels and their methods of production. The main highlight is chitosan-based hydrogels as biocompatible and medically relevant hydrogels for drug delivery. PMID:26430453

  1. Environmental applications of chitosan and its derivatives.

    PubMed

    Yong, Soon Kong; Shrivastava, Manoj; Srivastava, Prashant; Kunhikrishnan, Anitha; Bolan, Nanthi

    2015-01-01

    Chitosan originates from the seafood processing industry and is one of the most abundant of bio-waste materials. Chitosan is a by-product of the alkaline deacetylation process of chitin. Chemically, chitosan is a polysaccharide that is soluble in acidic solution and precipitates at higher pHs. It has great potential for certain environmental applications, such as remediation of organic and inorganic contaminants, including toxic metals and dyes in soil, sediment and water, and development of contaminant sensors. Traditionally, seafood waste has been the primary source of chitin. More recently, alternative sources have emerged such as fungal mycelium, mushroom and krill wastes, and these new sources of chitin and chitosan may overcome seasonal supply limitations that have existed. The production of chitosan from the above-mentioned waste streams not only reduces waste volume, but alleviates pressure on landfills to which the waste would otherwise go. Chitosan production involves four major steps, viz., deproteination, demineralization, bleaching and deacetylation. These four processes require excessive usage of strong alkali at different stages, and drives chitosan's production cost up, potentially making the application of high-grade chitosan for commercial remediation untenable. Alternate chitosan processing techniques, such as microbial or enzymatic processes, may become more cost-effective due to lower energy consumption and waste generation. Chitosan has proved to be versatile for so many environmental applications, because it possesses certain key functional groups, including - OH and -NH2 . However, the efficacy of chitosan is diminished at low pH because of its increased solubility and instability. These deficiencies can be overcome by modifying chitosan's structure via crosslinking. Such modification not only enhances the structural stability of chitosan under low pH conditions, but also improves its physicochemical characteristics, such as porosity

  2. Blood contact properties of ascorbyl chitosan.

    PubMed

    Yalinca, Z; Yilmaz, E; Taneri, B; Bullici, F; Tuzmen, S

    2013-01-01

    Ascorbyl chitosan was synthesized by heating chitosan with ascorbic acid in isopropanol. The products were characterized by FTIR and C-13 NMR spectroscopies, SEM, and elemental analysis. Blood contact properties of ascorbyl chitosans were evaluated. The ascorbyl chitosans demonstrated to have increased lipid-lowering activity in comparison to chitosan alone upon contact with human blood serum in in vitro conditions. Furthermore, the total cholesterol/HDL ratio was improved towards the desirable ideal values after three hours contact with ascorbyl chitosan samples. The lipid-lowering activity increased with ascorbyl substitution. The inherent nonspecific adsorption capability of chitosan due to its chelating power with several different functional groups was exhibited by ascorbyl chitosans as well. This behavior was exemplified in a simultaneous decrease in the total iron values of the volunteers together with lower lipid levels. Furthermore, ascorbyl chitosans were observed to have less hemocompatibility but increased anticoagulant activity when compared to chitosan alone. Additional in vivo studies are necessary to support these results and to investigate further the advantages and disadvantages of these materials to prove their safety prior to clinical applications. PMID:23862665

  3. Pharmacokinetics and biodegradation of chitosan in rats

    NASA Astrophysics Data System (ADS)

    Li, Hui; Jiang, Zhiwen; Han, Baoqin; Niu, Shuyi; Dong, Wen; Liu, Wanshun

    2015-10-01

    Chitosan, an excellent biomedical material, has received a widespread in vivo application. In contrast, its metabolism and distribution once being implanted were less documented. In this study, the pharmacokinetics and biodegradation of fluorescein isothiocyanate (FITC) labeled and muscle implantation administrated chitosan in rats were investigated with fluorescence spectrophotometry, histological assay and gel chromatography. After implantation, chitosan was degraded gradually during its distribution to diverse organs. Among the tested organs, liver and kidney were found to be the first two highest in chitosan content, which was followed by heart, brain and spleen. Urinary excretion was believed to be the major pathway of chitosan elimination, yet 80% of chitosan administered to rats was not trackable in their urine. This indicated that the majority of chitosan was degraded in tissues. In average, the molecular weight of the degradation products of chitosan in diverse organs and urine was found to be <65 kDa. This further confirmed the in vivo degradation of chitosan. Our findings provided new evidences for the intensive and safe application of chitosan as a biomedical material.

  4. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

    PubMed Central

    Li, Xiaosong; Min, Min; Du, Nan; Gu, Ying; Hode, Tomas; Naylor, Mark; Chen, Dianjun; Nordquist, Robert E.; Chen, Wei R.

    2013-01-01

    With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development. PMID:23533454

  5. Characterization of chitosan composites with various clays.

    PubMed

    Lewandowska, Katarzyna; Sionkowska, Alina; Kaczmarek, Beata; Furtos, Gabriel

    2014-04-01

    The structural properties, thermal behaviour and mechanical properties of composites of chitosan (Ch) with nanoclay (montmorillonite, MMT) and/or nanoclays after surface modification have been characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA) and a tensile tests. The microstructure obtained by SEM and AFM microscopy for unmodified chitosan and its composites showed that particles are relatively well dispersed in the chitosan matrix. However, the increasing concentration of the chitosan solution from 1% to 2% decreases the homogeneity of the surface of the composites. In the case of chitosan composite with modified nanoclay (contains 25-30 wt.% of octadecylamine), the lack of particles aggregates in polymer matrix independent of the concentration of chitosan solution was observed. Generally, addition of nanoclay after its surface modification improved the mechanical and thermal properties of the composite much more than montmorillonite without modification. PMID:24530323

  6. Specific optical rotation indicatrices of chitosan films

    NASA Astrophysics Data System (ADS)

    Rudenko, Darya A.; Shipovskaya, Anna B.

    2016-04-01

    The optical activity of chitosan films in the forms of polysalt (chitosan acetate) and polybase was studied. The specific optical rotation [α] of all our films was negative. The absolute values of [α] of polybasic chitosan films was by an order of magnitude higher than that for polysalt films. A dependence of [α] on the orientation angle of the sample relative to the direction of the polarization vector of the incident light beam in the plane perpendicular to this beam was established. Specific optical rotation indicatrices of the chitosan films of both chemical forms were plotted.

  7. Nanoindentation of Chitosan Doped with Silver Nanoparticles

    NASA Astrophysics Data System (ADS)

    Palumbo, Matthew; Teklu, Alem; Kuthirummal, Narayanan; Levi-Polyachenko, Nicole; Department of Physics; Astronomy, College of Charleston Collaboration; Department of Plastic; Reconstructive Surgery, Wake Forest University Health Sciences Collaboration

    Imaging and spectroscopic analysis via nanoindentation was performed with the Nanosurf EasyScan2 AFM on the pure and silver doped chitosan samples allowing for a more localized determination of their stiffness, hardness, and reduced Young's modulus. The pure chitosan sample was tested to have a stiffness of 0.367 N/m, a hardness of 1.12 GPa, and a reduced Young's modulus of 30.5 MPa. The film with 5mg Ag nanoparticle per gram of chitosan was tested on the boundaries between the chitosan and Ag nanoparticles to show an increase in stiffness of about 4.6% at 0.384 N/m, an increase in hardness of about 5.4% at 1.18 GPa, and an increase in the reduced Young's modulus of about 5.0% at 3.2 MPa in comparison to the pure chitosan sample. On the other hand, upon increasing the doping to 10mg Ag nanoparticle per gram of chitosan showed a decrease in stiffness of about 6.3% at 0.344 N/m, a decrease in hardness of about 27.0% at 0.820 GPa, and a decrease in the reduced Young's modulus of about 6.0% at 28.7 MPa in comparison to the pure chitosan sample. Obviously, films doped with 5mg Ag nanoparicle per gram of chitosan provided the composites with improved mechanical strength compared to chitosan alone.

  8. Combinatorial-Designed Epidermal Growth Factor Receptor-Targeted Chitosan Nanoparticles for Encapsulation and Delivery of Lipid-Modified Platinum Derivatives in Wild-Type and Resistant Non-Small-Cell Lung Cancer Cells.

    PubMed

    Nascimento, Ana Vanessa; Singh, Amit; Bousbaa, Hassan; Ferreira, Domingos; Sarmento, Bruno; Amiji, Mansoor M

    2015-12-01

    Development of efficient and versatile drug delivery platforms to overcome the physical and biological challenges in cancer therapeutics is an area of great interest, and novel materials are actively sought for such applications. Recent strides in polymer science have led to a combinatorial approach for generating a library of materials with different functional identities that can be "mixed and matched" to attain desired characteristics of a delivery vector. We have applied the combinatorial design to chitosan (CS), where the polymer backbone has been modified with polyethylene glycol, epidermal growth factor receptor-binding peptide, and lipid derivatives of varying chain length to encapsulate hydrophobic drugs. Cisplatin, cis-([PtCl2(NH3)2]), is one of the most potent chemotherapy drugs broadly administered for cancer treatment. Cisplatin is a hydrophilic drug, and in order for it to be encapsulated in the developed nanosystems, it was modified with lipids of varying chain length. The library of four CS derivatives and six platinum derivatives was self-assembled in aqueous medium and evaluated for physicochemical characteristics and cytotoxic effects in platinum-sensitive and -resistant lung cancer cells. The results show that the lipid-modified platinate encapsulation into CS nanoparticles significantly improved cellular cytotoxicity of the drug. In this work, we have also reinforced the idea that CS is a multifaceted system that can be as successful in delivering small molecules as it has been as a nucleic acids carrier. PMID:26523837

  9. A review on chitosan-cellulose blends and nanocellulose reinforced chitosan biocomposites: Properties and their applications.

    PubMed

    H P S, Abdul Khalil; Saurabh, Chaturbhuj K; A S, Adnan; Nurul Fazita, M R; Syakir, M I; Davoudpour, Y; Rafatullah, M; Abdullah, C K; M Haafiz, M K; Dungani, R

    2016-10-01

    Chitin is one of the most abundant natural polymers in world and it is used for the production of chitosan by deacetylation. Chitosan is antibacterial in nature, non-toxic, and biodegradable thus it can be used for the production of biodegradable film which is a green alternative to commercially available synthetic counterparts. However, their poor mechanical and thermal properties restricted its wide spread applications. Chitosan is highly compatible with other biopolymers thus its blending with cellulose and/or incorporation of nanofiber isolated from cellulose namely cellulose nanofiber and cellulose nanowhiskers are generally useful. Cellulosic fibers in nano scale are attractive reinforcement in chitosan to produce environmental friendly composite films with improved physical properties. Thus chitosan based composites have wide applicability and potential in the field of biomedical, packaging and water treatment. This review summarises properties and preparation procedure of chitosan-cellulose blends and nano size cellulose reinforcement in chitosan bionanocomposites for different applications. PMID:27312632

  10. Echogenic Glycol Chitosan Nanoparticles for Ultrasound-Triggered Cancer Theranostics

    PubMed Central

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

    2015-01-01

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

  11. Chitosan Coagulation to Improve Microbial and Turbidity Removal by Ceramic Water Filtration for Household Drinking Water Treatment

    PubMed Central

    Abebe, Lydia S.; Chen, Xinyu; Sobsey, Mark D.

    2016-01-01

    The use of porous ceramic filters is promoted globally for household water treatment, but these filters are ineffective in removing viruses from water. In order to increase virus removal, we combine a promising natural coagulant, chitosan, as a pretreatment for ceramic water filters (CWFs) and evaluate the performance of this dual barrier water treatment system. Chitosan is a non-toxic and biodegradable organic polymer derived by simple chemical treatments from chitin, a major source of which is the leftover shells of crustacean seafoods, such as shrimp, prawns, crabs, and lobsters. To determine the effectiveness of chitosan, model test water was contaminated with Escherichia coli K011 and coliphage MS2 as a model enteric bacterium and virus, respectively. Kaolinite clay was used to model turbidity. Coagulation effectiveness of three types of modified chitosans was determine at various doses ranging from 5 to 30 mg/L, followed by flocculation and sedimentation. The pre-treated supernatant water was then decanted into the CWF for further treatment by filtration. There were appreciable microbial removals by chitosan HCl, acetate, and lactate pretreatment followed by CWF treatment, with mean reductions (95% CI) between 4.7 (±1.56) and 7.5 (±0.02) log10 for Escherichia coli, and between 2.8 (±0.10) and 4.5 (±1.04) log10 for MS2. Turbidity reduction with chitosan treatment and filtration consistently resulted in turbidities < 1 NTU, which meet turbidity standards of the US EPA and guidance by the World Health Organization (WHO). According to WHO health-based microbial removal targets for household water treatment technology, chitosan coagulation achieved health protective targets for both viruses and bacteria. Therefore, the results of this study support the use of chitosan to improve household drinking water filtration processes by increasing virus and bacteria reductions. PMID:26927152

  12. Chitosan Coagulation to Improve Microbial and Turbidity Removal by Ceramic Water Filtration for Household Drinking Water Treatment.

    PubMed

    Abebe, Lydia S; Chen, Xinyu; Sobsey, Mark D

    2016-03-01

    The use of porous ceramic filters is promoted globally for household water treatment, but these filters are ineffective in removing viruses from water. In order to increase virus removal, we combine a promising natural coagulant, chitosan, as a pretreatment for ceramic water filters (CWFs) and evaluate the performance of this dual barrier water treatment system. Chitosan is a non-toxic and biodegradable organic polymer derived by simple chemical treatments from chitin, a major source of which is the leftover shells of crustacean seafoods, such as shrimp, prawns, crabs, and lobsters. To determine the effectiveness of chitosan, model test water was contaminated with Escherichia coli K011 and coliphage MS2 as a model enteric bacterium and virus, respectively. Kaolinite clay was used to model turbidity. Coagulation effectiveness of three types of modified chitosans was determine at various doses ranging from 5 to 30 mg/L, followed by flocculation and sedimentation. The pre-treated supernatant water was then decanted into the CWF for further treatment by filtration. There were appreciable microbial removals by chitosan HCl, acetate, and lactate pretreatment followed by CWF treatment, with mean reductions (95% CI) between 4.7 (± 1.56) and 7.5 (± 0.02) log10 for Escherichia coli, and between 2.8 (± 0.10) and 4.5 (± 1.04) log10 for MS2. Turbidity reduction with chitosan treatment and filtration consistently resulted in turbidities < 1 NTU, which meet turbidity standards of the US EPA and guidance by the World Health Organization (WHO). According to WHO health-based microbial removal targets for household water treatment technology, chitosan coagulation achieved health protective targets for both viruses and bacteria. Therefore, the results of this study support the use of chitosan to improve household drinking water filtration processes by increasing virus and bacteria reductions. PMID:26927152

  13. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery.

    PubMed

    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

  14. 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

  15. Characterization of Chitosan Nanofiber Sheets for Antifungal Application

    PubMed Central

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-01-01

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young’s modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young’s modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID:26540046

  16. Chitosan/halloysite nanotubes bionanocomposites: structure, mechanical properties and biocompatibility.

    PubMed

    Liu, Mingxian; Zhang, Yun; Wu, Chongchao; Xiong, Sheng; Zhou, Changren

    2012-11-01

    Incorporation of nanosized reinforcements into chitosan usually results in improved properties and changed microstructures. Naturally occurred halloysite nanotubes (HNTs) are incorporated into chitosan for forming bionanocomposite films via solution casting. The electrostatic attraction and hydrogen bonding interactions between HNTs and chitosan are confirmed. HNTs are uniformly dispersed in chitosan matrix. The tensile strength and Young's modulus of chitosan are enhanced by HNTs. The storage modulus and glass transition temperature of chitosan/HNTs films also increase significantly. Blending with HNTs induces changes in surface nanotopography and increase of roughness of chitosan films. In vitro fibroblasts response demonstrates that both chitosan and chitosan/HNTs nanocomposite films are cytocompatibility even when the loading of HNTs is 10%. In summary, these results provide insights into understanding of the structural relationships of chitosan/HNTs bionanocomposite films in potential applications, such as scaffold materials in tissue engineering. PMID:22743347

  17. Template synthesized chitosan nano test tubes for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Perry, Jillian L. Moulton

    There is tremendous current interest in developing nanoscale drug delivery vehicles. Though intensive efforts have focused on developing spherical drug delivery vehicles, cylindrically shaped vehicles such as nanotubes offer many advantages. Typically, nanotubes can carry a larger inner payload than nanoparticles of the same diameter. Also, we can prepare nanotubes in templates whose geometries can be controlled, in turn allowing precise control over the length and diameter of the tubes. In addition, template synthesized nanotubes can be differentially functionalized on the inner and outer surfaces. Furthermore, templates that are closed on one end can be used to fabricate nano test tubes (closed on one end). The geometry of these nano test tubes allows them to be easily filled with a payload, the open end sealed with a nanoparticle to protect the payload from leaking out, and then the exterior of the tube can be functionalized with a targeting moiety. In an effort to develop such a system, we explored the fabrication of chitosan nano test tubes. Defect-free, chitosan nano test tubes of uniform size were synthesized within the pores of a nanoporous alumina template membrane. While the nano test tubes remained within the template membrane, their inner cavities were filled with a model payload. The payload was then trapped inside the nano test tubes by sealing the open ends of the tubes with latex nanoparticle caps. For proof-of-principle studies, imine linkages were used to attach the caps to the nano test tubes. To create a self-disassembling system, disulfide chemistry was used to covalently cap the nano test tubes. Once removed from the template, the exterior of the nano test tubes were modified with a targeting moiety, allowing them to be targeted to pathological sites. We have also shown that the chitosan nano test tubes are biodegradable by two systems: enzymatic cleavage by lysozymes and disulfide cleavage of the crosslinker by reducing environments

  18. Characterization of calcium carbonate/chitosan composites

    SciTech Connect

    Gonsalves, K.E.; Zhang, S.

    1995-12-31

    The crystal growth of calcium carbonate on a chitosan substrate was achieved using a supersaturated calcium carbonate solution, by using various additives, polyacrylic acid (PAA). Polyacrylic acid modified the chitosan-film surface and promoted the nucleation of calcium carbonate crystals.

  19. Synthesis and characterization of chitosan alkyl urea.

    PubMed

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

    2016-07-10

    Chitosan is a versatile material employed for various purposes in many fields including the development of chiral stationary phases for enantioseparation. Chitosan alkyl urea is a kind of intermediate used to prepare enantioseparation materials. In order to synthesize the intermediates, in the present work, a new way to prepare chitosan alkyl urea has been established: chitosan was first reacted with methyl chloroformate yielding N-methoxyformylated chitosan, which was then converted to chitosan alkyl urea through amine-ester exchange reaction. With a large excess of methyl chloroformate and primary amine of low stereohindrance, the amino group in chitosan could be almost completely converted to ureido group. The as-prepared chitosan alkyl urea derivatives were characterized by IR, (1)H NMR, (13)C NMR,(1)H-(1)H COSY and (1)H-(13)C HSQC NMR spectra. The chemical shifts of hydrogen and carbon atoms of glucose unit were assigned. It was found that the degree of substitution was obviously lower if cyclopropyl amine, aniline, tert-butyl amine and diethyl amine were used as reactants for the amine-ester exchange reaction. The reason was explained with the aid of theoretical calculations. PMID:27106154

  20. Antimicrobial and mechanical properties of β-cyclodextrin inclusion with essential oils in chitosan films.

    PubMed

    Sun, Xiuxiu; Sui, Siyao; Ference, Christopher; Zhang, Yifan; Sun, Shi; Zhou, Ninghui; Zhu, Wenjun; Zhou, Kequan

    2014-09-01

    Chitosan films incorporated with various concentrations of the complex of β-cyclodextrin and essential oils (β-CD/EO) were prepared and investigated for antimicrobial, mechanical, and physical properties. Four bacterial strains that commonly contaminate food products were chosen as target bacteria to evaluate the antimicrobial activity of the prepared films. The incorporation of β-CD/EO significantly increased the antimicrobial activities of the chitosan films against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Listeria monocytogenes. It was also found that tensile strength (TS) of chitosan film was significantly increased with the incorporation of the β-cyclodextrin and 0.75% essential oils complex. The elongation at break (EB) decreased with the increasing concentrations of essential oils. Inclusion of the complex of β-cyclodextrin and 0.25% essential oils also significantly decreased water vapor permeability (WVP) of chitosan films. Our results suggest that chitosan films containing β-CD/EO could be used as active food-packaging material. PMID:25141280

  1. Efficient mucosal delivery of optical contrast agents using imidazole-modified chitosan

    NASA Astrophysics Data System (ADS)

    Ghosn, Bilal; van de Ven, Anne L.; Tam, Justina; Gillenwater, Ann; Sokolov, Konstantin V.; Richards-Kortum, Rebecca; Roy, Krishnendu

    2010-01-01

    The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy. Chitosan-IAA was found to reversibly enhance mucosal permeability in a rapid, reproducible manner, facilitating transepithelial delivery of optical contrast agents. Permeation enhancement occurred through an active process, resulting in the delivery of contrast agents via a paracellular or a combined paracellular/transcellular route depending on size. Coadministration of epidermal growth factor receptor-targeted antibodies with chitosan-IAA facilitated specific labeling and discrimination between paired normal and malignant human oral biopsies. Together, these data suggest that chitosan-IAA is a promising topical permeation enhancer for mucosal delivery of optical contrast agents.

  2. Hydrodynamic Delivery of Chitosan-Folate-DNA Nanoparticles in Rats with Adjuvant-Induced Arthritis

    PubMed Central

    Shi, Qin; Wang, Huijie; Tran, Covi; Qiu, Xingping; Winnik, Françoise M.; Zhang, Xiaoling; Dai, Kerong; Benderdour, Mohamed; Fernandes, Julio C.

    2011-01-01

    50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. β-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1β and PGE2 concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticles in vitro/in vivo and could decrease inflammation in arthritic rats. PMID:21274258

  3. Hydrogels made from chitosan and silver nitrate.

    PubMed

    Kozicki, Marek; Kołodziejczyk, Marek; Szynkowska, Małgorzata; Pawlaczyk, Aleksandra; Leśniewska, Ewa; Matusiak, Aleksandra; Adamus, Agnieszka; Karolczak, Aleksandra

    2016-04-20

    This work describes a gelation of chitosan solution with silver nitrate. Above the critical concentration of chitosan (c*), continuous hydrogels of chitosan-silver can be formed. At lower concentrations, the formation of nano- and micro-hydrogels is discussed. The sol-gel analysis was performed to characterise the hydrogels' swelling properties. Moreover, the following were employed: (i) mechanical testing of hydrogels, (ii) inductively coupled plasma-optical emission spectroscopy (ICP-OES) for the measurement of silver concentration, (iii) scanning electron microscopy (SEM) to examine the morphology of products obtained, and (iv) dynamic light scattering (DLS) and UV-vis spectrophotometry to examine products formed at low concentration of chitosan (cchitosan used that showed no such activity. PMID:26876830

  4. Chitosan mouthwash: toxicity and in vivo validation.

    PubMed

    Costa, E M; Silva, S; Costa, M R; Pereira, M; Campos, D A; Odila, J; Madureira, A R; Cardelle-Cobas, A; Tavaria, F K; Rodrigues, A S; Pintado, M M

    2014-10-13

    A previous study showed that a chitosan mouthwash would be a valid alternative to current mouthwashes as it demonstrated, in vitro, significantly higher antibiofilm activity than two commercial mouthwashes. As such, the aim of this work was to verify the safety of the developed product and to validate, in vivo, the biological activity ascertained in vitro. Chitosan mouthwash safety was evaluated through Ames, MTT and V79 chromosomal aberration assay while antimicrobial activity was evaluated through in vivo assays. The results showed that the chitosan mouthwash was safe, presenting lower cytotoxicity than a commercial mouthwash, and that it effectively reduced viable counts of Streptococcus spp. and Enterococcus spp. by ca. 5.5 log of CFU. Furthermore, in direct comparison with a commercial mouthwash the chitosan mouthwash possessed significantly higher antimicrobial activity. The conjunction of these results proves that the chitosan mouthwash is a safe, effective, natural alternative to the existent chemical mouthwashes. PMID:25037365

  5. Functional properties of chitosan-based films.

    PubMed

    Leceta, I; Guerrero, P; de la Caba, K

    2013-03-01

    Chitosan-based films plasticized with glycerol were prepared by casting with the aim to obtain environmentally friendly materials for packaging applications. Different contents of glycerol were incorporated into chitosan solutions to improve mechanical properties and all films obtained were flexible and transparent. It was observed that the transparency and good behaviour of the films against UV radiation were not affected by chitosan molecular weight or glycerol content. Moreover, chitosan-based films exhibited excellent barrier properties against water vapour and oxygen, even with the addition of glycerol. The effect of the plasticizer on the properties has been explained using Fourier transform infrared (FTIR) spectroscopic analysis. The changes observed in the intensity of the bands showed that glycerol interacts with chitosan, which could be confirmed by total soluble matter (TSM). PMID:23465939

  6. Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells.

    PubMed

    Chien, Rao-Chi; Yen, Ming-Tsung; Mau, Jeng-Leun

    2016-03-15

    Chitosan was prepared by alkaline N-deacetylation of chitin obtained from shiitake stipes and crab shells and its antimicrobial and antitumor activities were studied. Chitosan from shiitake stipes and crab shells exhibited excellent antimicrobial activities against eight species of Gram positive and negative pathogenic bacteria with inhibition zones of 11.4-26.8mm at 0.5mg/ml. Among chitosan samples, shiitake chitosan C120 was the most effective with inhibition zones of 16.4-26.8mm at 0.5mg/ml. In addition, shiitake and crab chitosan showed a moderate anti-proliferative effect on IMR 32 and Hep G2 cells. At 5mg/ml, the viability of IMR 32 cells incubated with chitosan was 68.8-85.0% whereas that of Hep G2 cells with chitosan was 60.4-82.9%. Overall, shiitake chitosan showed slightly better antimicrobial and antitumor activities than crab chitosan. Based on the results obtained, shiitake and crab chitosan were strong antimicrobial agents and moderate antitumor agents. PMID:26794761

  7. 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

  8. Functional modification of chitosan for biomedical application

    NASA Astrophysics Data System (ADS)

    Tang, Ruogu

    Chitosan is a linear polysaccharide. Normally commercial chitosan consists of randomly distributed beta-(1-4)-linked D-glucosamine (deacetylated proportion) and N-acetyl-D-glucosamine (acetylated proportion) together. Chitosan has been proved to be a multifunctional biopolymer that presents several unique properties due to free amino groups in the repeating unit therefore chitosan has been widely applied in various areas. To be specific, provided by the excellent biocompatibility, chitosan is expected to be used in biological and medical applications including wound dressing, implants, drug carrier/delivery, etc. In this thesis, we worked on chitosan functionalization for biomedical application. The thesis are composed of three parts: In the first part, we focused on modifying the chitosan thin film, chemically introducing the nitric oxide functional groups on chitosan film. We covalently bonded small molecule diazeniumdiolates onto the chitosan films and examined the antimicrobial function and biocompatibility. Commercial chitosan was cast into films from acidic aqueous solutions. Glutaraldehyde reacted with the chitosan film to introduce aldehyde groups onto the chitosan film (GA-CS film). GA-CS reacted with a small molecule NO donor, NOC-18, to covalently immobilize NONO groups onto the polymer (NO-CS film). The-CHO and [NONO] group were verified by FT IR, UV and Griess reagent. The NO releasing rate in aqueous solution and and thermal stability were studied quantitatively to prove its effectiveness. A series of antimicrobial tests indicated that NO-CS films have multiple functions: 1. It could inhibit the bacteria growth in nutrient rich environment; 2. It could directly inactivate bacteria and biofilm; 3. It could reduce the bacteria adherence on the film surface as well as inhibit biofilm formation. In addition, the NO-CS film was proved to be biocompatible with cell and it was also compatible with other antibiotics like Amoxicillin. In the second part, we

  9. Insights into and relative effect of chitosan-H, chitosan-H-propolis, chitosan-H-propolis-nystatin and chitosan-H-nystatin on dentine bond strength

    PubMed Central

    Perchyonok, Victoria Tamara; Zhang, Shengmiao; Grobler, Sias R.; Oberholzer, Theunis G.

    2013-01-01

    Objective: The purpose of the study was to design and evaluate novel functional chitosan hydrogels (chitosan-H-propolis, chitosan-H-propolis-nystatin and chitosan-H-nystatin) by using the chitosan-H polymer as “dual function restorative materials”. Materials and Methods: The nystatin/antioxidant carrier gel was prepared by dispersion of the corresponding component in glycerol and 3% acetic acid with 5% chitosan gelling agent was then added to the dispersion with continuous mixing. The natural bio-adhesive functionalized chitosan hydrogels were combined with built in drug delivery system and bio-actives such as propolis in order to increase the dentin bond strength capacity and maintain therapeutic properties of the alternative drug delivery system. The surface morphology, release behaviors (physiological pH and also in acidic conditions), stability of nystatin:antioxidant:chitosan and the effect of the hydrogels on the shear bond strength of dentin were also evaluated. Statistical Analysis Used: Non-parametric ANOVA test was used to asses significance of higher shear bond values than dentine treated or not treated with phosphoric acid. Results: The release of both nystatin and propolis confer the added benefit of dual action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to commercially available nystatin alone. Neither the release of nystatin nor the antioxidant stability was affected by storage. Chitosan-H, chitosan-propolis, chitosan-nystatin and chitosan-nystatin-propolis treated dentine gives significantly (P < 0.05) higher shear bond values (P < 0.05) than dentine treated or not treated with phosphoric acid. Conclusion: The added benefits of their unique functionality involve increased dentin adhesive bond strengths (after 24 h and after 6 months) and positive influence on the nystatin release. Nystatin was a model therapeutic agent, evaluating the concept of using functional materials

  10. Delivery of chitosan/dsRNA nanoparticles for silencing of wing development vestigial (vg) gene in Aedes aegypti mosquitoes.

    PubMed

    Ramesh Kumar, D; Saravana Kumar, P; Gandhi, M Rajiv; Al-Dhabi, Naif Abdullah; Paulraj, M Gabriel; Ignacimuthu, S

    2016-05-01

    RNA interference (RNAi) has been used as a gene silencing strategy by the introduction of long double stranded RNA (dsRNA) for the control of pest insects. The aim of the present study was to examine whether the expression of vg gene which is responsible for wing development, can be repressed by chitosan/dsRNA based nanoparticles in Aedes aegypti. The vestigial gene (vg) was amplified from adult mosquito and cloned in pLitmus28i vector. Genetically engineered recombinant plasmid was transformed into RNase III deficient strain for synthesis of bacterially expressed dsRNA. Nanoparticles were prepared via electrostatic interaction between cationic polymer chitosan and anionic nucleic acids (dsRNA). The formation of chitosan/dsRNAnanoparticles and their size were confirmed by Atomic force microscopy (AFM). Chitosan/dsRNA mediated knockdown of Enhanced Green Fluorescence Protein (EGFP) was demonstrated in Sf21 cells. Further, we tested whether such an approach could be used to target vg gene in Ae. aegypti. The results showed that chitosan/dsRNA caused significant mortality, delayed growth development and caused adult wing-malformation. A qRT-PCR analysis confirmed that the chitosan/dsRNA mediated transcriptional level was downregulated. Our findings suggest that vg gene intervention strategies through RNAi can emerge as viable option for pest control. PMID:26794313

  11. Dextran-doxorubicin/chitosan nanoparticles for solid tumor therapy.

    PubMed

    Bisht, Savita; Maitra, Amarnath

    2009-01-01

    Chemotherapy is a major therapeutic approach for the treatment of localized and metastasized cancers. Whereas potent chemotherapeutic agents seem promising in the test tube, clinical trials often fail due to unfavorable pharmacokinetics, poor delivery, low local concentrations, and limited accumulation in the target cell. The pathophysiology of the tumor vasculature and stromal compartment presents a major obstacle to effective delivery of agents to solid tumors. Poor perfusion of the tumor, arterio-venous shunting, necrotic and hypoxic areas, as well as a high interstitial fluid pressure work against favorable drug uptake. Thus, targeted drug delivery using long-circulating particulate drug carriers such as hydrogels of controlled size (<100 nm diameter) holds immense potential to improve the treatment of cancer by selectively providing therapeutically effective drug concentrations at the tumor site [through enhanced permeability and retention (EPR) effect] while reducing undesirable side effects. This review focuses on the progress of targeted delivery of nanoparticulated anticancer drug such as doxorubicin chemically conjugated with dextran and encapsulated in chitosan nanoparticles to solid tumor with reduced side effect of drug. Regulated particle size and long circulation of these hydrogel nanoparticles in blood help them accumulate in tumor tissue through EPR effect as evident from the significant regression of the tumor volume. The cardiotoxicity of doxorubicin can be minimized by coupling the drug with dextran and encapsulating it in chitosan nanoparticles. PMID:20049807

  12. The effect of chitosan concentration on the electrical property of chitosan-blended cellulose electroactive paper

    NASA Astrophysics Data System (ADS)

    Jang, Sang-Dong; Kim, Joo-Hyung; Zhijiang, Cai; Kim, Jaehwan

    2009-01-01

    We studied the effect of chitosan blending on the electrical property of chitosan-blended cellulose electroactive paper (EAPap) under different humidity conditions. As the chitosan blending ratio increased, the real part of the dielectric constant of chitosan-blended cellulose EAPap increased while the dielectric loss factor decreased. From the curve fitting of the measured data using an electrode polarization model, it was found that increasing the chitosan ratio in the EAPap might promote a decrease in the relaxation time of the EAPap, resulting in an increase of the ion mobility and dc conductivity. Over 30% of the chitosan blending ratio, a gradual increment of the ion mobility of the EAPap was observed at 40% relative humidity, while a quadratic increment of the mobility was found at 60% relative humidity condition. This kind of ion-mobility-enhanced cellulose EAPap can be used not only for bending actuators but also for medical applications such as blood clotting patches.

  13. Evaluation of antibacterial efficiency of chitosan and chitosan nanoparticles on cariogenic streptococci: an in vitro study

    PubMed Central

    Aliasghari, Azam; Rabbani Khorasgani, Mohammad; Vaezifar, Sedigheh; Rahimi, Fateh; Younesi, Habibollah; Khoroushi, Maryam

    2016-01-01

    Background and Objectives: The most prevalent and worldwide oral disease is dental caries that affects a significant proportion of the world population. There are some classical approaches for control, prevention and treatment of this pathologic condition; however, the results are still not completely successful. Therefore new methods are needed for better management of this important challenge. Chitosan is a natural and non-toxic polysaccharide with many biological applications, particularly as an antimicrobial agent. Chitosan nanoparticle is a bioactive and environment friendly material with unique physicochemical properties. The aim of the present study was to investigate the antimicrobial effect of chitosan and nano-chitosan on the most important cariogenic streptococci. Materials and Methods: For evaluation of antimicrobial effect of chitosan and nano-chitosan against oral streptococci broth micro-dilution method was carried out for four bacterial species; Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguis and Streptococcus salivarius. Also the effect of these materials on adhesion of above bacteria was evaluated. One-way ANOVA and post hoc Tukey test were used for statistical analysis. Results: The MICs of chitosan for S. mutans, S. sanguis, S. salivarius and S. sobrinus were 1.25, 1.25, 0.625 and 0.625 mg/mL, respectively. The MIC of chitosan nanoparticle for S. mutans, S. salivarius and S. sobrinus was 0.625 mg/mL and for S. sanguis was 0.312 mg/mL. Chitosan and chitosan nanoparticles at a concentration of 5 mg/mL also reduced biofilm formation of S. mutans up to 92.5% and 93.4%, respectively. Conclusion: The results of this study supported the use of chitosan and chitosan nanoparticles as antimicrobial agents against cariogenic Streptococci. PMID:27307974

  14. Coloration of cotton fibers using nano chitosan.

    PubMed

    Wijesena, Ruchira N; Tissera, Nadeeka D; de Silva, K M Nalin

    2015-12-10

    A method of coloration of cotton fabrics with nano chitosan is proposed. Nano chitosan were prepared using crab shell chitin nanofibers through alkaline deacetylation process. Average nano fiber diameters of nano chitosan were 18 nm to 35 nm and the lengths were in the range of 0.2-1.3 μm according to the atomic force microscope study. The degree of deacetylation of the material was found to be 97.3%. The prepared nano chitosan dyed using acid blue 25 (2-anthraquinonesulfonic acid) and used as the coloration agent for cotton fibers. Simple wet immersion method was used to color the cotton fabrics by nano chitosan dispersion followed by acid vapor treatment. Scanning electron microscope and atomic force microscope study of the treated cotton fiber revealed that the nano chitosan were consistently deposited on the cotton fiber surface and transformed in to a thin polymer layer upon the acid vapor treatment. The color strength of the dyed fabrics could be changed by changing the concentration of dyed nano chitosan dispersion. PMID:26428115

  15. Probing cellular behaviors through nanopatterned chitosan membranes

    NASA Astrophysics Data System (ADS)

    Yang, Chung-Yao; Sung, Chun-Yen; Shuai, Hung-Hsun; Cheng, Chao-Min; Yeh, Andrew

    2013-08-01

    This paper describes a high-throughput method for developing physically modified chitosan membranes to probe the cellular behavior of MDCK epithelial cells and HIG-82 fibroblasts adhered onto these modified membranes. To prepare chitosan membranes with micro/nanoscaled features, we have demonstrated an easy-to-handle, facile approach that could be easily integrated with IC-based manufacturing processes with mass production potential. These physically modified chitosan membranes were observed by scanning electron microscopy to gain a better understanding of chitosan membrane surface morphology. After MDCK cells and HIG-82 fibroblasts were cultured on these modified chitosan membranes for various culture durations (i.e. 1, 2, 4, 12 and 24 h), they were investigated to decipher cellular behavior. We found that both cells preferred to adhere onto a flat surface rather than on a nanopatterned surface. However, most (> 80%) of the MDCK cells showed rounded morphology and would suspend in the cultured medium instead of adhering onto the planar surface of negatively nanopatterned chitosan membranes. This means different cell types (e.g. fibroblasts versus epithelia) showed distinct capabilities/preferences of adherence for materials of varying surface roughness. We also showed that chitosan membranes could be re-used at least nine times without significant contamination and would provide us consistency for probing cell-material interactions by permitting reuse of the same substrate. We believe these results would provide us better insight into cellular behavior, specifically, microscopic properties and characteristics of cells grown under unique, nanopatterned cell-interface conditions.

  16. Chitosan as a starting material for wound healing applications.

    PubMed

    Patrulea, V; Ostafe, V; Borchard, G; Jordan, O

    2015-11-01

    Chitosan and its derivatives have attracted great attention due to their properties beneficial for application to wound healing. The main focus of the present review is to summarize studies involving chitosan and its derivatives, especially N,N,N-trimethyl-chitosan (TMC), N,O-carboxymethyl-chitosan (CMC) and O-carboxymethyl-N,N,N-trimethyl-chitosan (CMTMC), used to accelerate wound healing. Moreover, formulation strategies for chitosan and its derivatives, as well as their in vitro, in vivo and clinical applications in wound healing are described. PMID:26614560

  17. In vitro study on apoptotic cell death by effective magnetic hyperthermia with chitosan-coated MnFe2O4

    NASA Astrophysics Data System (ADS)

    Oh, Yunok; Lee, Nohyun; Kang, Hyun Wook; Oh, Junghwan

    2016-03-01

    Magnetic nanoparticles (MNPs) have been widely investigated as a hyperthermic agent for cancer treatment. In this study, thermally responsive Chitosan-coated MnFe2O4 (Chitosan-MnFe2O4) nanoparticles were developed to conduct localized magnetic hyperthermia for cancer treatment. Hydrophobic MnFe2O4 nanoparticles were synthesized via thermal decomposition and modified with 2,3-dimercaptosuccinic acid (DMSA) for further conjugation of chitosan. Chitosan-MnFe2O4 nanoparticles exhibited high magnetization and excellent biocompatibility along with low cell cytotoxicity. During magnetic hyperthermia treatment (MHT) with Chitosan-MnFe2O4 on MDA-MB 231 cancer cells, the targeted therapeutic temperature was achieved by directly controlling the strength of the external AC magnetic fields. In vitro Chitosan-MnFe2O4-assisted MHT at 42 °C led to drastic and irreversible changes in cell morphology and eventual cellular death in association with the induction of apoptosis through heat dissipation from the excited magnetic nanoparticles. Therefore, the Chitosan-MnFe2O4 nanoparticles with high biocompatibility and thermal capability can be an effective nano-mediated agent for MHT on cancer.

  18. Effects of carboxymethyl chitosan on the blood system of rats

    SciTech Connect

    Fu, Dawei; Han, Baoqin; Dong, Wen; Yang, Zhao; Lv, You; Liu, Wanshun

    2011-04-29

    Highlights: {yields} We report, for the first time, the safety of carboxymethyl chitosan in blood system. {yields} CM-Chitosan has no significant effects on coagulation function of rats. {yields} CM-Chitosan has no significant effects on anticoagulation performance of rats. {yields} CM-Chitosan has no significant effects on fibrinolytic function of rats. {yields} CM-Chitosan has no significant effects on hemorheology of rats. -- Abstract: Carboxymethyl chitosan (CM-chitosan), a derivative of chitosan, was extensively studied in the biomedical materials field for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CM-chitosan in the blood system are lacking. In this study CM-chitosan was implanted into the abdominal cavity of rats to determine blood indexes at different times and to evaluate the effects of CM-chitosan on the blood system of rats. Coagulation function was reflected by thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4) indexes; anti-coagulation performance was assessed by the index of antithrombinIII (ATIII); fibrinolytic function was reflected by plasminogen (PLG) and fibrin degradation product (FDP) indexes; and blood viscosity (BV) and plasma viscosity (PV) indexes reflected hemorheology. Results showed that CM-chitosan has no significant effects on the blood system of rats, and provides experimental basis for CM-chitosan to be applied in the field of biomedical materials.

  19. Fluorescent Bioactive Corrole Grafted-Chitosan Films.

    PubMed

    Barata, Joana F B; Pinto, Ricardo J B; Vaz Serra, Vanda I R C; Silvestre, Armando J D; Trindade, Tito; Neves, Maria Graça P M S; Cavaleiro, José A S; Daina, Sara; Sadocco, Patrizia; Freire, Carmen S R

    2016-04-11

    Transparent corrole grafted-chitosan films were prepared by chemical modification of chitosan with a corrole macrocycle, namely, 5,10,15-tris(pentafluorophenyl)corrole (TPFC), followed by solvent casting. The obtained films were characterized in terms of absorption spectra (UV-vis), FLIM (fluorescence lifetime imaging microscopy), structure (FTIR, XPS), thermal stability (TGA), thermomechanical properties (DMA), and antibacterial activity. The results showed that the chemical grafting of chitosan with corrole units did not affect its film-forming ability and that the grafting yield increased with the reaction time. The obtained transparent films presented fluorescence which increases with the amount of grafted corrole units. Additionally, all films showed bacteriostatic effect against S. aureus, as well as good thermomechanical properties and thermal stability. Considering these features, promising applications may be envisaged for these corrole-chitosan films, such as biosensors, bioimaging agents, and bioactive optical devices. PMID:26899016

  20. Biophysical studies on chitosan-coated liposomes.

    PubMed

    Mady, Mohsen M; Darwish, Mirhane M; Khalil, Safaa; Khalil, Wafaa M

    2009-10-01

    Liposomes have been used as delivery vehicles for stabilizing drugs, overcoming barriers to cellular and tissue uptake, and for directing their contents toward specific sites in vivo. Chitosan is a biological macromolecule derived from crustacean shells and has several emerging applications in drug development, obesity control, and tissue engineering. In the present work, the interaction between chitosan and dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by transmission electron microscopy (TEM), zeta potential, solubilization using the nonionic detergent octylglucoside (OG), as well as Fourier transform infrared (FTIR) spectroscopy and viscosity measurements. The coating of DPPC liposomes by a chitosan layer was confirmed by electron microscope images and the zeta potential of liposomes. Coating of liposome by chitosan resulted in an increase in liposomal size by addition of a layer of 92 +/- 27.1 nm. The liposomal zeta potential became increasingly positive as chitosan concentration increased from 0.1 to 0.3% w/v, then it held at a relatively constant value. The amount of detergent needed to completely solubilize the liposomal membrane was increased after coating of liposomes with chitosan, indicating an increased membrane resistance to the detergent and hence a change in the natural membrane permeation properties. In the analysis of FTIR spectra of DPPC, the symmetric and antisymmetric CH(2) (at 2,800-3,000 cm(-1)) bands and the C=O (at 1,740 cm(-1)) stretching band were investigated in the absence and presence of the chitosan. It was concluded that appropriate combining of the liposomal and chitosan characteristics might be utilized for the improvement of the therapeutic efficacy of liposomes as a drug delivery system. PMID:19649627

  1. Effect of chitosan molecular weight on rheological behavious of chitosan modified nanoclay at highly hydrated state

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effect of chitosan molecular weight (M(cs)) on the rheological properties of chitosan modified clay (CMCs) at highly hydrated state was investigated. With special emphasis on its effect on the thixotropy of CMCs, the structure recovery at rest after underwent a pre-shearing process was further perfo...

  2. Effect of Chitosan Properties on Immunoreactivity.

    PubMed

    Ravindranathan, Sruthi; Koppolu, Bhanu Prasanth; Smith, Sean G; Zaharoff, David A

    2016-01-01

    Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application. PMID:27187416

  3. A novel thermoresponsive hydrogel based on chitosan.

    PubMed

    Schuetz, Yannic B; Gurny, Robert; Jordan, Olivier

    2008-01-01

    Injectable thermosetting chitosan hydrogels are attractive systems for drug delivery and tissue engineering that combine biodegradability, biocompatibility and the ability to form in situ gel-like implants. Thermally-induced gelation relies advantageously on biopolymer secondary interactions, avoiding potentially toxic polymerization reactions that may occur with in situ polymerizing formulations. In view of a biomedical use, such formulations have to be sterilizable and storable on extended periods without losing their thermosetting properties. These two key features have been studied in the present paper. Chitosans from two different sources were added with several phosphate-free polyols or polyoses as gelling agents. Despite a reduction in chitosan molecular weight following autoclaving, the hydrogels prepared with autoclaved chitosan showed the desired thermosetting properties. Hence, chitosan steam sterilization combined with aseptic preparation of the hydrogel allows a sterile formulation to be obtained. Whereas thermosetting hydrogels were shown to be unstable when refrigerated, freezing was shown to be conceivable as a storage method. When trehalose or mannitol was used as stabilizing agent, the formulation reconstituted from a lyophilizate displayed thermosetting properties and was still injectable, paving the way to the development of a clinically utilizable, novel chitosan thermosetting hydrogel. PMID:17884402

  4. Effect of Chitosan Properties on Immunoreactivity

    PubMed Central

    Ravindranathan, Sruthi; Koppolu, Bhanu prasanth; Smith, Sean G.; Zaharoff, David A.

    2016-01-01

    Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application. PMID:27187416

  5. Maillard reaction products from chitosan-xylan ionic liquid solution.

    PubMed

    Luo, Yuqiong; Ling, Yunzhi; Wang, Xiaoying; Han, Yang; Zeng, Xianjie; Sun, Runcang

    2013-10-15

    A facile method is reported to prepare Maillard reaction products (MRPs) from chitosan and xylan in co-solvent ionic liquid. UV absorbance and fluorescence changes were regarded as indicators of the occurrence of Maillard reaction. FT-IR, NMR, XRD and TG were used to investigate the structure of chitosan-xylan conjugate. The results revealed that when chitosan reacted with xylan in ionic liquid, the hydrogen bonds in chitosan were destroyed, the facts resulted in the formation of chitosan-xylan MRPs. Moreover, when the mass ratio of chitosan to xylan was 1:1, the Maillard reaction proceeded easily. In addition, relatively high antioxidant property was also noted for the chitosan-xylan conjugate with mass ratio 1:1. So the obtained chitosan-xylan MRP is a promising antioxidant agent for food industry. PMID:23987419

  6. Chitosan Tethered Colloidal Gold Nanospheres for Drug Delivery Applications.

    PubMed

    Hari, Kalpana; Kumpati, Premkumar

    2016-01-01

    Gold Nanospheres (AuNS) have been widely explored as an emerging system for various biomedical applications including drug delivery, bioimaging and photomedicine. However, method of synthesizing nanoparticles and its toxicity including bioaccumulation has been a problem of concern. In the present study, we explored the appropriateness of 12.0 ±1.99 nm chitosan reduced AuNS in vivo models with respect to its bioavailability and toxicity against various concentrations (2.5-7.5 mg/kg). Administration of AuNS did not show any signs of morbidity. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis of blood (0.156 ± 0.154), urine (0.084 ± 0.08) and tissues indicates gradual dissipation and obligatory clearance within 24 h time interval. Nevertheless, pres- ence of AuNS in blood after 24 h confirms the bioavailability of AuNS demonstrating the evidence for no immune clearance and efficient tissue uptake. Further, brain shows the lowest quantity of injected AuNS. From this result, we determine this chitosan monolayer protected AuNS could cross the blood brain barrier and enter to the neural tissues. Interestingly there was no evidence of toxicity in any of the organs. In conclusion, our data suggest that AuNS injected though tail vain were easily taken up by tissues and does not produce sub-acute physiological damage even at high concentrations tested, supporting chitosan reduced AuNS as biocompatible, nontoxic nanoconjugates for targeted drug delivery and other biomedical applications. PMID:27398449

  7. Influence of chitosan coating on magnetic nanoparticles in endothelial cells and acute tissue biodistribution.

    PubMed

    Agotegaray, Mariela; Campelo, Adrián; Zysler, Roberto; Gumilar, Fernanda; Bras, Cristina; Minetti, Alejandra; Massheimer, Virginia; Lassalle, Verónica

    2016-08-01

    Chitosan coating on magnetic nanoparticles (MNPs) was studied on biological systems as a first step toward the application in the biomedical field as drug-targeted nanosystems. Composition of MNPs consists of magnetite functionalized with oleic acid and coated with the biopolymer chitosan or glutaraldehyde-cross-linked chitosan. The influence of the biopolymeric coating has been evaluated by in vitro and in vivo assays on the effects of these MNPs on rat aortic endothelial cells (ECs) viability and on the random tissue distribution in mice. Results were correlated with the physicochemical properties of the nanoparticles. Nitric oxide (NO) production by ECs was determined, considering that endothelial NO represents one of the major markers of ECs function. Cell viability was studied by MTT assay. Different doses of the MNPs (1, 10 and 100 μg/mL) were assayed, revealing that MNPs coated with non-cross-linked chitosan for 6 and 24 h did not affect neither NO production nor cell viability. However, a significant decrease in cell viability was observed after 36 h treatment with the highest dose of this nanocarrier. It was also revealed that the presence and dose of glutaraldehyde in the MNPs structureimpact on the cytotoxicity. The study of the acute tissue distribution was performed acutely in mice after 24 h of an intraperitoneal injection of the MNPs and sub acutely, after 28 days of weekly administration. Both formulations greatly avoided the initial clearance by the reticuloendothelial system (RES) in liver. Biological properties found for N1 and N2 in the performed assays reveal that chitosan coating improves biocompatibility of MNPs turning these magnetic nanosystems as promising devices for targeted drug delivery. PMID:27251857

  8. Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications

    PubMed Central

    Cheung, Randy Chi Fai; Ng, Tzi Bun; Wong, Jack Ho; Chan, Wai Yee

    2015-01-01

    Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted. PMID:26287217

  9. Pyridine-grafted chitosan derivative as an antifungal agent.

    PubMed

    Jia, Ruixiu; Duan, Yunfei; Fang, Qiang; Wang, Xiangyang; Huang, Jianying

    2016-04-01

    Pyridine moieties were introduced into chitosan by nucleophilic substitution to afford N-(1-carboxybutyl-4-pyridinium) chitosan chloride (pyridine chitosan). The resulting chitosan derivative was well characterized, and its antifungal activity was examined, based on the inhibition of mycelial growth and spore germination. The results indicated that pyridine chitosan exhibited enhanced antifungal activity by comparison with pristine chitosan. The values of the minimum inhibitory concentration and the minimal fungicidal concentration of pyridine chitosan against Fulvia fulva were 0.13 mg/ml and 1 mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13 mg/ml and 4 mg/ml, respectively. Severe morphological changes of pyridine chitosan-treated B. cinerea were observed, indicative that pyridine chitosan could damage and deform the structure of fungal hyphae and subsequently inhibit strain growth. Non-toxicity of pyridine chitosan was demonstrated by an acute toxicity study. These results are beneficial for assessing the potential utilization of this chitosan derivative and for exploring new functional antifungal agents with chitosan in the food industry. PMID:26593505

  10. Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

    PubMed Central

    Malhotra, Meenakshi; Tomaro-Duchesneau, Catherine; Saha, Shyamali; Kahouli, Imen; Prakash, Satya

    2013-01-01

    Recently, cell-penetrating peptides have been proposed to translocate antibodies, proteins, and other molecules in targeted drug delivery. The proposed study presents the synthesis and characterization of a peptide-based chitosan nanoparticle for small interfering RNA (siRNA) delivery, in-vitro. Specifically, the synthesis included polyethylene glycol (PEG), a hydrophilic polymer, and trans-activated transcription (TAT) peptide, which were chemically conjugated on the chitosan polymer. The conjugation was achieved using N-Hydroxysuccinimide-PEG-maleimide (heterobifunctional PEG) as a cross-linker, with the bifunctional PEG facilitating the amidation reaction through its N-Hydroxysuccinimide group and reacting with the amines on chitosan. At the other end of PEG, the maleimide group was chemically conjugated with the cysteine-modified TAT peptide. The degree of substitution on chitosan with PEG and on PEG with TAT was confirmed using colorimetric assays. The resultant polymer was used to form nanoparticles complexing siRNA, which were then characterized for particle size, morphology, cellular uptake, and cytotoxicity. The nanoparticles were tested in-vitro on mouse neuroblastoma cells (Neuro2a). Particle size and surface charge were characterized and an optimal pH condition and PEG molecular weight were determined to form sterically stable nanoparticles. Results indicate 7.5% of the amines in chitosan polymer were conjugated to the PEG and complete conjugation of TAT peptide was observed on the synthesized PEGylated chitosan polymer. Compared with unmodified chitosan nanoparticles, the nanoparticles formed at pH 6 were monodispersed and of <100 nm in size, exhibiting maximum cell transfection ability and very low cytotoxicity. Thus, this research may be of significance in translocating biotherapeutic molecules for intracellular delivery applications. PMID:23723699

  11. In vitro treatments of Echinococcus granulosus with fungal chitosan, as a novel biomolecule

    PubMed Central

    Rahimi-Esboei, Bahman; Fakhar, Mahdi; Chabra, Aroona; Hosseini, Mahboobeh

    2013-01-01

    Objective To determined the antiparasitic activity of the isolated chitosan from Penicillium viridicatum, Penicillium aurantiogriseum and commercial chitosan against protoscolicidal of hydatid cysts were determined. Methods After isolating chitosan from fungal cell walls, four concentrations (50, 100, 200, 400 µg/mL) of each type of prepared chitosan and commercial chitosan were used for 10, 30, 60, and 180 min, respectively. Results Among different type of chitosan, commercial chitosan with the highest degree of deacetylation showed high scolicidal activity in vitro. Fungal chitosan could be recommended, as good as commercial chitosan, for hydatic cysts control. Conclusions It seems to be a good alternative to synthetic and chemical scolicidal. PMID:24075347

  12. Design, characterization and in vitro evaluation of 5-aminosalicylic acid loaded N-succinyl-chitosan microparticles for colon specific delivery.

    PubMed

    Mura, C; Nácher, A; Merino, V; Merino-Sanjuán, M; Manconi, M; Loy, G; Fadda, A M; Díez-Sales, O

    2012-06-01

    The objective of this study was to prepare NS-chitosan microparticles for the delivery of 5-aminosalicylic acid (5-ASA) to the colon. Microparticles can spread out over a large area of colon allowing a more effective local efficacy of 5-ASA. N-Succinyl-chitosan was chosen as carrier system because of its excellent pharmaceutical properties in colon drug targeting such as poor solubility in acid environment, biocompatibility, mucoadhesive properties, and low toxicity. It was prepared by introducing succinic group into chitosan N-terminals of the glucosamine units. 5-ASA loaded NS-chitosan microparticles were prepared using spray-drying. As a control, a matrix obtained by freeze-drying technique was also prepared and tested. Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction studies show the 5-ASA/NS-chitosan electrostatic interactions in both the systems. Mean size of the microparticles was around 5 μm, zeta potential value of both systems was always negative. Scanning electron microscopy (SEM) images show an acceptable spherical non porous structure of microparticles. In vitro swelling and drug release studies were in accordance with the polymer properties, showing the highest swelling ratio and drug release at pH=7.4 (colonic pH) where microparticles were able to deliver more than 90% of 5-ASA during 24h experiments. Rheological studies are in accordance with the swelling and release studies. PMID:22341520

  13. Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells.

    PubMed

    Santos-Carballal, B; Aaldering, L J; Ritzefeld, M; Pereira, S; Sewald, N; Moerschbacher, B M; Götte, M; Goycoolea, F M

    2015-01-01

    Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan-hsa-miRNA-145 (CS-miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS-miRNA nanocomplexes were produced with a range of (+/-) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS-miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS-miRNA complexes offer a promising non-viral platform for breast cancer gene therapy. PMID:26324407

  14. Role of pH-responsiveness in the design of chitosan-based cancer nanotherapeutics: A review.

    PubMed

    Suarato, Giulia; Li, Weiyi; Meng, Yizhi

    2016-12-01

    There is a continuous demand for sensitive and efficient cancer drug delivery systems that, when administered at low concentrations, are capable of detecting early-stage pathological conditions and increasing patient survival without adverse side effects. Recent developments in the design of chitosan-based smart drug delivery nanocomplexes are able to respond to the distinctive features of the tumor microenvironment and have provided powerful tools for cancer targeted treatment. Due to its biocompatibility and pH-responsiveness, chitosan has emerged as a promising candidate for the formulation of novel, supramolecular multifunctional materials. This review will first present an overview of the characteristics of solid tumors and their microenvironment, with a particular emphasis on the role of pH as a key factor. In the second part of the review, the stimuli-responsive potential of chitosan-based micelles, current challenges in delivery, and strategies to improve therapeutic efficacy will be discussed. PMID:27016506

  15. Safety evaluation of chitosan and chitosan acid salts from Panurilus argus lobster.

    PubMed

    Lagarto, Alicia; Merino, Nelson; Valdes, Odalys; Dominguez, Jesus; Spencer, Evelyn; de la Paz, Nilia; Aparicio, Guillermo

    2015-01-01

    Chitosan is a natural polymer with excellent properties such as biocompatibility, biodegradability, non-toxicity and adsorptive abilities. We obtained chitosan derived from Panurilus argus lobster shell and its lactate and acetate salts to introduce in pharmaceutical industry. We examined the single and repeated dose toxicity of chitosan and its lactate and acetate salts. Single oral doses of 2000 mg/kg were well tolerated for all three materials. In the repeat dose tests, animals treated with chitosan only show a slight erythrocytes increase. Variations in erythrocyte and leukocyte count and some biochemical parameters were observed in animals treated with chitosan acid salts. One g/kg orally was found to be the subacute NOAEL for chitosan due to the hematological findings observed were not considered adverse. Chitosans obtained from Panurilus argus lobster shell have low toxicity and may be safe in rats because it did not cause any lethality or changes in the general behavior in both the single and repeated dose toxicity studies. PMID:25450835

  16. Formation and dissolution of chitosan/pyrophosphate nanoparticles: is the ionic crosslinking of chitosan reversible?

    PubMed

    Cai, Yuhang; Lapitsky, Yakov

    2014-03-01

    Ionically crosslinked chitosan particles with submicron dimensions attract widespread interest as materials for controlled release. To this end, we have examined the formation and dissolution of nanoparticles prepared by crosslinking chitosan with pyrophosphate (PPi). The formation of these particles required a critical PPi concentration (which increased with the chitosan concentration), and their z-average hydrodynamic diameters could be predictably tuned from roughly 60 to 220 nm by varying the concentration of the parent chitosan solutions. Unlike the nanoparticles crosslinked with the commonly used tripolyphosphate (TPP), which coagulated and precipitated when TPP was in excess, the chitosan/PPi nanoparticles remained colloidally stable even at high PPi concentrations. Moreover, the analysis of their dissolution revealed hysteresis in the particle formation/dissolution cycle, where portions of the crosslinked chitosan/PPi complexes remained stably intact at PPi concentrations below those required for their formation. This irreversible behavior was surmised to reflect the cooperativity of chitosan/PPi binding and was qualitatively modeled using the Bragg-Williams theory. PMID:24333908

  17. Hg(II) removal from water by chitosan and chitosan derivatives: a review.

    PubMed

    Miretzky, P; Cirelli, A Fernandez

    2009-08-15

    Mercury (Hg) is one of the most toxic heavy metals commonly found in the global environment. Its toxicity is related to the capacity of its compounds to bioconcentrate in organisms and to biomagnify through food chain. A wide range of adsorbents has been used for removing Hg(II) from contaminated water. Chitosan is obtained by alkaline deacetylation of chitin. The adsorption capacity of chitosan depends on the origin of the polysaccharide, and on the experimental conditions in the preparation, that determine the degree of deacetylation. A great number of chitosan derivatives have been obtained by crosslinking with glutaraldehyde or epichlorohydrin among others or by grafting new functional groups on the chitosan backbone with the aim of adsorbing Hg(II). The new functional groups are incorporated to change the pH range for Hg(II) sorption and/or to change the sorption sites in order to increase sorption selectivity. The chemical modification affords a wide range of derivatives with modified properties for specific applications. Hg(II) adsorption on chitosan or chitosan derivatives is now assumed to occur through several single or mixed interactions: chelation or coordination on amino groups in a pendant fashion or in combination with vicinal hydroxyl groups, electrostatic attraction in acidic media or ion exchange with protonated amino groups. This review reports the recent developments in the Hg(II) removal in waste water treatment, using chitosan and its derivatives in order to provide useful information about the different technologies. When possibly the adsorption capacity of chitosan and chitosan derivatives under different experimental conditions is reported to help to compare the efficacy of the Hg(II) removal process. A comparison with the adsorption capacity of other low-cost adsorbents is also tabled. PMID:19232467

  18. Towards a less biased dissolution of chitosan.

    PubMed

    Thevarajah, Joel J; Bulanadi, Jerikho C; Wagner, Manfred; Gaborieau, Marianne; Castignolles, Patrice

    2016-09-01

    The dissolution of polysaccharides is notoriously challenging, especially when one needs a "true" solution. Factors influencing chitosan's solubility include composition, also known as degree of acetylation (DA). The dissolution of chitosan was investigated by visual observation, size-exclusion chromatography (SEC), pressure mobilization (PM), free-solution capillary electrophoresis (CE) and real-time solution-state NMR spectroscopy. Aqueous HCl dissolves around 15% more chitosan than the commonly used aqueous acetic acid (AcOH), however aggregates were detected in SEC suggesting incomplete dissolution. Significant deacetylation of chitosan over the period needed for dissolution at high temperature was observed by NMR spectroscopy in DCl by about 20% of the initial DA value. Accurate DA determination by NMR spectroscopy may thus be possible only in the solid state (with a precision within 1% on the DA % scale above a DA of 10%). Overall a compromise between maximum solubilization and minimum degradation is required in attempting to obtain a "true" solution of chitosan. The completeness of the dissolution may be more influenced by the average DA than by molar mass. PMID:27543035

  19. Specific interactions in modified chitosan systems.

    PubMed

    Rinaudo, M; Auzely, R; Vallin, C; Mullagaliev, I

    2005-01-01

    This paper concerns the bulk and interfacial properties of a series of alkylated chitosans having different alkyl chain lengths grafted randomly along the main chitosan chain. Chitosan has a low degree of acetylation (5%); on chitosan derivatives, the role of the degree of grafting and of length of the alkyl chains are examined. The optimum alkyl chain length is C12 and the degree of grafting 5% to get physical gelation based on the formation of hydrophobic domains. The cross-linking is essentially controlled by the salt concentration: it is shown that 0.025 M AcONa is needed to screen electrostatic interchain repulsions. Hydrophobic interactions produce highly non-Newtonian behavior with large thinning behavior; this behavior is suppressed in the presence of cyclodextrins able to cap the hydrophobic alkyl chains. The interfacial properties of the chitosan derivatives were tested for the air/aqueous solution interfaces. Specifically, the role of their structure on the kinetic of film formation was examined showing that excess of external salt favors the stabilization of the interfacial film. The derivatives with a higher degree of substitution and longer alkyl chains are more efficient and give a higher elastic modulus compared to the model surfactant as a result of the chain properties. PMID:16153074

  20. Chitosan-silica hybrid porous membranes.

    PubMed

    Pandis, Christos; Madeira, Sara; Matos, Joana; Kyritsis, Apostolos; Mano, João F; Ribelles, José Luis Gómez

    2014-09-01

    Chitosan-silica porous hybrids were prepared by a novel strategy in order to improve the mechanical properties of chitosan (CHT) in the hydrogel state. The inorganic silica phase was introduced by sol-gel reactions in acidic medium inside the pores of already prepared porous scaffolds. In order to make the scaffolds insoluble in acidic media chitosan was cross-linked by genipin (GEN) with an optimum GEN concentration of 3.2 wt.%. Sol-gel reactions took place with Tetraethylorthosilicate (TEOS) and 3-glycidoxypropyltrimethoxysilane (GPTMS) acting as silica precursors. GPTMS served also as a coupling agent between the free amino groups of chitosan and the silica network. The morphology study of the composite revealed that the silica phase appears as a layer covering the chitosan membrane pore walls. The mechanical properties of the hybrids were characterized by means of compressive stress-strain measurements. By immersion in water the hybrids exhibit an increase in elastic modulus up to two orders of magnitude. PMID:25063153

  1. Degradation of chitosan-based materials after different sterilization treatments

    NASA Astrophysics Data System (ADS)

    San Juan, A.; Montembault, A.; Gillet, D.; Say, J. P.; Rouif, S.; Bouet, T.; Royaud, I.; David, L.

    2012-02-01

    Biopolymers have received in recent years an increasing interest for their potential applications in the field of biomedical engineering. Among the natural polymers that have been experimented, chitosan is probably the most promising in view of its exceptional biological properties. Several techniques may be employed to sterilize chitosan-based materials. The aim of our study was to compare the effect of common sterilization treatments on the degradation of chitosan-based materials in various physical states: solutions, hydrogels and solid flakes. Four sterilization methods were compared: gamma irradiation, beta irradiation, exposure to ethylene oxide and saturated water steam sterilization (autoclaving). Exposure to gamma or beta irradiation was shown to induce an important degradation of chitosan, regardless of its physical state. The chemical structure of chitosan flakes was preserved after ethylene oxide sterilization, but this technique has a limited use for materials in the dry state. Saturated water steam sterilization of chitosan solutions led to an important depolymerization. Nevertheless, steam sterilization of chitosan flakes bagged or dispersed in water was found to preserve better the molecular weight of the polymer. Hence, the sterilization of chitosan flakes dispersed in water would represent an alternative step for the preparation of sterilized chitosan solutions. Alternatively, autoclaving chitosan physical hydrogels did not significantly modify the macromolecular structure of the polymer. Thus, this method is one of the most convenient procedures for the sterilization of physical chitosan hydrogels after their preparation.

  2. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    PubMed Central

    Andersen, Toril; Bleher, Stefan; Flaten, Gøril Eide; Tho, Ingunn; Mattsson, Sofia; Škalko-Basnet, Nataša

    2015-01-01

    Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances. PMID:25574737

  3. Effects of sulfate chitosan derivatives on nonalcoholic fatty liver disease

    NASA Astrophysics Data System (ADS)

    Yu, Mingming; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

    2014-06-01

    Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentration emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly ameliorated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

  4. Chitosan nanoparticles conjugate with trypsin and trypsin inhibitor.

    PubMed

    Chanphai, P; Tajmir-Riahi, H A

    2016-06-25

    Chitosan-protein conjugates are widely used in therapeutic drug delivery. We report the bindings of chitosan nanoparticles with trypsin (try) and trypsin inhibitor (tryi), using thermodynamic analysis and multiple spectroscopic methods. Thermodynamic parameters ΔS, ΔH and ΔG showed chitosan-protein bindings occur mainly via H-bonding and van der Waals contacts with trypsin inhibitor forming more stable conjugate than trypsin. As chitosan size increased more stable polymer-protein conjugate was formed. Chitosan complexation induces more perturbations of trypsin inhibitor structure than trypsin with reduction of protein alpha-helix and major increase of random structure. The negative value of ΔG indicates spontaneous protein-chitosan complexation at room temperature. Chitosan nanoparticles can be used to transport trypsin and trypsin inhibitor. PMID:27083826

  5. Chitosan Fibers Modified with HAp/β–TCP Nanoparticles

    PubMed Central

    Wawro, Dariusz; Pighinelli, Luciano

    2011-01-01

    This paper describes a method for preparing chitosan fibers modified with hydroxyapatite (HAp), tricalcium phosphate (β-TCP), and HAp/β-TCP nanoparticles. Fiber-grade chitosan derived from the northern shrimp (Pandalus borealis) and nanoparticles of tricalcium phosphate (β-TCP) and hydroxyapatite (HAp) suspended in a diluted chitosan solution were used in the investigation. Diluted chitosan solution containing nanoparticles of Hap/β-TCP was introduced to a 5.16 wt% solution of chitosan in 3.0 wt% acetic acid. The properties of the spinning solutions were examined. Chitosan fibers modified with nanoparticles of HAp/β-TCP were characterized by a level of tenacity and calcium content one hundred times higher than that of regular chitosan fibers. PMID:22174598

  6. Using nano-chitosan for harvesting microalga Nannochloropsis sp.

    PubMed

    Farid, Mohammad Sadegh; Shariati, Ahmad; Badakhshan, Amir; Anvaripour, Bagher

    2013-03-01

    In this study, chitosan and nano-chitosan were used as flocculants agents for harvesting microalga Nannochloropsis sp. chitosan was modified to nano-chitosan by crosslinking with sodium tripolyphosphate. The effects of type and dosage of flocculants and the pH of the culture were investigated on biomass recovery. Optimum dosages for both bio-flocculants were found. The results showed that the dosage of flocculant consumption decreases by 40% and biomass recovery increases by 9% when nano-chitosan instead of chitosan is used as flocculant agent. Also, the recycled water from the harvesting process was reused which increases the growth of microalgae by about 7%. Finally, the cost analysis of harvesting process showed the feasibility of using nano-chitosan as flocculation agent. PMID:23415940

  7. Quantum dot/glycol chitosan fluorescent nanoconjugates

    NASA Astrophysics Data System (ADS)

    Mansur, Alexandra AP; Mansur, Herman S.

    2015-04-01

    In this study, novel carbohydrate-based nanoconjugates combining chemically modified chitosan with semiconductor quantum dots (QDs) were designed and synthesised via single-step aqueous route at room temperature. Glycol chitosan (G-CHI) was used as the capping ligand aiming to improve the water solubility of the nanoconjugates to produce stable and biocompatible colloidal systems. UV-visible (UV-vis) spectroscopy, photoluminescence (PL) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy were used to characterise the synthesis and the relative stability of biopolymer-capped semiconductor nanocrystals. The results clearly demonstrated that the glycol chitosan derivative was remarkably effective at nucleating and stabilising semiconductor CdS quantum dots in aqueous suspensions under acidic, neutral, and alkaline media with an average size of approximately 2.5 nm and a fluorescent activity in the visible range of the spectra.

  8. Comparison and Characterisation of Regenerated Chitosan from 1-Butyl-3-methylimidazolium Chloride and Chitosan from Crab Shells

    PubMed Central

    Arnold, Lyndon

    2015-01-01

    Chitosan is a biopolymer derived from chitin which is naturally occurring in the exoskeleton of crustaceans. This paper reports dissolution and regeneration of chitosan by directly dissolving in an ionic liquid solvent, 1-butyl-3-methylimidazolium chloride (BMIMCl). This will provide an ideal platform to solubilise these kinds of polymers to achieve the dissolution. The current study dissolved chitosan from crab shell utilising BMIMCl as a solvent and characterised the resultant regenerated polymer. The regenerated chitosan showed increased hydrogen bonding when characterised by Fourier transform infrared (FTIR) spectral analysis. In addition, the study also compared the characteristics of regenerated and generic chitosan. The regenerated chitosan was also evaluated for antimicrobial properties and showed to possess antibacterial features similar to the commercial grade. This method can be utilised in future for blending of polymers with chitosan in a dissolved phase. PMID:26090452

  9. Construction of Ang2-siRNA chitosan magnetic nanoparticles and the effect on Ang2 gene expression in human malignant melanoma cells

    PubMed Central

    LIU, ZHAO-LIANG; YOU, CAI-LIAN; WANG, BIAO; LIN, JIAN-HONG; HU, XUE-FENG; SHAN, XIU-YING; WANG, MEI-SHUI; ZHENG, HOU-BING; ZHANG, YAN-DING

    2016-01-01

    The aim of the present study was to construct angiopoietin-2 (Ang2)-small interfering (si)RNA chitosan magnetic nanoparticles and to observe the interference effects of the nanoparticles on the expression of the Ang2 gene in human malignant melanoma cells. Ang2-siRNA chitosan magnetic nanoparticles were constructed and transfected into human malignant melanoma cells in vitro. Red fluorescent protein expression was observed, and the transfection efficiency was analyzed. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the inhibition efficiency of Ang2 gene expression. Ang2-siRNA chitosan magnetic nanoparticles were successfully constructed, and at a mass ratio of plasmid to magnetic chitosan nanoparticles of 1:100, the transfection efficiency into human malignant melanoma cells was the highest of the ratios assessed, reaching 61.17%. RT-qPCR analysis showed that the magnetic chitosan nanoparticles effectively inhibited Ang2 gene expression in cells, and the inhibition efficiency reached 59.56% (P<0.05). Ang2-siRNA chitosan magnetic nanoparticles were successfully constructed. The in vitro studies showed that the nanoparticles inhibited Ang2 gene expression in human malignant melanoma tumor cells, which laid the foundation and provided experimental evidence for additional future in vivo studies of intervention targeting malignant melanoma tumor growth in nude mice. PMID:27313729

  10. Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release.

    PubMed

    Wu, Juan; Jiang, Wei; Tian, Renbing; Shen, Yewen; Jiang, Wei

    2016-10-01

    In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future. PMID:27464586

  11. Solid polymer electrolyte from phosphorylated chitosan

    SciTech Connect

    Fauzi, Iqbal Arcana, I Made

    2014-03-24

    Recently, the need of secondary battery application continues to increase. The secondary battery which using a liquid electrolyte was indicated had some weakness. A solid polymer electrolyte is an alternative electrolytes membrane which developed in order to replace the liquid electrolyte type. In the present study, the effect of phosphorylation on to polymer electrolyte membrane which synthesized from chitosan and lithium perchlorate salts was investigated. The effect of the component’s composition respectively on the properties of polymer electrolyte, was carried out by analyzed of it’s characterization such as functional groups, ion conductivity, and thermal properties. The mechanical properties i.e tensile resistance and the morphology structure of membrane surface were determined. The phosphorylation processing of polymer electrolyte membrane of chitosan and lithium perchlorate was conducted by immersing with phosphoric acid for 2 hours, and then irradiated on a microwave for 60 seconds. The degree of deacetylation of chitosan derived from shrimp shells was obtained around 75.4%. Relative molecular mass of chitosan was obtained by viscometry method is 796,792 g/mol. The ionic conductivity of chitosan membrane was increase from 6.33 × 10{sup −6} S/cm up to 6.01 × 10{sup −4} S/cm after adding by 15 % solution of lithium perchlorate. After phosphorylation, the ionic conductivity of phosphorylated lithium chitosan membrane was observed 1.37 × 10{sup −3} S/cm, while the tensile resistance of 40.2 MPa with a better thermal resistance. On the strength of electrolyte membrane properties, this polymer electrolyte membrane was suggested had one potential used for polymer electrolyte in field of lithium battery applications.

  12. Herstellung von Chitosan und einige Anwendungen

    NASA Astrophysics Data System (ADS)

    Struszczyk, Marcin Henryk

    2001-05-01

    1. Die Deacetylierung von crabshell - Chitosan führte gleichzeitig zu einem drastischen Abfall der mittleren viscosimetrischen Molmasse ( Mv), insbesondere wenn die Temperatur und die Konzentration an NaOH erhöht werden. Diese Parameter beeinflussten jedoch nicht den Grad der Deacetylierung (DD). Wichtig ist jedoch die Quelle des Ausgangsmaterials: Chitin aus Pandalus borealis ist ein guter Rohstoff für die Herstellung von Chitosan mit niedrigem DD und gleichzeitig hoher mittlerer Mv, während Krill-Chitin (Euphausia superba) ein gutes Ausgangsmaterial zur Herstellung von Chitosan mit hohem DD und niedrigem Mv ist. Chitosan, das aus Insekten (Calliphora erythrocephala), unter milden Bedingungen (Temperatur: 100°C, NaOH-Konzentration: 40 %, Zeit: 1-2h ) hergestellt wurde, hatte die gleichen Eigenschaften hinsichtlich DD und Mv wie das aus Krill hergestellte Chitosan. Der Bedarf an Zeit, Energie und NaOH ist für die Herstellung von Insekten-Chitosan geringer als für crabshell-Chitosan vergleichbare Resultaten für DD und Mv. 2. Chitosan wurde durch den Schimmelpilz Aspergillus fumigatus zu Chitooligomeren fermentiert. Die Ausbeute beträgt 25%. Die Chitooligomere wurden mit Hilfe von HPLC und MALDI-TOF-Massenspektrmetrie identifiziert. Die Fermentationsmischung fördert die Immunität von Pflanzen gegen Bakterien und Virusinfektion. Die Zunahme der Immunität schwankt jedoch je nach System Pflanze-Pathogen. Die Fermentation von Chitosan durch Aspergillus fumigatus könnte eine schnelle und billige Methode zur Herstellung von Chitooligomeren mit guter Reinheit und Ausbeute sein. Eine partiell aufgereinigte Fermentationsmischung dieser Art könnte in der Landwirtschaft als Pathogeninhibitor genutzt werden. Durch kontrollierte Fermentation, die Chitooligomere in definierter Zusammensetzung (d.h. definierter Verteilung des Depolymerisationsgrades) liefert, könnte man zu Mischungen kommen, die für die jeweilige Anwendung eine optimale Bioaktivität besitzen. 3

  13. Enteric Viral Surrogate Reduction by Chitosan.

    PubMed

    Davis, Robert; Zivanovic, Svetlana; Davidson, P Michael; D'Souza, Doris H

    2015-12-01

    Enteric viruses are a major problem in the food industry, especially as human noroviruses are the leading cause of nonbacterial gastroenteritis. Chitosan is known to be effective against some enteric viral surrogates, but more detailed studies are needed to determine the precise application variables. The main objective of this work was to determine the effect of increasing chitosan concentration (0.7-1.5% w/v) on the cultivable enteric viral surrogates, feline calicivirus (FCV-F9), murine norovirus (MNV-1), and bacteriophages (MS2 and phiX174) at 37 °C. Two chitosans (53 and 222 kDa) were dissolved in water (53 kDa) or 1% acetic acid (222 KDa) at 0.7-1.5%, and were then mixed with each virus to obtain a titer of ~5 log plaque-forming units (PFU)/mL. These mixtures were incubated for 3 h at 37 °C. Controls included untreated viruses in phosphate-buffered saline and viruses were enumerated by plaque assays. The 53 kDa chitosan at the concentrations tested reduced FCV-F9, MNV-1, MS2, and phi X174 by 2.6-2.9, 0.1-0.4, 2.6-2.8, and 0.7-0.9 log PFU/mL, respectively, while reduction by 222 kDa chitosan was 2.2-2.4, 0.8-1.0, 2.6-5.2, and 0.5-0.8 log PFU/mL, respectively. The 222 kDa chitosan at 1 and 0.7% w/v in acetic acid (pH 4.5) caused the greatest reductions of MS2 by 5.2 logs and 2.6 logs, respectively. Overall, chitosan treatments showed the greatest reduction of MS2, followed by FCV-F9, phi X174, and MNV-1. These two chitosans may contribute to the reduction of enteric viruses at the concentrations tested but would require use of other hurdles to eliminate food borne viruses. PMID:26162243

  14. Chitosan-Polypyrrole Fiber for Strain Sensor.

    PubMed

    Lee, Songjun; Yi, Byung-Ju; Chun, Kyoung-Yong; Lee, Jaeah; Kim, Youn Tae; Cha, Eun-Jong; Kim, Seon Jeong

    2015-03-01

    A chitosan/polypyrrole composited fiber as bio-compatible materials for artificial muscles is investigated. The chitosan/polypyrrole fiber (CPF) is fabricated by in-situ chemical polymerization of pyrrole monomer solution using FeCl3 as an oxidant. The electrical resistivity of the fiber is changed according to the strain variation applied to the both ends of the specimen. The sensor built by using the CPF has a higher gauge factor (4) compared to conventional metal strain gauges (~2) indicating a suitable material for delicate force control in sensing work. PMID:26413701

  15. Chitosan Effects on Plant Systems

    PubMed Central

    Malerba, Massimo; Cerana, Raffaella

    2016-01-01

    Chitosan (CHT) is a natural, safe, and cheap product of chitin deacetylation, widely used by several industries because of its interesting features. The availability of industrial quantities of CHT in the late 1980s enabled it to be tested in agriculture. CHT has been proven to stimulate plant growth, to protect the safety of edible products, and to induce abiotic and biotic stress tolerance in various horticultural commodities. The stimulating effect of different enzyme activities to detoxify reactive oxygen species suggests the involvement of hydrogen peroxide and nitric oxide in CHT signaling. CHT could also interact with chromatin and directly affect gene expression. Recent innovative uses of CHT include synthesis of CHT nanoparticles as a valuable delivery system for fertilizers, herbicides, pesticides, and micronutrients for crop growth promotion by a balanced and sustained nutrition. In addition, CHT nanoparticles can safely deliver genetic material for plant transformation. This review presents an overview on the status of the use of CHT in plant systems. Attention was given to the research that suggested the use of CHT for sustainable crop productivity. PMID:27347928

  16. Chitosan Effects on Plant Systems.

    PubMed

    Malerba, Massimo; Cerana, Raffaella

    2016-01-01

    Chitosan (CHT) is a natural, safe, and cheap product of chitin deacetylation, widely used by several industries because of its interesting features. The availability of industrial quantities of CHT in the late 1980s enabled it to be tested in agriculture. CHT has been proven to stimulate plant growth, to protect the safety of edible products, and to induce abiotic and biotic stress tolerance in various horticultural commodities. The stimulating effect of different enzyme activities to detoxify reactive oxygen species suggests the involvement of hydrogen peroxide and nitric oxide in CHT signaling. CHT could also interact with chromatin and directly affect gene expression. Recent innovative uses of CHT include synthesis of CHT nanoparticles as a valuable delivery system for fertilizers, herbicides, pesticides, and micronutrients for crop growth promotion by a balanced and sustained nutrition. In addition, CHT nanoparticles can safely deliver genetic material for plant transformation. This review presents an overview on the status of the use of CHT in plant systems. Attention was given to the research that suggested the use of CHT for sustainable crop productivity. PMID:27347928

  17. SOLVENT PURIFICATION AND FLUOR SELECTION FOR GADOLINIUM-LOADED LIQUID SCINTILLATORS

    SciTech Connect

    Kesete, T.; Storm, A.; Hahn, R. L.; Yeh, M.; Seleem, S.

    2007-01-01

    The last decade has seen huge progress in the study of neutrinos, elementary sub-atomic particles. Continued growth in the fi eld of neutrino research depends strongly on the calculation of the neutrino mixing angle θ13, a fundamental neutrino parameter that is needed as an indicative guideline for proposed next-generation neutrino experiments. Experiments involving reactor antineutrinos are favored for the calculation of θ13 because their derivation equation for θ13 is relatively simple and unambiguous. A Gd-loaded liquid scintillator (Gd-LS) is the centerpiece of the detector and it consists of ~99% aromatic solvent, ~0.1% Gd, and < 1% fl uors. Key required characteristics of the Gd-LS are long-term chemical stability, high optical transparency, and high photon production by the scintillator. This summer’s research focused on two important aspects of the detector: (1) purifi cation of two selected scintillation solvents, 1, 2, 4-trimethylbenzene (PC) and linear alkyl benzene (LAB), to improve the optical transparency and long-term chemical stability of the Gd-LS, and (2) investigation of the added fl uors to optimize the photon production. Vacuum distillation and column separation were used to purify PC and LAB, respectively. Purifi cation was monitored using UV-visible absorption spectra and verifi ed in terms of decreased solvent absorption at 430nm. Absorption in PC at 430nm decreased by a factor slightly >10 while the absorption in LAB was lowered by a factor of ~5. Photon production for every possible combination of two solvents, four primary shifters, and two secondary shifters was determined by measuring the Compton-Scattering excitation induced by an external Cs-137 gamma source (Eγ ~ 662-keV). The ideal shifter concentration was identifi ed by measuring the photon production as a function of shifter quantity in a series of samples. Results indicate that 6g/L p-terphenyl with 150mg/L 1,4-Bis(2-methylstyryl)-benzene (bis-MSB) produces the maximum light yield for PC and 6g/L 2-(4-biphenylyl)-5-(4-tert-butyl-phenyl)-1,3,4-oxadiazole with 50mg/L bis-MSB optimizes the light yield for LAB. Future work should focus on obtaining the fl uorescence spectra for each of the shifters and studying the optical transparency of the LS as a function of shifter quantity.

  18. Development of a gadolinium-loaded liquid scintillator for the Hanaro short baseline prototype detector

    NASA Astrophysics Data System (ADS)

    Yeo, In Sung; Joo, Kyung Kwang; So, Sun Heang; Song, Sook Hyung; Kim, Hong Joo; So, Jung Ho; Park, Kang Soon; Ma, Kyung Ju; Jeon, Eun Ju; Kim, Jin Yu; Kim, Young Duk; Lee, Jason; Lee, Jeong-Yeon; Sun, Gwang-Min

    2014-02-01

    We propose a new experiment on the site of the Korea Atomic Energy Research Institute (KAERI) located at Daejeon, Korea. The Hanaro short baseline (SBL) nuclear reactor with a thermal power output 30 MW is used to investigate a reactor neutrino anomaly. A Hanaro SBL prototype detector having a 60- l volume has been constructed ˜6 m away from the reactor core. A gadolinium (Gd)-loaded liquid scintillator (LS) is used as an active material to trigger events. The selection of the LS is guided by physical and technical requirements, as well as safety considerations. A linear alkyl benzene (LAB) is used as a base solvent of the Hanaro SBL prototype detector. Three g/ l of PPO and 30 mg/ l of bis-MSB are dissolved to formulate the LAB-based LS. Then, a 0.5% gadolinium (Gd) complex with carboxylic acid is loaded into the LAB-based LS by using the liquidliquid extraction method. In this paper, we will summarize all the characteristics of the Gd-loaded LAB-based LS for the Hanaro prototype detector.

  19. Herstellung von Chitosan und einige Anwendungen

    NASA Astrophysics Data System (ADS)

    Struszczyk, Marcin Henryk

    2001-05-01

    1. Die Deacetylierung von crabshell - Chitosan führte gleichzeitig zu einem drastischen Abfall der mittleren viscosimetrischen Molmasse ( Mv), insbesondere wenn die Temperatur und die Konzentration an NaOH erhöht werden. Diese Parameter beeinflussten jedoch nicht den Grad der Deacetylierung (DD). Wichtig ist jedoch die Quelle des Ausgangsmaterials: Chitin aus Pandalus borealis ist ein guter Rohstoff für die Herstellung von Chitosan mit niedrigem DD und gleichzeitig hoher mittlerer Mv, während Krill-Chitin (Euphausia superba) ein gutes Ausgangsmaterial zur Herstellung von Chitosan mit hohem DD und niedrigem Mv ist. Chitosan, das aus Insekten (Calliphora erythrocephala), unter milden Bedingungen (Temperatur: 100°C, NaOH-Konzentration: 40 %, Zeit: 1-2h ) hergestellt wurde, hatte die gleichen Eigenschaften hinsichtlich DD und Mv wie das aus Krill hergestellte Chitosan. Der Bedarf an Zeit, Energie und NaOH ist für die Herstellung von Insekten-Chitosan geringer als für crabshell-Chitosan vergleichbare Resultaten für DD und Mv. 2. Chitosan wurde durch den Schimmelpilz Aspergillus fumigatus zu Chitooligomeren fermentiert. Die Ausbeute beträgt 25%. Die Chitooligomere wurden mit Hilfe von HPLC und MALDI-TOF-Massenspektrmetrie identifiziert. Die Fermentationsmischung fördert die Immunität von Pflanzen gegen Bakterien und Virusinfektion. Die Zunahme der Immunität schwankt jedoch je nach System Pflanze-Pathogen. Die Fermentation von Chitosan durch Aspergillus fumigatus könnte eine schnelle und billige Methode zur Herstellung von Chitooligomeren mit guter Reinheit und Ausbeute sein. Eine partiell aufgereinigte Fermentationsmischung dieser Art könnte in der Landwirtschaft als Pathogeninhibitor genutzt werden. Durch kontrollierte Fermentation, die Chitooligomere in definierter Zusammensetzung (d.h. definierter Verteilung des Depolymerisationsgrades) liefert, könnte man zu Mischungen kommen, die für die jeweilige Anwendung eine optimale Bioaktivität besitzen. 3

  20. Folate mediated histidine derivative of quaternised chitosan as a gene delivery vector.

    PubMed

    Morris, Viola B; Sharma, Chandra P

    2010-04-15

    Folate targeted gene delivery vectors showed enhanced accumulation in folate receptor expressing tumor model. In the present work, the water solubility and transfection efficiency of chitosans were improved by modifying the depolymerised trimethylated chitosans with histidine moiety. Folate mediated targeting was induced by conjugating poly(ethylene glycol)-folate (PEG-FA) on histidine modified chitosan polymer having low molecular weight of 15 kDa and high degree of quaternisation (HTFP15-H). The zeta potential and size of the HTFP15-H/pDNA nanoparticles were determined using dynamic light scattering technique and the results were confirmed by transmission electron microscopy (TEM). The morphology of the nanoparticles was found spherical in shape having core-shell nanostructure. The HTFP15-H derivative found to buffer in the pH range from 10 to 4. The blood compatibility in terms of percentage hemolysis, erythrocyte aggregation and also by platelet activation was found to be significantly improved compared to the control vector PEI. At a concentration of 10 microg the derivative promote the cell growth up to 139% compared to control at normal cell growing conditions. The transfection efficiency in KB cell line, which over expresses the folate receptor (FR) in presence of 10% fetal bovine serum (FBS) was also found to be comparable to the control. Moreover the enhanced cellular and nuclear uptake due to the conjugation of both folic acid and histidine makes it a potential vector for gene delivery applications. PMID:20117198

  1. Thermochemical characteristics of chitosan-polylactide copolymers

    NASA Astrophysics Data System (ADS)

    Goruynova, P. E.; Larina, V. N.; Smirnova, N. N.; Tsverova, N. E.; Smirnova, L. A.

    2016-05-01

    The energies of combustion of chitosan and its block-copolymers with different polylactide contents are determined in a static bomb calorimeter. Standard enthalpies of combustion and formation are calculated for these substances. The dependences of the thermochemical characteristics on block-copolymer composition are determined and discussed.

  2. 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.

  3. The Use of chitosan in The Formation of Silver Nanoparticles, Chitosanic Nanoparticles and Fibrous Structures

    NASA Astrophysics Data System (ADS)

    Abdelgawad, Abdelrahman Mohamed

    Nanoscale materials have attracted much attention in the last two decades due to their unique properties. The size effect attains new chemical and physical properties to these materials. Nanoparticles and nanofiber are major component of nanomaterials and they have heavily investigated in the literature for different applications. Nanoparticles could be produced from both metals as well as polymers. Chitosan, which is a natural polymer, can be used as capping agent in the preparation of metallic nanoparticles and itself, can produce nanoparticles. The utilization of nanoparticles and nanofibers for wound dressing materials is a very popular approach. Acquiring antibacterial properties to the wound dressing materials could be obtained either by formulation of nanomaterials composites or direct chemical modification of the substance. To improve the antibacterial properties of chitosan two approaches were applied. First, is through the formulation of chitosan with silver nanoparticles and the formation of nanofiber mats. In this study, the concepts of green chemistry were applied and silver nanoparticles were prepared in high concentration using chitosan as a capping polymer and glucose as a reducing agent. Nanofiber mats of polyvinyl alcohol/chitosan/silvernanoparticles were produced via electrospinning. The antibacterial activity of these fibers shows bactericidal effect against E. coli at low concentrations of Ag-NPs. In the second approach, direct chemical modification of chitosan was performed by grafting of Iodoacetic acid to the amino group at carbon-2. The chemical structure of chitosan Iodoacetamide derivative (CIA) was confirmed by FTIR and H1-NMR. The derivative was amorphous and water soluble at neutral pH. The minimum inhibitory concentration of CIA, against E. coli, was 400ig/mL and the derivative was bacteriostatic after 4h of treatment. Nanofiber mats of polyvinyl alcohol/chitosan/chitosan Iodoacetamide were produced via electrospinning. The

  4. Gd-DTPA Adsorption on Chitosan/Magnetite Nanocomposites

    NASA Astrophysics Data System (ADS)

    Pylypchuk, Ie. V.; Kołodyńska, D.; Kozioł, M.; Gorbyk, P. P.

    2016-03-01

    The synthesis of the chitosan/magnetite nanocomposites is presented. Composites were prepared by co-precipitation of iron(II) and iron(III) salts by aqueous ammonia in the 0.1 % chitosan solution. It was shown that magnetite synthesis in the chitosan medium does not affect the magnetite crystal structure. The thermal analysis data showed 4.6 % of mass concentration of chitosan in the hybrid chitosan/magnetite composite. In the concentration range of initial Gd-DTPA solution up to 0.4 mmol/L, addition of chitosan to magnetite increases the adsorption capacity and affinity to Gd-DTPA complex. The Langmuir and Freundlich adsorption models were applied to describe adsorption processes. Nanocomposites were characterized by scanning electron microscopy (SEM), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and specific surface area determination (ASAP) methods.

  5. Chitosan-based scaffolds for bone tissue engineering

    PubMed Central

    Levengood, Sheeny Lan; Zhang, Miqin

    2014-01-01

    Bone defects requiring grafts to promote healing are frequently occurring and costly problems in health care. Chitosan, a biodegradable, naturally occurring polymer, has drawn considerable attention in recent years as scaffolding material in tissue engineering and regenerative medicine. Chitosan is especially attractive as a bone scaffold material because it supports the attachment and proliferation of osteoblast cells as well as formation of mineralized bone matrix. In this review, we discuss the fundamentals of bone tissue engineering and the unique properties of chitosan as a scaffolding material to treat bone defects for hard tissue regeneration. We present the common methods for fabrication and characterization of chitosan scaffolds, and discuss the influence of material preparation and addition of polymeric or ceramic components or biomolecules on chitosan scaffold properties such as mechanical strength, structural integrity, and functional bone regeneration. Finally, we highlight recent advances in development of chitosan-based scaffolds with enhanced bone regeneration capability. PMID:24999429

  6. Gd-DTPA Adsorption on Chitosan/Magnetite Nanocomposites.

    PubMed

    Pylypchuk, Ie V; Kołodyńska, D; Kozioł, M; Gorbyk, P P

    2016-12-01

    The synthesis of the chitosan/magnetite nanocomposites is presented. Composites were prepared by co-precipitation of iron(II) and iron(III) salts by aqueous ammonia in the 0.1 % chitosan solution. It was shown that magnetite synthesis in the chitosan medium does not affect the magnetite crystal structure. The thermal analysis data showed 4.6 % of mass concentration of chitosan in the hybrid chitosan/magnetite composite. In the concentration range of initial Gd-DTPA solution up to 0.4 mmol/L, addition of chitosan to magnetite increases the adsorption capacity and affinity to Gd-DTPA complex. The Langmuir and Freundlich adsorption models were applied to describe adsorption processes. Nanocomposites were characterized by scanning electron microscopy (SEM), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and specific surface area determination (ASAP) methods. PMID:27030468

  7. Structural evaluation of phospholipidic nanovesicles containing small amounts of chitosan.

    PubMed

    Mertins, Omar; Cardoso, Mateus Borba; Pohlmann, Adriana Raffin; da Silveira, Nádya Pesce

    2006-08-01

    In this study we present a full characterization of nanovesicles containing soybean phosphatidylcholine and polysaccharide chitosan. The nanovesicles were prepared by the reverse phase evaporation method, including the preparation of reverse micelles followed by the formation of an organogel, which is dispersed in water to yield the final liposomal particles. Structural changes as a function of the chitosan amount and the filter porosity used in the nanovesicles preparation were studied employing Static and Dynamic Light Scattering as well as Small Angle X-ray Scattering. The hydrodynamic radius of the nanovesicles ranged between 106 and 287 nm, depending on the chitosan contents and the filter porosity. A comparison with nanovesicles free of chitosan indicates the existence of higher contents of multilamellar structures that depends on the chitosan concentration in the vesicles containing chitosan. Typical spherical vesicles having nanometric diameters with polydispersity mostly desired in the biomedical area could only be achieved by filtration through a 0.45 microm porous filter. PMID:17037851

  8. Activity of Chitosans in combination with antibiotics in Pseudomonas aeruginosa

    PubMed Central

    Tin, San; Sakharkar, Kishore R.; Lim, Chu Sing; Sakharkar, Meena K.

    2009-01-01

    Chitosan and its derivative water soluble Chitosan oligosaccharide are used in a variety of applications in pharmaceutical preparations. In this study, 2 wild (ATCC 15729 and PAO1) and 2 mutant strains (PT121 and PT149) of P. aeruginosa are investigated for drug-drug interactions in vitro. 10 antimicrobial agents (antibiotics) are combined with different degree of deacetylated Chitosans and Chitosan oligosaccharide. All the chitosans show synergistic activity with sulfamethoxazole, a sulfonamide antimicrobial agent. It is interesting to observe that the MIC value for the MexEF-OprN overexpressing mutant strain of P. aeruginosa is 5 fold higher than the other strains under investigation suggesting a possible role of this efflux pump in Sulfamethoxazole efflux. The findings suggest on the use of chitosans as enhancing agent in combination with antibiotics in pharmaceutical preparations. PMID:19173037

  9. Hydrothermally Treated Chitosan Hydrogel Loaded with Copper and Zinc Particles as a Potential Micronutrient-Based Antimicrobial Feed Additive.

    PubMed

    Rajasekaran, Parthiban; Santra, Swadeshmukul

    2015-01-01

    Large-scale use of antibiotics in food animal farms as growth promoters is considered as one of the driving factors behind increasing incidence of microbial resistance. Several alternatives are under investigation to reduce the amount of total antibiotics used in order to avoid any potential transmission of drug resistant microbes to humans through food chain. Copper sulfate and zinc oxide salts are used as feed supplement as they exhibit antimicrobial properties in addition to being micronutrients. However, higher dosage of copper and zinc (often needed for growth promoting effect) to animals is not advisable because of potential environmental toxicity arising from excreta. Innovative strategies are needed to utilize the complete potential of trace minerals as growth promoting feed supplements. To this end, we describe here the development and preliminary characterization of hydrothermally treated chitosan as a delivery vehicle for copper and zinc nanoparticles that could act as a micronutrient-based antimicrobial feed supplement. Material characterization studies showed that hydrothermal treatment makes a chitosan hydrogel that rearranged to capture the copper and zinc metal particles. Systemic antimicrobial assays showed that this chitosan biopolymer matrix embedded with copper (57.6 μg/ml) and zinc (800 μg/ml) reduced the load of model gut bacteria (target organisms of growth promoting antibiotics), such as Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Lactobacillus fermentum under in vitro conditions. Particularly, the chitosan/copper/zinc hydrogel exhibited significantly higher antimicrobial effect against L. fermentum, one of the primary targets of antibiotic growth promoters. Additionally, the chitosan matrix ameliorated the cytotoxicity levels of metal supplements when screened against a murine macrophage cell line RAW 264.7 and in TE-71, a murine thymic epithelial cell line. In this proof-of-concept study, we show that by using

  10. Hydrothermally Treated Chitosan Hydrogel Loaded with Copper and Zinc Particles as a Potential Micronutrient-Based Antimicrobial Feed Additive

    PubMed Central

    Rajasekaran, Parthiban; Santra, Swadeshmukul

    2015-01-01

    Large-scale use of antibiotics in food animal farms as growth promoters is considered as one of the driving factors behind increasing incidence of microbial resistance. Several alternatives are under investigation to reduce the amount of total antibiotics used in order to avoid any potential transmission of drug resistant microbes to humans through food chain. Copper sulfate and zinc oxide salts are used as feed supplement as they exhibit antimicrobial properties in addition to being micronutrients. However, higher dosage of copper and zinc (often needed for growth promoting effect) to animals is not advisable because of potential environmental toxicity arising from excreta. Innovative strategies are needed to utilize the complete potential of trace minerals as growth promoting feed supplements. To this end, we describe here the development and preliminary characterization of hydrothermally treated chitosan as a delivery vehicle for copper and zinc nanoparticles that could act as a micronutrient-based antimicrobial feed supplement. Material characterization studies showed that hydrothermal treatment makes a chitosan hydrogel that rearranged to capture the copper and zinc metal particles. Systemic antimicrobial assays showed that this chitosan biopolymer matrix embedded with copper (57.6 μg/ml) and zinc (800 μg/ml) reduced the load of model gut bacteria (target organisms of growth promoting antibiotics), such as Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Lactobacillus fermentum under in vitro conditions. Particularly, the chitosan/copper/zinc hydrogel exhibited significantly higher antimicrobial effect against L. fermentum, one of the primary targets of antibiotic growth promoters. Additionally, the chitosan matrix ameliorated the cytotoxicity levels of metal supplements when screened against a murine macrophage cell line RAW 264.7 and in TE-71, a murine thymic epithelial cell line. In this proof-of-concept study, we show that by using

  11. Chitin and Chitosan as Direct Compression Excipients in Pharmaceutical Applications

    PubMed Central

    Badwan, Adnan A.; Rashid, Iyad; Al Omari, Mahmoud M.H.; Darras, Fouad H.

    2015-01-01

    Despite the numerous uses of chitin and chitosan as new functional materials of high potential in various fields, they are still behind several directly compressible excipients already dominating pharmaceutical applications. There are, however, new attempts to exploit chitin and chitosan in co-processing techniques that provide a product with potential to act as a direct compression (DC) excipient. This review outlines the compression properties of chitin and chitosan in the context of DC pharmaceutical applications. PMID:25810109

  12. Antimicrobial effect of chitosan nanoparticles on streptococcus mutans biofilms.

    PubMed

    Chávez de Paz, Luis E; Resin, Anton; Howard, Kenneth A; Sutherland, Duncan S; Wejse, Peter L

    2011-06-01

    Nanoparticle complexes were prepared from chitosans of various molecular weights (MW) and degrees of deacetylation (DD). The antimicrobial effect was assessed by the Live/Dead BacLight technique in conjunction with confocal scanning laser microscopy (CSLM) and image analysis. Nanocomplexes prepared from chitosans with high MW showed a low antimicrobial effect (20 to 25% of cells damaged), whereas those prepared from low-MW chitosans showed high antimicrobial effect (>95% of cells damaged). PMID:21498764

  13. Antimicrobial Effect of Chitosan Nanoparticles on Streptococcus mutans Biofilms▿

    PubMed Central

    Chávez de Paz, Luis E.; Resin, Anton; Howard, Kenneth A.; Sutherland, Duncan S.; Wejse, Peter L.

    2011-01-01

    Nanoparticle complexes were prepared from chitosans of various molecular weights (MW) and degrees of deacetylation (DD). The antimicrobial effect was assessed by the Live/Dead BacLight technique in conjunction with confocal scanning laser microscopy (CSLM) and image analysis. Nanocomplexes prepared from chitosans with high MW showed a low antimicrobial effect (20 to 25% of cells damaged), whereas those prepared from low-MW chitosans showed high antimicrobial effect (>95% of cells damaged). PMID:21498764

  14. Application of chitin and chitosan derivatives in the pharmaceutical field.

    PubMed

    Kato, Yoshinori; Onishi, Hiraku; Machida, Yoshiharu

    2003-10-01

    Chitin and chitosan derivatives are used as excipients and drug carriers in the pharmaceutical field. Their derivatization contributed to expansion of application and decrease toxicity. Chitosan is used as an excipient in oral dosage form. Chitosan tablet can exhibit a sustained drug release compared to commercial products. Films prepared using chitin or chitosan have been developed as wound dressings, oral mucoadhesive and water-resisting adhesive by virtue of their release characteristics and adhesion. Intratumoral administration of gadopentetic acid-chitosan complex nanoparticles (approximately 430 nm in diameter) has been more effective for gadolinium neutron-capture therapy compared with a group treated with the solution. Compared to intragastrical feeding with diphtheria toxoid (DT) in PBS, a strong enhancement of the systemic (IgG) and local (IgA) immune responses against DT has been observed in mice fed with DT loaded chitosan microparticles (approximately 4.7 microm in size). When DNA-loaded chitosan microspheres (1.15 - 1.28 microm) were intramuscularly administrated into mice, high beta-galactosidase and luciferase productions were obtained even after a long post-transfection period (12 weeks). N-Succinyl-chitosan (Suc-Chi) has been studied for cancer chemotherapy as a drug carrier and the conjugates of mitomycin C with Suc-Chi exhibited good antitumor activities against various tumors. Furthermore, trimethyl-chitosan and monocarboxymethyl-chitosan has been shown to be effective as intestinal absorption enhancers due to their physiological properties. Chitosan-thioglycolic acid conjugates has been found to be a promising candidate as scaffold material in tissue engineering due to their physicochemical properties. This review summarizes the application of chitin and chitosan derivatives for hospital preparations and drug carriers. PMID:14529420

  15. Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

    PubMed Central

    Huang, Bei-Bei; Li, Guo-Feng; Luo, Jing-Hui; Duan, Lian; Nobuaki, Kishimoto; Akira, Yamamoto

    2008-01-01

    AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol significantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10% totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rebamipide across the jejunum, ileum and the colon, and

  16. Chemical modification of graphite surfaces using chitosan as a mediator

    SciTech Connect

    Hatley, M.E.; Albahadily, F.N.

    1995-12-01

    Several techniques for modifying graphite surfaces have been utilized the last two decades. Some of these techniques have a few limitations which include monolayer coverage and nonspecific binding to the graphite surfaces. In this report, we describe a novel approach to modify graphite surfaces using chitosan. The graphite is coated with an acidic chitosan solution. After drying, a chitosan film is formed on the graphite surfaces. Glutaraldehyde is attached to the chitosan through an amide linkage. The desired modifiers which contain amine groups are then attached to the free end of the glutaraldehyde. Utilization of the modified graphite surfaces in paste electrodes will be discussed.

  17. Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects

    PubMed Central

    Xu, Long; Huang, Yun-An; Zhu, Qiu-Jin; Ye, Chun

    2015-01-01

    Chitosan is widely used in molecular imprinting technology (MIT) as a functional monomer or supporting matrix because of its low cost and high contents of amino and hydroxyl functional groups. The various excellent properties of chitosan, which include nontoxicity, biodegradability, biocompatibility, and attractive physical and mechanical performances, make chitosan a promising alternative to conventional functional monomers. Recently, chitosan molecularly-imprinted polymers have gained considerable attention and showed significant potential in many fields, such as curbing environmental pollution, medicine, protein separation and identification, and chiral-compound separation. These extensive applications are due to the polymers’ desired selectivity, physical robustness, and thermal stability, as well as their low cost and easy preparation. Cross-linkers, which fix the functional groups of chitosan around imprinted molecules, play an important role in chitosan molecularly-imprinted polymers. This review summarizes the important cross-linkers of chitosan molecularly-imprinted polymers and illustrates the cross-linking mechanism of chitosan and cross-linkers based on the two glucosamine units. Finally, some significant attempts to further develop the application of chitosan in MIT are proposed. PMID:26262607

  18. Surface active properties of chitosan and its derivatives.

    PubMed

    Elsabee, Maher Z; Morsi, Rania Elsayed; Al-Sabagh, A M

    2009-11-01

    This review discusses the definition of surface active agents and specifically natural polymeric surface active agents. Chitosan by itself was found to have weak surface activity since it has no hydrophobic segments. Chemical modifications of chitosan could improve such surface activity. This is achieved by introducing hydrophobic substituents in its glucosidic group. Several examples of chitosan derivatives with surfactant activity have been surveyed. The surface active polymers form micelles and aggregates which have enormous importance in the entrapment of water-insoluble drugs and consequently applications in the controlled drug delivery and many biomedical fields. Chitosan also interacts with several substrates by electrostatic and hydrophobic interactions with considerable biomedical applications. PMID:19682870

  19. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations. PMID:24818769

  20. Chitosan grafted monomethyl fumaric acid as a potential food preservative.

    PubMed

    Khan, Imran; Ullah, Shafi; Oh, Deog-Hwan

    2016-11-01

    The present study aims at in vitro antibacterial and antioxidant activity evaluation of chitosan modified with monomethyl fumaric acid (MFA) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as mediator. Three different kinds of chitosan derivatives Ch-Ds-1,Ch-Ds-2 and Ch-Ds-3 were synthesized by feeding different concentration of MFA. The chemical structures of resulting materials were characterized by (1)H NMR, (13)C NMR, HR-XRD, FT-IR and TNBS assay. The results showed that Ch-Ds-1, Ch-Ds-2 and Ch-Ds-3 were successfully synthesized. The % amino groups of chitosan modified by MFA were evaluated by TNBS assay and ranging from 1.82±0.05% to 7.88±0.04%. All the chitosan derivatives are readily soluble in water and swelled by dimethyl sulfoxide (DMSO), toluene and dimethyl formamide (DMF). The antioxidant activity for all the chitosan derivatives have been significantly improved (P<0.05) compared to the chitosan. Upon antibacterial activity at pH 4.0, all the chitosan derivatives showed significant (P<0.05) antibacterial activity against Gram positive Staphylococcus aureus, Listeria monocytogenes strains and Gram negative Escherichia coli and Salmonella enteritidis strains compared to chitosan. In conclusion, MFA modified chitosan has shown enhanced activities along with solubility, and could be used as a novel food preservative and packaging material for long time food safety and security. PMID:27516253

  1. Pharmacokinetics and biodegradation performance of a hydroxypropyl chitosan derivative

    NASA Astrophysics Data System (ADS)

    Shao, Kai; Han, Baoqin; Dong, Wen; Song, Fulai; Liu, Weizhi; Liu, Wanshun

    2015-10-01

    Hydroxypropyl chitosan (HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical and pharmaceutical fields. However, it is not yet known about its pharmacokinetics and biodegradation performance, which are crucial for its clinical applications. In order to lay a foundation for its further applications and exploitations, here we carried out fluorescence intensity and GPC analyses to determine the pharmacokinetics mode of fluorescein isothiocyanate-labeled HP-chitosan (FITC-HP-chitosan) and its biodegradability. The results showed that after intraperitoneal administration at a dose of 10 mg per rat, FITC-HP-chitosan could be absorbed rapidly and distributed to liver, kidney and spleen through blood. It was indicated that FITC-HP-chitosan could be utilized effectively, and 88.47% of the FITC-HP-chitosan could be excreted by urine within 11 days with a molecular weight less than 10 kDa. Moreover, our data indicated that there was an obvious degradation process occurred in liver (< 10 kDa at 24 h). In summary, HP-chitosan has excellent bioavailability and biodegradability, suggesting the potential applications of hydroxypropyl-modified chitosan as materials in drug delivery, tissue engineering and biomedical area.

  2. Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects.

    PubMed

    Xu, Long; Huang, Yun-An; Zhu, Qiu-Jin; Ye, Chun

    2015-01-01

    Chitosan is widely used in molecular imprinting technology (MIT) as a functional monomer or supporting matrix because of its low cost and high contents of amino and hydroxyl functional groups. The various excellent properties of chitosan, which include nontoxicity, biodegradability, biocompatibility, and attractive physical and mechanical performances, make chitosan a promising alternative to conventional functional monomers. Recently, chitosan molecularly-imprinted polymers have gained considerable attention and showed significant potential in many fields, such as curbing environmental pollution, medicine, protein separation and identification, and chiral-compound separation. These extensive applications are due to the polymers' desired selectivity, physical robustness, and thermal stability, as well as their low cost and easy preparation. Cross-linkers, which fix the functional groups of chitosan around imprinted molecules, play an important role in chitosan molecularly-imprinted polymers. This review summarizes the important cross-linkers of chitosan molecularly-imprinted polymers and illustrates the cross-linking mechanism of chitosan and cross-linkers based on the two glucosamine units. Finally, some significant attempts to further develop the application of chitosan in MIT are proposed. PMID:26262607

  3. Improvement of chitosan adsorption onto cellulosic fabrics by plasma treatment.

    PubMed

    Fras Zemljic, Lidija; Persin, Zdenka; Stenius, Per

    2009-05-11

    Oxygen plasma treatment was applied in order to improve the adsorption of chitosan onto viscose fabric. Modification of the surface and adsorption of chitosan was monitored by determination of XPS spectra, determination of contact angles from rates of water imbibition, and conductometric titration. The plasma treatment resulted in hydrophilization of the surfaces through oxidation. The hydrophilic surfaces were stable for at least 24 h. The treatment also yielded binding sites that resulted in over 20% increase of the amount of chitosan adsorbed over that adsorbed on nontreated fabric. Layers of chitosan adsorbed after plasma treatment were substantially more active as antimicrobial agents than those on nontreated surfaces. PMID:19301906

  4. New antimicrobial chitosan derivatives for wound dressing applications.

    PubMed

    Dragostin, Oana Maria; Samal, Sangram Keshari; Dash, Mamoni; Lupascu, Florentina; Pânzariu, Andreea; Tuchilus, Cristina; Ghetu, Nicolae; Danciu, Mihai; Dubruel, Peter; Pieptu, Dragos; Vasile, Cornelia; Tatia, Rodica; Profire, Lenuta

    2016-05-01

    Chitosan is a non-toxic, biocompatible, biodegradable natural cationic polymer known for its low imunogenicity, antimicrobial, antioxidant effects and wound-healing activity. To improve its therapeutic potential, new chitosan-sulfonamide derivatives have been designed to develop new wound dressing biomaterials. The structural, morphological and physico-chemical properties of synthesized chitosan derivatives were analyzed by FT-IR, (1)H NMR spectroscopy, scanning electron microscopy, swelling ability and porosity. Antimicrobial, in vivo testing and biodegradation behavior have been also performed. The chitosan derivative membranes showed improved swelling and biodegradation rate, which are important characteristics required for the wound healing process. The antimicrobial assay evidenced that chitosan-based sulfadiazine, sulfadimethoxine and sulfamethoxazole derivatives were the most active. The MTT assay showed that some of chitosan derivatives are nontoxic. Furthermore, the in vivo study on burn wound model induced in Wistar rats demonstrated an improved healing effect and enhanced epithelialization of chitosan-sulfonamide derivatives compared to neat chitosan. The obtained results strongly recommend the use of some of the newly developed chitosan derivatives as antimicrobial wound dressing biomaterials. PMID:26876993

  5. Application of Ferriferous Oxide Modified by Chitosan in Gene Delivery

    PubMed Central

    Kuang, Yu; Yuan, Tun; Zhang, Zhongwei; Li, Mingyuan; Yang, Yuan

    2012-01-01

    New approaches to improve the traditional gene carriers are still required. Here we explore Fe3O4 modified with degradable polymers that enhances gene delivery and target delivery using permanent magnetic field. Two magnetic Fe3O4 nanoparticles coated with chitosan (CTS) and polyethylene glycol (PEG) were synthesized by means of controlled chemical coprecipitation. Plasmid pEGFP was encapsulated as a reported gene. The ferriferous oxide complexes were approximately spherical; surface charge of CTS-Fe3O4 and PEG-Fe3O4 was about 20 mv and 0 mv, respectively. The controlled release of DNA from the CTS-Fe3O4 nanoparticles was observed. Concurrently, a desired Fe3O4 concentration of less than 2 mM was verified as safe by means of a cytotoxicity test in vitro. Presence of the permanent magnetic field significantly increased the transfection efficiency. Furthermore, the passive target property and safety of magnetic nanoparticles were also demonstrated in an in vivo test. The novel gene delivery system was proved to be an effective tool required for future target expression and gene therapy in vivo. PMID:23326667

  6. Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration.

    PubMed

    Ma, Shiqing; Adayi, Aidina; Liu, Zihao; Li, Meng; Wu, Mingyao; Xiao, Linghao; Sun, Yingchun; Cai, Qing; Yang, Xiaoping; Zhang, Xu; Gao, Ping

    2016-01-01

    Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration. PMID:27546177

  7. Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves.

    PubMed

    Meyer, Cora; Stenberg, Lena; Gonzalez-Perez, Francisco; Wrobel, Sandra; Ronchi, Giulia; Udina, Esther; Suganuma, Seigo; Geuna, Stefano; Navarro, Xavier; Dahlin, Lars B; Grothe, Claudia; Haastert-Talini, Kirsten

    2016-01-01

    Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction. PMID:26517563

  8. Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration

    PubMed Central

    Ma, Shiqing; Adayi, Aidina; Liu, Zihao; Li, Meng; Wu, Mingyao; Xiao, Linghao; Sun, Yingchun; Cai, Qing; Yang, Xiaoping; Zhang, Xu; Gao, Ping

    2016-01-01

    Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration. PMID:27546177

  9. Chitosan promotes immune responses, ameliorates glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, but enhances lactate dehydrogenase levels in normal mice in vivo

    PubMed Central

    YEH, MING-YANG; SHIH, YUNG-LUEN; CHUNG, HSUEH-YU; CHOU, JASON; LU, HSU-FENG; LIU, CHIA-HUI; LIU, JIA-YOU; HUANG, WEN-WEN; PENG, SHU-FEN; WU, LUNG-YUAN; CHUNG, JING-GUNG

    2016-01-01

    Chitosan, a naturally derived polymer, has been shown to possess antimicrobial and anti-inflammatory properties; however, little is known about the effect of chitosan on the immune responses and glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) activities in normal mice. The aim of the present study was to investigate whether chitosan has an effect on the immune responses and GOT, GPT and LDH activities in mice in vivo. BALB/c mice were divided into four groups. The negative control group was treated with a normal diet; the positive control group was treated with a normal diet plus orally administered acetic acid and two treatment groups were treated with a normal diet plus orally administered chitosan in acetic acid at doses of 5 and 20 mg/kg, respectively, every other day for 24 days. Mice were weighed during the treatment, and following the treatment, blood was collected, and liver and spleen samples were isolated and weighted. The blood samples were used for measurement of white blood cell markers, and the spleen samples were used for analysis of phagocytosis, natural killer (NK) cell activity and cell proliferation using flow cytometry. The results indicated that chitosan did not markedly affect the body, liver and spleen weights at either dose. Chitosan increased the percentages of CD3 (T-cell marker), CD19 (B-cell marker), CD11b (monocytes) and Mac-3 (macrophages) when compared with the control group. However, chitosan did not affect the phagocytic activity of macrophages in peripheral blood mononuclear cells, although it decreased it in the peritoneal cavity. Treatment with 20 mg/kg chitosan led to a reduction in the cytotoxic activity of NK cells at an effector to target ratio of 25:1. Chitosan did not significantly promote B-cell proliferation in lipopolysaccharide-pretreated cells, but significantly decreased T-cell proliferation in concanavalin A-pretreated cells, and decreased the activity of

  10. Multimodal in vivo MRI and NIRF imaging of bladder tumor using peptide conjugated glycol chitosan nanoparticles

    NASA Astrophysics Data System (ADS)

    Key, Jaehong; Dhawan, Deepika; Knapp, Deborah W.; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Leary, James F.

    2012-03-01

    Exact detection and complete removal of cancer is a key point to minimize cancer recurrence. However, it is currently very difficult to detect small tumors inside human body and continuously monitor tumors using a non-invasive imaging modality. Presently, positron emission tomography (PET) can provide the most sensitive cancer images in the human body. However, PET imaging has very limited imaging time because they typically use isotopes with short halflives. PET imaging cannot also visualize anatomical information. Magnetic resonance imaging (MRI) can provide highresolution images inside the body but it has a low sensitivity, so MRI contrast agents are necessary to enhance the contrast of tumor. Near infrared fluorescent (NIRF) imaging has a good sensitivity to visualize tumor using optical probes, but it has a very limited tissue penetration depth. Therefore, we developed multi-modality nanoparticles for MRI based diagnosis and NIRF imaging based surgery of cancer. We utilized glycol chitosan of 350 nm as a vehicle for MRI contrast agents and NIRF probes. The glycol chitosan nanoparticles were conjugated with NIRF dye, Cy5.5 and bladder cancer targeting peptides to increase the internalization of cancer. For MR contrast effects, iron oxide based 22 nm nanocubes were physically loaded into the glycol chitosan nanoparticles. The nanoparticles were characterized and evaluated in bladder tumor bearing mice. Our study suggests the potential of our nanoparticles by both MRI and NIRF imaging for tumor diagnosis and real-time NIRF image-guided tumor surgery.

  11. Paraquat-loaded alginate/chitosan nanoparticles: preparation, characterization and soil sorption studies.

    PubMed

    Silva, Mariana dos Santos; Cocenza, Daniela Sgarbi; Grillo, Renato; de Melo, Nathalie Ferreira Silva; Tonello, Paulo Sérgio; de Oliveira, Luciana Camargo; Cassimiro, Douglas Lopes; Rosa, André Henrique; Fraceto, Leonardo Fernandes

    2011-06-15

    Agrochemicals are amongst the contaminants most widely encountered in surface and subterranean hydrological systems. They comprise a variety of molecules, with properties that confer differing degrees of persistence and mobility in the environment, as well as different toxic, carcinogenic, mutagenic and teratogenic potentials, which can affect non-target organisms including man. In this work, alginate/chitosan nanoparticles were prepared as a carrier system for the herbicide paraquat. The preparation and physico-chemical characterization of the nanoparticles was followed by evaluation of zeta potential, pH, size and polydispersion. The techniques employed included transmission electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. The formulation presented a size distribution of 635 ± 12 nm, polydispersion of 0.518, zeta potential of -22.8 ± 2.3 mV and association efficiency of 74.2%. There were significant differences between the release profiles of free paraquat and the herbicide associated with the alginate/chitosan nanoparticles. Tests showed that soil sorption of paraquat, either free or associated with the nanoparticles, was dependent on the quantity of organic matter present. The results presented in this work show that association of paraquat with alginate/chitosan nanoparticles alters the release profile of the herbicide, as well as its interaction with the soil, indicating that this system could be an effective means of reducing negative impacts caused by paraquat. PMID:21493003

  12. Brain Localization and Neurotoxicity Evaluation of Polysorbate 80-Modified Chitosan Nanoparticles in Rats

    PubMed Central

    Yuan, Zhong-Yue; Hu, Yu-Lan; Gao, Jian-Qing

    2015-01-01

    The toxicity evaluation of inorganic nanoparticles has been reported by an increasing number of studies, but toxicity studies concerned with biodegradable nanoparticles, especially the neurotoxicity evaluation, are still limited. For example, the potential neurotoxicity of Polysorbate 80-modified chitosan nanoparticles (Tween 80-modified chitosan nanoparticles, TmCS-NPs), one of the most widely used brain targeting vehicles, remains unknown. In the present study, TmCS-NPs with a particle size of 240 nm were firstly prepared by ionic cross-linking of chitosan with tripolyphosphate. Then, these TmCS-NPs were demonstrated to be entered into the brain and specially deposited in the frontal cortex and cerebellum after systemic injection. Moreover, the concentration of TmCS-NPs in these two regions was found to decrease over time. Although no obvious changes were observed for oxidative stress in the in vivo rat model, the body weight was found to remarkably decreased in a dose-dependent manner after exposure to TmCS-NPs for seven days. Besides, apoptosis and necrosis of neurons, slight inflammatory response in the frontal cortex, and decrease of GFAP expression in the cerebellum were also detected in mouse injected with TmCS-NPs. This study is the first report on the sub-brain biodistribution and neurotoxicity studies of TmCS-NPs. Our results provide new insights into the toxicity evaluation of nanoparticles and our findings would help contribute to a better understanding of the neurotoxicity of biodegradable nanomaterials used in pharmaceutics. PMID:26248340

  13. Ion-imprinted chitosan gel beads for selective adsorption of Ag⁺ from aqueous solutions.

    PubMed

    Zhang, Meng; Helleur, Robert; Zhang, Yan

    2015-10-01

    In this study, the Ag(+)-imprinted chitosan gel beads were synthesized to selectively adsorb Ag(+) from bimetallic aqueous solutions containing the same molar concentration of Ag(+) and Cu(2+). The Ag(+)-imprinting not only helps to achieve extremely high selectivity of Ag(+), but also enhances the uptake capacity of the target Ag(+) by protecting some amine groups, the primary binding sites of metal ions from cross-linking. The maximum uptake of Ag(+) by the ion-imprinted chitosan beads was found to be 89.20 mg g(-1) at 25.0°C with an initial Ag(+) concentration of 352.95 mg L(-1) and the biosorbent dosage of 1.0 g L(-1). The adsorption equilibrium and kinetics of Ag(+) by the ion-imprinted chitosan beads can be better described by Langmuir isotherm and the intraparticle diffusion model. FTIR and XPS analyses suggested that amine functional groups involve the binding of Ag(+) via complexation at higher solution pH (3.0 ≤ pH ≤ 5.0) and ion exchange at lower solution pH (1.0 ≤ pH < 3.0). PMID:26076618

  14. Selective cell recruitment and spatially controlled cell attachment on instructive chitosan surfaces functionalized with antibodies.

    PubMed

    Custódio, C A; Frias, A M; del Campo, A; Reis, R L; Mano, J F

    2012-12-01

    Bioactive constructs to guide cellular mobilization and function have been proposed as an approach for a new generation of biomaterials in functional tissue engineering. Adult mesenchymal stem cells have been widely used as a source for cell based therapeutic strategies, namely tissue engineering. This is a heterogeneous cell population containing many subpopulations with distinct regenerative capacity. Thus, one of the issues for the effective clinical use of stem cells in tissue engineering is the isolation of a highly purified, expandable specific subpopulation of stem cells. Antibody functionalized biomaterials could be promising candidates to isolate and recruit specific cell types. Here we propose a new concept of instructive biomaterials that are able to recruit and purify specific cell types from a mixed cell population. This biomimetic concept uses a target-specific chitosan substrate to capture specific adipose derived stem cells. Specific antibodies were covalently immobilized onto chitosan membranes using bis[sulfosuccinimidyl] suberate (BS3). Quartz crystal microbalance (QCM) was used to monitor antibody immobilization/adsorption onto the chitosan films. Specific antibodies covalently immobilized, kept their bioactivity and captured specific cell types from a mixed cell population. Microcontact printing allowed to covalently immobilize antibodies in patterns and simultaneously a spatial control in cell attachment. PMID:23109106

  15. A Chitin Synthase and Its Regulator Protein Are Critical for Chitosan Production and Growth of the Fungal Pathogen Cryptococcus neoformans†

    PubMed Central

    Banks, Isaac R.; Specht, Charles A.; Donlin, Maureen J.; Gerik, Kimberly J.; Levitz, Stuart M.; Lodge, Jennifer K.

    2005-01-01

    Chitin is an essential component of the cell wall of many fungi. Chitin also can be enzymatically deacetylated to chitosan, a more flexible and soluble polymer. Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningoencephalitis, particularly in immunocompromised patients. In this work, we show that both chitin and chitosan are present in the cell wall of vegetatively growing C. neoformans yeast cells and that the levels of both rise dramatically as cells grow to higher density in liquid culture. C. neoformans has eight putative chitin synthases, and strains with any one chitin synthase deleted are viable at 30°C. In addition, C. neoformans genes encode three putative regulator proteins, which are homologs of Saccharomyces cerevisiae Skt5p. None of these three is essential for viability. However, one of the chitin synthases (Chs3) and one of the regulators (Csr2) are important for growth. Cells with deletions in either CHS3 or CSR2 have several shared phenotypes, including sensitivity to growth at 37°C. The similarity of their phenotypes also suggests that Csr2 specifically regulates chitin synthesis by Chs3. Lastly, both chs3Δ and the csr2Δ mutants are defective in chitosan production, predicting that Chs3-Csr2 complex with chitin deacetylases for conversion of chitin to chitosan. These data suggest that chitin synthesis could be an excellent antifungal target. PMID:16278457

  16. Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

    PubMed Central

    Santos-Carballal, B.; Aaldering, L. J.; Ritzefeld, M.; Pereira, S.; Sewald, N.; Moerschbacher, B. M.; Götte, M.; Goycoolea, F. M.

    2015-01-01

    Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan–hsa-miRNA-145 (CS–miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS–miRNA nanocomplexes were produced with a range of (+/−) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS–miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS–miRNA complexes offer a promising non-viral platform for breast cancer gene therapy. PMID:26324407

  17. Immobilization of catalase on chitosan and amino acid- modified chitosan beads.

    PubMed

    Başak, Esra; Aydemir, Tülin

    2013-08-01

    Bovine liver catalase was covalently immobilized onto amino acid-modified chitosan beads. The beads were characterized with SEM, FTIR, TGA and the effects of immobilization on optimum pH and temperature, thermostability, reusability were evaluated. Immobilized catalase showed the maximal enzyme activity at pH 7.0 at 30°C. The kinetic parameters, Km and Vmax, for immobilized catalase on alanine-chitosan beads and lysine-chitosan beads were estimated to be 25.67 mM, 27 mM and 201.39 μmol H2O2/min, 197.50 μmol H2O2/min, respectively. The activity of the immobilized catalase on Ala-CB and Lys-CB retained 40% of its high initial activity after 100 times of reuse. PMID:23316810

  18. Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility.

    PubMed

    Norowski, Peter A; Fujiwara, Tomoko; Clem, William C; Adatrow, Pradeep C; Eckstein, Eugene C; Haggard, Warren O; Bumgardner, Joel D

    2015-05-01

    Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue infiltration into the graft space during dental procedures that involve bone grafting. Chitosan materials have shown promise as GBR barrier membranes, due to their biocompatibility and predictable biodegradability, but degradation rates may still be too high for clinical applications. In this study, chitosan GBR membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%), with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent, in order to extend the degradation to meet the clinical target time frame of 4-6 months. Membranes were evaluated for fibre diameter, tensile strength, biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5 or 10 mm, resulted in median fibre diameters 184, 144 and 154 nm for uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined by Fourier transform infrared spectroscopy, showed a decrease in N-H stretch as genipin levels were increased. Genipin-crosslinked mats exhibited only 22% degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16 weeks in vitro. The ultimate tensile strength of the mats was increased by 165% to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally, genipin-crosslinked mats supported the proliferation of SAOS-2 cells in a 5 day growth study, similar to uncrosslinked mats. These results suggest that electrospun chitosan mats may benefit from genipin crosslinking and have the potential to meet clinical degradation time frames for GBR applications. PMID:23166109

  19. Development and evaluation of chitosan and chitosan derivative nanoparticles containing insulin for oral administration.

    PubMed

    Hecq, J; Siepmann, F; Siepmann, J; Amighi, K; Goole, J

    2015-01-01

    Chitosan and chitosan derivative-based nanoparticles loaded with insulin were prepared by self-assembly, via electrostatic interactions between the negatively charged drug and the positively charged polymers. In the investigated chitosan derivatives, the amine groups were substituted to different extents (33, 52 or 99%) by 2-hydroxypropyl-3-trimethyl ammonium groups, rendering the polymers permanently positively charged, irrespective of the pH. This is an important property for this type of advanced drug delivery system, since the pH value changes throughout the gastrointestinal tract and electrostatic interactions are of crucial importance for the stability of the nanoparticles. Permanent positive charges are also in favor of mucoadhesion. In contrast, the electric charges of chitosan molecules depend on the pH of the surrounding medium. Since the solubility of the chitosan derivatives increased due to the introduction of quaternary ammonium groups, sodium tripolyphosphate (TPP) was added to the systems to create supplementary cross-links and stabilize the nanoparticles. The presence of TPP influenced both the dissolution of the polymer matrix as well as the resulting release kinetics. The underlying drug release mechanisms were found to be more complex than simple diffusion under constant conditions, likely involving also ionic interactions and matrix dissolution. The most promising formulation was based on a chitosan derivative with 33% substitution degree and characterized by a Z-average of 142 ± 10 nm, a zeta potential of 29 ± 1 mV, an encapsulation efficacy of 52 ± 3% and, most importantly, the release of insulin was sustained for more than 210 min. PMID:26006329

  20. Spectroscopy analysis of chitosan-glibenclamide hydrogels.

    PubMed

    Delgadillo-Armendariz, Nancy-Liliana; Rangel-Vázquez, Norma-Aurea; García-Castañón, Alejandra-Ibeth

    2014-01-01

    The structure of glibenclamide, 5-chloro-N-(2-{4-[(cyclohexylamino)carbonyl] aminosulfonyl}phenyl) ethyl)-2-methoxybenzamide, an important antidiabetic drug, has been studied both chitosan using theoretical calculations like Gibbs free energy, electrostatic potential, FTIR and NMR spectroscopy. Fourier transform infrared (FT-IR) spectroscopy reveals information about the molecular interactions of chemical components and is useful to characterization of hydrogel. Nucleophilic and electrophilic regions were calculated using the electrostatic potential. PMID:24216118

  1. Spheroid formation of mesenchymal stem cells on chitosan and chitosan-hyaluronan membranes.

    PubMed

    Huang, Guo-Shiang; Dai, Lien-Guo; Yen, Betty L; Hsu, Shan-hui

    2011-10-01

    Stem cells can lose their primitive properties during in vitro culture. The culture substrate may affect the behavior of stem cells as a result of cell-substrate interaction. The maintenance of self-renewal for adult human mesenchymal stem cells (MSCs) by a biomaterial substrate, however, has not been reported in literature. In this study, MSCs isolated from human adipose (hADAS) and placenta (hPDMC) were cultured on chitosan membranes and those further modified by hyaluronan (chitosan-HA). It was observed that the MSCs of either origin formed three-dimensional spheroids that kept attached on the membranes. Spheroid formation was associated with the increased MMP-2 expression. Cells on chitosan-HA formed spheroids more quickly and the size of spheroids were larger than on chitosan alone. The expression of stemness marker genes (Oct4, Sox2, and Nanog) for MSCs on the materials was analyzed by the real-time RT-PCR. It was found that formation of spheroids on chitosan and chitosan-HA membranes helped to maintain the expression of stemness marker genes of MSCs compared to culturing cells on polystyrene dish. The maintenance of stemness marker gene expression was especially remarkable in hPDMC spheroids (vs. hADAS spheroids). Blocking CD44 by antibodies prevented the spheroid formation and decreased the stemness gene expression moderately; while treatment by Y-27632 compound inhibited the spheroid formation and significantly decreased the stemness gene expression. Upon chondrogenic induction, the MSC spheroids showed higher levels of Sox9, aggrecan, and collagen type II gene expression and were stained positive for glycosaminoglycan and collagen type II. hPDMC had better chondrogenic differentiation potential than hADAS upon induction. Our study suggested that the formation of adhered spheroids on chitosan and chitosan-HA membranes may sustain the expression of stemness marker genes of MSCs and increase their chondrogenic differentiation capacity. The Rho

  2. Self-assemblies on chitosan nanohydrogels.

    PubMed

    Brunel, Fabrice; Véron, Laurent; David, Laurent; Domard, Alain; Verrier, Bernard; Delair, Thierry

    2010-04-01

    Nanohydrogels of pure chitosan, containing neither potentially toxic solvent nor chemical cross-linker, were obtained by an ammonia-induced physical gelation of a reverse emulsion of a chitosan solution in a triglyceride mixture as an organic phase. The resulting colloids were obtained with a controlled size distribution and displayed a positive surface charge. Assemblies with various macromolecules were investigated as a first step toward new nano-carriers for bioactive molecules. Chondroitin sulfate formed polyelectrolyte complexes with the positively charged surface of the nanogels, leading to negative chitosan-based colloidal hydrogels with preservation of the original average size of the dispersion. The mode of assembly of HIV-1 p24 protein with these colloids relied on multiple interactions between the protein and the hydrogels, irrespective of their surface charges. Anyhow, the amounts of loaded protein remained limited, suggesting a surface association. The assembly of an immunoglobulin (IgG) was markedly different from p24. No association was detected with the positive colloidal hydrogels whereas a very high loading capacity could be obtained with the negative ones. So, this work reports that fully biodegradable submicrometric physical hydrogels could be obtained from naturally occurring polymers. These gels could cargo a variety of biomolecules making them versatile carriers with many potential applications in Life Sciences. PMID:20166229

  3. Synthesis and characterization of oil-chitosan composite spheres.

    PubMed

    Huang, Keng-Shiang; Wang, Chih-Yu; Yang, Chih-Hui; Grumezescu, Alexandru Mihai; Lin, Yung-Sheng; Kung, Chao-Pin; Lin, I-Yin; Chang, Yi-Ching; Weng, Wei-Jie; Wang, Wei-Ting

    2013-01-01

    Oil-chitosan composite spheres were synthesized by encapsulation of sunflower seed oil in chitosan droplets, dropping into NaOH solution and in situ solidification. Hydrophilic materials (i.e., iron oxide nanoparticles) and lipophilic materials (i.e., rhodamine B or epirubicin) could be encapsulated simultaneously in the spheres in a one step process. The diameters of the prepared spheres were 2.48 ± 0.11 mm (pure chitosan spheres), 2.31 ± 0.08 mm (oil-chitosan composites), 1.49 ± 0.15 mm (iron-oxide embedded oil-chitosan composites), and 1.69 ± 0.1 mm (epirubicin and iron oxide encapsulated oil-chitosan composites), respectively. Due to their superparamagnetic properties, the iron-oxide embedded oil-chitosan composites could be guided by a magnet. A lipophilic drug (epirubicin) could be loaded in the spheres with encapsulation rate measured to be 72.25%. The lipophilic fluorescent dye rhodamine B was also loadable in the spheres with red fluorescence being observed under a fluorescence microscope. We have developed a novel approach to an in situ process for fabricating oil-chitosan composite spheres with dual encapsulation properties, which are potential multifunctional drug carriers. PMID:23681059

  4. Mucoadhesive 4-carboxybenzenesulfonamide-chitosan with antibacterial properties.

    PubMed

    Suvannasara, Phruetchika; Juntapram, Kotchakorn; Praphairaksit, Nalena; Siralertmukul, Krisana; Muangsin, Nongnuj

    2013-04-15

    The mucoadhesive property of chitosan, especially in an acidic (chitosan. Four different feeding ratios of 4-carboxybenzensulfonamide (4-CBS) to chitosan in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a coupling agent were investigated. The 0.2:1 (w/w) ratio 4-CBS:chitosan revealed a 20-fold stronger mucoadhesion to mucin type II than the native chitosan in the simulated gastric fluid (SGF; pH 1.2), and a swelling ratio after 1 h in water, SGF and simulated intestinal fluid (pH 7.4) of about 2.9-, 3.0- and 3.4-fold higher than that of chitosan, respectively. In tissue culture, the 4-CBS-chitosan, like chitosan, were found to be non-cytotoxic to the Vero, KB, MCF-7 and NCI-H187 cell lines but showed potential antibacterial activity against Escherichia coli and Staphlyococcus aureus as model gram-negative and gram-positive bacteria, respectively. PMID:23544535

  5. Electrosprayed 4-carboxybenzenesulfonamide-chitosan microspheres for acetazolamide delivery.

    PubMed

    Suvannasara, Phruetchika; Siralertmukul, Krisana; Muangsin, Nongnuj

    2014-03-01

    4-Carboxybenzensulfonamide-chitosan (4-CBS-chitosan) microspheres were prepared by electrospraying with acetazolamide (ACZ) as a model drug. The obtained 4-CBS-chitosan microspheres with or without ACZ-loading were characterized by Fourier transform infrared spectroscopy, differential scanning colorimetry, scanning electron microscopy and particle size analyses. The crystalline form and the stability of ACZ in a basic solution was determined using X-ray single crystal analysis. 4-CBS-chitosan had 90% encapsulation efficiency for ACZ compared to 47% of encapsulation efficiency (EE) obtained from native chitosan, forming 3.1 μm diameter microspheres with a low polydispersity index (0.4). After an initial burst release (58% in 5 min), ACZ-loaded 4-CBS-chitosan gave a sustained release of ACZ (∼ 100% over 3h) in simulated gastric fluid (0.1N HCl; pH 1.2), which was better than that seen for the release from ACZ-loaded chitosan (44% over 1.5h). Thus, 4-CBS-chitosan microspheres are a possible drug carrier in acidic conditions, such as at the gastric mucosal wall. PMID:24360896

  6. Barrier properties of nano silicon carbide designed chitosan nanocomposites.

    PubMed

    Pradhan, Gopal C; Dash, Satyabrata; Swain, Sarat K

    2015-12-10

    Nano silicon carbide (SiC) designed chitosan nanocomposites were prepared by solution technique. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used for studying structural interaction of nano silicon carbide (SiC) with chitosan. The morphology of chitosan/SiC nanocomposites was investigated by field emission scanning electron microscope (FESEM), and high resolution transmission electron microscope (HRTEM). The thermal stability of chitosan was substantially increased due to incorporation of stable silicon carbide nanopowder. The oxygen permeability of chitosan/SiC nanocomposites was reduced by three folds as compared to the virgin chitosan. The chemical resistance properties of chitosan were enhanced due to the incorporation of nano SiC. The biodegradability was investigated using sludge water. The tensile strength of chitosan/SiC nanocomposites was increased with increasing percentage of SiC. The substantial reduction in oxygen barrier properties in combination with increased thermal stability, tensile strength and chemical resistance properties; the synthesized nanocomposite may be suitable for packaging applications. PMID:26428100

  7. Electrically Conductive Chitosan/Carbon Scaffolds for Cardiac Tissue Engineering

    PubMed Central

    2015-01-01

    In this work, carbon nanofibers were used as doping material to develop a highly conductive chitosan-based composite. Scaffolds based on chitosan only and chitosan/carbon composites were prepared by precipitation. Carbon nanofibers were homogeneously dispersed throughout the chitosan matrix, and the composite scaffold was highly porous with fully interconnected pores. Chitosan/carbon scaffolds had an elastic modulus of 28.1 ± 3.3 KPa, similar to that measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m. The scaffolds were seeded with neonatal rat heart cells and cultured for up to 14 days, without electrical stimulation. After 14 days of culture, the scaffold pores throughout the construct volume were filled with cells. The metabolic activity of cells in chitosan/carbon constructs was significantly higher as compared to cells in chitosan scaffolds. The incorporation of carbon nanofibers also led to increased expression of cardiac-specific genes involved in muscle contraction and electrical coupling. This study demonstrates that the incorporation of carbon nanofibers into porous chitosan scaffolds improved the properties of cardiac tissue constructs, presumably through enhanced transmission of electrical signals between the cells. PMID:24417502

  8. Antimicrobial and physicochemical properties of chitosan-HPMC-based films.

    PubMed

    Möller, Heike; Grelier, Stéphane; Pardon, Patrick; Coma, Véronique

    2004-10-20

    To prepare composite films from biopolymers with anti-listerial activity and moisture barrier properties, the antimicrobial efficiency of chitosan-hydroxy propyl methyl cellulose (HPMC) films, chitosan-HPMC films associated with lipid, and chitosan-HPMC films chemically modified by cross-linking were evaluated. In addition, the physicochemical properties of composite films were evaluated to determine their potential for food applications. The incorporation of stearic acid into the composite chitosan-HPMC film formulation decreased water sensitivity such as initial solubility in water and water drop angle. Thus, cross-linking of composite chitosan-HPMC, using citric acid as the cross-linking agent, led to a 40% reduction in solubility in water. The water vapor transfer rate of HPMC film, approximately 270 g x m(-2) x day(-1) x atm(-1), was improved by incorporating chitosan and was further reduced 40% by the addition of stearic acid and/or cross-linking. Anti-listerial activity of films was determined on solid medium by a numeration technique. Chitosan-HPMC-based films, with and without stearic acid, inhibited the growth of Listeria monocytogenes completely. On the other hand, a loss of antimicrobial activity after chemical cross-linking modification was observed. FTIR and 13C NMR analyses were then conducted in order to study a potential chemical modification of biopolymers such as a chemical reaction with the amino group of chitosan. To complete the study, the mechanical properties of composite films were determined from tensile strength assays. PMID:15479027

  9. Biopolymers produced from gelatin and chitosan using polyphenols

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chitin, and its derivative chitosan, is an abundant waste product derived from crustaceans (e.g. crab). It has unique properties which enable its use in, but not limited to, cosmetic, medical, and food applications. Chitosan has recently been studied, in conjunction with other waste carbohydrates ...

  10. Migration of canine neutrophils to chitin and chitosan.

    PubMed

    Usami, Y; Okamoto, Y; Minami, S; Matsuhashi, A; Kumazawa, N H; Tanioka, S; Shigemasa, Y

    1994-12-01

    Suspension of chitin and chitosan particles (mean size of 1 micron) were found to attract canine neutrophils chemotactically as determined by a checkerboard assay through polycarbonate filter with 5 microns pore size in Blind well chamber. Suspension of chitin induced chemokinetic migrations of the neutrophils. These evidences might reflect accumulation of neutrophils to chitin- and chitosan-implanted regions in dogs. PMID:7696425