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Sample records for carbon nanotube-mediated delivery

  1. Impact of carbondiimide crosslinker used for magnetic carbon nanotube mediated GFP plasmid delivery

    NASA Astrophysics Data System (ADS)

    Hao, Yuzhi; Xu, Peng; He, Chuan; Yang, Xiaoyan; Huang, Min; Xing, James; Chen, Jie

    2011-07-01

    1-ethyl-3-(3-dimethylaminopropyl) carbondiimide hydrochloride (EDC) is commonly used as a crosslinker to help bind biomolecules, such as DNA plasmids, with nanostructures. However, EDC often remains, after a crosslink reaction, in the micro-aperture of the nanostructure, e.g., carbon nanotube. The remaining EDC shows positive green fluorescent signals and makes a nanostructure with a strong cytotoxicity which induces cell death. The toxicity of EDC was confirmed on a breast cancer cell line (MCF-7) and two leukemic cell lines (THP-1 and KG-1). The MCF-7 cells mainly underwent necrosis after treatment with EDC, which was verified by fluorescein isothiocyanate (FITC) annexin V staining, video microscopy and scanning electronic microscopy (SEM). If the EDC was not removed completely, the nanostructures with remaining EDC produced a green fluorescent background that could interfere with flow cytometry (FACS) measurement and result in false information about GFP plasmid delivery. Effective methods to remove residual EDC on macromolecules were also developed.

  2. Impact of carbondiimide crosslinker used for magnetic carbon nanotube mediated GFP plasmid delivery.

    PubMed

    Hao, Yuzhi; Xu, Peng; He, Chuan; Yang, Xiaoyan; Huang, Min; Xing, James; Chen, Jie

    2011-07-15

    1-Ethyl-3-(3-dimethylaminopropyl) carbondiimide hydrochloride (EDC) is commonly used as a crosslinker to help bind biomolecules, such as DNA plasmids, with nanostructures. However, EDC often remains, after a crosslink reaction, in the micro-aperture of the nanostructure, e.g., carbon nanotube. The remaining EDC shows positive green fluorescent signals and makes a nanostructure with a strong cytotoxicity which induces cell death. The toxicity of EDC was confirmed on a breast cancer cell line (MCF-7) and two leukemic cell lines (THP-1 and KG-1). The MCF-7 cells mainly underwent necrosis after treatment with EDC, which was verified by fluorescein isothiocyanate (FITC) annexin V staining, video microscopy and scanning electronic microscopy (SEM). If the EDC was not removed completely, the nanostructures with remaining EDC produced a green fluorescent background that could interfere with flow cytometry (FACS) measurement and result in false information about GFP plasmid delivery. Effective methods to remove residual EDC on macromolecules were also developed.

  3. Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing

    PubMed Central

    Al-Jamal, Khuloud T.; Gherardini, Lisa; Bardi, Giuseppe; Nunes, Antonio; Guo, Chang; Bussy, Cyrill; Herrero, M. Antonia; Bianco, Alberto; Prato, Maurizio; Kostarelos, Kostas; Pizzorusso, Tommaso

    2011-01-01

    Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits. PMID:21690348

  4. Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model.

    PubMed

    Podesta, Jennifer E; Al-Jamal, Khuloud T; Herrero, M Antonia; Tian, Bowen; Ali-Boucetta, Hanene; Hegde, Vikas; Bianco, Alberto; Prato, Maurizio; Kostarelos, Kostas

    2009-05-01

    Carbon nanotubes are novel nanomaterials that are thought to offer potential benefits to a variety of biomedical and clinical applications. In this study, the treatment of a human lung carcinoma model in vivo using siRNA sequences leading to cytotoxicity and cell death is carried out using either cationic liposomes (DOTAP:cholesterol) or amino-functionalized multi-walled carbon nanotubes (MWNT - NH(+)(3)). Validation for the most cytotoxic siRNA sequence using a panel of human carcinoma and murine cells reveals that the proprietary siTOX sequence is human specific and can lead to significant cytotoxic activities delivered both by liposome or MWNT - NH(+)(3) in vitro. A comparative study using both types of vector indicates that only MWNT - NH(+)(3):siRNA complexes administered intratumorally can elicit delayed tumor growth and increased survival of xenograft-bearing animals. siTOX delivery via the cationic MWNT - NH(+)(3) is biologically active in vivo by triggering an apoptotic cascade, leading to extensive necrosis of the human tumor mass. This suggests that carbon-nanotube-mediated delivery of siRNA by intratumoral administration leads to successful and statistically significant suppression of tumor volume, followed by a concomitant prolongation of survival of human lung tumor-bearing animals. The direct comparison between carbon nanotubes and liposomes demonstrates the potential advantages offered by carbon nanotubes for the intracellular delivery of therapeutic agents in vivo. The present work may act as the impetus for further studies to explore the therapeutic capacity of chemically functionalized carbon nanotubes to deliver siRNA directly into the cytoplasm of target cells and achieve effective therapeutic silencing in various disease indications where local delivery is feasible or desirable.

  5. Water transport inside carbon nanotubes mediated by phonon-induced oscillating friction.

    PubMed

    Ma, Ming; Grey, François; Shen, Luming; Urbakh, Michael; Wu, Shuai; Liu, Jefferson Zhe; Liu, Yilun; Zheng, Quanshui

    2015-08-01

    The emergence of the field of nanofluidics in the last decade has led to the development of important applications including water desalination, ultrafiltration and osmotic energy conversion. Most applications make use of carbon nanotubes, boron nitride nanotubes, graphene and graphene oxide. In particular, understanding water transport in carbon nanotubes is key for designing ultrafiltration devices and energy-efficient water filters. However, although theoretical studies based on molecular dynamics simulations have revealed many mechanistic features of water transport at the molecular level, further advances in this direction are limited by the fact that the lowest flow velocities accessible by simulations are orders of magnitude higher than those measured experimentally. Here, we extend molecular dynamics studies of water transport through carbon nanotubes to flow velocities comparable with experimental ones using massive crowd-sourced computing power. We observe previously undetected oscillations in the friction force between water and carbon nanotubes and show that these oscillations result from the coupling between confined water molecules and the longitudinal phonon modes of the nanotube. This coupling can enhance the diffusion of confined water by more than 300%. Our results may serve as a theoretical framework for the design of new devices for more efficient water filtration and osmotic energy conversion devices.

  6. Water transport inside carbon nanotubes mediated by phonon-induced oscillating friction.

    PubMed

    Ma, Ming; Grey, François; Shen, Luming; Urbakh, Michael; Wu, Shuai; Liu, Jefferson Zhe; Liu, Yilun; Zheng, Quanshui

    2015-08-01

    The emergence of the field of nanofluidics in the last decade has led to the development of important applications including water desalination, ultrafiltration and osmotic energy conversion. Most applications make use of carbon nanotubes, boron nitride nanotubes, graphene and graphene oxide. In particular, understanding water transport in carbon nanotubes is key for designing ultrafiltration devices and energy-efficient water filters. However, although theoretical studies based on molecular dynamics simulations have revealed many mechanistic features of water transport at the molecular level, further advances in this direction are limited by the fact that the lowest flow velocities accessible by simulations are orders of magnitude higher than those measured experimentally. Here, we extend molecular dynamics studies of water transport through carbon nanotubes to flow velocities comparable with experimental ones using massive crowd-sourced computing power. We observe previously undetected oscillations in the friction force between water and carbon nanotubes and show that these oscillations result from the coupling between confined water molecules and the longitudinal phonon modes of the nanotube. This coupling can enhance the diffusion of confined water by more than 300%. Our results may serve as a theoretical framework for the design of new devices for more efficient water filtration and osmotic energy conversion devices. PMID:26149236

  7. Water transport inside carbon nanotubes mediated by phonon-induced oscillating friction

    NASA Astrophysics Data System (ADS)

    Ma, Ming; Grey, François; Shen, Luming; Urbakh, Michael; Wu, Shuai; Liu, Jefferson Zhe; Liu, Yilun; Zheng, Quanshui

    2015-08-01

    The emergence of the field of nanofluidics in the last decade has led to the development of important applications including water desalination, ultrafiltration and osmotic energy conversion. Most applications make use of carbon nanotubes, boron nitride nanotubes, graphene and graphene oxide. In particular, understanding water transport in carbon nanotubes is key for designing ultrafiltration devices and energy-efficient water filters. However, although theoretical studies based on molecular dynamics simulations have revealed many mechanistic features of water transport at the molecular level, further advances in this direction are limited by the fact that the lowest flow velocities accessible by simulations are orders of magnitude higher than those measured experimentally. Here, we extend molecular dynamics studies of water transport through carbon nanotubes to flow velocities comparable with experimental ones using massive crowd-sourced computing power. We observe previously undetected oscillations in the friction force between water and carbon nanotubes and show that these oscillations result from the coupling between confined water molecules and the longitudinal phonon modes of the nanotube. This coupling can enhance the diffusion of confined water by more than 300%. Our results may serve as a theoretical framework for the design of new devices for more efficient water filtration and osmotic energy conversion devices.

  8. Carbon Nanotubes-Mediated Reduction of Hematite by Shewanella oneidensis MR-1

    NASA Astrophysics Data System (ADS)

    Shoji, K.; Xu, S.; Wang, L.; Yang, Y.; Patel, A.

    2015-12-01

    The worldwide carbon nanotubes (CNTs) industry is rapidly expanding with production capacity exceeding several thousand tons per year. After the service lives, CNTs will be ultimately released into the environment with their concentrations in soils increasing by 0.4-147 ng/kg/year and the consequent environmental impacts have received more and more attentions. Effects of CNTs on the redox reactions of Fe have not been studied, although the CNT-bound quinone functional groups can potentially act as an electron shuttle. In this study, we investigated the impact of multi-walled carbon nanotubes (MWCNTs) on the reduction of hematite by metal-respiring bacterium Shewanella oneidensis MR-1. Our results showed that the presence of MWCNT with concentration ranging from 0.05 to 1 g/L inhibited the reduction of hematite (Fe2O3) by up to 35%, likely due to the toxicity effects of MWCNTs. However, the microbially-reduced MWCNTs (0.1 g/L) stimulated the reduction of Fe(III) by 3.6 times, indicating the potential role of MWCNTs as an electron shuttle. These results suggest MWCNTs play a dual role in regulating the microbial reduction of hematite through both toxicity effects and electron shuttle. We plan to further explore the mechanism for the impact of MWCNTs on the redox reactions of iron by studying the influences of carboxyl functionalized MWCNTs, analyzing the impact of MWCNTs on bacterial growth and characterizing the quinone functional groups in MWCNTs. Potential results will provide a novel perception for the impact of CNTs on the biogeochemical cycles of iron.The worldwide carbon nanotubes (CNTs) industry is rapidly expanding with production capacity exceeding several thousand tons per year. After the service lives, CNTs will be ultimately released into the environment with their concentrations in soils increasing by 0.4-147 ng/kg/year and the consequent environmental impacts have received more and more attentions. Effects of CNTs on the redox reactions of Fe have not

  9. Carbon Nanotube-Mediated Photothermal Disruption of Endosomes/Lysosomes Reverses Doxorubicin Resistance in MCF-7/ADR Cells.

    PubMed

    Pai, Chin-Ling; Chen, Yu-Chun; Hsu, Chia-Yen; Su, Hong-Lin; Lai, Ping-Shan

    2016-04-01

    Cancer is the leading cause of human death worldwide. Although many scientists work to fight this disease, multiple drug resistance is a predominant obstacle for effective cancer therapy. In drug-resistant MCF-7/ADR cells, the acidic organelles with lower pH value than normal one can cause the protonation of anthracycline drugs, inducing drug accumulation in these organelles. In this study, single-walled carbon nanotubes with polyethylene glycol phospholipids surface modification (PEGylated SWNTs) were utilized as near infrared-activated drug carriers for doxorubicin (DOX) delivery against MCF-7/ADR cells. Our results showed that a concentration-dependent temperature increase was observed in a solution of PEGylated SWNTs with 808 nm laser irradiation, whereas a water solution showed no significant changes in temperature under a thermal camera using the same irradiation dose. Interestingly, PEGylated DOX-SWNTs enhanced the nuclear accumulation of DOX with 808 nm irradiation whereas free DOX or PEGylated DOX-SWNTs revealed discrete red spots in MCF-7/ADR cells by confocal microscopic observation. Cell viability of PEGylated DOX-SWNTs-treated cells was also significantly decreased after 808 nm laser irradiation. Thus, photothermally activated PEGylated SWNTs can be a potential nanocarrier to deliver DOX into cancer cells and successfully overcome drug-resistant behavior in MCF-7/ADR breast cancer cells. PMID:27301189

  10. Sub-second carbon-nanotube-mediated microwave sintering for high-conductivity silver patterns on plastic substrates

    NASA Astrophysics Data System (ADS)

    Jung, Sunshin; Chun, Su Jin; Han, Joong Tark; Woo, Jong Seok; Shon, Cha-Hwa; Lee, Geon-Woong

    2016-02-01

    A method of microwave sintering that is mediated by carbon nanotubes (CNTs) has been developed to obtain high-conductivity Ag patterns on the top of heat-sensitive plastic substrates within a short time. The Ag patterns are printed on CNTs formed on plastic substrates and rapidly heated to a great extent by the heat transferred from the microwave-heated CNTs. The conductivity of the microwave-sintered Ag patterns reaches ~39% that of bulk Ag within 1 s without substrate deformation. Furthermore, microwave sintering enhances the adhesion of Ag patterns to the thermoplastic substrates because the sintering causes interfacial fusion between the Ag patterns and the substrates, and CNTs physically connect the patterns with the substrates.A method of microwave sintering that is mediated by carbon nanotubes (CNTs) has been developed to obtain high-conductivity Ag patterns on the top of heat-sensitive plastic substrates within a short time. The Ag patterns are printed on CNTs formed on plastic substrates and rapidly heated to a great extent by the heat transferred from the microwave-heated CNTs. The conductivity of the microwave-sintered Ag patterns reaches ~39% that of bulk Ag within 1 s without substrate deformation. Furthermore, microwave sintering enhances the adhesion of Ag patterns to the thermoplastic substrates because the sintering causes interfacial fusion between the Ag patterns and the substrates, and CNTs physically connect the patterns with the substrates. Electronic supplementary information (ESI) available: Temperature difference in Ag/CNT/PC samples; the carbon content and electrical performance after microwave sintering; microwave sintering of Ag/CNT patterns; physical connection between the substrate and sintered Ag lines; touch-piano (figure and movie). See DOI: 10.1039/c5nr08082g

  11. Carbon Nanotubes Hybrid Hydrogels in Drug Delivery: A Perspective Review

    PubMed Central

    Hampel, Silke; Spizzirri, Umile Gianfranco; Parisi, Ortensia Ilaria; Picci, Nevio; Iemma, Francesca

    2014-01-01

    The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review. PMID:24587993

  12. Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

    SciTech Connect

    Saha, Dipendu; Warren, Kaitlyn E; Naskar, Amit K

    2014-01-01

    Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1. The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.

  13. Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery.

    PubMed

    Tewes, Frederic; Gobbo, Oliviero L; Ehrhardt, Carsten; Healy, Anne Marie

    2016-01-20

    Amorphous calcium carbonate (ACC) is known to interact with proteins, for example, in biogenic ACC, to form stable amorphous phases. The control of amorphous/crystalline and inorganic/organic ratios in inhalable calcium carbonate microparticles may enable particle properties to be adapted to suit the requirements of dry powders for pulmonary delivery by oral inhalation. For example, an amorphous phase can immobilize and stabilize polypeptides in their native structure and amorphous and crystalline phases have different mechanical properties. Therefore, inhalable composite microparticles made of inorganic (i.e., calcium carbonate and calcium formate) and organic (i.e., hyaluronan (HA)) amorphous and crystalline phases were investigated for peptide and protein pulmonary aerosol delivery. The crystalline/amorphous ratio and polymorphic form of the inorganic component was altered by changing the microparticle drying rate and by changing the ammonium carbonate and HA initial concentration. The bioactivity of the model peptide, salmon calcitonin (sCT), coprocessed with alpha-1-antitrypsin (AAT), a model protein with peptidase inhibitor activity, was maintained during processing and the microparticles had excellent aerodynamic properties, making them suitable for pulmonary aerosol delivery. The bioavailability of sCT after aerosol delivery as sCT and AAT-loaded composite microparticles to rats was 4-times higher than that of sCT solution.

  14. Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery.

    PubMed

    Tewes, Frederic; Gobbo, Oliviero L; Ehrhardt, Carsten; Healy, Anne Marie

    2016-01-20

    Amorphous calcium carbonate (ACC) is known to interact with proteins, for example, in biogenic ACC, to form stable amorphous phases. The control of amorphous/crystalline and inorganic/organic ratios in inhalable calcium carbonate microparticles may enable particle properties to be adapted to suit the requirements of dry powders for pulmonary delivery by oral inhalation. For example, an amorphous phase can immobilize and stabilize polypeptides in their native structure and amorphous and crystalline phases have different mechanical properties. Therefore, inhalable composite microparticles made of inorganic (i.e., calcium carbonate and calcium formate) and organic (i.e., hyaluronan (HA)) amorphous and crystalline phases were investigated for peptide and protein pulmonary aerosol delivery. The crystalline/amorphous ratio and polymorphic form of the inorganic component was altered by changing the microparticle drying rate and by changing the ammonium carbonate and HA initial concentration. The bioactivity of the model peptide, salmon calcitonin (sCT), coprocessed with alpha-1-antitrypsin (AAT), a model protein with peptidase inhibitor activity, was maintained during processing and the microparticles had excellent aerodynamic properties, making them suitable for pulmonary aerosol delivery. The bioavailability of sCT after aerosol delivery as sCT and AAT-loaded composite microparticles to rats was 4-times higher than that of sCT solution. PMID:26692360

  15. Carbon nanotubes for delivery of small molecule drugs.

    PubMed

    Wong, Bin Sheng; Yoong, Sia Lee; Jagusiak, Anna; Panczyk, Tomasz; Ho, Han Kiat; Ang, Wee Han; Pastorin, Giorgia

    2013-12-01

    In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous attention as promising nanocarriers, owing to their distinct characteristics, such as high surface area, enhanced cellular uptake and the possibility to be easily conjugated with many therapeutics, including both small molecules and biologics, displaying superior efficacy, enhanced specificity and diminished side effects. While most CNT-based drug delivery system (DDS) had been engineered to combat cancers, there are also emerging reports that employ CNTs as either the main carrier or adjunct material for the delivery of various non-anticancer drugs. In this review, the delivery of small molecule drugs is expounded, with special attention paid to the current progress of in vitro and in vivo research involving CNT-based DDSs, before finally concluding with some consideration on inevitable complications that hamper successful disease intervention with CNTs. PMID:23954402

  16. Carbon nanotubes for delivery of small molecule drugs.

    PubMed

    Wong, Bin Sheng; Yoong, Sia Lee; Jagusiak, Anna; Panczyk, Tomasz; Ho, Han Kiat; Ang, Wee Han; Pastorin, Giorgia

    2013-12-01

    In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous attention as promising nanocarriers, owing to their distinct characteristics, such as high surface area, enhanced cellular uptake and the possibility to be easily conjugated with many therapeutics, including both small molecules and biologics, displaying superior efficacy, enhanced specificity and diminished side effects. While most CNT-based drug delivery system (DDS) had been engineered to combat cancers, there are also emerging reports that employ CNTs as either the main carrier or adjunct material for the delivery of various non-anticancer drugs. In this review, the delivery of small molecule drugs is expounded, with special attention paid to the current progress of in vitro and in vivo research involving CNT-based DDSs, before finally concluding with some consideration on inevitable complications that hamper successful disease intervention with CNTs.

  17. Fluidic delivery of homogeneous solutions through carbon tube bundles

    NASA Astrophysics Data System (ADS)

    Srikar, R.; Yarin, A. L.; Megaridis, C. M.

    2009-07-01

    A wide array of technological applications requires localized high-rate delivery of dissolved compounds (in particular, biological ones), which can be achieved by forcing the solutions or suspensions of such compounds through nano or microtubes and their bundled assemblies. Using a water-soluble compound, the fluorescent dye Rhodamine 610 chloride, frequently used as a model drug release compound, it is shown that deposit buildup on the inner walls of the delivery channels and its adverse consequences pose a severe challenge to implementing pressure-driven long-term fluidic delivery through nano and microcapillaries, even in the case of such homogeneous solutions. Pressure-driven delivery (3-6 bar) of homogeneous dye solutions through macroscopically-long (~1 cm) carbon nano and microtubes with inner diameters in the range 100 nm-1 µm and their bundled parallel assemblies is studied experimentally and theoretically. It is shown that the flow delivery gradually shifts from fast convection-dominated (unobstructed) to slow jammed convection, and ultimately to diffusion-limited transport through a porous deposit. The jamming/clogging phenomena appear to be rather generic: they were observed in a wide concentration range for two fluorescent dyes in carbon nano and microtubes, as well as in comparable transparent glass microcapillaries. The aim of the present work is to study the physics of jamming, rather than the chemical reasons for the affinity of dye molecules to the tube walls.

  18. Novel Carbon Nanomaterial Coating for Dispersibility, Delivery and Sensing

    NASA Astrophysics Data System (ADS)

    Swierczewska, Magdalena

    Carbon nanomaterials have been cited to provide great potential in biomedical applications such as in vivo imaging, drug delivery, and biomarker detection. Yet poor dispersibility in physiological conditions greatly limits their biomedical promise. As with most nanoparticles, the surface interaction with biological systems is the driving force towards effective activity in vivo, namely exhibiting dispersion, low cytotoxicity, and molecular targetability. Therefore, by surface engineering carbon nanomaterials with a distinct biocompatible coating, their applications in imaging, drug delivery, biomarker detection, and therapy can be empowered. We render carbon nanomaterials useful for such in vivo biomedical applications by providing dispersibility, delivery and sensing capabilities with a facile surface coating method. A single, yet multifunctional, hyaluronic acid-based biosurfactant was strategically chosen to meet the design criteria. The amphiphilic material, hyaluronic acid-5beta-cholanic acid (HACA), is an efficient dispersing agent for carbon nanomaterials, including single-walled carbon nanotubes (SWCNTs), in physiological conditions for a sustained period of time. Furthermore, the biological activity and cancer cell targeting of HACA wrapped SWCNTs (HACA-SWCNTs) were evaluated in vitro and in vivo utilizing imaging techniques intrinsic to SWCNTs, HACA, and HACA-SWCNTs. Fluorescent dye-labeled HACA-SWCNTs were designed to activate fluorescence signals intracelluarly, not only serving as an approach to image cellular uptake but also to determine the coating efficacy of HACA onto SWCNTs. SWCNT localization within cells was also confirmed by tracking the intrinsic Raman signals of carbon nanomaterials. In vivo photoacoustic, fluorescence, and positron emission tomography imaging display high tumor targeting capability of HACA-SWCNTs in a murine tumor model. Once targeted, HACA-SWCNTs have potential to serve as photothermal tumor ablation agents after laser

  19. Modification of nanostructured calcium carbonate for efficient gene delivery.

    PubMed

    Zhao, Dong; Wang, Chao-Qun; Zhuo, Ren-Xi; Cheng, Si-Xue

    2014-06-01

    In this study, a facile method to modify nanostructured calcium carbonate (CaCO3) gene delivery systems by adding calcium phosphate (CaP) component was developed. CaCO3/CaP/DNA nanoparticles were prepared by the co-precipitation of Ca(2+) ions with plasmid DNA in the presence of carbonate and phosphate ions. For comparison, CaCO3/DNA nanoparticles and CaP/DNA co-precipitates were also prepared. The effects of carbonate ion/phosphate ion (CO3(2-)/PO4(3-)) ratio on the particle size and gene delivery efficiency were investigated. With an appropriate CO3(2-)/PO4(3-) ratio, the co-existence of carbonate and phosphate ions could control the size of co-precipitates effectively, and CaCO3/CaP/DNA nanoparticles with a decreased size and improved stability could be obtained. The in vitro gene transfections mediated by different nanoparticles in 293T cells and HeLa cells were carried out, using pGL3-Luc as a reporter plasmid. The gene transfection efficiency of CaCO3/CaP/DNA nanoparticles could be significantly improved as compared with CaCO3/DNA nanoparticles and CaP/DNA co-precipitates. The confocal microscopy study indicated that the cellular uptake and nuclear localization of CaCO3/CaP/DNA nanoparticles were significantly enhanced as compared with unmodified CaCO3/DNA nanoparticles.

  20. Cisplatin@US-tube Carbon Nanocapsules For Enhanced Chemotherapeutic Delivery

    PubMed Central

    Guven, Adem; Rusakova, Irene A.; Lewis, Michael T.; Wilson, Lon J.

    2012-01-01

    The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivity, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon nanotube (CNT) materials have also garnered attention in the area of drug delivery. In this study, we describe the preparation, characterization, and in vitro testing of a new ultra-short single-walled carbon nanotube (US-tube)-based drug delivery system for the treatment of cancer. In particular, the encapsulation of cisplatin (CDDP), a widely-used anticancer drug, within US-tubes has been achieved, and the resulting CDDP@US-tube material characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively-coupled optical emission spectrometry (ICP-OES). Dialysis studies performed in phosphate-buffered saline (PBS) at 37 °C have demonstrated that CDDP release from CDDP@US-tubes can be controlled (retarded) by wrapping the CDDP@US-tubes with Pluronic-F108 surfactant. Finally, the anticancer activity of pluronic-wrapped CDDP@US-tubes has been evaluated against two different breast cancer cell lines, MCF-7 and MDA-MB-231, and found to exhibit enhanced cytotoxicity over free CDDP after 24 hours. These studies have laid the foundation for developing US-tube-based delivery of chemotherapeutics, with drug release mainly limited to within cancer cells only. PMID:22078812

  1. Gene Delivery Potential of Biofunctional Carbonate Apatite Nanoparticles in Lungs

    PubMed Central

    Alhaji, Suleiman Yusuf; Chowdhury, Ezharul Houque; Rosli, Rozita

    2014-01-01

    Existing nonviral gene delivery systems to lungs are inefficient and associated with dose limiting toxicity in mammalian cells. Therefore, carbonate apatite (CO3Ap) nanoparticles were examined as an alternative strategy for effective gene delivery to the lungs. This study aimed to (1) assess the gene delivery efficiency of CO3Ap in vitro and in mouse lungs, (2) evaluate the cytotoxicity effect of CO3Ap/pDNA in vitro, and (3) characterize the CO3Ap/pDNA complex formulations. A significantly high level of reporter gene expression was detected from the lung cell line transfected with CO3Ap/pDNA complex prepared in both serum and serum-free medium. Cytotoxicity analysis revealed that the percentage of the viable cells treated with CO3Ap to be almost similar to the untreated cells. Characterization analyses showed that the CO3Ap/pDNA complexes are in a nanometer range with aggregated spherical structures and tended to be more negatively charged. In the lung of mice, highest level of transgene expression was observed when CO3Ap (8 μL) was complexed with 40 μg of pDNA at day 1 after administration. Although massive reduction of gene expression was seen beyond day 1 post administration, the level of expression remained significant throughout the study period. PMID:25143941

  2. Single-wall carbon nanotubes based anticancer drug delivery system

    NASA Astrophysics Data System (ADS)

    Tripisciano, C.; Kraemer, K.; Taylor, A.; Borowiak-Palen, E.

    2009-08-01

    Conventional administration of chemotherapeutic agents is compromised by their lack of selectivity which is the cause of a lethal effect accomplishment on healthy tissues. Since therapeutic and diagnostic agents could functionalize the structure of carbon nanotubes (CNTs), the development of CNTs as drug containers would pave the way to their employment as nanovectors into the cells. Here a study on cisplatin (Cis-Diamminedichloroplatinum (CDDP) - a platinum-based chemotherapy drug) embedding to single-wall CNTs (SWCNTs) is shown.Being sure that the anticancer drug discharge occurred, in vitro analysis have been performed. The inhibition of prostate cancer cells (PC3 and DU145) viability from tubes encapsulating cisplatin proved the efficiency of the produced delivery system.

  3. Recent advancements in carbon nanofiber and carbon nanotube applications in drug delivery and tissue engineering.

    PubMed

    Stout, David A

    2015-01-01

    Since the discovery and synthesis of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) over a decade ago, researchers have envisioned and discovered new potential applications for these materials. CNTs and CNFs have rapidly become a platform technology for a variety of uses, including biomedical applications due to their mechanical, electrical, thermal, optical and structural properties. CNTs and CNFs are also advantageous due to their ability to be produced in many different shapes and sizes. Since their discovery, of the many imaginable applications, CNTs and CNFs have gained a significant amount of attention and therapeutic potential in tissue engineering and drug delivery applications. In recent years, CNTs and CNFs have made significant contributions in designing new strategies for, delivery of pharmaceuticals, genes and molecular probes into cells, stem cell therapies and assisting in tissue regeneration. Furthermore, it is widely expressed that these materials will significantly contribute to the next generation of health care technologies in treating diseases and contributing to tissue growth. Hence, this review seeks to explore the recent advancements, current status and limitations of CNTs and CNFs for drug delivery and tissue engineering applications.

  4. Carbon nanotubes buckypapers for potential transdermal drug delivery.

    PubMed

    Schwengber, Alex; Prado, Héctor J; Zilli, Darío A; Bonelli, Pablo R; Cukierman, Ana L

    2015-12-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT-drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. PMID:26354234

  5. Theranostic applications of carbon nanomaterials in cancer: Focus on imaging and cargo delivery.

    PubMed

    Chen, Daiqin; Dougherty, Casey A; Zhu, Kaicheng; Hong, Hao

    2015-07-28

    Carbon based nanomaterials have attracted significant attention over the past decades due to their unique physical properties, versatile functionalization chemistry, and biological compatibility. In this review, we will summarize the current state-of-the-art applications of carbon nanomaterials in cancer imaging and drug delivery/therapy. The carbon nanomaterials will be categorized into fullerenes, nanotubes, nanohorns, nanodiamonds, nanodots and graphene derivatives based on their morphologies. The chemical conjugation/functionalization strategies of each category will be introduced before focusing on their applications in cancer imaging (fluorescence/bioluminescence, magnetic resonance (MR), positron emission tomography (PET), single-photon emission computed tomography (SPECT), photoacoustic, Raman imaging, etc.) and cargo (chemo/gene/therapy) delivery. The advantages and limitations of each category and the potential clinical utilization of these carbon nanomaterials will be discussed. Multifunctional carbon nanoplatforms have the potential to serve as optimal candidates for image-guided delivery vectors for cancer.

  6. Isolation of carbon nanohorn assemblies and their potential for intracellular delivery

    NASA Astrophysics Data System (ADS)

    Fan, Xiaobin; Tan, Juan; Zhang, Guoliang; Zhang, Fengbao

    2007-05-01

    Attributed to its distinctive dahlia-flowerlike structure and already desirable size (usually <100 nm), carbon nanohorn assemblies (CNHs), a new member of the fullerene family, are a potential vehicle for intracellular delivery. This paper shows that isolated CNHs and nanoscale CNH agglomerates can be successfully isolated by a copolymer (Gum Arabic) through steric stabilization. In vitro study shows that the modified CNHs are nontoxic and may be used as a promising vehicle for intracellular delivery.

  7. Applications of Carbon-Based Nanomaterials for Drug Delivery in Oncology

    NASA Astrophysics Data System (ADS)

    Levi-Polyachenko, Nicole H.; Carroll, David L.; Stewart, John H.

    The goal of this chapter is to introduce carbon nanomaterials and highlight research focused on their use as cancer therapeutics. The physical properties of fullerenes and carbon nanotubes, including their spectral characteristics are described. Current oncology treatment regimes are described to provide an overview of where carbon nanomaterials may have significant value in further development of the established standards of care procedures. Photodynamic therapy and drug delivery using fullerene C60 is explored. Thermal ablation techniques using carbon nanotubes are explained and alternate hyperthermic methods using carbon nanotubes are described. Specifically, carbon nanotubes are examined for their potential contribution to the currently practiced clinical therapy intraperitoneal hyperthermic chemoperfusion. Nanotubes and nanohorns filled with chemotherapeutic agents are examined as are different methods for filling and containment of drug moieties. The attachment of active molecules to fullerenes is described with examples for use in oncology. Toxicity issues are explored and the future directions and potential for carbon nanomaterial types concludes the chapter.

  8. Efficient delivery of DNA into bovine preimplantation embryos by multiwall carbon nanotubes

    PubMed Central

    Munk, Michele; Ladeira, Luiz O.; Carvalho, Bruno C.; Camargo, Luiz S. A.; Raposo, Nádia R. B.; Serapião, Raquel V.; Quintão, Carolina C. R.; Silva, Saulo R.; Soares, Jaqueline S.; Jorio, Ado; Brandão, Humberto M.

    2016-01-01

    The pellucid zone (PZ) is a protective embryonic cells barrier against chemical, physical or biological substances. This put, usual transfection methods are not efficient for mammal oocytes and embryos as they are exclusively for somatic cells. Carbon nanotubes have emerged as a new method for gene delivery, and they can be an alternative for embryos transfection, however its ability to cross the PZ and mediated gene transfer is unknown. Our data confirm that multiwall carbon nanotubes (MWNTs) can cross the PZ and delivery of pDNA into in vitro-fertilized bovine embryos. The degeneration rate and the expression of genes associated to cell viability were not affected in embryos exposed to MWNTs. Those embryos, however, had lower cell number and higher apoptotic cell index, but this did not impair the embryonic development. This study shows the potential utility of the MWNT for the development of new method for delivery of DNA into bovine embryos. PMID:27642034

  9. Efficient delivery of DNA into bovine preimplantation embryos by multiwall carbon nanotubes.

    PubMed

    Munk, Michele; Ladeira, Luiz O; Carvalho, Bruno C; Camargo, Luiz S A; Raposo, Nádia R B; Serapião, Raquel V; Quintão, Carolina C R; Silva, Saulo R; Soares, Jaqueline S; Jorio, Ado; Brandão, Humberto M

    2016-01-01

    The pellucid zone (PZ) is a protective embryonic cells barrier against chemical, physical or biological substances. This put, usual transfection methods are not efficient for mammal oocytes and embryos as they are exclusively for somatic cells. Carbon nanotubes have emerged as a new method for gene delivery, and they can be an alternative for embryos transfection, however its ability to cross the PZ and mediated gene transfer is unknown. Our data confirm that multiwall carbon nanotubes (MWNTs) can cross the PZ and delivery of pDNA into in vitro-fertilized bovine embryos. The degeneration rate and the expression of genes associated to cell viability were not affected in embryos exposed to MWNTs. Those embryos, however, had lower cell number and higher apoptotic cell index, but this did not impair the embryonic development. This study shows the potential utility of the MWNT for the development of new method for delivery of DNA into bovine embryos. PMID:27642034

  10. Feedback regulated drug delivery vehicles: carbon dioxide responsive cationic hydrogels for antidote release.

    PubMed

    Satav, Sunita S; Bhat, Shreedhar; Thayumanavan, S

    2010-07-12

    A possible approach to handling the harmful side effects of an analgesic overdose, without losing its therapeutic potential, involves feedback regulated delivery of an antidote. For example, overdose of morphine causes hypoventilation, an inadequate ventilation to perform gas exchanges in lungs leading to increased CO2 concentration in the blood. Taking advantage of CO2 as a toxicity marker, a hydrogel-based delivery vehicle containing dimethylamino groups [poly(N,N-dimethylaminoethyl methacrylate) cross-linked by trimethylolpropane trimethacrylate] was designed. Stimulus controlled swelling of these hydrogels in naloxone delivery is discussed. A remarkable control over naloxone release was achieved against the concentration of the biomarker. The overall stimuli response of the gel could be enhanced further by encapsulating carbonic anhydrase, a metalloenzyme known to catalyze the reversible hydration of CO2. Thus, a feedback regulated drug delivery vehicle based on toxicity biomarker strategy was modeled successfully, which has the potential to mitigate risks associated with drug overdose.

  11. Unique applications of Carbon nanotubes in medical imaging, bio-sensors and vaccine delivery

    NASA Astrophysics Data System (ADS)

    Lemon, Rebekah; Miller, Lauren; Vaseashta, Ashok

    2004-03-01

    The dimensionality of a system has profound influence on its physical behavior. With advances in technology over the past few decades, it has become possible to fabricate and study reduced-dimensional systems, such as carbon nanotubes (CNTs). Carbon nanotubes are especially promising candidate for cold cathode field emitter because of their electrical properties, high aspect ratio, and small radius of curvature at the tips. Electron emission from the carbon nanotubes is investigated. As a result of this investigation, several prototype devices have been suggested that operate with low swing voltages with sufficient current densities for medical imaging. Physical characteristics that allow improved current stability and long lifetime operation for bio-sensors are presented. Carbon nanotubes offer tremendous applications in on-demand drug delivery. Research describing antigen-antibody interactions and immune responses using peptide-carbon nanotubes is presented. The aim of this brief overview is to illustrate the useful characteristics of carbon nanotubes and its possible biomedical applications.

  12. Corking Nitrogen-Doped Carbon Nanotube Cups with Gold Nanoparticles for Biodegradable Drug Delivery Applications.

    PubMed

    Burkert, Seth C; Star, Alexander

    2015-12-02

    Carbon nanomaterials have been proposed as effective drug delivery devices; however their perceived biopersistence and toxicological profile may hinder their applications in medical therapeutics. Nitrogen doping of carbon nanotubes results in a unique "stacked-cup" structure, with cups held together through van der Waals forces. Disrupting these weak interactions yields individual and short-stacked nanocups that can subsequently be corked with gold nanoparticles, resulting in sealed containers for delivery of cargo. Peroxidase-catalyzed reactions can effectively uncork these containers, followed by complete degradation of the graphitic capsule, resulting in effective release of therapeutic cargo while minimizing harmful side effects. The protocols reported herein describe the synthesis of stacked nitrogen-doped carbon nanotube cups followed by effective separation into individual cups and gold nanoparticle cork formation resulting in loaded and sealed containers.

  13. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  14. Corking Nitrogen-Doped Carbon Nanotube Cups with Gold Nanoparticles for Biodegradable Drug Delivery Applications.

    PubMed

    Burkert, Seth C; Star, Alexander

    2015-01-01

    Carbon nanomaterials have been proposed as effective drug delivery devices; however their perceived biopersistence and toxicological profile may hinder their applications in medical therapeutics. Nitrogen doping of carbon nanotubes results in a unique "stacked-cup" structure, with cups held together through van der Waals forces. Disrupting these weak interactions yields individual and short-stacked nanocups that can subsequently be corked with gold nanoparticles, resulting in sealed containers for delivery of cargo. Peroxidase-catalyzed reactions can effectively uncork these containers, followed by complete degradation of the graphitic capsule, resulting in effective release of therapeutic cargo while minimizing harmful side effects. The protocols reported herein describe the synthesis of stacked nitrogen-doped carbon nanotube cups followed by effective separation into individual cups and gold nanoparticle cork formation resulting in loaded and sealed containers. PMID:26629615

  15. Carbon Nanotubes in Cancer Therapy and Drug Delivery

    PubMed Central

    Elhissi, Abdelbary M. A.; Ahmed, Waqar; Hassan, Israr Ul; Dhanak, Vinod. R.; D'Emanuele, Antony

    2012-01-01

    Carbon nanotubes (CNTs) have been introduced recently as a novel carrier system for both small and large therapeutic molecules. CNTs can be functionalized (i.e., surface engineered) with certain functional groups in order to manipulate their physical or biological properties. In addition to the ability of CNTs to act as carriers for a wide range of therapeutic molecules, their large surface area and possibility to manipulate their surfaces and physical dimensions have been exploited for use in the photothermal destruction of cancer cells. This paper paper will discuss the therapeutic applications of CNTs with a major focus on their applications for the treatment of cancer. PMID:22028974

  16. Functionalization of carbon nanomaterials by evolutionary molecular engineering: potential application in drug delivery systems.

    PubMed

    Shiba, Kiyotaka

    2006-01-01

    By virtue of the progress made in evolutionary molecular engineering, peptide aptamers that specifically recognize target molecules are now routinely created using a peptide phage display system. The system was originally developed for isolating peptides that specifically recognized biomacromolecules (e.g. proteinous receptors), but are now also being used to acquire peptide motifs that bind to inorganic materials, such as semiconductors, metals and carbon nanomaterials. We have created the peptide aptamer against carbon nanohorns, a vesicular carbon nanomaterial whose size is 80-100 nm in diameter. By combining the peptide motif that has affinity to the surfaces of carbon nanohorns with peptide aptamers that can target specific organs, we can functionalize the carbon nanomaterial to provide novel types of carriers for drug delivery systems. PMID:17046797

  17. [PLANT GENETIC TRANSFORMATION USING CARBON NANOTUBES FOR DNA DELIVERY].

    PubMed

    Burlaka, O M; Pirko, Ya V; Yemets, A I; Blume, Ya B

    2015-01-01

    The possibility of exploiting carbon nanotubes (CNTs)-based nanocarriers to deliver genes into protoplasts, callus and mesophyll explants of plants was examined. Using single-walled CNTs (SWCNTs) at the concentration of 20 μg/ml and multi-walled CNTs (MWCNTs) at the concentration of 15 μg/ml genetic transformation of Nicotiana tabacum L. mesophyll protoplasts with plasmid pGreen 0029 was carried out and transient expression of reporter yfp gene in the protoplasts was observed. Using SWCNTs at the concentration of 40 μg/ml and MWCNTs at the concentration of 30 μg/ml genetic transformation of N. tabacum callus and leaf explants with nptII gene as a part of plasmid pGreen 0029 was carried out. As a result plant regeneration on selective medium containing 50 mg/lkanamycin was shown. SWCNTs-based nanocarriers de-onstrated their appli-ability to transform protoplasts as well as walled plant cells. Whereas, MWCNTs-based nano-arriers were suitable only for transformation of proto-lasts due to the limiting role of cellulose walls in cell penetration.

  18. Targeted delivery of carbon nanotubes to cancer cells

    NASA Astrophysics Data System (ADS)

    Chakravarty, Pavitra

    CD22 is broadly expressed on human B cell lymphomas. Monoclonal anti-CD22 antibodies (MAbs) alone, or coupled to toxins, have been used to selectively target these tumors both in severe combined immunodeficient (SCID) mice with xenografted human lymphomas and in patients. Single-walled carbon nanotubes (CNTs) attached to antibodies or peptides represent another approach to targeting cancer cells. CNTs convert absorbed near-infrared (NIR) light into heat, which can thermally ablate cells in the vicinity of the CNTs. We have made MAb-CNT constructs where the MAb was either noncovalently or covalently coupled to CNTs, and investigated their ability to bind specifically to cells and to thermally ablate them after exposure to NIR light. The specific binding of these MAb-CNT constructs to antigen-positive and antigen-negative cells was demonstrated in vitro by using CD22+CD25 - Daudi cells, CD22-CD25+ phytohemagglutinin (PHA)-activated normal human peripheral blood mononuclear cells (PBMCs) and CNTs coupled non-covalently or covalently to either anti-CD22 or anti-CD25. We then demonstrated that the MAb-CNTs could bind to tumor cells expressing the relevant antigen but not to cells lacking the antigen. Furthermore we showed that, following exposure to NIR light, the cells could be thermally ablated. We also determined the stability of the MAb-CNTs in conditions designed to mimic the in vivo environment, i.e. mouse serum at 37°C. We then use the intrinsic Raman signature of CNTs to study the circulation and tissue distribution of intravenously injected MAb-CNTs in a murine xenograft model of lymphoma in vivo over a period of 24 hrs. We demonstrated that the MAb-CNTs have a short half-life in blood and that most of them are cleared by the reticuloendothelial system (RES). In the current embodiment, these constructs would therefore be of limited effectiveness in vivo.

  19. Carbon nanotubes part I: preparation of a novel and versatile drug-delivery vehicle

    PubMed Central

    Karimi, Mahdi; Solati, Navid; Amiri, Mohammad; Mirshekari, Hamed; Mohamed, Elmira; Taheri, Mahdiar; Hashemkhani, Mahshid; Saeidi, Ahad; Estiar, Mehrdad Asghari; Kiani, Parnian; Ghasemi, Amir; Basri, Seyed Masoud Moosavi; Aref, Amir R

    2015-01-01

    Introduction It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by Iijima, who described them as “rolled graphite sheets inserted into each other”. Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. Areas covered This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. Expert opinion In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts. PMID:25601356

  20. Crystalline magnetic carbon nanoparticle assisted photothermal delivery into cells using CW near-infrared laser beam

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Koymen, Ali R.; Mohanty, Samarendra K.

    2014-05-01

    Efficient and targeted delivery of impermeable exogenous material such as small molecules, proteins, and plasmids into cells in culture as well as in vivo is of great importance for drug, vaccine and gene delivery for different therapeutic strategies. Though advent of optoporation by ultrafast laser microbeam has allowed spatial targeting in cells, the requirement of high peak power to create holes on the cell membrane is not practical and also challenging in vivo. Here, we report development and use of uniquely non-reactive crystalline magnetic carbon nanoparticles (CMCNPs) for photothermal delivery (PTD) of impermeable dyes and plasmids encoding light-sensitive proteins into cells using low power continuous wave near-infrared (NIR) laser beam. Further, we utilized the magnetic nature of these CMCNPs to localize them in desired region by external magnetic field, thus minimizing the required number of nanoparticles. We discovered that irradiation of the CMCNPs near the desired cell(s) with NIR laser beam leads to temperature rise that not only stretch the cell-membrane to ease delivery, it also creates fluid flow to allow mobilization of exogenous substances to the delivery. Due to significant absorption properties of the CMCNPs in the NIR therapeutic window, PTD under in vivo condition is highly possible.

  1. Glutathione-mediated mesoporous carbon as a drug delivery nanocarrier with carbon dots as a cap and fluorescent tracer

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Han, Lu; Zhang, Yue; Chang, Yan-Qin; Chen, Xu-Wei; He, Rong-Huan; Shu, Yang; Wang, Jian-Hua

    2016-09-01

    This work describes a novel and general redox-responsive controlled drug delivery-release nanocarrier with mesoporous carbon nanoparticles (MCNs) gated by customized fluorescent carbon dots (CDs). The modification of MCNs with a disulfide unit enables the system to be sensitive to intracellular glutathione (GSH). The CDs anchoring onto the surface of the MCNs via an electrostatic interaction block the mesopores and thus prevent the leakage of doxorubicin (DOX) loaded inside the channel of the MCNs. Upon the addition of GSH at the physiological environment, the integrity of the system is disrupted due to the dissociation of the disulfide bond; meanwhile stripping the CDs opens the gate and thus triggers the rapid release of the encapsulated DOX. The fluorescence of the CDs is quenched/‘turned off’ when linking to the MCNs, while it is restored/‘turned on’ when detaching the CDs from the surface of the MCNs. Thus the fluorescent CDs serve as both a controllable drug release gatekeeper and a fluorescent probe for the visualization of the drug delivery process. By combining these inherent capabilities, the present drug delivery system may be a promising route for designing custom-made visual controlled-release nanodevices specifically governed by in situ stimulus in the cells.

  2. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    PubMed Central

    2011-01-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies. PMID:21995320

  3. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    NASA Astrophysics Data System (ADS)

    Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

    2011-10-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

  4. Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

    PubMed Central

    Coyuco, Jurja C; Liu, Yuanjie; Tan, Bee-Jen; Chiu, Gigi NC

    2011-01-01

    Although carbon nanomaterials (CNMs) have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp) efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes), carboxylic acid functionalized single-walled carbon nanotubes (f SWCNT-COOH) and poly(ethylene glycol) functionalized single-walled carbon nanotubes (f SWCNT-PEG), using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Of the three CNMs, f SWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that f SWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that f SWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of f SWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with f SWCNT-COOH, suggestive of P-gp inhibition. Of note, f SWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug delivery, and the differential effects on the intestinal epithelium imparted by different types of CNMs would create unique opportunities for drug-specific oral

  5. Modeling the biophysical effects in a carbon beam delivery line by using Monte Carlo simulations

    NASA Astrophysics Data System (ADS)

    Cho, Ilsung; Yoo, SeungHoon; Cho, Sungho; Kim, Eun Ho; Song, Yongkeun; Shin, Jae-ik; Jung, Won-Gyun

    2016-09-01

    The Relative biological effectiveness (RBE) plays an important role in designing a uniform dose response for ion-beam therapy. In this study, the biological effectiveness of a carbon-ion beam delivery system was investigated using Monte Carlo simulations. A carbon-ion beam delivery line was designed for the Korea Heavy Ion Medical Accelerator (KHIMA) project. The GEANT4 simulation tool kit was used to simulate carbon-ion beam transport into media. An incident energy carbon-ion beam with energy in the range between 220 MeV/u and 290 MeV/u was chosen to generate secondary particles. The microdosimetric-kinetic (MK) model was applied to describe the RBE of 10% survival in human salivary-gland (HSG) cells. The RBE weighted dose was estimated as a function of the penetration depth in the water phantom along the incident beam's direction. A biologically photon-equivalent Spread Out Bragg Peak (SOBP) was designed using the RBE-weighted absorbed dose. Finally, the RBE of mixed beams was predicted as a function of the depth in the water phantom.

  6. Carbon Nanotubes in Biology and Medicine: In vitro and in vivo Detection, Imaging and Drug Delivery

    PubMed Central

    Liu, Zhuang; Tabakman, Scott; Welsher, Kevin; Dai, Hongjie

    2010-01-01

    Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications in the past few years. In this comprehensive review, we summarize the main results from our and other groups in this field and clarify that surface functionalization is critical to the behavior of carbon nanotubes in biological systems. Ultrasensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of biomolecules on the hydrophobic nanotube surface. Electrical nanosensors based on nanotubes provide a label-free approach to biological detection. Surface-enhanced Raman spectroscopy of carbon nanotubes opens up a method of protein microarray with detection sensitivity down to 1 fmol/L. In vitro and in vivo toxicity studies reveal that highly water soluble and serum stable nanotubes are biocompatible, nontoxic, and potentially useful for biomedical applications. In vivo biodistributions vary with the functionalization and possibly also size of nanotubes, with a tendency to accumulate in the reticuloendothelial system (RES), including the liver and spleen, after intravenous administration. If well functionalized, nanotubes may be excreted mainly through the biliary pathway in feces. Carbon nanotube-based drug delivery has shown promise in various In vitro and in vivo experiments including delivery of small interfering RNA (siRNA), paclitaxel and doxorubicin. Moreover, single-walled carbon nanotubes with various interesting intrinsic optical properties have been used as novel photoluminescence, Raman, and photoacoustic contrast agents for imaging of cells and animals. Further multidisciplinary explorations in this field may bring new opportunities in the realm of biomedicine. PMID:20174481

  7. A pH-sensitive, biobased calcium carbonate aragonite nanocrystal as a novel anticancer delivery system.

    PubMed

    Shafiu Kamba, Abdullahi; Ismail, Maznah; Tengku Ibrahim, Tengku Azmi; Zakaria, Zuki Abu Bakar

    2013-01-01

    The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO₃/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO₃/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO₃/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO₃ nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.

  8. Innovative Delivery of siRNA to Solid Tumors by Super Carbonate Apatite

    PubMed Central

    Wu, Xin; Yamamoto, Hirofumi; Nakanishi, Hiroyuki; Yamamoto, Yuki; Inoue, Akira; Tei, Mitsuyoshi; Hirose, Hajime; Uemura, Mamoru; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Hossain, Sharif; Akaike, Toshihiro; Matsuura, Nariaki; Doki, Yuichiro; Mori, Masaki

    2015-01-01

    RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors. PMID:25738937

  9. Carbon nanotubes part II: a remarkable carrier for drug and gene delivery

    PubMed Central

    Karimi, Mahdi; Solati, Navid; Ghasemi, Amir; Estiar, Mehrdad Asghari; Hashemkhani, Mahshid; Kiani, Parnian; Mohamed, Elmira; Saeidi, Ahad; Taheri, Mahdiar; Avci, Pinar; Aref, Amir R; Amiri, Mohammad; Baniasadi, Fazel; Hamblin, Michael R

    2015-01-01

    Introduction Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis. Areas covered Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment. Expert opinion CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects. PMID:25613837

  10. Carbon nanotubes as delivery systems for respiratory disease: do the dangers outweigh the potential benefits?

    PubMed Central

    Bonner, James C

    2012-01-01

    Nanoparticle drug-delivery systems offer the potential for improved efficacy of treatment, and yet there are also potential risks associated with these novel therapeutic strategies. An attractive property of carbon nanotubes (CNTs) is that the tube- or fiber-like structure allows for extensive functionalization and loading of cargo. However, a large body of evidence indicates that CNTs may have adverse effects if used in drug delivery as they have been shown to cause pulmonary fibrosis and exacerbate lung disease in rodents with pre-existing lung diseases. Major factors that cause these toxic effects are the high aspect ratio, durability and residual metal content that generate reactive oxygen species. Therefore, careful consideration should be given to the possibility that lung inflammation or fibrosis could be significant side effects caused by a CNT-based drug-delivery system, thereby outweighing any potential beneficial effects of therapeutic treatment. However, functionalization of CNTs to modulate aspect ratio, biodegradability and to remove residual metals could allow for safe design of CNTs for use in drug delivery in certain circumstances. PMID:22082164

  11. Delivery.

    PubMed

    Miller, Thomas A

    2013-11-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms.

  12. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  13. Delivery of small interfering RNAs in human cervical cancer cells by polyethylenimine-functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Huang, Yuan-Pin; Lin, I.-Jou; Chen, Chih-Chen; Hsu, Yi-Chiang; Chang, Chi-Chang; Lee, Mon-Juan

    2013-06-01

    Carbon nanotubes are capable of penetrating the cell membrane and are widely considered as potential carriers for gene or drug delivery. Because the C-C and C=C bonds in carbon nanotubes are nonpolar, functionalization is required for carbon nanotubes to interact with genes or drugs as well as to improve their biocompatibility. In this study, polyethylenimine (PEI)-functionalized single-wall (PEI-NH-SWNTs) and multiwall carbon nanotubes (PEI-NH-MWNTs) were produced by direct amination method. PEI functionalization increased the positive charge on the surface of SWNTs and MWNTs, allowing carbon nanotubes to interact electrostatically with the negatively charged small interfering RNAs (siRNAs) and to serve as nonviral gene delivery reagents. PEI-NH-MWNTs and PEI-NH-SWNTs had a better solubility in water than pristine carbon nanotubes, and further removal of large aggregates by centrifugation produced a stable suspension of reduced particle size and improved homogeneity and dispersity. The amount of grafted PEI estimated by thermogravimetric analysis was 5.08% ( w/ w) and 5.28% ( w/ w) for PEI-NH-SWNTs and PEI-NH-MWNTs, respectively. For the assessment of cytotoxicity, various concentrations of PEI-NH-SWNTs and PEI-NH-MWNTs were incubated with human cervical cancer cells, HeLa-S3, for 48 h. PEI-NH-SWNTs and PEI-NH-MWNTs induced cell deaths in a dose-dependent manner but were less cytotoxic compared to pure PEI. As determined by electrophoretic mobility shift assay, siRNAs directed against glyceraldehyde-3-phosphate dehydrogenase (siGAPDH) were completely associated with PEI-NH-SWNTs or PEI-NH-MWNTs at a PEI-NH-SWNT/siGAPDH or PEI-NH-MWNT/siGAPDH mass ratio of 80:1 or 160:1, respectively. Furthermore, PEI-NH-SWNTs and PEI-NH-MWNTs successfully delivered siGAPDH into HeLa-S3 cells at PEI-NH-SWNT/siGAPDH and PEI-NH-MWNT/siGAPDH mass ratios of 1:1 to 20:1, resulting in suppression of the mRNA level of GAPDH to an extent similar to that of DharmaFECT, a common transfection

  14. Dissolved and particulate organic carbon exports from 4 Venezuelan rivers: effects of developing world urbanization on coastal carbon delivery

    NASA Astrophysics Data System (ADS)

    Masiello, C. A.; Perez, T.; Giuliante, A.; Rasse, R. J.; Hockaday, W. C.; Barnes, R. T.; Hernandez, J.; Donoso, L.

    2012-12-01

    Tropical and subtropical rivers play an increasingly important role in the delivery of riverine material to the coasts, and South America is the single largest source of all forms of dissolved organic matter to the ocean [Harrison et al., 2005]. Like much of the developing world, South American countries are urbanizing rapidly, a process that is likely to alter the characteristics and amount of carbon exported by rivers to the coasts. Compounding the measurement challenges are issues of basin size: small rivers release disproportionately large amounts of material to the ocean, but monitoring individual small basins is typically challenging, especially in the tropics. Here we present 4 years of monthly measurements of DOC and POC export from the four South American rivers that drain into the Cariaco Basin: the Tuy, Unare, Neverí, and Manzanares. Three of these rivers (Tuy, Neverí, and Manzanares) are mountainous, sharing the same geologic parent material and ecosystem, but varying in degree of urbanization. The Tuy drains Caracas (> 4 million people), and is significantly impacted by untreated wastewater. The Neverí and Manzanares host small cities at their mouths (3-400,000 people). Wastewater from Cumaná, at the mouth of the Manzanares, is released offshore, reducing its impact on the river's carbon cycle. The Unare is a flat river draining an ecosystem dominated by agriculture and savannah. In this presentation we will discuss the effects of tropical urbanization on the carbon export from small, mountainous rivers, focusing on delivery of DOC and POC to the coasts.

  15. DNA-carbon dots function as fluorescent vehicles for drug delivery.

    PubMed

    Ding, Han; Du, Feiyue; Liu, Pengchang; Chen, Zhijun; Shen, Jiacong

    2015-04-01

    Carbon dots (CDs) are a new representative in the carbon-based material family, attracting tremendous interest in a large variety of fields, including biomedicine. In this report, we described a facile and green system for synthesizing DNA-CDs using genomic DNA isolated from Escherichia coli. DNA-CDs can be purified using a simple column centrifugation-based system. During DNA-CD synthesis, ribose was collapsed, accompanied by the release of nitrogen, and several new bonds (C-OH, N-O, and N-P) were formed, while the other covalent bonds of DNA were largely maintained. The presence of abundant chemical groups, such as amino or hydroxyl groups on DNA-CDs, may facilitate their future functionalization. These highly biocompatible DNA-CDs can serve as a new type of fluorescent vehicle for cell imaging and drug delivery studies. Our research may hasten the development of CDs for prominent future biomedical applications.

  16. Prevention of colitis by controlled oral drug delivery of carbon monoxide.

    PubMed

    Steiger, Christoph; Uchiyama, Kazuhiko; Takagi, Tomohisa; Mizushima, Katsura; Higashimura, Yasuki; Gutmann, Marcus; Hermann, Cornelius; Botov, Svetlana; Schmalz, Hans-Günther; Naito, Yuji; Meinel, Lorenz

    2016-10-10

    Carbon monoxide (CO) is an endogenous signal transmitter involved in numerous physiological processes including the gastrointestinal (GI) homeostasis. CO has been recognized as potential new therapeutic agent for motility related and inflammatory disorders of the GI tract. A therapeutic use, however, is challenged by inappropriate drug delivery modes. Here we describe a micro scale Oral Carbon Monoxide Release System (M-OCORS) designed for localized and controlled exposure of the GI tract with in situ generated CO. M-OCORS allowed for controlled release profiles lasting for several minutes or up to almost one day. These in vitro release profiles translated into a large pharmacokinetic design space following oral administration in mice and measured as CO-hemoglobin (CO-Hb) formation. M-OCORS with a release profile featuring exposure of the intestine was profiled in two independently performed studies demonstrating preventive effects in chemically induced colitis. M-OCORS significantly reduced damage scores and prevented upregulation of colitis biomarkers.

  17. Potential of surface-eroding poly(ethylene carbonate) for drug delivery to macrophages.

    PubMed

    Bohr, Adam; Water, Jorrit J; Wang, Yingya; Arnfast, Lærke; Beck-Broichsitter, Moritz

    2016-09-25

    Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the tuberculosis drug rifampicin to study the characteristics and performance of PEC as a potential carrier for controlled drug delivery to macrophages. All drug-loaded PLGA and PEC films were amorphous indicating good miscibility of the drug in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more rapidly and near-linearly via enzyme mediated surface erosion (by cholesterol esterase). Drug release studies performed with polymer films indicated a diffusion/erosion dependent delivery behavior for PLGA while an almost zero-order drug release profile was observed from PEC due to the controlled polymer degradation process. When exposed to polymer degradation products the murine macrophage cell line J774A.1 showed less susceptibility to PEC than to PLGA. However, when seeding the macrophages on PLGA and PEC films no relevant difference in cell proliferation/growth kinetics was observed. Overall, this study emphasizes that PEC is an attractive polymer for controlled drug release and could provide superior performance to PLGA for some drug delivery applications including the treatment of macrophage infections. PMID:27492019

  18. Fabrication of Alginate/Calcium Carbonate Hybrid Microparticles for Synergistic Drug Delivery.

    PubMed

    Peng, Yan; Sun, Hua-Yan; Wang, Zong-Chun; Xu, Xiao-Ding; Song, Jin-Chun; Gong, Zuo-Jiong

    2016-01-01

    A hybrid drug delivery system coloaded with different drugs for synergistic drug delivery was developed. Alginate/calcium carbonate (CaCO3) hybrid microparticles (MPs) were fabricated via a facile coprecipitation method under mild conditions without using any organic solvent and surfactant. Due to the incorporation of negatively charged alginate chains onto the surface, the obtained hybrid MPs with spherical morphology showed good colloidal stability in an aqueous solution. An antitumor drug (doxorubicin, DOX) and a drug resistance reversal agent (verapamil, VP) were coloaded in the hybrid MPs simultaneously to obtain dual-drug-loaded MPs (DOX/VP/MP). Due to the presence of inorganic CaCO3 (∼54 wt%), the drugs could be loaded in the hybrid MPs with high encapsulation efficiency and the drug release could be effectively sustained. The cell growth inhibition of the drug-loaded MPs was evaluated in HeLa cells. An in vitro study showed DOX/VP/MP exhibited higher cell growth inhibition as compared with DOX monodrug-loaded MPs (DOX/MP). These results suggest the hybrid MPs can potentially be used as a synergistic drug delivery platform for cancer chemotherapy.

  19. Fabrication of Alginate/Calcium Carbonate Hybrid Microparticles for Synergistic Drug Delivery.

    PubMed

    Peng, Yan; Sun, Hua-Yan; Wang, Zong-Chun; Xu, Xiao-Ding; Song, Jin-Chun; Gong, Zuo-Jiong

    2016-01-01

    A hybrid drug delivery system coloaded with different drugs for synergistic drug delivery was developed. Alginate/calcium carbonate (CaCO3) hybrid microparticles (MPs) were fabricated via a facile coprecipitation method under mild conditions without using any organic solvent and surfactant. Due to the incorporation of negatively charged alginate chains onto the surface, the obtained hybrid MPs with spherical morphology showed good colloidal stability in an aqueous solution. An antitumor drug (doxorubicin, DOX) and a drug resistance reversal agent (verapamil, VP) were coloaded in the hybrid MPs simultaneously to obtain dual-drug-loaded MPs (DOX/VP/MP). Due to the presence of inorganic CaCO3 (∼54 wt%), the drugs could be loaded in the hybrid MPs with high encapsulation efficiency and the drug release could be effectively sustained. The cell growth inhibition of the drug-loaded MPs was evaluated in HeLa cells. An in vitro study showed DOX/VP/MP exhibited higher cell growth inhibition as compared with DOX monodrug-loaded MPs (DOX/MP). These results suggest the hybrid MPs can potentially be used as a synergistic drug delivery platform for cancer chemotherapy. PMID:26528767

  20. Potential of surface-eroding poly(ethylene carbonate) for drug delivery to macrophages.

    PubMed

    Bohr, Adam; Water, Jorrit J; Wang, Yingya; Arnfast, Lærke; Beck-Broichsitter, Moritz

    2016-09-25

    Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the tuberculosis drug rifampicin to study the characteristics and performance of PEC as a potential carrier for controlled drug delivery to macrophages. All drug-loaded PLGA and PEC films were amorphous indicating good miscibility of the drug in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more rapidly and near-linearly via enzyme mediated surface erosion (by cholesterol esterase). Drug release studies performed with polymer films indicated a diffusion/erosion dependent delivery behavior for PLGA while an almost zero-order drug release profile was observed from PEC due to the controlled polymer degradation process. When exposed to polymer degradation products the murine macrophage cell line J774A.1 showed less susceptibility to PEC than to PLGA. However, when seeding the macrophages on PLGA and PEC films no relevant difference in cell proliferation/growth kinetics was observed. Overall, this study emphasizes that PEC is an attractive polymer for controlled drug release and could provide superior performance to PLGA for some drug delivery applications including the treatment of macrophage infections.

  1. PLGA-Carbon Nanotube Conjugates for Intercellular Delivery of Caspase-3 into Osteosarcoma Cells

    PubMed Central

    Cheng, Qingsu; Blais, Marc-Olivier; Harris, Greg; Jabbarzadeh, Ehsan

    2013-01-01

    Cancer has arisen to be of the most prominent health care issues across the world in recent years. Doctors have used physiological intervention as well as chemical and radioactive therapeutics to treat cancer thus far. As an alternative to current methods, gene delivery systems with high efficiency, specificity, and safety that can reduce side effects such as necrosis of tissue are under development. Although viral vectors are highly efficient, concerns have arisen from the fact that viral vectors are sourced from lethal diseases. With this in mind, rod shaped nano-materials such as carbon nanotubes (CNTs) have become an attractive option for drug delivery due to the enhanced permeability and retention effect in tumors as well as the ability to penetrate the cell membrane. Here, we successfully engineered poly (lactic-co-glycolic) (PLGA) functionalized CNTs to reduce toxicity concerns, provide attachment sites for pro-apoptotic protein caspase-3 (CP3), and tune the temporal release profile of CP3 within bone cancer cells. Our results showed that CP3 was able to attach to functionalized CNTs, forming CNT-PLGA-CP3 conjugates. We show this conjugate can efficiently transduce cells at dosages as low as 0.05 μg/ml and suppress cell proliferation up to a week with no further treatments. These results are essential to showing the capabilities of PLGA functionalized CNTs as a non-viral vector gene delivery technique to tune cell fate. PMID:24312611

  2. Fluorescent carbon dot modified mesoporous silica nanocarriers for redox-responsive controlled drug delivery and bioimaging.

    PubMed

    Jiao, Jian; Liu, Chang; Li, Xian; Liu, Jie; Di, Donghua; Zhang, Ying; Zhao, Qinfu; Wang, Siling

    2016-12-01

    In this paper, a smart nanocarrier (MSNs-SS-CDPAA) is developed for redox-responsive controlled drug delivery and in vivo bioimaging by grafting fluorescent carbon dots to the surface of mesoporous silica nanoparticles (MSNs) via disulfide bonds. The polyanion polymer poly(acrylic acid) (PAA) was used to prepare the carboxyl-abundant carbon dots (CDPAA) by hydrothermal polymerization. The negatively charged CDPAA were anchored to the openings of MSNs containing the disulfide bonds through amidation and were used as gatekeepers for trapping the drugs within the pores. The in vitro release results indicated that the prepared MSNs-SS-CDPAA/DOX showed highly redox-responsive drug release in pH 7.4 and pH 5.0 PBS. In addition, the redox-responsive release mechanism was studied by measurement of the Zeta potential and fluorescence spectrophotometry. The prepared MSNs-SS-CDPAA exhibited excellent biocompatibility and fluorescence properties. Confocal laser scanning microscopy (CLSM) showed that MSNs-SS-CDPAA could emit blue, green and red fluorescence at an excitation wavelength of 408, 488 and 561nm, respectively. In addition, MSNs-SS-CDPAA/DOX exhibited a high cellular uptake as shown by CDPAA imaging and a therapeutic effect on cancer cells by MTT assay. This study describes a novel strategy for simultaneously controlled drug delivery and real-time imaging to track the behavior of nanoparticles during tumor therapy. PMID:27569517

  3. Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery.

    PubMed

    Smith, Bryan Ronain; Ghosn, Eliver Eid Bou; Rallapalli, Harikrishna; Prescher, Jennifer A; Larson, Timothy; Herzenberg, Leonore A; Gambhir, Sanjiv Sam

    2014-06-01

    In cancer imaging, nanoparticle biodistribution is typically visualized in living subjects using 'bulk' imaging modalities such as magnetic resonance imaging, computerized tomography and whole-body fluorescence. Accordingly, nanoparticle influx is observed only macroscopically, and the mechanisms by which they target cancer remain elusive. Nanoparticles are assumed to accumulate via several targeting mechanisms, particularly extravasation (leakage into tumour). Here, we show that, in addition to conventional nanoparticle-uptake mechanisms, single-walled carbon nanotubes are almost exclusively taken up by a single immune cell subset, Ly-6C(hi) monocytes (almost 100% uptake in Ly-6C(hi) monocytes, below 3% in all other circulating cells), and delivered to the tumour in mice. We also demonstrate that a targeting ligand (RGD) conjugated to nanotubes significantly enhances the number of single-walled carbon nanotube-loaded monocytes reaching the tumour (P < 0.001, day 7 post-injection). The remarkable selectivity of this tumour-targeting mechanism demonstrates an advanced immune-based delivery strategy for enhancing specific tumour delivery with substantial penetration.

  4. Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery

    NASA Astrophysics Data System (ADS)

    Smith, Bryan Ronain; Ghosn, Eliver Eid Bou; Rallapalli, Harikrishna; Prescher, Jennifer A.; Larson, Timothy; Herzenberg, Leonore A.; Gambhir, Sanjiv Sam

    2014-06-01

    In cancer imaging, nanoparticle biodistribution is typically visualized in living subjects using `bulk' imaging modalities such as magnetic resonance imaging, computerized tomography and whole-body fluorescence. Accordingly, nanoparticle influx is observed only macroscopically, and the mechanisms by which they target cancer remain elusive. Nanoparticles are assumed to accumulate via several targeting mechanisms, particularly extravasation (leakage into tumour). Here, we show that, in addition to conventional nanoparticle-uptake mechanisms, single-walled carbon nanotubes are almost exclusively taken up by a single immune cell subset, Ly-6Chi monocytes (almost 100% uptake in Ly-6Chi monocytes, below 3% in all other circulating cells), and delivered to the tumour in mice. We also demonstrate that a targeting ligand (RGD) conjugated to nanotubes significantly enhances the number of single-walled carbon nanotube-loaded monocytes reaching the tumour (P < 0.001, day 7 post-injection). The remarkable selectivity of this tumour-targeting mechanism demonstrates an advanced immune-based delivery strategy for enhancing specific tumour delivery with substantial penetration.

  5. Delivery of carboplatin by carbon-based nanocontainers mediates increased cancer cell death

    NASA Astrophysics Data System (ADS)

    Arlt, M.; Haase, D.; Hampel, S.; Oswald, S.; Bachmatiuk, A.; Klingeler, R.; Schulze, R.; Ritschel, M.; Leonhardt, A.; Fuessel, S.; Büchner, B.; Kraemer, K.; Wirth, M. P.

    2010-08-01

    Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of nanocarriers seems to be an efficient and promising approach for drug delivery. Their chemical and mechanical stability and their possible multifunctionality render tubular nanomaterials, such as carbon nanotubes (CNTs) and carbon nanofibres (CNFs), promising delivery agents for anticancer drugs. The goal of the present study was to investigate CNTs and CNFs in order to deliver carboplatin in vitro. No significant intrinsic toxicity of unloaded materials was found, confirming their biocompatibility. Carboplatin was loaded onto CNTs and CNFs, revealing a loading yield of 0.20 mg (CNT-CP) and 0.13 mg (CNF-CP) platinum per milligram of material. The platinum release depended on the carrier material. Whereas CNF-CP marginally released the drug, CNT-CP functioned as a drug depot, constantly releasing up to 68% within 14 days. The cytotoxicity of CNT-CP and CNF-CP in urological tumour cell lines was dependent on the drug release. CNT-CP was identified to be more effective than CNF-CP concerning the impairment of proliferation and clonogenic survival of tumour cells. Moreover, carboplatin, which was delivered by CNT-CP, exhibited a higher anticancer activity than free carboplatin.

  6. Silica-Based Carbon Source Delivery for In-situ Bioremediation Enhancement

    NASA Astrophysics Data System (ADS)

    Zhong, L.; Lee, M. H.; Lee, B.; Yang, S.

    2015-12-01

    Colloidal silica aqueous suspensions undergo viscosity increasing and gelation over time under favorable geochemical conditions. This property of silica suspension can potentially be applied to deliver remedial amendments to the subsurface and establish slow release amendment sources for enhanced remediation. In this study, silica-based delivery of carbon sources for in-situ bioremediation enhancement is investigated. Sodium lactate, vegetable oil, ethanol, and molasses have been studied for the interaction with colloidal silica in aqueous suspensions. The rheological properties of the carbon source amendments and silica suspension have been investigated. The lactate-, ethanol-, and molasses-silica suspensions exhibited controllable viscosity increase and eventually became gels under favorable geochemical conditions. The gelation rate was a function of the concentration of silica, salinity, amendment, and temperature. The vegetable oil-silica suspensions increased viscosity immediately upon mixing, but did not perform gelation. The carbon source release rate from the lactate-, ethanol-, and molasses-silica gels was determined as a function of silica, salinity, amendment concentration. The microbial activity stimulation and in-situ bioremediation enhancement by the slow-released carbon from the amendment-silica gels will be demonstrated in future investigations planned in this study.

  7. Delivery of Molecules into Human Corneal Endothelial Cells by Carbon Nanoparticles Activated by Femtosecond Laser

    PubMed Central

    Jumelle, Clotilde; Mauclair, Cyril; Houzet, Julien; Bernard, Aurélien; He, Zhiguo; Forest, Fabien; Peoc’h, Michel; Acquart, Sophie; Gain, Philippe; Thuret, Gilles

    2015-01-01

    Corneal endothelial cells (CECs) form a monolayer at the innermost face of the cornea and are the engine of corneal transparency. Nevertheless, they are a vulnerable population incapable of regeneration in humans, and their diseases are responsible for one third of corneal grafts performed worldwide. Donor corneas are stored in eye banks for security and quality controls, then delivered to surgeons. This period could allow specific interventions to modify the characteristics of CECs in order to increase their proliferative capacity, increase their resistance to apoptosis, or release immunosuppressive molecules. Delivery of molecules specifically into CECs during storage would therefore open up new therapeutic perspectives. For clinical applications, physical methods have a more favorable individual and general benefit/risk ratio than most biological vectors, but are often less efficient. The delivery of molecules into cells by carbon nanoparticles activated by femtosecond laser pulses is a promising recent technique developed on non-adherent cells. The nanoparticles are partly consummated by the reaction releasing CO and H2 gas bubbles responsible for the shockwave at the origin of cell transient permeation. Our aim was to develop an experimental setting to deliver a small molecule (calcein) into the monolayer of adherent CECs. We confirmed that increased laser fluence and time exposure increased uptake efficiency while keeping cell mortality below 5%. We optimized the area covered by the laser beam by using a motorized stage allowing homogeneous scanning of the cell culture surface using a spiral path. Calcein uptake reached median efficiency of 54.5% (range 50.3–57.3) of CECs with low mortality (0.5%, range (0.55–1.0)). After sorting by flow cytometry, CECs having uptaken calcein remained viable and presented normal morphological characteristics. Delivery of molecules into CECs by carbon nanoparticles activated by femtosecond laser could prove useful for

  8. VEGF-induced angiogenesis following localized delivery via injectable, low viscosity poly(trimethylene carbonate).

    PubMed

    Amsden, Brian G; Timbart, Laurianne; Marecak, Dale; Chapanian, Rafi; Tse, M Yat; Pang, Stephen C

    2010-07-14

    The purpose of this study was to examine the potential of low molecular weight poly(trimethylene carbonate) for localized vascular endothelial growth factor (VEGF) delivery. Poly(trimethylene carbonate) of various molecular weights was prepared by ring-opening polymerization initiated by 1-octanol. The resultant polymers were liquid at room temperature with low glass transition temperatures and viscosities at 37 degrees C that permitted their injection through an 18 (1/2) G 1.5'' needle. Particles consisting of VEGF co-lyophilized with trehalose were mixed into the polymers and the rate of release of VEGF was assessed in vitro. With a 1% particle loading, VEGF was released from the polymer at a rate of 20 ng/day over a period of 3 weeks. This release behavior was independent of the molecular weight of polymer used. Increasing the VEGF content in the lyophilized particles did not increase the VEGF release rate, an effect attributed to the solubility limit of VEGF in the solution formed upon dissolution of the particles. The VEGF released retained its bioactivity at greater than 95% of that of as-lyophilized VEGF, as assessed using a human aortic endothelial cell proliferation assay. This high bioactivity was supported by in vivo release experiments, wherein VEGF containing polymer implants induced the generation of significantly greater numbers of blood vessels towards the polymer implant than controls. The blood vessels did not remain stable and were reduced in number by three weeks, due to the unsustained and low concentration of VEGF released. This formulation approach, of using a low viscosity polymer delivery vehicle, is potentially useful for localized delivery of acid-sensitive proteins, such as VEGF. PMID:20381557

  9. Delivery of Molecules into Human Corneal Endothelial Cells by Carbon Nanoparticles Activated by Femtosecond Laser.

    PubMed

    Jumelle, Clotilde; Mauclair, Cyril; Houzet, Julien; Bernard, Aurélien; He, Zhiguo; Forest, Fabien; Peoc'h, Michel; Acquart, Sophie; Gain, Philippe; Thuret, Gilles

    2015-01-01

    Corneal endothelial cells (CECs) form a monolayer at the innermost face of the cornea and are the engine of corneal transparency. Nevertheless, they are a vulnerable population incapable of regeneration in humans, and their diseases are responsible for one third of corneal grafts performed worldwide. Donor corneas are stored in eye banks for security and quality controls, then delivered to surgeons. This period could allow specific interventions to modify the characteristics of CECs in order to increase their proliferative capacity, increase their resistance to apoptosis, or release immunosuppressive molecules. Delivery of molecules specifically into CECs during storage would therefore open up new therapeutic perspectives. For clinical applications, physical methods have a more favorable individual and general benefit/risk ratio than most biological vectors, but are often less efficient. The delivery of molecules into cells by carbon nanoparticles activated by femtosecond laser pulses is a promising recent technique developed on non-adherent cells. The nanoparticles are partly consummated by the reaction releasing CO and H2 gas bubbles responsible for the shockwave at the origin of cell transient permeation. Our aim was to develop an experimental setting to deliver a small molecule (calcein) into the monolayer of adherent CECs. We confirmed that increased laser fluence and time exposure increased uptake efficiency while keeping cell mortality below 5%. We optimized the area covered by the laser beam by using a motorized stage allowing homogeneous scanning of the cell culture surface using a spiral path. Calcein uptake reached median efficiency of 54.5% (range 50.3-57.3) of CECs with low mortality (0.5%, range (0.55-1.0)). After sorting by flow cytometry, CECs having uptaken calcein remained viable and presented normal morphological characteristics. Delivery of molecules into CECs by carbon nanoparticles activated by femtosecond laser could prove useful for future

  10. Delivery of Molecules into Human Corneal Endothelial Cells by Carbon Nanoparticles Activated by Femtosecond Laser.

    PubMed

    Jumelle, Clotilde; Mauclair, Cyril; Houzet, Julien; Bernard, Aurélien; He, Zhiguo; Forest, Fabien; Peoc'h, Michel; Acquart, Sophie; Gain, Philippe; Thuret, Gilles

    2015-01-01

    Corneal endothelial cells (CECs) form a monolayer at the innermost face of the cornea and are the engine of corneal transparency. Nevertheless, they are a vulnerable population incapable of regeneration in humans, and their diseases are responsible for one third of corneal grafts performed worldwide. Donor corneas are stored in eye banks for security and quality controls, then delivered to surgeons. This period could allow specific interventions to modify the characteristics of CECs in order to increase their proliferative capacity, increase their resistance to apoptosis, or release immunosuppressive molecules. Delivery of molecules specifically into CECs during storage would therefore open up new therapeutic perspectives. For clinical applications, physical methods have a more favorable individual and general benefit/risk ratio than most biological vectors, but are often less efficient. The delivery of molecules into cells by carbon nanoparticles activated by femtosecond laser pulses is a promising recent technique developed on non-adherent cells. The nanoparticles are partly consummated by the reaction releasing CO and H2 gas bubbles responsible for the shockwave at the origin of cell transient permeation. Our aim was to develop an experimental setting to deliver a small molecule (calcein) into the monolayer of adherent CECs. We confirmed that increased laser fluence and time exposure increased uptake efficiency while keeping cell mortality below 5%. We optimized the area covered by the laser beam by using a motorized stage allowing homogeneous scanning of the cell culture surface using a spiral path. Calcein uptake reached median efficiency of 54.5% (range 50.3-57.3) of CECs with low mortality (0.5%, range (0.55-1.0)). After sorting by flow cytometry, CECs having uptaken calcein remained viable and presented normal morphological characteristics. Delivery of molecules into CECs by carbon nanoparticles activated by femtosecond laser could prove useful for future

  11. Carbon nanotubes as vectors for gene therapy: past achievements, present challenges and future goals.

    PubMed

    Bates, Katie; Kostarelos, Kostas

    2013-12-01

    Promising therapeutic and prophylactic effects have been achieved following advances in the gene therapy research arena, giving birth to the new generation of disease-modifying therapeutics. The greatest challenge that gene therapy vectors still face is the ability to deliver sufficient genetic payloads in order to enable efficient gene transfer into target cells. A wide variety of viral and non-viral gene therapy vectors have been developed and explored over the past 10years, including carbon nanotubes. In this review we will address the application of carbon nanotubes as non-viral vectors in gene therapy with the aim to give a perspective on the past achievements, present challenges and future goals. A series of important topics concerning carbon nanotubes as gene therapy vectors will be addressed, including the benefits that carbon nanotubes offer over other non-viral delivery systems. Furthermore, a perspective is given on what the ideal genetic cargo to deliver using carbon nanotubes is and finally the geno-pharmacological impact of carbon nanotube-mediated gene therapy is discussed.

  12. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy

    NASA Astrophysics Data System (ADS)

    Yang, Lei; Wang, Zheran; Wang, Ju; Jiang, Weihua; Jiang, Xuewei; Bai, Zhaoshi; He, Yunpeng; Jiang, Jianqi; Wang, Dongkai; Yang, Li

    2016-03-01

    Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared

  13. Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery

    PubMed Central

    John, Agnes Aruna; Subramanian, Aruna Priyadharshni; Vellayappan, Muthu Vignesh; Balaji, Arunpandian; Mohandas, Hemanth; Jaganathan, Saravana Kumar

    2015-01-01

    Neuroregeneration is the regrowth or repair of nervous tissues, cells, or cell products involved in neurodegeneration and inflammatory diseases of the nervous system like Alzheimer’s disease and Parkinson’s disease. Nowadays, application of nanotechnology is commonly used in developing nanomedicines to advance pharmacokinetics and drug delivery exclusively for central nervous system pathologies. In addition, nanomedical advances are leading to therapies that disrupt disarranged protein aggregation in the central nervous system, deliver functional neuroprotective growth factors, and change the oxidative stress and excitotoxicity of affected neural tissues to regenerate the damaged neurons. Carbon nanotubes and graphene are allotropes of carbon that have been exploited by researchers because of their excellent physical properties and their ability to interface with neurons and neuronal circuits. This review describes the role of carbon nanotubes and graphene in neuroregeneration. In the future, it is hoped that the benefits of nanotechnologies will outweigh their risks, and that the next decade will present huge scope for developing and delivering technologies in the field of neuroscience. PMID:26170663

  14. PEGylated single-walled carbon nanotubes as nanocarriers for cyclosporin A delivery.

    PubMed

    Hadidi, Naghmeh; Kobarfard, Farzad; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

    2013-06-01

    Single-walled carbon nanotubes (SWCNTs) have attracted the attention of many researchers due to their remarkable physicochemical features and have been found to be a new family of nanovectors for the delivery of therapeutic molecules. The ability of these nanostructures to load large amounts of drug molecules on their outer surface has been considered as the main advantage by many investigators. Here, we report the development of a PEGylated SWCNT-mediated delivery system for cyclosporin A (CsA) as a potent immunosuppressive agent. The available OH group in the CsA structure was first linked to a bi-functional linker (i.e., succinic anhydride) in order to provide a COOH terminal group. CsA succinylation process was optimized by using the modified simplex method. The resulting compound, CsA-CO-(CH(2))(2)-COOH, was then grafted onto the exterior surface of SWCNTs, previously PEGylated with phospholipid-PEG(5000)-NH(2) conjugates, through the formation of an amide bond with the free amine group of PEGylated SWCNTs. Drug loading, stability of the PEGylated SWCNT-CsA complex, and in vitro release of the drug were evaluated. Loading efficiencies of almost 72% and 68% were achieved by UV spectrophotometry and elemental analysis methods, respectively. It was observed that 57.3% of cyclosporine was released from CsA-Pl-PEG(5000)-SWCNTs after 3 days. In this investigation, we conjugated CsA to an amine-terminated phospholipid-polyethylene glycol chain attached on SWCNTs via a cleavable ester bond and demonstrated the possible potential of PEGylated SWCNT-based systems for CsA delivery.

  15. Ferromagnetic filled carbon nanotubes and nanoparticles: synthesis and lipid-mediated delivery into human tumor cells

    NASA Astrophysics Data System (ADS)

    Mönch, I.; Meye, A.; Leonhardt, A.; Krämer, K.; Kozhuharova, R.; Gemming, T.; Wirth, M. P.; Büchner, B.

    2005-04-01

    We describe the synthesis and the properties of Fe-filled multi-walled carbon nanotubes (MWNTs) and nanoparticles (NP) produced by chemical vapor deposition (CVD). We have employed ferrocene as a starting substance and oxidized Si-wafers as substrates. The magnetic properties and the interaction of the material with bladder cancer cells were determined. After the addition of NP suspensions to cultured cells, no adhesion of the nanoparticles/nanotubes (NT/NP) to the cell membrane and also no cellular uptake were observed. However, the preincubation of the (NT/NP) suspension with cationic lipid caused an efficient delivery of the lipid-nanostructure complexes into the cytoplasm within 2 h after adding to the culture medium.

  16. Micellar stabilized single-walled carbon nanotubes for a pH-sensitive delivery of doxorubicin.

    PubMed

    Farvadi, F; Tamaddon, A M; Abolmaali, S S; Sobhani, Z; Yousefi, G H

    2014-01-01

    Single-walled carbon nanotubes (SWNTs) are among the promising nano-devices for delivery of therapeutic agents. Yet the drastic hydrophobic natures of SWNTs make their handling and hence application difficult. Several researches have been conducted to make them more hydrophilic and water dispersible and less toxic. Among the different approaches, dispersion methods exploit different reagents such as surfactants and block copolymers. The question is whether these so called dispersed SWNTs are stable enough and suitable for biomedical applications. Herein we aimed to functionalize SWNT surface by dioleoylphosphatidylethanolamine-polyethylene glycol (PL-PEG) and sodium deoxycholate (SDC) micelles and compare their efficacy in SWNT stabilization for biomedical application such as delivery of doxorubicin. Shortening and water dispersion of SWNTs were carried out by ultrasonication in aqueous solutions at different concentrations of SDC or PL-PEG micelle and assessed by UV-Vis-NIR spectroscopy. The stability of SWNT dispersions were assessed over the time and in the presence of salt by macroscopic observation and UV-Vis-NIR spectroscopy. Doxorubicin loading and release were carried out under different pH conditions. SWNT dispersions were stable in water for at least several weeks at room temperature, but SDC prepared dispersions were prone to agglomeration in the presence of salt and doxorubicin. The critical PL-PEG concentration for stability in physiologic conditions was about 5 times its critical micelle concentration. Doxorubicin loading was pH dependent and its release was triggered in acidic condition of tumor medium. PMID:25598794

  17. Hydrophilic mesoporous carbon nanospheres with high drug-loading efficiency for doxorubicin delivery and cancer therapy

    PubMed Central

    Wang, Huan; Li, Xiangui; Ma, Zhiqiang; Wang, Dan; Wang, Linzhao; Zhan, Jieqiong; She, Lan; Yang, Feng

    2016-01-01

    In this study, a highly effective transmembrane delivery vehicle based on PEGylated oxidized mesoporous carbon nanosphere (oMCN@PEG) was successfully fabricated in a facile strategy. oMCN@PEG exhibited a narrow size distribution of 90 nm, excellent hydrophilicity, good biocompatibility, and a very high loading efficiency for doxorubicin (DOX). The drug system (oMCN@DOX@PEG) exhibited excellent stability under neutral pH conditions, but with dramatic releases of DOX at reduced pH conditions. Pharmacokinetics study revealed that oMCN@DOX@PEG could prolong the circulation of DOX in the blood stream. The endocytosis, cytotoxicity, and anticancer effect in vitro and in vivo of the drug-loaded nanoparticles were also evaluated. Our results showed that the nanoparticles efficiently penetrated the membrane of tumor cells, subsequently released drugs, and efficiently inhibited the growth of cancer cells both in vitro and in vivo. Especially, oMCN@DOX@PEG also exhibited significant antimetastasis effect in advanced stage of malignant cancer, improving the survival time of tumor-bearing mice. The results suggested that oMCN@PEG might be a promising anticancer drug delivery vehicle for cancer therapy. PMID:27175077

  18. Functionalized Single-Walled Carbon Nanotubes as Rationally Designed Vehicles for Tumor-Targeted Drug Delivery

    SciTech Connect

    Chen,J.; Wong,S.; Chen, S.; Zhao, X.; Kuznetsova, L.V.; and Ojima, I.

    2008-11-14

    A novel single-walled carbon nanotube (SWNT)-based tumor-targeted drug delivery system (DDS) has been developed, which consists of a functionalized SWNT linked to tumor-targeting modules as well as prodrug modules. There are three key features of this nanoscale DDS: (a) use of functionalized SWNTs as a biocompatible platform for the delivery of therapeutic drugs or diagnostics, (b) conjugation of prodrug modules of an anticancer agent (taxoid with a cleavable linker) that is activated to its cytotoxic form inside the tumor cells upon internalization and in situ drug release, and (c) attachment of tumor-recognition modules (biotin and a spacer) to the nanotube surface. To prove the efficacy of this DDS, three fluorescent and fluorogenic molecular probes were designed, synthesized, characterized, and subjected to the analysis of the receptor-mediated endocytosis and drug release inside the cancer cells (L1210FR leukemia cell line) by means of confocal fluorescence microscopy. The specificity and cytotoxicity of the conjugate have also been assessed and compared with L1210 and human noncancerous cell lines. Then, it has unambiguously been proven that this tumor-targeting DDS works exactly as designed and shows high potency toward specific cancer cell lines, thereby forming a solid foundation for further development.

  19. Non-covalently functionalized single-walled carbon nanotube for topical siRNA delivery into melanoma.

    PubMed

    Siu, King Sun; Chen, Di; Zheng, Xiufen; Zhang, Xusheng; Johnston, Nathan; Liu, Yanling; Yuan, Ken; Koropatnick, James; Gillies, Elizabeth R; Min, Wei-Ping

    2014-03-01

    RNAi can specifically regulate gene expression, but efficient delivery of siRNA in vivo is difficult while it has been shown that modified carbon nanotubes (CNT) protect siRNA, facilitate entry into cells and enhance transdermal drugs delivery. Single-walled carbon nanotubes (SWCNT) were functionalized non-covalently with succinated polyethyleimine (PEI-SA). In this study, the water soluble CNT, PEI-SA/CNT (IS/C) were isolated and characterized, the gene silencing induced by IS/C/siRNA complexes was achieved in vitro in B16-F10 cells. In vivo delivery was topically applied to shaved mouse skin, as well as topically to a C57BL/6 mice melanoma model. We found significant uptake of Cy3-labeled siRNA specific to Braf (siBraf) and gene silencing in the tumor tissue. Treatment with IS/C/siBraf resulted in attenuation of tumor growth over a 25-day period. This new delivery method has provided a new possibility for future siRNA delivery and therapy, which providing insight for the potential application and development of CNT-based siRNA delivery.

  20. Molecular insights on the cyclic peptide nanotube-mediated transportation of antitumor drug 5-fluorouracil.

    PubMed

    Liu, Huifang; Chen, Jian; Shen, Qing; Fu, Wei; Wu, Wei

    2010-12-01

    Self-assembled cyclic peptide nanotubes (CPNs) show a potential use in drug delivery. In this study, the CPN composed of (Trp-D-Leu)(4)-Gln-D-Leu was synthesized and tested for the transport of the antitumor drug 5-fluorouracil (5-FU). CPN-mediated release of 5-FU from liposomes experimentally tested the transportation function of the synthetic CPNs. To explore the transportation mechanism of CPNs, computational studies have been performed on the CPN models stacked by 8 subunits, including conventional molecular dynamics (CMD) simulations, and steered molecular dynamics (SMD) simulations in the environment of hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer. Our CMD simulations demonstrated that the ortho-CPN is the most stable nanotube, in which the Gln residue is in the ortho-position relative to other residues. The calculated diffusion coefficient value for inner water molecules was 1.068 × 10(-5) cm(2)·s(-1), almost half that of the bulky water and 24 times faster than that of the typical gramicidin A channel. The CPN conserved its hollow structure along the 10 ns CMD simulations, with a tile angle of 50° relative to the normal of DMPC membrane. Results from SMD simulations showed that the 5-FU molecule was transported by hopping through different potential energy minima distributed along subunits, and finally exited the nanotube by escaping from the kink region at the last two subunits. The hopping of 5-FU was driven by switching from hydrophobic interactions between 5-FU and the interior wall of the nanotube to hydrogen bonding interactions of 5-FU with the backbone carbonyl group and amide group of ortho-CPN. The calculated binding free energy profile of 5-FU interacting with the CPN indicated that there was an energy well near the outer end of the nanotube.

  1. Non-Covalent Functionalization of Carbon Nanovectors with an Antibody Enables Targeted Drug Delivery

    PubMed Central

    Berlin, Jacob M.; Pham, Tam T.; Sano, Daisuke; Mohamedali, Khalid A.; Marcano, Daniela C.; Myers, Jeffrey N.; Tour, James M.

    2011-01-01

    Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through non-covalent interactions. Such non-covalent assembly could enable high-throughput screening of drug/antibody combinations. PMID:21736358

  2. Multi-functionalized carbon dots as theranostic nanoagent for gene delivery in lung cancer therapy

    PubMed Central

    Wu, Yu-Fen; Wu, Hsi-Chin; Kuan, Chen-Hsiang; Lin, Chun-Jui; Wang, Li-Wen; Chang, Chien-Wen; Wang, Tzu-Wei

    2016-01-01

    Theranostics, an integrated therapeutic and diagnostic system, can simultaneously monitor the real-time response of therapy. Different imaging modalities can combine with a variety of therapeutic moieties in theranostic nanoagents. In this study, a multi-functionalized, integrated theranostic nanoagent based on folate-conjugated reducible polyethylenimine passivated carbon dots (fc-rPEI-Cdots) is developed and characterized. These nanoagents emit visible blue photoluminescence under 360 nm excitation and can encapsulate multiple siRNAs (EGFR and cyclin B1) followed by releasing them in intracellular reductive environment. In vitro cell culture study demonstrates that fc-rPEI-Cdots is a highly biocompatible material and a good siRNA gene delivery carrier for targeted lung cancer treatment. Moreover, fc-rPEI-Cdots/pooled siRNAs can be selectively accumulated in lung cancer cells through receptor mediated endocytosis, resulting in better gene silencing and anti-cancer effect. Combining bioimaging of carbon dots, stimulus responsive property, gene silencing strategy, and active targeting motif, this multi-functionalized, integrated theranostic nanoagent may provide a useful tool and platform to benefit clinicians adjusting therapeutic strategy and administered drug dosage in real time response by monitoring the effect and tracking the development of carcinomatous tissues in diagnostic and therapeutic aspects. PMID:26880047

  3. Low viscosity poly(trimethylene carbonate) for localized drug delivery: rheological properties and in vivo degradation.

    PubMed

    Timbart, Laurianne; Tse, M Yat; Pang, Stephen C; Babasola, Oladunni; Amsden, Brian G

    2009-08-11

    The purpose of this study is to examine the potential of low-molecular-weight poly(trimethylene carbonate) for localized delivery for acid-sensitive drugs. Poly(trimethylene carbonate) of various molecular weights is prepared by ring-opening polymerization initiated by octan-1-ol and co-initiated/catalyzed by tin 2-ethylhexanoate. The resultant polymers are amorphous with low glass transition temperatures and viscosities at 37 degrees C that permit their injection through an 18(1\\2) G 1.5'' needle. Their biocompatibility and the influence of the molecular weight on the rate of degradation are assessed in vivo through subcutaneous implantation in rats over 40 weeks. The polymers are well tolerated in vivo, and degrade in a fashion dependent on their initial molecular weight. For very low initial molecular weight (620 Da) and for high initial molecular weight (2,400 Da), polymer mass loss is a result of dissolution of the soluble low molecular chains from the bulk. This is contrasted by the results obtained for an intermediate initial molecular weight (1,600 Da), for which polymer mass loss is a result of both dissolution and enzymatic hydrolysis or oxidation as a result of reactive species secreted by activated macrophages at the implant surface. PMID:19253418

  4. Nanodiamond decorated liposomes as highly biocompatible delivery vehicles and a comparison with carbon nanotubes and graphene oxide

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Liu, Juewen

    2013-11-01

    Studying interactions between nano-carbons and lipid membranes is important for multiplexed drug delivery, device fabrication and for understanding toxicity. Herein, we report that nanodiamond (ND, sp3 carbon) forms a complex with highly biocompatible zwitterionic liposomes based on hydrogen bonding, which is confirmed by pH-dependent and urea-dependent assays. Despite such weak interaction, the complex is highly stable. Comparisons were made with two sp2 carbons: nanoscale graphene oxide (NGO) and carbon nanotubes (CNTs), where CNT adsorption is the weakest. Adsorption of the nano-carbons does not induce liposome leakage or affect lipid phase transition temperature. Therefore, the potential toxicity of nano-carbons is unlikely to be related to direct membrane damage. ND facilitates cellular uptake of liposomes and co-delivery of negatively charged calcein and positively charged doxorubicin has been demonstrated. ND has the lowest toxicity, while CNTs and NGO are slightly more toxic. The effect of introducing fusogenic lipids and cholesterol was further studied to understand the effect of lipid formulation.Studying interactions between nano-carbons and lipid membranes is important for multiplexed drug delivery, device fabrication and for understanding toxicity. Herein, we report that nanodiamond (ND, sp3 carbon) forms a complex with highly biocompatible zwitterionic liposomes based on hydrogen bonding, which is confirmed by pH-dependent and urea-dependent assays. Despite such weak interaction, the complex is highly stable. Comparisons were made with two sp2 carbons: nanoscale graphene oxide (NGO) and carbon nanotubes (CNTs), where CNT adsorption is the weakest. Adsorption of the nano-carbons does not induce liposome leakage or affect lipid phase transition temperature. Therefore, the potential toxicity of nano-carbons is unlikely to be related to direct membrane damage. ND facilitates cellular uptake of liposomes and co-delivery of negatively charged calcein and

  5. The covalent bioconjugate of multiwalled carbon nanotube and amino-modified linearized plasmid DNA for gene delivery.

    PubMed

    Geyik, Caner; Evran, Serap; Timur, Suna; Telefoncu, Azmi

    2014-01-01

    Carbon nanotubes (CNTs) are allotropes of carbon, which have unique physical, mechanical, and electronic properties. Among various biomedical applications, CNTs also attract interest as nonviral gene delivery systems. Functionalization of CNTs with cationic groups enables delivery of negatively charged DNA into cells. In contrast to this well-known strategy for DNA delivery, our approach included the covalent attachment of linearized plasmid DNA to carboxylated multiwalled CNTs (MWCNTs). Carboxyl groups were introduced onto MWCNTs by oxidative treatment, and then the carboxyl groups were activated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The whole pQE-70 vector including the gene encoding green fluorescent protein (GFP) was subjected to polymerase chain reaction (PCR) using the modified nucleotide N6-(6-Amino)hexyl-2'-deoxyadenosine-5'-triphosphate. Hence, free amino groups were introduced onto the linearized plasmid. Covalent bonding between the amino-modified plasmid DNA and the carboxylated MWCNTs was achieved via EDC chemistry. The resulting bioconjugate was successfully transformed into chemically competent Escherichia coli cells, without necessity of a heat-shock step at 42°C. The presence of Ca(2+) in transformation medium was required to neutralize the electrostatic repulsion between DNA and negatively charged outer layer of E. coli. The transformants, which were able to express GFP were inspected manually on ampicillin agar plates. Our study represents a novelty with respect to other noncovalent CNT gene delivery systems. Considering the interest for delivery of linear DNA fragments, our study could give insights into further studies.

  6. Carbon delivery to deep mineral horizons in Hawaiian rain forest soils

    NASA Astrophysics Data System (ADS)

    Marin-Spiotta, Erika; Chadwick, Oliver A.; Kramer, Marc; Carbone, Mariah S.

    2011-09-01

    This study aimed to better understand the mechanisms for soil organic matter delivery to and accumulation in mineral horizons of tropical rain forest, volcanic soils. We used soil morphology, lysimetry, isotopes, and spectroscopy to investigate the role of preferential flow paths in the delivery of carbon (C) to the subsoil. High rainfall, high primary productivity, and the dominance of highly reactive, short-range-order minerals combine to sequester substantial stocks of soil C with long mean residence times. The soils have large peds, separated by wide cracks, which form a network of channels propagating downward through the top 40 to 60 cm, facilitating macropore flow. The channel infillings and crack surfaces were enriched in organic material (OM) with lower C:N ratios, and had higher ammonium oxalate-extractable Al, and lower ammonium oxalate-extractable Fe than the adjacent mineral bulk soil. CP MAS 13C-NMR spectra of OM accumulating at depth showed strong signal intensities in the carboxyl and carbonyl C regions, indicative of organic acids, while decaying roots showed greater contributions of aromatic and O-alkyl C. The ratios of alkyl-to-O-alkyl C in the organic infillings were more similar to those of the bulk Bh and to dissolved organic matter than to those of decaying roots. Radiocarbon-based ages of OM infillings at >50 cm depth were significantly younger than the mineral soil (2000 years versus 7000 years). Respired CO2 from incubated soils showed that OM accumulating at depth is a mixture of modern and much older C, providing further evidence for the downward movement of fresh C.

  7. Dendrimer, liposomes, carbon nanotubes and PLGA nanoparticles: one platform assessment of drug delivery potential.

    PubMed

    Mody, Nishi; Tekade, Rakesh Kumar; Mehra, Neelesh Kumar; Chopdey, Prashant; Jain, Narendra Kumar

    2014-04-01

    Liposomes (LIP), nanoparticles (NP), dendrimers (DEN), and carbon nanotubes (CNTs), represent eminent classes of drug delivery devices. A study was carried out herewith by employing docetaxel (DTX) as model drug to assess their comparative drug delivery potentials. Under optimized conditions, highest entrapment of DTX was observed in CNT-based formulation (DTX-CNTs, 74.70 ± 4.9%) followed by nanoparticles (DTX-NP, 62.34 ± 1.5%), liposome (49.2 ± 1.51%), and dendrimers (28.26 ± 1.74%). All the formulations were found to be of nanometric size. In vitro release studies were carried out in PBS (pH 7.0 and 4.0), wherein all the formulations showed biphasic release pattern. Cytotoxicity assay in human cervical cancer SiHa cells inferred lowest IC50 value of 1,235.09 ± 41.93 nM with DTX-CNTs, followed by DTX-DEN, DTX-LIP, DTX-NP with IC50 values of 1,571.22 ± 151.27, 1,653.98 ± 72.89, 1,922.75 ± 75.15 nM, respectively. Plain DTX showed higher hemolytic toxicity of 22.48 ± 0.94%, however loading of DTX inside nanocarriers drastically reduced its hemolytic toxicity (DTX-DEN, 17.22 ± 0.48%; DTX-LIP, 4.13 ± 0.19%; DTX-NP, 6.43 ± 0.44%; DTX-CNTs, 14.87 ± 1.69%). PMID:24431104

  8. 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.

  9. pH-sensitive nano-crystals of carbonate apatite for smart and cell-specific transgene delivery.

    PubMed

    Chowdhury, E H

    2007-05-01

    The treatment of a human disease at a genetic level by either providing a cell with a functional gene or a nucleic acid sequence to precisely silence a harmful gene, is a powerful approach that could revolutionise clinical medicine. Despite the existence of both genetically engineered viral vectors and synthetically designed lipid- or polymer-based nanocarriers, an ideal delivery system in terms of safety and efficacy is still lacking. This editorial reports on the development of biocompatible, inorganic nanoparticles of carbonate apatite, which has the unique features essentially required for smart delivery, as well as for the expression of a genetic material in a mammalian cell.

  10. Nanodiamond decorated liposomes as highly biocompatible delivery vehicles and a comparison with carbon nanotubes and graphene oxide.

    PubMed

    Wang, Feng; Liu, Juewen

    2013-12-21

    Studying interactions between nano-carbons and lipid membranes is important for multiplexed drug delivery, device fabrication and for understanding toxicity. Herein, we report that nanodiamond (ND, sp(3) carbon) forms a complex with highly biocompatible zwitterionic liposomes based on hydrogen bonding, which is confirmed by pH-dependent and urea-dependent assays. Despite such weak interaction, the complex is highly stable. Comparisons were made with two sp(2) carbons: nanoscale graphene oxide (NGO) and carbon nanotubes (CNTs), where CNT adsorption is the weakest. Adsorption of the nano-carbons does not induce liposome leakage or affect lipid phase transition temperature. Therefore, the potential toxicity of nano-carbons is unlikely to be related to direct membrane damage. ND facilitates cellular uptake of liposomes and co-delivery of negatively charged calcein and positively charged doxorubicin has been demonstrated. ND has the lowest toxicity, while CNTs and NGO are slightly more toxic. The effect of introducing fusogenic lipids and cholesterol was further studied to understand the effect of lipid formulation.

  11. Controllable delivery of small-molecule compounds to targeted cells utilizing carbon nanotubes.

    PubMed

    Su, Zhengding; Zhu, Shuihan; Donkor, Apraku D; Tzoganakis, Costas; Honek, John F

    2011-05-11

    Carbon nanotubes (CNTs) have emerged as a new alternative and efficient tool for transporting molecules with biotechnological and biomedical applications, because of their remarkable physicochemical properties. Encapsulation of functional molecules into the hollow chambers of CNTs can not only stabilize encapsulated molecules but also generate new nanodevices. In this work, we have demonstrated that CNTs can function as controllable carriers to transport small-molecule compounds (SMCs) loaded inside their hollow tunnels onto targeted cells. Using indole as model compound, CNTs can protect indole molecules during transportation. Labeling indole-loaded CNTs (indole@CNTs) with EphB4-binding peptides generates cell-homing indole@CNTs (CIDs). CIDs can selectively target EphB4-expressing cells and release indole onto cell surfaces by near-infrared (NIR) irradiation. Released indole molecules exhibit significant cell-killing effects without causing local overheating. This establishes CNTs as excellent near-infrared controllable delivery vehicles for SMCs as selective cell-killing agents.

  12. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability. PMID:27305761

  13. Hyaluronic acid-modified multiwalled carbon nanotubes for targeted delivery of doxorubicin into cancer cells.

    PubMed

    Cao, Xueyan; Tao, Lei; Wen, Shihui; Hou, Wenxiu; Shi, Xiangyang

    2015-03-20

    Development of novel drug carriers for targeted cancer therapy with high efficiency and specificity is of paramount importance and has been one of the major topics in current nanomedicine. Here we report a general approach to using multifunctional multiwalled carbon nanotubes (MWCNTs) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, polyethyleneimine (PEI)-modified MWCNTs were covalently conjugated with fluorescein isothiocyanate (FI) and hyaluronic acid (HA). The formed MWCNT/PEI-FI-HA conjugates were characterized via different techniques and were used as a new carrier system to encapsulate the anticancer drug doxorubicin for targeted delivery to cancer cells overexpressing CD44 receptors. We show that the formed MWCNT/PEI-FI-HA/DOX complexes with a drug loading percentage of 72% are water soluble and stable. In vitro release studies show that the drug release rate under an acidic condition (pH 5.8, tumor cell microenvironment) is higher than that under physiological condition (pH 7.4). Cell viability assay demonstrates that the carrier material has good biocompatibility in the tested concentration range, and the MWCNT/PEI-FI-HA/DOX complexes can specifically target cancer cells overexpressing CD44 receptors and exert growth inhibition effect to the cancer cells. The developed HA-modified MWCNTs hold a great promise to be used as an efficient anticancer drug carrier for tumor-targeted chemotherapy.

  14. A new era of cancer treatment: carbon nanotubes as drug delivery tools

    PubMed Central

    Madani, Seyed Yazdan; Naderi, Naghmeh; Dissanayake, Oshani; Tan, Aaron; Seifalian, Alexander M

    2011-01-01

    Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology. PMID:22162655

  15. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.

  16. Carbon nanotubes in hyperthermia therapy

    PubMed Central

    Singh, Ravi; Torti, Suzy V.

    2013-01-01

    Thermal tumor ablation therapies are being developed with a variety of nanomaterials, including single-and multiwalled carbon nanotubes. Carbon nanotubes (CNTs) have attracted interest due to their potential for simultaneous imaging and therapy. In this review, we highlight in vivo applications of carbon nanotube-mediated thermal therapy (CNMTT) and examine the rationale for use of this treatment in recurrent tumors or those resistant to conventional cancer therapies. Additionally, we discuss strategies to localize and enhance the cancer selectivity of this treatment and briefly examine issues relating the toxicity and long term fate of CNTs. PMID:23933617

  17. Carbon nanotubes in hyperthermia therapy.

    PubMed

    Singh, Ravi; Torti, Suzy V

    2013-12-01

    Thermal tumor ablation therapies are being developed with a variety of nanomaterials, including single- and multiwalled carbon nanotubes. Carbon nanotubes (CNTs) have attracted interest due to their potential for simultaneous imaging and therapy. In this review, we highlight in vivo applications of carbon nanotube-mediated thermal therapy (CNMTT) and examine the rationale for use of this treatment in recurrent tumors or those resistant to conventional cancer therapies. Additionally, we discuss strategies to localize and enhance the cancer selectivity of this treatment and briefly examine issues relating the toxicity and long term fate of CNTs.

  18. Effective Drug Delivery, in vitro and in vivo, By Carbon-Based Nanovectors Non-Covalently Loaded With Unmodified Paclitaxel

    PubMed Central

    Berlin, Jacob M.; Leonard, Ashley D.; Pham, Tam T.; Sano, Daisuke; Marcano, Daniela C.; Yan, Shayou; Fiorentino, Stefania; Milas, Zvonimir L.; Kosynkin, Dmitry V.; Katherine Price, B.; Lucente-Schultz, Rebecca M.; Wen, XiaoXia; Gabriela Raso, M.; Craig, Suzanne L.; Tran, Hai T.; Myers, Jeffrey N.; Tour, James M.

    2010-01-01

    Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a classic example of this type of compound. Here we show that extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated (PEG-HCCs) are effective drug delivery vehicles when simply mixed with paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is stable for at least twenty weeks. The PTX/PEG-HCCs formulation was as effective as PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution studies suggest that the PEG-HCCs are not acutely toxic and, like many other nanomaterials, are primarily accumulated in the liver and spleen. This work demonstrates that carbon nanomaterials are effective drug delivery vehicles in vivo when non-covalently loaded with an unmodified drug. PMID:20681596

  19. Non-Covalently Functionalized of Single-Walled Carbon Nanotubes by DSPE-PEG-PEI for SiRNA Delivery.

    PubMed

    Siu, King Sun; Zhang, Yujuan; Zheng, Xiufen; Koropatnick, James; Min, Wei-Ping

    2016-01-01

    The expression of a gene can be specifically downregulated by small interfering RNA (SiRNA). Modified carbon nanotubes (CNT) can be used to protect SiRNA and facilitate its entry into cells. Regardless of that, simple and efficient functionalization of CNT is lacking. Effective SiRNA delivery can be carried out using non-covalently functionalized CNT, where non-covalent (versus covalent) functionalization is simpler and more expeditious. Non-covalently functionalized single walled carbon nanotubes (SWCNT) that include a lipopolymer are described here. Polyethylenimine (PEI) conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) was generated and the products used to disperse CNT to form DSPE-PEG-PEI/CNT (DGI/C), an agent capable of facilitating SiRNA delivery to cells in vitro and organs and cells in vivo.

  20. Reciprocal effects of the chirality and the surface functionalization on the drug delivery permissibility of carbon nanotubes.

    PubMed

    Skandani, Amir Alipour; Al-Haik, Marwan

    2013-12-28

    The drug delivery admissibility of nanomaterials such as carbon nanotubes and their uncertain interactions with live tissues and organs have sparked ongoing research efforts. To boost the selective diffusivity of single walled carbon nanotubes (SWCNTs), surface functionalization was adopted in several experimental attempts. Numerous studies had identified polyethylene glycol (PEG) as a bio-compatible surfactant to carbon nanotubes. In this study, a large scale, atomistic molecular dynamic simulation was utilized to disclose the cellular exposure and uptake mechanisms of PEG-functionalized single walled carbon nanotubes (f-SWCNTs) into a lipid bilayer cell membrane. Results showed that with PEGs attached to a SWCNT, the penetration depth and speed can be controlled. Also, the simulations revealed that the adhesion energy between the nanotube and the lipid membrane is affected considerably, in the presence of PEGs, by the chirality of the SWCNTs.

  1. The Use of Multi-Walled Carbon Nanotubes as Possible Carrier in Drug Delivery System for Aspirin

    NASA Astrophysics Data System (ADS)

    Yusof, Alias Mohd.; Buang, Nor Aziah; Yean, Lee Sze; Ibrahim, Mohd. Lokman

    2009-06-01

    Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper will present a brief overview of drugs adsorbed onto the surface of carbon nanotubes via sonication method. The surface area of carbon nanotubes was measured by methylene blue method, Carbon nanotubes synthesized by catalytic chemical vapor deposition (CCVD) method were purified and functionalized in a mixture of concentrated acids (H2SO4:HNO3 = 3:1) at room temperature (25° C) via sonication in water bath, yielding carboxylic acid group on the CNTs' surface. CNT was successfully loaded with 48 %(w/w) aspirin molecules by suspending CNTs in a solution of aspirin in alcohol. Analysis of loaded CNTs by Field Emission-Scanning Electron Microscope (FESEM), Fourier Transform Infrared Spectrum (FITR) and UV-visible Spectroscopy confirmed the loading of the drug onto the CNTs. The work presented is a prelude to the direction of using carbon nanotubes as a drug delivery system to desired sites in human body.

  2. A New Carbon Nanotube-Based Breast Cancer Drug Delivery System: Preparation and In Vitro Analysis Using Paclitaxel.

    PubMed

    Shao, Wei; Paul, Arghya; Rodes, Laetitia; Prakash, Satya

    2015-04-01

    Paclitaxel (PTX) is one of the most important drugs for breast cancer; however, the drug effects are limited by its systematic toxicity and poor water solubility. Nanoparticles have been applied for delivery of cancer drugs to overcome their limitations. Toward this goal, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of human serum albumin (HSA) nanoparticles for loading of antitumor agent PTX. The nanosized macromolecular SWNT-drug carrier (SWNT-HSA) was characterized by TEM, UV-Vis-NIR spectrometry, and TGA. The SWNT-based drug carrier displayed high intracellular delivery efficiency (cell uptake rate of 80%) in breast cancer MCF-7 cells, as examined by fluorescence-labeled drug carriers, suggesting the needle-shaped SWNT-HSA drug carrier was able to transport drugs across cell membrane despite its macromolecular structure. The drug loading on SWNT-based drug carrier was through high binding affinity of PTX to HSA proteins. The PTX formulated with SWNT-HSA showed greater growth inhibition activity in MCF-7 breast cancer cells than PTX formulated with HSA nanoparticle only (cell viability of 63 vs 70% in 48 h and 53 vs 62% in 72 h). The increased drug efficacy could be driven by SWNT-mediated cell internalization. These data suggest that the developed SWNT-based antitumor agent is functional and effective. However, more studies for in vivo drug delivery efficacy and other properties are needed before this delivery system can be fully realized. PMID:27101155

  3. Single-walled carbon nanotube and graphene: Nano-delivery of Gambogic acid increases its cytotoxicty in various cancer cells

    NASA Astrophysics Data System (ADS)

    Saeed, Lamya M.

    Nanomedicine is a new branch of medicine that has been developed due to the critical need to treat challenging diseases, especially cancer since it remains a significant cause of morbidity and mortality worldwide and the second most common cause of death after heart disease in the USA. One of the most important health care applications of nanomedicine concerns the development of drug delivery systems. Graphene (Gn), an atom-thick carbon monolayer of sp2- bonded carbon atoms arranged in a two dimensional (2D) honeycomb crystal lattice, and single-walled carbon nanotubes (SWCNTs) (1D, tubular) are among the most promising nanomaterials with the capability of delivering drugs or small therapeutic molecules to cancerous cells. For example, they have been used as vehicles for the anti-cancer, low-toxicity drug Gambogic acid (GA). Here, the cytotoxicity of GA in breast (MCF-7), pancreatic (PANC-1), cervical (HELA), ovarian (NCI/ADR), and prostate (PC3) cancer cells was assessed to determine what effect nanodelivery by either Gn or SWCNTs had on the efficacy of this promising drug. The nanomaterials showed no toxicity at the concentrations used. The inhibition of cell proliferation and apoptosis of the cells was due to the effects of GA which was significantly enhanced by nanodelivery. Such delivery of GA by either Gn or SWCNTs represents a first step toward assessing their effectiveness in more complex, targeted nano-delivery in vivo settings and signals their potential application in the treatment of cancer.

  4. Assessment of changes in nutrient and sediment delivery to and carbon accumulation in coastal oceans of the Eastern United States

    NASA Astrophysics Data System (ADS)

    Bergamaschi, B. A.; Smith, R. A.; Shih, J. S.; Sohl, T. L.; Sleeter, B. M.; Zhu, Z.

    2014-12-01

    Land-use and land-cover distributions are primary determinants of terrestrial fluxes of sediments and nutrients to coastal oceans. Sediment and nutrient delivery to coastal waters have already been significantly altered by changes in population and land use, resulting in modified patterns of coastal production and carbon storage. Continued population growth and increasing agricultural areal extent and intensity are expected to accelerate these changes. The USGS LandCarbon project developed prospective future land use and land cover projections based on IPCC scenarios A1b, A2 and B1 to 2050 as the basis for a multitude of biogeochemical assessments. We assessed the impacts on delivery of nutrients and sediments to the coastal ocean, and concomitant carbon storage. Fluxes were estimated using the SPARROW model, calibrated on historical water quality measurements. Significantly greater fluxes of nutrients and sediments to coastal waters by 2050 are projected by the model. For example, for the Eastern United States, nitrate fluxes for 2050 are projected to be16 to 52 percent higher than the baseline year, depending on scenario. As a consequence, an associated increase in the frequency and duration of coastal and estuarine hypoxia events and harmful algal blooms could be expected. Model estimates indicate that these prospective future nutrient and sediment fluxes will increase carbon storage rates in coastal waters by 18 to 56 percent in some regions.

  5. Non-covalent functionalization of single-walled carbon nanotubes with modified polyethyleneimines for efficient gene delivery.

    PubMed

    Behnam, Behzad; Shier, Wayne T; Nia, Azadeh Hashem; Abnous, Khalil; Ramezani, Mohammad

    2013-09-15

    Functionalized carbon nanotubes (CNTs) have been recently emerged as important class of vectors for delivery of DNA and other biomolecules into various cells. In this study, single-walled carbon nanotubes (SWNTs) were functionalized by non-covalent binding of hydrophobic moieties, which were covalently linked to polyethyleneimines (PEIs). PEIs of three molecular weights (25, 10 and 1.8kDa) were used. CNTs were functionalized with the PEI series either through phospholipid moiety (via a polyethyleneglycol linker) or through directly-attached long (18 carbons) or intermediate (10 carbons) hydrophobic alkyl moieties. All PEI-functionalized CNTs exhibited good stability and dispersibility in biological media. Visualizing of functionalized CNTs and lack of aggregation were confirmed by atomic force microscopy. The PEI derivatives bound to CNTs retained the ability to fully condense plasmid DNA at low N/P ratios and substantial buffering capacity in the endosomal pH range. PEI-functionalized CNTs exhibited increased transfection efficiency compared to underivatized PEIs up to 19-fold increase being observed in the functionalized CNT with the smallest PEI tested, the smallest hydrophobic attachment moiety tested and no linker. Also PEI-functionalized CNTs were effective gene delivery vectors in vivo following tail vein injection in mice with the largest expression occurring with the vector PEI-functionalized through a polyethyleneglycol linker.

  6. Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System Modulate Immune Response in Vitro and in Vivo.

    PubMed

    Xing, Jie; Liu, Zhenguang; Huang, Yifan; Qin, Tao; Bo, Ruonan; Zheng, Sisi; Luo, Li; Huang, Yee; Niu, Yale; Wang, Deyun

    2016-08-01

    Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a β-1,3-glucohexaose with β-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 μg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 μg/mL) and an equivalent concentration of lentinan (3.2 μg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity

  7. Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System Modulate Immune Response in Vitro and in Vivo.

    PubMed

    Xing, Jie; Liu, Zhenguang; Huang, Yifan; Qin, Tao; Bo, Ruonan; Zheng, Sisi; Luo, Li; Huang, Yee; Niu, Yale; Wang, Deyun

    2016-08-01

    Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a β-1,3-glucohexaose with β-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 μg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 μg/mL) and an equivalent concentration of lentinan (3.2 μg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity

  8. Transactivator of transcription (TAT) peptide– chitosan functionalized multiwalled carbon nanotubes as a potential drug delivery vehicle for cancer therapy

    PubMed Central

    Dong, Xia; Liu, Lanxia; Zhu, Dunwan; Zhang, Hailing; Leng, Xigang

    2015-01-01

    Carbon nanotube (CNT)-based drug delivery vehicles might find great potential in cancer therapy via the combination of chemotherapy with photothermal therapy due to the strong optical absorbance of CNTs in the near-infrared region. However, the application of CNTs in cancer therapy was considerably constrained by their lack of solubility in aqueous medium, as well as the cytotoxicity caused by their hydrophobic surface. Intracellular delivery efficiency is another factor determining the application potential of CNTs in cancer therapy. In the present study, low-molecular-weight chitosan conjugated with transactivator of transcription (TAT) peptide was used for noncovalent functionalization of multiwalled carbon nanotubes (MWCNTs), aiming at providing a more efficient drug delivery vehicle for cancer therapy. The TAT–chitosan-conjugated MWCNTs (MWCNTs-TC) were further investigated for their water solubility, cytotoxicity, cell-penetrating capability, and accumulation in tumor. It was found that MWCNTs-TC were essentially nontoxic with satisfying water solubility, and they were more efficient in terms of cancer-targeted intracellular transport both in vitro and in vivo as compared with chitosan-modified MWCNTs (MWCNTs-CS), suggesting the great application potential of MWCNTs-TC in cancer therapy. PMID:26082633

  9. Transactivator of transcription (TAT) peptide- chitosan functionalized multiwalled carbon nanotubes as a potential drug delivery vehicle for cancer therapy.

    PubMed

    Dong, Xia; Liu, Lanxia; Zhu, Dunwan; Zhang, Hailing; Leng, Xigang

    2015-01-01

    Carbon nanotube (CNT)-based drug delivery vehicles might find great potential in cancer therapy via the combination of chemotherapy with photothermal therapy due to the strong optical absorbance of CNTs in the near-infrared region. However, the application of CNTs in cancer therapy was considerably constrained by their lack of solubility in aqueous medium, as well as the cytotoxicity caused by their hydrophobic surface. Intracellular delivery efficiency is another factor determining the application potential of CNTs in cancer therapy. In the present study, low-molecular-weight chitosan conjugated with transactivator of transcription (TAT) peptide was used for noncovalent functionalization of multiwalled carbon nanotubes (MWCNTs), aiming at providing a more efficient drug delivery vehicle for cancer therapy. The TAT-chitosan-conjugated MWCNTs (MWCNTs-TC) were further investigated for their water solubility, cytotoxicity, cell-penetrating capability, and accumulation in tumor. It was found that MWCNTs-TC were essentially nontoxic with satisfying water solubility, and they were more efficient in terms of cancer-targeted intracellular transport both in vitro and in vivo as compared with chitosan-modified MWCNTs (MWCNTs-CS), suggesting the great application potential of MWCNTs-TC in cancer therapy.

  10. Synthesis and characterization of polyamidoamine dendrimer-coated multi-walled carbon nanotubes and their application in gene delivery systems

    NASA Astrophysics Data System (ADS)

    Pan, Bifeng; Cui, Daxiang; Xu, Ping; Ozkan, Cengiz; Feng, Gao; Ozkan, Mihri; Huang, Tuo; Chu, Bingfeng; Li, Qing; He, Rong; Hu, Guohan

    2009-03-01

    With the aim of improving the amount and delivery efficiency of genes taken by carbon nanotubes into human cancer cells, different generations of polyamidoamine dendrimer modified multi-walled carbon nanotubes (dMNTs) were fabricated, and characterized by high-resolution transmission electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis, revealing the presence of dendrimer capped on the surface of carbon nanotubes. The dMNTs fully conjugated with FITC-labeled antisense c-myc oligonucleotides (asODN), those resultant asODN-dMNTs composites were incubated with human breast cancer cell line MCF-7 cells and MDA-MB-435 cells, and liver cancer cell line HepG2 cells, and confirmed to enter into tumor cells within 15 min by laser confocal microscopy. These composites inhibited the cell growth in time- and dose-dependent means, and down-regulated the expression of the c-myc gene and C-Myc protein. Compared with the composites of CNT-NH2-asODN and dendrimer-asODN, no. 5 generation of dendrimer-modified MNT-asODN composites exhibit maximal transfection efficiencies and inhibition effects on tumor cells. The intracellular gene transport and uptake via dMNTs should be generic for the mammalian cell lines. The dMNTs have potentials in applications such as gene or drug delivery for cancer therapy and molecular imaging.

  11. PEGylated Carbon Nanocapsule: A Universal Reactor and Carrier for In Vivo Delivery of Hydrophobic and Hydrophilic Nanoparticles.

    PubMed

    Rammohan, Amritha; Mishra, Gargi; Mahaling, Binapani; Tayal, Lokesh; Mukhopadhyay, Ahana; Gambhir, Sanjay; Sharma, Ashutosh; Sivakumar, Sri

    2016-01-13

    We have developed PEGylated mesoporous carbon nanocapsule as a universal nanoreactor and carrier for the delivery of highly crystalline hydrophobic/hydrophilic nanoparticles (NPs) which shows superior biocompatibility, dispersion in body fluids, good biodistribution and NPs independent cellular uptake mechanism. The hydrophobic/hydrophilic NPs without surface modification were synthesized in situ inside the cavities of mesoporous carbon capsules (200-850 nm). Stable and inert nature of carbon capsules in a wide range of reaction conditions like high temperature and harsh solvents, make it suitable for being used as nano/microreactors for the syntheses of a variety of NPs for bioimaging applications, such as NaYF4:Eu(3+)(5%), LaVO4:Eu(3+)(10%), GdVO4:Eu(3+)(10%), Y2O3:Eu(3+)(5%), GdF3:Tb(3+)(10%), Mo, Pt, Pd, Au, and Ag. Multiple types of NPs (Y2O3:Eu(3+)(5%) (hydrophobic) and GdF3:Tb(3+)(10%) (hydrophilic)) were coloaded inside the carbon capsules to create a multimodal agent for magneto-fluorescence imaging. Our in vivo study clearly suggests that carbon capsules have biodistribution in many organs including liver, heart, spleen, lungs, blood pool, and muscles.

  12. Water/carbonate stripping for CO.sub.2 capture adsorber regeneration and CO.sub.2 delivery to photoautotrophs

    SciTech Connect

    Chance, Ronald; Koros, William J.; McCool, Benjamin; Noel, James

    2015-08-11

    The invention provides systems and methods for the delivery of carbon to photoautotrophs. The invention utilizes low energy regeneration of adsorbent for CO.sub.2 capture and provides for effective CO.sub.2 loading into liquids useful for photoautotroph growth and/or production of photosynthetic products, such as biofuels, via photoautotrophic culture media. The inventive system comprises a fluid/membrane/fluid contactor that provides selective transfer of molecular CO.sub.2 via a dense (non-porous) membrane from a carbonate-based CO.sub.2 snipping solution to a culture medium where the CO.sub.2 is consumed by a photoautotroph for the production of biofuels, biofuel precursors or other commercial products.

  13. The LandCarbon Web Application: Advanced Geospatial Data Delivery and Visualization Tools for Communication about Ecosystem Carbon Sequestration and Greenhouse Gas Fluxes

    NASA Astrophysics Data System (ADS)

    Thomas, N.; Galey, B.; Zhu, Z.; Sleeter, B. M.; Lehmer, E.

    2015-12-01

    The LandCarbon web application (http://landcarbon.org) is a collaboration between the U.S. Geological Survey and U.C. Berkeley's Geospatial Innovation Facility (GIF). The LandCarbon project is a national assessment focused on improved understanding of carbon sequestration and greenhouse gas fluxes in and out of ecosystems related to land use, using scientific capabilities from USGS and other organizations. The national assessment is conducted at a regional scale, covers all 50 states, and incorporates data from remote sensing, land change studies, aquatic and wetland data, hydrological and biogeochemical modeling, and wildfire mapping to estimate baseline and future potential carbon storage and greenhouse gas fluxes. The LandCarbon web application is a geospatial portal that allows for a sophisticated data delivery system as well as a suite of engaging tools that showcase the LandCarbon data using interactive web based maps and charts. The web application was designed to be flexible and accessible to meet the needs of a variety of users. Casual users can explore the input data and results of the assessment for a particular area of interest in an intuitive and interactive map, without the need for specialized software. Users can view and interact with maps, charts, and statistics that summarize the baseline and future potential carbon storage and fluxes for U.S. Level 2 Ecoregions for 3 IPCC emissions scenarios. The application allows users to access the primary data sources and assessment results for viewing and download, and also to learn more about the assessment's objectives, methods, and uncertainties through published reports and documentation. The LandCarbon web application is built on free and open source libraries including Django and D3. The GIF has developed the Django-Spillway package, which facilitates interactive visualization and serialization of complex geospatial raster data. The underlying LandCarbon data is available through an open application

  14. In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers

    PubMed Central

    Genina, Elina A.; Svenskaya, Yulia I.; Yanina, Irina Yu.; Dolotov, Leonid E.; Navolokin, Nikita A.; Bashkatov, Alexey N.; Terentyuk, Georgy S.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Gorin, Dmitry A.; Tuchin, Valery V.; Sukhorukov, Gleb B.

    2016-01-01

    We have developed a method for delivery of biocompatible CaCO3 microcontainers (4.0 ± 0.8 µm) containing Fe3O4 nanoparticles (14 ± 5 nm) into skin in vivo using fractional laser microablation (FLMA) provided by a pulsed Er:YAG laser system. Six laboratory rats have been used for the microcontainer delivery and weekly monitoring implemented using an optical coherence tomography and a standard histological analysis. The use of FLMA allowed for delivery of the microcontainers to the depth about 300 μm and creation of a depot in dermis. On the seventh day we have observed the dissolving of the microcontainers and the release of nanoparticles into dermis. PMID:27375927

  15. A bio-recognition device developed onto nano-crystals of carbonate apatite for cell-targeted gene delivery.

    PubMed

    Chowdhury, E H; Akaike, Toshihiro

    2005-05-20

    The DNA delivery to mammalian cells is an essential tool for analyzing gene structure, regulation, and function. The approach holds great promise for the further development of gene therapy techniques and DNA vaccination strategies to treat and control diseases. Here, we report on the establishment of a cell-specific gene delivery and expression system by physical adsorption of a cell-recognition molecule on the nano-crystal surface of carbonate apatite. As a model, DNA/nano-particles were successfully coated with asialofetuin to facilitate uptake by hepatocyte-derived cell lines through the asialoglycoprotein receptor (ASGPr) and albumin to prevent non-specific interactions of the particles with cell-surface. The resulting composite particles with dual surface properties could accelerate DNA uptake and enhance expression to a notable extent. Nano-particles coated with transferrin in the same manner dramatically enhanced transgene expression in the corresponding receptor-bearing cells and thus our newly developed strategy represents a universal phenomenon for anchoring a bio-recognition macromolecule on the apatite crystal surface for targeted gene delivery, having immediate applications in basic research laboratories and great promise for gene therapy.

  16. Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes.

    PubMed

    Lu, Yu-Jen; Wei, Kuo-Chen; Ma, Chen-Chi M; Yang, Shin-Yi; Chen, Jyh-Ping

    2012-01-01

    By combining the advantage of multi-walled carbon nanotubes (MWCNTs) and iron oxide magnetic nanoparticles (MNs), we develop a magnetic dual-targeted nanocarrier for drug delivery. MWCNTs were functionalized with poly(acrylic acid) through free radical polymerization, decorated with MNs, conjugated with a targeting ligand folic acid (FA), for loading of an anti-cancer drug doxorubicin (DOX). The proposed methodology provides dual targeted delivery of the anti-cancer drug to cancer cells under the guidance of a magnetic field and through ligand-receptor interactions. The chemico-physical properties of the nanocarrier were characterized, in addition to its drug loading efficiency and drug releasing characteristics. Doxorubicin could be loaded to MWCNTs with high efficiency via π-π stacking and hydrogen bonding and showed enhanced cytotoxicity toward U87 human glioblastoma cells compared with free DOX. From transmission electron microscopy and confocal laser scanning microscopy, we confirmed that DOX-FA-MN-MWCNT could be efficiently taken up by U87 cells with subsequent intracellular release of DOX, followed by transport of DOX into the nucleus with the nanocarrier left in the cytoplasm. These properties make the magnetic nanocarrier a potential candidate for targeted delivery of DOX for cancer treatment.

  17. A review on engineering of cellulosic cigarette paper to reduce carbon monoxide delivery of cigarettes.

    PubMed

    Shen, Jing; Li, Jinsong; Qian, Xueren; Ren, Wanshan; Fatehi, Pedram

    2014-01-30

    In cigarette production, the cellulosic paper essentially derived from flax fibers or other fiber materials is used as the wrapping material. During smoking of cigarettes, the highly toxic carbon monoxide is produced. To decrease the amount of carbon monoxide emission in the mainstream smoke, the engineering of all cigarette components including cellulosic cigarette paper and tobacco column is critical. This review summarizes the concepts related to engineering of cigarette paper. These mainly include permeability control, increased use of burn additives, optimization of fiber basis weight, engineering of calcium carbonate fillers, and incorporation of catalysts/oxidants. In particular, catalytic and/or oxidative conversion of carbon monoxide to carbon dioxide has been very widely reported. The control of permeability/diffusivity of cigarette paper is also of critical importance for enhanced diffusion of carbon monoxide out of the cigarette. The development of new concepts and combination of various concepts may lead to breakthroughs in this area.

  18. The delivery of dissolved organic carbon from a forested hillslope to a headwater stream in southeastern Pennsylvania, USA

    NASA Astrophysics Data System (ADS)

    Mei, Yi; Hornberger, George M.; Kaplan, Louis A.; Newbold, J. Denis; Aufdenkampe, Anthony K.

    2014-07-01

    Riparian soils, rich in organic carbon, act as a source of dissolved organic carbon (DOC) to the adjacent stream, but the hydrologic factors that control the delivery of DOC are not well characterized. A mechanistic two-dimensional, variably saturated flow and reactive transport finite element model (FEM) was developed to explore both biodegradable DOC (BDOC) and refractory DOC (RDOC) delivery processes during storms for a hillslope transect in a southeastern Pennsylvania Piedmont watershed. The model indicated that DOC concentrations in outflow from a hillslope peaked on the falling limb of the discharge hydrograph, a temporal sequence consistent with a flushing hypothesis. Factors that control the lag time between the stream water peak discharge and peak DOC concentration were analyzed using a Monte Carlo simulation coupled with a multiple linear regression. The results are consistent with previous studies showing that the majority of DOC delivered to a stream during storms originates from the riparian zone. Further, the model suggests that the duration of the flood wave and hydraulic properties of the riparian soil play important roles in controlling the lag time between peak discharge and peak DOC concentration in outflow from a hillslope.

  19. Water-soluble carbon nanotube compositions for drug delivery and medicinal applications

    DOEpatents

    Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dmitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jr., Jodie L.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; Milas, Zvonimir L.; Mason, Kathy A.; Milas, Luka

    2014-07-22

    Compositions comprising a plurality of functionalized carbon nanotubes and at least one type of payload molecule are provided herein. The compositions are soluble in water and PBS in some embodiments. In certain embodiments, the payload molecules are insoluble in water. Methods are described for making the compositions and administering the compositions. An extended release formulation for paclitaxel utilizing functionalized carbon nanotubes is also described.

  20. Efficient intracellular delivery of molecules with high cell viability using nanosecond-pulsed laser-activated carbon nanoparticles.

    PubMed

    Sengupta, Aritra; Kelly, Sean C; Dwivedi, Nishant; Thadhani, Naresh; Prausnitz, Mark R

    2014-03-25

    Conventional physical and chemical methods that efficiently deliver molecules into cells are often associated with low cell viability. In this study, we evaluated the cellular effects of carbon nanoparticles believed to emit photoacoustic waves due to nanosecond-pulse laser activation to test the hypothesis that this method could achieve efficient intracellular delivery while maintaining high cell viability. Suspensions of DU145 human prostate carcinoma cells, carbon black (CB) nanoparticles, and calcein were exposed to 5-9 ns long laser pulses of near-infrared (1064 nm wavelength) light and then analyzed by flow cytometry for intracellular uptake of calcein and cell viability by propidium iodide staining. We found that intracellular uptake increased and in some cases saturated at high levels with only small losses in cell viability as a result of increasing laser fluence, laser exposure time, and as a unifying parameter, the total laser energy. Changing interpulse spacing between 0.1 and 10 s intervals showed no significant change in bioeffects, suggesting that the effects of each pulse were independent when spaced by at least 0.1 s intervals. Pretreatment of CB nanoparticles to intense laser exposure followed by mixing with cells also had no significant effect on uptake or viability. Similar uptake and viability were seen when CB nanoparticles were substituted with India ink, when DU145 cells were substituted with H9c2 rat cardiomyoblast cells, and when calcein was substituted with FITC-dextran. The best laser exposure conditions tested led to 88% of cells with intracellular uptake and close to 100% viability, indicating that nanosecond-pulse laser-activated carbon nanoparticles can achieve efficient intracellular delivery while maintaining high cell viability.

  1. Basin-Scale Exports vs. Coastal Delivery of Carbon, Nutrients and Particulates Above and Below Arctic River Deltas

    NASA Astrophysics Data System (ADS)

    Striegl, R. G.; Tank, S. E.; Weeks, G.; Holmes, R. M.; McClelland, J. W.

    2014-12-01

    Recent studies have substantially improved our understanding of water, sediment and materials exports by arctic rivers. Seasonality of exports, particularly during the spring freshet, is better quantified, as are the inland sources of water and sediment discharge and the source and chemical character of other material exports, including carbon and nutrients. Measurements on small rivers discharging directly to the Arctic Ocean and lacking complex deltas can accurately quantify local inputs to coastal regions. However, the majority of hydrologic inputs to the Arctic Ocean derive from 6 major Eurasian and North American rivers. Water, sediment, and chemical exports from these rivers are typically measured above head of tide, far inland, and commonly above large river deltas. These deltas settle particles and provide favorable environments for deposition, storage, and biogeochemical consumption, production, and transformation of aquatic carbon and nutrients. Consequently, basin exports measured above river deltas likely misrepresent actual delivery to coastal regions. In addition to accumulating sediment, observed and modeled arctic delta effects include enrichment of the organic content of suspended solids, increased dissolved organic carbon and nitrogen (DOC; DON) concentration, decreased inorganic nutrient concentration, and settling and likely increased bioavailability of particle associated contaminants, such as mercury. Increased DOC concentration in the Mackenzie River delta has also been associated with a change in DOC quality, with increased potential for biodegradation of DOC and decreased potential for photodegradation of DOC from head of tide to within the delta. For the most part, assessments of differences between head of tide basin exports and coastal delivery tend to be qualitative rather than quantitative, largely because of difficulties quantifying tidally affected flow. This points to the need to resolve data gaps, improve quantitative assessments

  2. Efficient Intracellular Delivery of Molecules with High Cell Viability Using Nanosecond-Pulsed Laser-Activated Carbon Nanoparticles

    PubMed Central

    2015-01-01

    Conventional physical and chemical methods that efficiently deliver molecules into cells are often associated with low cell viability. In this study, we evaluated the cellular effects of carbon nanoparticles believed to emit photoacoustic waves due to nanosecond-pulse laser activation to test the hypothesis that this method could achieve efficient intracellular delivery while maintaining high cell viability. Suspensions of DU145 human prostate carcinoma cells, carbon black (CB) nanoparticles, and calcein were exposed to 5–9 ns long laser pulses of near-infrared (1064 nm wavelength) light and then analyzed by flow cytometry for intracellular uptake of calcein and cell viability by propidium iodide staining. We found that intracellular uptake increased and in some cases saturated at high levels with only small losses in cell viability as a result of increasing laser fluence, laser exposure time, and as a unifying parameter, the total laser energy. Changing interpulse spacing between 0.1 and 10 s intervals showed no significant change in bioeffects, suggesting that the effects of each pulse were independent when spaced by at least 0.1 s intervals. Pretreatment of CB nanoparticles to intense laser exposure followed by mixing with cells also had no significant effect on uptake or viability. Similar uptake and viability were seen when CB nanoparticles were substituted with India ink, when DU145 cells were substituted with H9c2 rat cardiomyoblast cells, and when calcein was substituted with FITC-dextran. The best laser exposure conditions tested led to 88% of cells with intracellular uptake and close to 100% viability, indicating that nanosecond-pulse laser-activated carbon nanoparticles can achieve efficient intracellular delivery while maintaining high cell viability. PMID:24547946

  3. Coral skeletal carbon isotopes (δ13C and Δ14C) record the delivery of terrestrial carbon to the coastal waters of Puerto Rico

    USGS Publications Warehouse

    Moyer, R.P.; Grottoli, A.G.

    2011-01-01

    Tropical small mountainous rivers deliver a poorly quantified, but potentially significant, amount of carbon to the world's oceans. However, few historical records of land-ocean carbon transfer exist for any region on Earth. Corals have the potential to provide such records, because they draw on dissolved inorganic carbon (DIC) for calcification. In temperate systems, the stable- (δ13C) and radiocarbon (Δ14C) isotopes of coastal DIC are influenced by the δ13C and Δ14C of the DIC transported from adjacent rivers. A similar pattern should exist in tropical coastal DIC and hence coral skeletons. Here, δ13C and Δ14C measurements were made in a 56-year-old Montastraea faveolata coral growing ~1 km from the mouth of the Rio Fajardo in eastern Puerto Rico. Additionally, the δ13C and Δ14C values of the DIC of the Rio Fajardo and its adjacent coastal waters were measured during two wet and dry seasons. Three major findings were observed: (1) synchronous depletions of both δ13C and Δ14C in the coral skeleton are annually coherent with the timing of peak river discharge, (2) riverine DIC was always more depleted in δ13C and Δ14C than seawater DIC, and (3) the correlation of δ13C and Δ14C was the same in both coral skeleton and the DIC of the river and coastal waters. These results indicate that coral skeletal δ13C and Δ14C are recording the delivery of riverine DIC to the coastal ocean. Thus, coral records could be used to develop proxies of historical land-ocean carbon flux for many tropical regions. Such information could be invaluable for understanding the role of tropical land-ocean carbon flux in the context of land-use change and global climate change.

  4. Coral skeletal carbon isotopes (δ13C and Δ14C) record the delivery of terrestrial carbon to the coastal waters of Puerto Rico

    USGS Publications Warehouse

    Moyer, R.P.; Grottoli, A.G.

    2011-01-01

    Tropical small mountainous rivers deliver a poorly quantified, but potentially significant, amount of carbon to the world's oceans. However, few historical records of land-ocean carbon transfer exist for any region on Earth. Corals have the potential to provide such records, because they draw on dissolved inorganic carbon (DIC) for calcification. In temperate systems, the stable- (??13C) and radiocarbon (??14C) isotopes of coastal DIC are influenced by the ??13C and ??14C of the DIC transported from adjacent rivers. A similar pattern should exist in tropical coastal DIC and hence coral skeletons. Here, ??13C and ??14C measurements were made in a 56-year-old Montastraea faveolata coral growing ~1 km from the mouth of the Rio Fajardo in eastern Puerto Rico. Additionally, the ??13C and ??14C values of the DIC of the Rio Fajardo and its adjacent coastal waters were measured during two wet and dry seasons. Three major findings were observed: (1) synchronous depletions of both ??13C and ??14C in the coral skeleton are annually coherent with the timing of peak river discharge, (2) riverine DIC was always more depleted in ??13C and ??14C than seawater DIC, and (3) the correlation of ??13C and ??14C was the same in both coral skeleton and the DIC of the river and coastal waters. These results indicate that coral skeletal ??13C and ??14C are recording the delivery of riverine DIC to the coastal ocean. Thus, coral records could be used to develop proxies of historical land-ocean carbon flux for many tropical regions. Such information could be invaluable for understanding the role of tropical land-ocean carbon flux in the context of land-use change and global climate change. ?? 2011 United States Geological Survey.

  5. Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles as lymphatic targeted drug delivery vehicles.

    PubMed

    Yang, Dong; Yang, Feng; Hu, Jianhua; Long, Jiang; Wang, Changchun; Fu, Deliang; Ni, Quanxing

    2009-08-01

    Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles were readily taken up into lymph vessels and delivered gemcitabine to lymph nodes with high efficiency under the guidance of a magnetic field.

  6. Fullerene release from the inside of carbon nanotubes: A possible route toward drug delivery

    NASA Astrophysics Data System (ADS)

    Simon, Ferenc; Peterlik, Herwig; Pfeiffer, Rudolf; Bernardi, Johannes; Kuzmany, Hans

    2007-09-01

    The filling and depletion of carbon nanotubes with C 60 fullerenes is reported using solvents. We use X-ray diffractometry and Raman spectroscopy to show that large diameter carbon nanotubes can be filled with fullerenes using methanol with a high efficiency and can be also removed from the inside of the tubes using dichlorobenzene. The latter solvent effectively removes weakly bound C 60s from inside the large diameter tubes, which is explained by the high solubility of C 60 in dichlorobenzene.

  7. A preloaded amorphous calcium carbonate/doxorubicin@silica nanoreactor for pH-responsive delivery of an anticancer drug.

    PubMed

    Zhao, Yang; Luo, Zhong; Li, Menghuan; Qu, Qiuyu; Ma, Xing; Yu, Shu-Hong; Zhao, Yanli

    2015-01-12

    Biomedical applications of nontoxic amorphous calcium carbonate (ACC) nanoparticles have mainly been restricted because of their aqueous instability. To improve their stability in physiological environments while retaining their pH-responsiveness, a novel nanoreactor of ACC-doxorubicin (DOX)@silica was developed for drug delivery for use in cancer therapy. As a result of its rationally engineered structure, this nanoreactor maintains a low drug leakage in physiological and lysosomal/endosomal environments, and responds specifically to pH 6.5 to release the drug. This unique ACC-DOX@silica nanoreactor releases DOX precisely in the weakly acidic microenvironment of cancer cells and results in efficient cell death, thus showing its great potential as a desirable chemotherapeutic nanosystem for cancer therapy.

  8. Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing.

    PubMed

    Kam, Nadine Wong Shi; Liu, Zhuang; Dai, Hongjie

    2005-09-14

    We present a novel functionalization scheme for single-walled carbon nanotubes (SWNTs) to afford nanotube-biomolecule conjugates with the incorporation of cleavable bonds to enable controlled molecular releasing from nanotube surfaces, thus creating "smart" nanomaterials with high potential for chemical and biological applications. With this versatile functionalization, we demonstrate transporting, enzymatic cleaving and releasing of DNA from SWNT transporters, and subsequent nuclear translocation of DNA oligonucleotides in mammalian cells. We further show highly efficient delivery of siRNA by SWNTs and achieving more potent RNAi functionality than a widely used conventional transfection agent. Thus, the novel functionalization of SWNTs with cleavable bonds is highly promising for a wide range of applications including gene and protein therapy.

  9. Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective effects of a recombinant vaccine against Aeromonas hydrophila.

    PubMed

    Gong, Yu-Xin; Zhu, Bin; Liu, Guang-Lu; Liu, Lei; Ling, Fei; Wang, Gao-Xue; Xu, Xin-Gang

    2015-01-01

    To reduce the economic losses caused by diseases in aquaculture industry, more efficient and economic prophylactic measures should be urgently investigated. In this research, the effects of a novel functionalized single-walled carbon nanotubes (SWCNTs) applied as a delivery vehicle for recombinant Aeromonas hydrophila vaccine administration via bath or injection in juvenile grass carp were studied. The results showed that SWCNT as a vector for the recombinant protein aerA, augmented the production of specific antibodies, apparently stimulated the induction of immune-related genes, and induced higher level of survival rate compared with free aerA subunit vaccine. Furthermore, we compared the routes of bath and intramuscular injection immunization by SWCNTs-aerA vaccine, and found that similar antibody levels induced by SWCNTs-aerA were observed in both immunization routes. Meanwhile, a similar relative percentage survival (approximately 80%) was found in both a 40 mg/L bath immunization group, and a 20 μg injection group. The results indicate that functionalized SWCNTs could be a promising delivery vehicle to potentiate the immune response of recombinant vaccines, and might be used to vaccinate juvenile fish by bath administration method.

  10. Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel

    PubMed Central

    Naderi, Naghmeh; Madani, Seyed Y.; Mosahebi, Afshin; Seifalian, Alexander M.

    2015-01-01

    Background Carbon nanotubes (CNTs) have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell-targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. Methods The efficacy of a single-walled carbon nanotubes (SWCNTs)-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX) to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS) to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and ultraviolet–visible–near-infrared (UV–Vis–NIR). Additionally, their cytotoxic effects on Colon cancer cell (HT-29) and Breast cancer cell (MCF-7) lines were assessed in vitro. Results TEM, FTIR, and UV–Vis–NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX–POSS–SWCNT, PTX–POSS–Ab–SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT), POSS–SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS–SWCNT samples compared to cell-only controls. Conclusion The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues. PMID:26356347

  11. Efficient in vitro and in vivo pulmonary delivery of nucleic acid by carbon dot-based nanocarriers.

    PubMed

    Pierrat, Philippe; Wang, Rongrong; Kereselidze, Dimitri; Lux, Marie; Didier, Pascal; Kichler, Antoine; Pons, Françoise; Lebeau, Luc

    2015-05-01

    Cationic carbon dots were fabricated by pyrolysis of citric acid and bPEI25k under microwave radiation. Various nanoparticles were produced in a 20-30% yield through straightforward modifications of the reaction parameters (stoichiometry of the reactants and energy supply regime). Particular attention was paid to the purification of the reaction products to ensure satisfactory elimination of the residual starting polyamine. Intrinsic properties of the particles (size, surface charge, photoluminescence and quantum yield) were measured and their ability to form stable complexes with nucleic acid was determined. Their potential to deliver plasmid DNA or small interfering RNA to various cell lines was investigated and compared to that of bPEI25k. The pDNA in vitro transfection efficiency of these carbon dots was similar to that of the parent PEI, as was their cytotoxicity. The higher cytotoxicity of bPEI25k/siRNA complexes when compared to that of the CD/siRNA complexes however had marked consequences on the gene silencing efficiency of the two carriers. These results are not fully consistent with those in some earlier reports on similar nanoparticles, revealing that toxicity of the carbon dots strongly depends on their protocol of fabrication. Finally, these carriers were evaluated for in vivo gene delivery through the non-invasive pulmonary route in mice. High transgene expression was obtained in the lung that was similar to that obtained with the golden standard formulation GL67A, but was associated with significantly lower toxicity. Post-functionalization of these carbon dots with PEG or targeting moieties should significantly broaden their scope and practical implications in improving their in vivo transfection efficiency and biocompatibility. PMID:25771019

  12. Delivery of nitric oxide to the interior of mammalian cell by carbon nanotube: MD simulation.

    PubMed

    Raczyński, Przemysław; Górny, Krzysztof; Dawid, Aleksander; Gburski, Zygmunt

    2014-07-15

    Computer simulations have been performed to study the nanoindentation of phospholipid bilayer by the single-walled armchair carbon nanotube, filled with the nitric oxide molecules. The process has been simulated by means of molecular dynamics (MD) technique at physiological temperature T = 310 K with a constant pulling velocity of the nanotube. The force acting on the nanotube during membrane penetration has been calculated. We show that the indentation by carbon nanotube does not permanently destroy the membrane structure (self-sealing of the membrane occurs). The mobility of nitric oxide molecules during the membrane nanoindentation is discussed.

  13. Atomic scale observation of oxygen delivery during silver–oxygen nanoparticle catalysed oxidation of carbon nanotubes

    PubMed Central

    Yue, Yonghai; Yuchi, Datong; Guan, Pengfei; Xu, Jia; Guo, Lin; Liu, Jingyue

    2016-01-01

    To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars–van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes. PMID:27406595

  14. Atomic scale observation of oxygen delivery during silver-oxygen nanoparticle catalysed oxidation of carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Yue, Yonghai; Yuchi, Datong; Guan, Pengfei; Xu, Jia; Guo, Lin; Liu, Jingyue

    2016-07-01

    To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars-van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes.

  15. Atomic scale observation of oxygen delivery during silver-oxygen nanoparticle catalysed oxidation of carbon nanotubes.

    PubMed

    Yue, Yonghai; Yuchi, Datong; Guan, Pengfei; Xu, Jia; Guo, Lin; Liu, Jingyue

    2016-07-13

    To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars-van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes.

  16. Atomic scale observation of oxygen delivery during silver-oxygen nanoparticle catalysed oxidation of carbon nanotubes.

    PubMed

    Yue, Yonghai; Yuchi, Datong; Guan, Pengfei; Xu, Jia; Guo, Lin; Liu, Jingyue

    2016-01-01

    To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars-van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes. PMID:27406595

  17. Non-metallic nanomaterials in cancer theranostics: a review of silica- and carbon-based drug delivery systems

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Cheng; Huang, Xin-Chun; Luo, Yun-Ling; Chang, Yung-Chen; Hsieh, You-Zung; Hsu, Hsin-Yun

    2013-08-01

    The rapid development in nanomaterials has brought great opportunities to cancer theranostics, which aims to combine diagnostics and therapy for cancer treatment and thereby improve the healthcare of patients. In this review we focus on the recent progress of several cancer theranostic strategies using mesoporous silica nanoparticles and carbon-based nanomaterials. Silicon and carbon are both group IV elements; they have been the most abundant and significant non-metallic substances in human life. Their intrinsic physical/chemical properties are of critical importance in the fabrication of multifunctional drug delivery systems. Responsive nanocarriers constructed using these nanomaterials have been promising in cancer-specific theranostics during the past decade. In all cases, either a controlled texture or the chemical functionalization is coupled with adaptive properties, such as pH-, light-, redox- and magnetic field- triggered responses. Several studies in cells and mice models have implied their underlying therapeutic efficacy; however, detailed and long-term in vivo clinical evaluations are certainly required to make these bench-made materials compatible in real bedside circumstances.

  18. One-step preparation of hydrophilic carbon nanofiber containing magnetic Ni nanoparticles materials and their application in drug delivery.

    PubMed

    Wang, Chih-Jen; Chen, Tse-Ching; Lin, Jarrn-Horng; Huang, Pei-Rong; Tsai, Hsing-Jui; Chen, Ching-Shiun

    2015-02-15

    A one-step process for the synthesis of hydrophilic carbon nanofibers (CNFs) through CO2 hydrogenation on NiNa/Al2O3 was developed for the loading and targeted delivery of the anticancer drug doxorubicin (DOX). CNFs that were synthesized on NiNa/Al2O3 for 9 h at 500 °C exhibited an adequate magnetic response and a large content of hydrophilic oxygen-containing functional groups on the carbon surface, resulting in excellent colloidal solution. The CNF material exhibited a highly efficient capacity for DOX adsorption, particularly at pH 9.0. The loading and release of DOX was strongly pH dependent, possibly due to electrostatic and π-π stacking interactions between DOX and CNF sample. The Langmuir isotherm and pseudo second-order kinetics of DOX-loaded CNFs were well-modeled for the process of DOX adsorption. DOX-loaded CNF targeted cancer cells more selectively and effectively than free DOX and exhibited a marked tendency to kill HeLa cancer cells and reduced toxicity to normal human primary fibroblast (HPF) cells.

  19. Utilization of bio-degradable fermented tapioca to synthesized low toxicity of carbon nanotubes for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Nurulhuda, I.; Poh, R.; Mazatulikhma, M. Z.; Salman, A. H. A.; Haseeb, A. K.; Rusop, M.

    2016-07-01

    Carbon nanotubes (CNT) have potential biomedical applications, and investigations are shifting towards the production of such nanotubes using renewable natural sources. CNTs were synthesized at various temperatures of 700, 750, 800, 850 and 900 °C, respectively, using a local fermented food known as "tapai ubi" or fermented tapioca as a precursor. The liquid part of this fermented food was heated separately at 80°C and channeled directly into the furnace system that employs the thermal chemical vapor deposition (CVD) method. Ferrocene, which was the catalyst was placed in furnace 1 in the thermal CVD process. The resulting CNTs produced from the process were studied using field emission scanning electron microscopy (FESEM) and raman spectroscopy. The FESEM images showed the growth morphology of the CNTs at the different temperatures employed. It was observed that the higher the synthesis temperature up to a point, the diameter of CNTs produced, after which the diameter increased. CNTs with helical structures were observed at 700 °C with a diameter range of 111 - 143 nm. A more straightened structure was observed at 750 °C with a diameter range of 59 - 121 nm. From 800 °C onwards, the diameters of the CNTs were less than 60 nm. Raman analysis revealed the present of D, G and G' peak were observed at 1227-1358, 1565-1582, and 2678-2695 cm-1, respectively. The highest degree of crystallity of the carbon nanotubes synthesized were obtained at 800 °C. The radial breathing mode (RBM) were in range between 212-220 and 279-292 cm-1. Carbon nanotubes also being functionalized with Polyethylene bis(amine) Mw2000 (PEG 2000-NH2) and showed highly cells viability compared to non-functionalized CNT. The nanotubes synthesized will be applied as drug delivery in future study.

  20. Sterilization of corticosteroids for ocular and pulmonary delivery with supercritical carbon dioxide.

    PubMed

    Zani, Franca; Veneziani, Cristina; Bazzoni, Elena; Maggi, Loretta; Caponetti, Giovanni; Bettini, Ruggero

    2013-06-25

    Glucocorticosteroids, a class of drugs widely used in the treatment of allergies, airways inflammation and inflammatory ocular diseases, are often difficult to sterilize due to their inherent sensibility to heat or irradiation induced degradation. Being often in form of suspension, obviously the final medicinal product cannot be sterilized by filtration. The effectiveness of supercritical CO2 (SC-CO2) based method for the sterilization of food and biomedical materials is well documented in the literature. Few reports are available on the sterilization of drugs especially in powder form with SC-CO2. The aim of the present work was to investigate the suitability of SC-CO2 at mild temperature for the decontamination of two model corticosteroid powders (beclometasone dipropionate and budesonide) both in dry or wet form. We found that SC treatment in wet environment reduces by at least six orders of magnitude the contamination of micronized steroidal drugs while retaining the particle size distribution. The findings of this work are of particular interest for the application in the case of aqueous suspension of steroids for aerosol therapy or ocular delivery, where the sterilization process with SC-CO2 could be carried out directly on the bulk of the final formulation.

  1. Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy.

    PubMed

    Hassan, Hatem A F M; Smyth, Lesley; Wang, Julie T-W; Costa, Pedro M; Ratnasothy, Kulachelvy; Diebold, Sandra S; Lombardi, Giovanna; Al-Jamal, Khuloud T

    2016-10-01

    Although anti-cancer immuno-based combinatorial therapeutic approaches have shown promising results, efficient tumour eradication demands further intensification of anti-tumour immune response. With the emerging field of nanovaccinology, multi-walled carbon nanotubes (MWNTs) have manifested prominent potentials as tumour antigen nanocarriers. Nevertheless, the utilization of MWNTs in co-delivering antigen along with different types of immunoadjuvants to antigen presenting cells (APCs) has not been investigated yet. We hypothesized that harnessing MWNT for concurrent delivery of cytosine-phosphate-guanine oligodeoxynucleotide (CpG) and anti-CD40 Ig (αCD40), as immunoadjuvants, along with the model antigen ovalbumin (OVA) could potentiate immune response induced against OVA-expressing tumour cells. We initially investigated the effective method to co-deliver OVA and CpG using MWNT to the APC. Covalent conjugation of OVA and CpG prior to loading onto MWNTs markedly augmented the CpG-mediated adjuvanticity, as demonstrated by the significantly increased OVA-specific T cell responses in vitro and in C57BL/6 mice. αCD40 was then included as a second immunoadjuvant to further intensify the immune response. Immune response elicited in vitro and in vivo by OVA, CpG and αCD40 was significantly potentiated by their co-incorporation onto the MWNTs. Furthermore, MWNT remarkably improved the ability of co-loaded OVA, CpG and αCD40 in inhibiting the growth of OVA-expressing B16F10 melanoma cells in subcutaneous or lung pseudo-metastatic tumour models. Therefore, this study suggests that the utilization of MWNTs for the co-delivery of tumour-derived antigen, CpG and αCD40 could be a competent approach for efficient tumours eradication.

  2. Sustained Release of Naproxen in a New Kind Delivery System of Carbon Nanotubes Hydrogel

    PubMed Central

    Peng, Xiahui; Zhuang, Qiang; Peng, Dongming; Dong, Qiuli; Tan, Lini; Jiao, Feipeng; Liu, Linqi; Liu, jingyu; Zhao, Chenxi; Wang, Xiaomei

    2013-01-01

    In this paper, carbon nanotubes (CNTs) were added into chitosan (CS) hydrogels in the form of chitosan modified CNTs (CS-CNTs) composites to prepare carbon nanotubes hydrogels (CNTs-GEL). The products, named CS-MWCNTs, were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Swelling properties and effect of pH on controlled release performance of the two kinds of hydrogels, CNTs- GEL and pure chitosan hydrogels without CNTs (GEL), were investigated respectively. The results showed that CNTs-GEL possess better controlled release performance than GEL. The releasing equilibrium time of CNTs-GEL was longer than that of GEL in both pH = w7.4 and pH=1.2 conditions, although the release ratios of the model drug are similar in the same pH buffer solutions. It is found that release kinetics is better fitted Ritger-Peppas empirical model indicating a fick-diffusion process in pH = 1.2, while in pH = 7.4 it was non-fick diffusion involving surface diffusion and corrosion diffusion processes. PMID:24523738

  3. Targeted delivery and controlled release of Paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes.

    PubMed

    Yu, Baodan; Tan, Li; Zheng, Runhui; Tan, Huo; Zheng, Lixia

    2016-11-01

    A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy. PMID:27524057

  4. Carbon nanotube lipid drug approach for targeted delivery of a chemotherapy drug in a human breast cancer xenograft animal model.

    PubMed

    Shao, Wei; Paul, Arghya; Zhao, Bin; Lee, Crystal; Rodes, Laetitia; Prakash, Satya

    2013-12-01

    Carbon nanotube (CNT) possesses excellent properties as a drug carrier. To overcome the challenge of drug functionalization with CNT, we have developed a lipid-drug approach for efficient drug loading onto CNT, in which a long chain lipid molecule is conjugated to the drug molecule so that the lipid-drug can be loaded directly onto CNT through binding of the lipid 'tail' in the drug molecule to CNT surfaces via hydrophobic interactions. In a proof-of-concept study, drug paclitaxel (PTX) was conjugated with a non-toxic lipid molecule docosanol for functionalization with CNT. Folic acid was also conjugated to CNT for targeted drug delivery. High level of drug loading onto SWNT could be achieved by lipid-drug approach. Conjugation of FA to SWNT-lipid-PTX led to an increase in cell penetration capacity, and the targeted SWNT-lipid-PTX showed much improved drug efficacy in vitro in comparison to free drug Taxol and non-targeted SWNT-lipid-PTX at 48 h (78.5% vs. 31.6% and 59.1% in cytotoxicity respectively, p < 0.01). In vivo analysis using a human breast cancer xenograft mice model also confirmed the improved drug efficacy. The targeted SWNT-lipid-PTX was found non-toxic as evaluated by biochemical analysis using blood samples, and by histological analysis of major organs.

  5. Solvothermal synthesis of cobalt ferrite nanoparticles loaded on multiwalled carbon nanotubes for magnetic resonance imaging and drug delivery.

    PubMed

    Wu, Huixia; Liu, Gang; Wang, Xue; Zhang, Jiamin; Chen, Yu; Shi, Jianlin; Yang, Hong; Hu, He; Yang, Shiping

    2011-09-01

    Multiwalled carbon nanotube (MWCNT)/cobalt ferrite (CoFe(2)O(4)) magnetic hybrids were synthesized by a solvothermal method. The reaction temperature significantly affected the structure of the resultant MWCNT/CoFe(2)O(4) hybrids, which varied from 6nm CoFe(2)O(4) nanoparticles uniformly coated on the nanotubes at 180°C to agglomerated CoFe(2)O(4) spherical particles threaded by MWCNTs and forming necklace-like nanostructures at 240°C. Based on the superparamagnetic property at room temperature and high hydrophilicity, the MWCNT/CoFe(2)O(4) hybrids prepared at 180°C (MWCNT/CoFe(2)O(4)-180) were further investigated for biomedical applications, which showed a high T(2) relaxivity of 152.8 Fe mM(-1)s(-1) in aqueous solutions, a significant negative contrast enhancement effect on cancer cells and, more importantly, low cytotoxicity and negligible hemolytic activity. The anticancer drug doxorubicin (DOX) can be loaded onto the hybrids and subsequently released in a sustained and pH-responsive way. The DOX-loaded hybrids exhibited notable cytotoxicity to HeLa cancer cells due to the intracellular release of DOX. These results suggest that MWCNT/CoFe(2)O(4)-180 hybrids may be used as both effective magnetic resonance imaging contrast agents and anticancer drug delivery systems for simultaneous cancer diagnosis and chemotherapy.

  6. Self-assembly of carbon nanotubes and antibodies on tumours for targeted, amplified delivery

    PubMed Central

    Mulvey, J. Justin; Villa, Carlos H.; McDevitt, Michael R.; Escorcia, Freddy E.; Casey, Emily; Scheinberg, David A.

    2013-01-01

    Single-walled carbon nanotubes (SWNTs) can deliver imaging agents or drugs to tumours and offer significant advantages over approaches based on antibodies or other nanomaterials. In particular, the nanotubes can carry a substantial amount of cargo (100 times more than a monoclonal antibody), but can still be rapidly eliminated from circulation by renal filtration, like a small molecule, due to their high aspect ratio. Here we show that SWNTs can target tumours in a two-step approach in which nanotubes modified with morpholino oligonucleotide sequences bind to cancer cells that have been pre-targeted with antibodies modified with oligonucleotide strands complementary to those on the nanotubes. The nanotubes can carry fluorophores or radioisotopes, and were shown to selectively bind to cancer cells in vitro and in tumour-bearing xenografted mice. The binding process is also found to lead to antigen capping and internalization of the antibody/nanotube complexes. The nanotube conjugates were labelled with both alpha-particle and gamma-ray emitting isotopes, at high specific activities. Conjugates labelled with alpha-particle generating 225Ac were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo. PMID:24077028

  7. Polyethyleneimine-modified calcium carbonate nanoparticles for p53 gene delivery.

    PubMed

    Chen, Cen; Han, Huafeng; Yang, Wei; Ren, Xiaoyuan; Kong, Xiangdong

    2016-03-01

    In this study, calcium carbonate (CaCO3) nanoparticles with spherical structure were regulated by arginine and successfully synthesized via a facile co-precipitation method. The average particle size of as-prepared CaCO3 was about 900 nm. The properties of nanostructured CaCO3 particles were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction and size distribution. After modified with polyethyleneimine (PEI), the ability of PEI-CaCO3 nanoparticles to carry GFP-marked p53 gene (pEGFP-C1-p53) into cancer cells to express P53 protein were studied. Meanwhile, the cytotoxicity, transfection efficiency, cells growth inhibition and the ability to induce apoptosis by expressed P53 protein were conducted to evaluate the performances of PEI-CaCO3 nanoparticles. The results show that prepared PEI-CaCO3 nanoparticles had good biocompatibility and low cytotoxicity in a certain concentration range. PEI-CaCO3 effectively transfected pEGFP-C1 gene into epithelial-like cancer cells. And with the expression of GFP-P53 fusion protein, pEGFP-C1-p53-gene-loaded PEI-CaCO3 particles significantly reduced the proliferation of cancer cells. These findings indicate that our PEI-modified CaCO3 nanoparticles are potential to be successfully used as carriers for gene therapy.

  8. Design of microencapsulated carbon nanotube-based microspheres and its application in colon targeted drug delivery.

    PubMed

    Zhou, Min; Peng, Zheng; Liao, Shuangquan; Li, Puwang; Li, Sidong

    2014-03-01

    The present study aims to prepare and evaluate carbon nanotubes (CNTs)-based colon-specific microspheres using irinotecan as a model of drug. The synthesis of CNTs-based microspheres including attachment of folate-chitosan conjugate and irinotecan to CNTs via non-covalent interaction, followed by microencapsulation with Eudragit S-100 by an oil-in-oil solvent evaporation technique. The obtained samples were characterized in case of surface morphology, drug loading efficiency and particle size. In vitro drug release behavior was studied in different pH medium and the obtained data were subjected to kinetic equations. It was found that the Eudragit-coated microparticles were spherical with smooth surface, and the particle size varied with the core/coat ratio. In vitro drug release shows that the irinotecan released in a slow and sustained fashion from the CNTs-based carriers without coating with Eudragit. No drug release was observed from Eudragit-coated microspheres when the medium pH below 7, while when the pH reached 7.4, the coating layer of Eudragit began to dissolve and a controlled release of irinotecan was observed. The cell viability test indicates that the drug free FA-CS decorated CNTs had no influence on the cell proliferation rates of HT-29 cells, while the irinotecan-loaded CNTs drug system proved to be the most cytotoxic.

  9. Polyethyleneimine-modified calcium carbonate nanoparticles for p53 gene delivery

    PubMed Central

    Chen, Cen; Han, Huafeng; Yang, Wei; Ren, Xiaoyuan; Kong, Xiangdong

    2016-01-01

    In this study, calcium carbonate (CaCO3) nanoparticles with spherical structure were regulated by arginine and successfully synthesized via a facile co-precipitation method. The average particle size of as-prepared CaCO3 was about 900 nm. The properties of nanostructured CaCO3 particles were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction and size distribution. After modified with polyethyleneimine (PEI), the ability of PEI-CaCO3 nanoparticles to carry GFP-marked p53 gene (pEGFP-C1-p53) into cancer cells to express P53 protein were studied. Meanwhile, the cytotoxicity, transfection efficiency, cells growth inhibition and the ability to induce apoptosis by expressed P53 protein were conducted to evaluate the performances of PEI-CaCO3 nanoparticles. The results show that prepared PEI-CaCO3 nanoparticles had good biocompatibility and low cytotoxicity in a certain concentration range. PEI-CaCO3 effectively transfected pEGFP-C1 gene into epithelial-like cancer cells. And with the expression of GFP-P53 fusion protein, pEGFP-C1-p53-gene-loaded PEI-CaCO3 particles significantly reduced the proliferation of cancer cells. These findings indicate that our PEI-modified CaCO3 nanoparticles are potential to be successfully used as carriers for gene therapy. PMID:26816656

  10. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery.

    PubMed

    Liu, Zhuang; Sun, Xiaoming; Nakayama-Ratchford, Nozomi; Dai, Hongjie

    2007-08-01

    We show that large surface areas exist for supramolecular chemistry on single-walled carbon nanotubes (SWNTs) prefunctionalized noncovalently or covalently by common surfactant or acid-oxidation routes. Water-soluble SWNTs with poly(ethylene glycol) (PEG) functionalization via these routes allow for surprisingly high degrees of pi-stacking of aromatic molecules, including a cancer drug (doxorubicin) with ultrahigh loading capacity, a widely used fluorescence molecule (fluorescein), and combinations of molecules. Binding of molecules to nanotubes and their release can be controlled by varying the pH. The strength of pi-stacking of aromatic molecules is dependent on nanotube diameter, leading to a method for controlling the release rate of molecules from SWNTs by using nanotube materials with suitable diameter. This work introduces the concept of "functionalization partitioning" of SWNTs, i.e., imparting multiple chemical species, such as PEG, drugs, and fluorescent tags, with different functionalities onto the surface of the same nanotube. Such chemical partitioning should open up new opportunities in chemical, biological, and medical applications of novel nanomaterials.

  11. Self-assembly of carbon nanotubes and antibodies on tumours for targeted amplified delivery

    NASA Astrophysics Data System (ADS)

    Mulvey, J. Justin; Villa, Carlos H.; McDevitt, Michael R.; Escorcia, Freddy E.; Casey, Emily; Scheinberg, David A.

    2013-10-01

    Single-walled carbon nanotubes (SWNTs) can deliver imaging agents or drugs to tumours and offer significant advantages over approaches based on antibodies or other nanomaterials. In particular, the nanotubes can carry a substantial amount of cargo (100 times more than a monoclonal antibody), but can still be rapidly eliminated from the circulation by renal filtration, like a small molecule, due to their high aspect ratio. Here we show that SWNTs can target tumours in a two-step approach in which nanotubes modified with morpholino oligonucleotide sequences bind to cancer cells that have been pretargeted with antibodies modified with oligonucleotide strands complementary to those on the nanotubes. The nanotubes can carry fluorophores or radioisotopes, and are shown to selectively bind to cancer cells in vitro and in tumour-bearing xenografted mice. The binding process is also found to lead to antigen capping and internalization of the antibody-nanotube complexes. The nanotube conjugates were labelled with both alpha-particle and gamma-ray emitting isotopes, at high specific activities. Conjugates labelled with alpha-particle-generating 225Ac were found to clear rapidly, thus mitigating radioisotope toxicity, and were shown to be therapeutically effective in vivo.

  12. How do carbon nanotubes serve as carriers for gemcitabine transport in a drug delivery system?

    PubMed

    Arsawang, Uthumporn; Saengsawang, Oraphan; Rungrotmongkol, Thanyada; Sornmee, Purinchaya; Wittayanarakul, Kitiyaporn; Remsungnen, Tawun; Hannongbua, Supot

    2011-02-01

    Aiming at understanding the molecular properties of the encapsulation of the anticancer drug gemcitabine in the single-walled carbon nanotube (SWCNT), molecular dynamics (MD) simulations were applied to the two scenarios; that of gemcitabine filling inside the SWCNT, and that of the drug in the free state. Inside the SWCNT, the cytosine ring of gemcitabine was found to form a π-π stacking conformation with the SWCNT surface, and this movement is not along the centerline of the tube from one end to the other of the tube where the distance from the center of gravity of the molecule to the surface is 4.7 Å. A tilted angle of 19° was detected between the cytosine ring of gemcitabine and the inner surface of SWCNT. In comparison to its conformation in the free form, no significant difference was observed on the torsion angle between the five- (ribose) and the six- (cytosine) membered rings. However, gemcitabine inside the SWCNT was found to have a lower number of solvating water molecules but with a stronger net solvation than the drug in the free state. This is due to the collaborative interactions between gemcitabine and the surface of the SWCNT. In addition, the steered molecular dynamics simulation (SMD) approach was employed to investigate the binding free energy for gemcitabine moving from one end to another end throughout the SWCNT. In excellent agreement with that yielded from the classical MD, the SMD energy profile confirms that the drug molecule prefers to locate inside the SWCNT. PMID:21167762

  13. Fabrication and Intracellular Delivery of Doxorubicin/Carbonate Apatite Nanocomposites: Effect on Growth Retardation of Established Colon Tumor

    PubMed Central

    Chowdhury, Ezharul Hoque; Wu, Xin; Hirose, Hajime; Haque, Amranul; Doki, Yuichiro; Mori, Masaki; Akaike, Toshihiro

    2013-01-01

    In continuing search for effective treatments of cancer, the emerging model aims at efficient intracellular delivery of therapeutics into tumor cells in order to increase the drug concentration. However, the implementation of this strategy suffers from inefficient cellular uptake and drug resistance. Therefore, pH-sensitive nanosystems have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms in endosomal or lysosomal acidic pH along with endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. Here, novel pH sensitive carbonate apatite has been fabricated to efficiently deliver anticancer drug Doxorubicin (DOX) to cancer cells, by virtue of its pH sensitivity being quite unstable under an acidic condition in endosomes and the desirable size of the resulting apatite-DOX for efficient cellular uptake as revealed by scanning electron microscopy. Florescence microscopy and flow cytometry analyses demonstrated significant uptake of drug (92%) when complexed with apatite nanoparticles. In vitro chemosensitivity assay revealed that apatite-DOX nanoparticles executed high cytotoxicity in several human cancer cell lines compared to free drugs and consequently apatite-DOX-facilitated enhanced tumor inhibitory effect was observed in colorectal tumor model within BALB/cA nude mice, thereby shedding light on their potential applications in cancer therapy. PMID:23613726

  14. Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery.

    PubMed

    Chen, Mei-Ling; He, Ye-Ju; Chen, Xu-Wei; Wang, Jian-Hua

    2012-11-27

    A novel and specific nanoplatform for in vitro simultaneous cancer-targeted optical imaging and magnetically guided drug delivery is developed by conjugating CdTe quantum dots with Fe(3)O(4)-filled carbon nanotubes (CNTs) for the first time. Fe(3)O(4) is filled into the interior of the CNTs, which facilitates magnetically guided delivery and improves the synergetic targeting efficiency. In comparison with that immobilized on the external surface of CNTs, the magnetite nanocrystals inside the CNTs protect it from agglomeration, enhance its chemical stability, and improve the drug loading capacity. It also avoids magnetic nanocrystals-induced quenching of fluorescence of the quantum dots. The SiO(2)-coated quantum dots (HQDs) attached on the surface of CNTs exhibit favorable fluorescence as the hybrid SiO(2) shells on the QDs surface prevent its fluorescence quenching caused by the CNTs. In addition, the hybrid SiO(2) shells also mitigate the toxicity of the CdTe QDs. By coating transferrin on the surface of the herein modified CNTs, it provides a dual-targeted drug delivery system to transport the doxorubicin hydrochloride (DOX) into Hela cells by means of an external magnetic field. The nanocarrier based on the multifunctional nanoplatform exhibits an excellent drug loading capability of ca. 110%, in addition to cancer-targeted optical imaging as well as magnetically guided drug delivery.

  15. Synthesis, characterization and in vitro evaluation of methotrexate conjugated fluorescent carbon nanoparticles as drug delivery system for human lung cancer targeting.

    PubMed

    Ajmal, Muhammad; Yunus, Uzma; Matin, Abdul; Haq, Noaman Ul

    2015-12-01

    Nanotechnology based cancer therapeutics have rapidly advanced towards the solution of many limitations associated with other drug delivery agents such as nonspecific distribution within the body, low water solubility and non-biocompatibility. Carbon nanoparticles have demonstrated unique properties that are useful to combat with these issues, including their properties dependent on size, high stability in different solvents, compatible size for drug delivery and ease of surface modifications. Fluorescent carbon nanoparticles with good water solubility were obtained from a carbohydrate source by acid assisted ultrasonic treatment at 35kHz for 4h. This simple and economical method can be used for large scale production. Electron microscopic, spectroscopic and thermo gravimetric analysis techniques were used to characterize these carbon nanoparticles. Functionalized CNPs were further conjugated with anticancer drug-methotrexate and used as fluorescent nano-carriers. In this research work, we determined the in vitro bioactivity of CNPs-methotrexate conjugates by lactate dehydrogenase assay, cell adhesion assay and sulforhodamine B assay in human lung carcinoma cell line (H157). The CNPs showed promising biocompatibility and CNPs-MTX conjugates demonstrated potent cytotoxic effects and high anticancer activities in human lung cancer cell line.

  16. Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

    PubMed

    Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

    2013-02-01

    Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

  17. Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

    PubMed

    Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

    2013-02-01

    Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors. PMID:23334699

  18. Thermo-sensitive liposomes loaded with doxorubicin and lysine modified single-walled carbon nanotubes as tumor-targeting drug delivery system.

    PubMed

    Zhu, Xiali; Xie, Yingxia; Zhang, Yingjie; Huang, Heqing; Huang, Shengnan; Hou, Lin; Zhang, Huijuan; Li, Zhi; Shi, Jinjin; Zhang, Zhenzhong

    2014-11-01

    This report focuses on the thermo-sensitive liposomes loaded with doxorubicin and lysine-modified single-walled carbon nanotube drug delivery system, which was designed to enhance the anti-tumor effect and reduce the side effects of doxorubicin. Doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes was prepared by reverse-phase evaporation method, the mean particle size was 232.0 ± 5.6 nm, and drug entrapment efficiency was 86.5 ± 3.7%. The drug release test showed that doxorubicin released more quickly at 42℃ than at 37℃. Compared with free doxorubicin, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes could efficiently cross the cell membranes and afford higher anti-tumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) cells in vitro. For in vivo experiments, the relative tumor volumes of the sarcomaia 180-bearing mice in thermo-sensitive liposomes group and doxorubicin group were significantly smaller than those of N.S. group. Meanwhile, the combination of near-infrared laser irradiation at 808 nm significantly enhanced the tumor growth inhibition both on SMMC-7721 cells and the sarcomaia 180-bearing mice. The quality of life such as body weight, mental state, food and water intake of sarcomaia 180 tumor-bearing mice treated with doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes were much higher than those treated with doxorubicin. In conclusion, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes combined with near-infrared laser irradiation at 808 nm may potentially provide viable clinical strategies for targeting delivery of anti-cancer drugs.

  19. Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotube) to assess their drug delivery potential: a theoretical molecular docking study.

    PubMed

    Shityakov, Sergey; Förster, Carola

    2013-01-01

    P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures. The theoretical results represented in this work show that fullerenes might be P-gp binders because of low levels of Gibbs free energy of binding (ΔG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding is energetically unfavourable, leading to a total decrease in binding affinity by elevation of the residual area (Ares), which also affects the π-π stacking mechanisms. Further, the obtained data could potentially call experimental studies using carbon nanostructures, such as SWCNT for development of drug delivery vehicles, to administer and assess drug-like chemical compounds to the target cells since organisms probably did not develop molecular sensing elements to detect these types of carbon molecules.

  20. pH-sensing nano-crystals of carbonate apatite: effects on intracellular delivery and release of DNA for efficient expression into mammalian cells.

    PubMed

    Chowdhury, E H; Maruyama, A; Kano, A; Nagaoka, M; Kotaka, M; Hirose, S; Kunou, M; Akaike, T

    2006-07-01

    Two unique and fascinating properties of carbonate apatite which are well-known in hard tissue engineering, have been unveiled, for the first time, for the development of the simplest, but most efficient non-viral gene delivery device - ability of preventing the growth of crystals needed for high frequency DNA transfer across a plasma membrane and a fast dissolution rate for effective release of DNA during endosomal acidification, leading to a remarkably high transgene expression (5 to 100-fold) in mammalian cells compared to the widely used transfecting agents. Moreover, by modulating the crystal dissolution rate of carbonate apatite through incorporation of fluoride or strontium into it, transfection activity could be dramatically controlled, thus shedding light on a new barrier in the non-viral route, which was overlooked so far. Thus we have developed an innovative technology with significant insights, that would come as a promising tool for both basic research laboratories and clinical settings.

  1. Single-walled carbon nanotubes noncovalently functionalized with lipid modified polyethylenimine for siRNA delivery in vitro and in vivo.

    PubMed

    Siu, King S; Zheng, Xiufen; Liu, Yanling; Zhang, Yujuan; Zhang, Xusheng; Chen, Di; Yuan, Ken; Gillies, Elizabeth R; Koropatnick, James; Min, Wei-Ping

    2014-10-15

    siRNA can downregulate the expression of specific genes. However, delivery to specific cells and tissues in vivo presents significant challenges. Modified carbon nanotubes (CNTs) have been shown to protect siRNA and facilitate its entry into cells. However, simple and efficient methods to functionalize CNTs are needed. Here, noncovalent functionalization of CNTs is performed and shown to effectively deliver siRNA to target cells. Specifically, single-walled CNTs were functionalized by noncovalent association with a lipopolymer. The lipopolymer (DSPE-PEG) was composed of a phospholipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and poly(ethylene glycol) (PEG). Three different ratios of polyethylenimine (PEI) to DSPE-PEG were synthesized and characterized and the products were used to disperse CNTs. The resulting materials were used for siRNA delivery in vitro and in vivo. The structural, biophysical, and biological properties of DGI/C and their complexes formed with siRNA were investigated. Cytotoxicity of the materials was low, and effective gene silencing in B16-F10 cells was demonstrated in vitro. In addition, significant uptake of siRNA as well as gene silencing in the liver was found following intravenous injection. This approach provides a new strategy for siRNA delivery and could provide insight for the development of noncovalently functionalized CNTs for siRNA therapy. PMID:25216445

  2. Sustained delivery of chondroitinase ABC by poly(propylene carbonate)-chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection.

    PubMed

    Ni, Shilei; Xia, Tongliang; Li, Xingang; Zhu, Xiaodong; Qi, Hongxu; Huang, Shanying; Wang, Jiangang

    2015-10-22

    We describe the sustained delivery of chondroitinase ABC (ChABC) in the hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS microspheres were mixed with acetonitrile, and micron fibers were generated by electrospinning. ChABC release was assessed in vitro with high-performance liquid chromatography (HPLC) and revealed stabilized and prolonged release. Moreover, the released ChABC showed sustained activity. PPC-CS micron fibers with or without ChABC were then implanted into a hemisected thoracic spinal cord. In the following 4 weeks, we examined functional recovery and performed immunohistochemical analyses. We found that sustained delivery of ChABC promoted axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron fibers without ChABC did not show these effects. The present findings suggest that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord injury treatment. Furthermore, the system described here may be useful for local delivery of other therapeutic agents. PMID:26315376

  3. Intracellular Delivery of Bioactive Cargos to Hard-to-Transfect Cells Using Carbon Nanosyringe Arrays under an Applied Centrifugal g-Force.

    PubMed

    Choi, Minsuk; Lee, Sang Ho; Kim, Won Bae; Gujrati, Vipul; Kim, Daejin; Lee, Jinju; Kim, Jae-Il; Kim, Hyungjun; Saw, Phei Er; Jon, Sangyong

    2016-01-01

    There is considerable interest in developing a common, universal platform for delivering biomacromolecules such as proteins and RNAs into diverse cells with high efficiency. Here, it is shown that carbon nanosyringe arrays (CNSAs) under an applied centrifugal g-force (cf-CNSAs) can deliver diverse bioactive cargos directly into the cytosol of hard-to-transfect cells with relatively high efficiency and reproducibility. The cf-CNSA platform, an optimized version of a previous CNSA-mediated intracellular delivery platform that adds a g-force feature, exhibits more rapid and superior delivery of cargos to various hard-to-transfect cells than is the case in the absence of g-force. Active species, including small interfering RNAs, plasmids, and proteins are successfully transported across plasma membrane barriers into various cells. By overcoming the limitations of currently available transfection methods, the cf-CNSA platform paves the way to universal delivery of a variety of cargos, facilitating the analysis of cellular responses in diverse cell types.

  4. Single-walled carbon nanotubes noncovalently functionalized with lipid modified polyethylenimine for siRNA delivery in vitro and in vivo.

    PubMed

    Siu, King S; Zheng, Xiufen; Liu, Yanling; Zhang, Yujuan; Zhang, Xusheng; Chen, Di; Yuan, Ken; Gillies, Elizabeth R; Koropatnick, James; Min, Wei-Ping

    2014-10-15

    siRNA can downregulate the expression of specific genes. However, delivery to specific cells and tissues in vivo presents significant challenges. Modified carbon nanotubes (CNTs) have been shown to protect siRNA and facilitate its entry into cells. However, simple and efficient methods to functionalize CNTs are needed. Here, noncovalent functionalization of CNTs is performed and shown to effectively deliver siRNA to target cells. Specifically, single-walled CNTs were functionalized by noncovalent association with a lipopolymer. The lipopolymer (DSPE-PEG) was composed of a phospholipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and poly(ethylene glycol) (PEG). Three different ratios of polyethylenimine (PEI) to DSPE-PEG were synthesized and characterized and the products were used to disperse CNTs. The resulting materials were used for siRNA delivery in vitro and in vivo. The structural, biophysical, and biological properties of DGI/C and their complexes formed with siRNA were investigated. Cytotoxicity of the materials was low, and effective gene silencing in B16-F10 cells was demonstrated in vitro. In addition, significant uptake of siRNA as well as gene silencing in the liver was found following intravenous injection. This approach provides a new strategy for siRNA delivery and could provide insight for the development of noncovalently functionalized CNTs for siRNA therapy.

  5. The use of halloysite clay and carboxyl-functionalised multi-walled carbon nanotubes for recombinant LipL32 antigen delivery enhanced the IgG response

    PubMed Central

    Hartwig, Daiane D; Bacelo, Kátia L; Oliveira, Thaís L; Schuch, Rodrigo; Seixas, Fabiana K; Collares, Tiago; Rodrigues, Oscar; Hartleben, Cláudia P; Dellagostin, Odir A

    2015-01-01

    We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations. PMID:25742273

  6. The use of halloysite clay and carboxyl-functionalised multi-walled carbon nanotubes for recombinant LipL32 antigen delivery enhanced the IgG response.

    PubMed

    Hartwig, Daiane D; Bacelo, Kátia L; Oliveira, Thaís L; Schuch, Rodrigo; Seixas, Fabiana K; Collares, Tiago; Rodrigues, Oscar; Hartleben, Cláudia P; Dellagostin, Odir A

    2015-02-01

    We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations.

  7. Vesicular (liposomal and nanoparticulated) delivery of curcumin: a comparative study on carbon tetrachloride–mediated oxidative hepatocellular damage in rat model

    PubMed Central

    Choudhury, Somsubhra Thakur; Das, Nirmalendu; Ghosh, Swarupa; Ghosh, Debasree; Chakraborty, Somsuta; Ali, Nahid

    2016-01-01

    The liver plays a vital role in biotransforming and extricating xenobiotics and is thus prone to their toxicities. Short-term administration of carbon tetrachloride (CCl4) causes hepatic inflammation by enhancing cellular reactive oxygen species (ROS) level, promoting mitochondrial dysfunction, and inducing cellular apoptosis. Curcumin is well accepted for its antioxidative and anti-inflammatory properties and can be considered as an effective therapeutic agent against hepatotoxicity. However, its therapeutic efficacy is compromised due to its insolubility in water. Vesicular delivery of curcumin can address this limitation and thereby enhance its effectiveness. In this study, it was observed that both liposomal and nanoparticulated formulations of curcumin could increase its efficacy significantly against hepatotoxicity by preventing cellular oxidative stress. However, the best protection could be obtained through the polymeric nanoparticle-mediated delivery of curcumin. Mitochondria have a pivotal role in ROS homeostasis and cell survivability. Along with the maintenance of cellular ROS levels, nanoparticulated curcumin also significantly (P<0.0001) increased cellular antioxidant enzymes, averted excessive mitochondrial destruction, and prevented total liver damage in CCl4-treated rats. The therapy not only prevented cells from oxidative damage but also arrested the intrinsic apoptotic pathway. In addition, it also decreased the fatty changes in hepatocytes, centrizonal necrosis, and portal inflammation evident from the histopathological analysis. To conclude, curcumin-loaded polymeric nanoparticles are more effective in comparison to liposomal curcumin in preventing CCl4-induced oxidative stress–mediated hepatocellular damage and thereby can be considered as an effective therapeutic strategy. PMID:27274242

  8. Poly(amino carbonate urethane)-based biodegradable, temperature and pH-sensitive injectable hydrogels for sustained human growth hormone delivery

    PubMed Central

    Phan, V. H. Giang; Thambi, Thavasyappan; Duong, Huu Thuy Trang; Lee, Doo Sung

    2016-01-01

    In this study, a new pH-/temperature-sensitive, biocompatible, biodegradable, and injectable hydrogel based on poly(ethylene glycol)-poly(amino carbonate urethane) (PEG-PACU) copolymers has been developed for the sustained delivery of human growth hormone (hGH). In aqueous solutions, PEG-PACU-based copolymers existed as sols at low pH and temperature (pH 6.0, 23 °C), whereas they formed gels in the physiological condition (pH 7.4, 37 °C). The physicochemical characteristics, including gelation rate, mechanical strength and viscosity, of the PEG-PACU hydrogels could be finely tuned by varying the polymer weight, pH and temperature of the copolymer. An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel, which exhibited a homogenous porous structure. In addition, an in vivo biodegradation study of the PEG-PACU hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site and the surrounding tissue. The hGH-loaded PEG-PACU copolymer solution readily formed a hydrogel in SD rats, which subsequently inhibited the initial hGH burst and led to the sustained release of hGH. Overall, the PEG-PACU-based copolymers prepared in this study are expected to be useful biomaterials for the sustained delivery of hGH. PMID:27436576

  9. 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.

  10. Poly(amino carbonate urethane)-based biodegradable, temperature and pH-sensitive injectable hydrogels for sustained human growth hormone delivery

    NASA Astrophysics Data System (ADS)

    Phan, V. H. Giang; Thambi, Thavasyappan; Duong, Huu Thuy Trang; Lee, Doo Sung

    2016-07-01

    In this study, a new pH-/temperature-sensitive, biocompatible, biodegradable, and injectable hydrogel based on poly(ethylene glycol)-poly(amino carbonate urethane) (PEG-PACU) copolymers has been developed for the sustained delivery of human growth hormone (hGH). In aqueous solutions, PEG-PACU-based copolymers existed as sols at low pH and temperature (pH 6.0, 23 °C), whereas they formed gels in the physiological condition (pH 7.4, 37 °C). The physicochemical characteristics, including gelation rate, mechanical strength and viscosity, of the PEG-PACU hydrogels could be finely tuned by varying the polymer weight, pH and temperature of the copolymer. An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel, which exhibited a homogenous porous structure. In addition, an in vivo biodegradation study of the PEG-PACU hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site and the surrounding tissue. The hGH-loaded PEG-PACU copolymer solution readily formed a hydrogel in SD rats, which subsequently inhibited the initial hGH burst and led to the sustained release of hGH. Overall, the PEG-PACU-based copolymers prepared in this study are expected to be useful biomaterials for the sustained delivery of hGH.

  11. Carbon nanospheres mediated delivery of nuclear matrix protein SMAR1 to direct experimental autoimmune encephalomyelitis in mice

    PubMed Central

    Chemmannur, Sijo V; Bhagat, Prasad; Mirlekar, Bhalchandra; Paknikar, Kishore M; Chattopadhyay, Samit

    2016-01-01

    Owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR−/−). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis. PMID:27274234

  12. Changes in Terrestrial Organic Carbon Delivery to the Colville River Delta and Adjacent Simpson's Lagoon Over the Late Holocene

    NASA Astrophysics Data System (ADS)

    Schreiner, K. M.; Bianchi, T. S.; Allison, M. A.; Miller, A. J.; Marcantonio, F.

    2012-04-01

    The Colville River in Alaska is the largest river in North America that drains only continuously permafrosted tundra, and as such provides a unique signal of historical changes in one of the world's most vulnerable areas to climate changes. Additionally, the Colville flows into Simpson's Lagoon, a shallow area of the Alaskan Beaufort coast protected by a barrier island chain, lessening the impacts of Arctic storms and ice grounding on sediment mixing. Cores collected from the Colville river delta in August of 2010 were found to be composed of muddy, organic-rich, well-laminated sediments. The 2.5 to 3 meter length of each core spans about one to two thousand years of Holocene history, including the entire Anthropocene and much of the late Holocene. Three cores were sampled for this data set, arranged latitudinally from the mouth of the Colville River east into Simpson's Lagoon. Samples were taken every 2 cm for the entire length of all cores. Bulk analyses including percent organic carbon, percent nitrogen, and stable carbon isotopic analysis were performed, and compound specific analyses including lignin-phenol and algal pigment analyses were performed. These analyses showed significant changes in carbon storage over the past one to two thousand years. There were also significant spatial differences in organic carbon inputs across the ~20km distance between the Colville mouth and the easternmost core. Lignin-phenol concentrations in surface sediments nearest to the river mouth correlated positively with reconstructed Alaskan North Slope temperatures, suggesting more terrestrial organic matter was delivered during higher temperature regimes. Molar C:N ratios and plant pigments correlated negatively and positively, respectively, with reconstructed Alaskan North Slope moisture regime, indicating greater algal inputs during wetter time periods. These data may in part be consistent with observed woody shrub encroachment and increasing expanse of permafrost lakes on the

  13. Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit

    PubMed Central

    Fagerstrom, K.; Hughes, J.; Rasmussen, T.; Callas, P.

    2000-01-01

    OBJECTIVE—To monitor the effect of a novel nicotine delivery device that may produce fewer carcinogens (Eclipse) on cigarette smoking, carbon monoxide and nicotine concentrations, and motivation to give up smoking. The smoker's own brand of cigarette and a nicotine replacement product (Nicotrol inhaler) were used as comparisons.
DESIGN—After baseline data were recorded, smokers were randomised to either Eclipse or inhaler for two weeks and then switched to the other product for another two weeks. Thereafter a second baseline was obtained.
SETTING AND PARTICIPANTS— Fifty smokers were included and data are reported for the 40 with complete data sets. The smokers were not trying to quit but were interested in trying a new product to reduce their risk. They visited a smoking clinic 10 times during the six week period of the trial.
INTERVENTION—No counselling to aid reduction by Eclipse or inhaler was given.
MAIN OUTCOME MEASURES—At each visit smoking status and carbon monoxide concentrations were recorded. In half of the visits withdrawal symptoms, attitudes towards smoking, heart rate, and blood nicotine concentrations were also recorded.
RESULTS—Eclipse use decreased the number of cigarettes smoked per day (cpd) from 19.1 cpd at baseline to 2.1 cpd (p < 0.001), but increased carbon monoxide concentrations in parts per million (ppm) from 21.0 ppm to 33.0 ppm (p < 0.001). A similar decrease in cigarettes smoked per day was seen with the Nicotrol inhaler, from 19.1 cpd to 4.8 cpd (p < 0.001), but carbon monoxide decreased from 21.0 ppm to 12.7 ppm (p < 0.001). The blood nicotine concentration remained fairly stable with Eclipse, increasing slightly from 16.8 ng/ml to 18.0 ng/ml, while for the inhaler a significant drop was noted, from 16.8 ng/ml to 12.2 ng/ml (p < 0.002). Craving and withdrawal did not increase with Eclipse. Few significant adverse events occurred with Eclipse.
CONCLUSIONS—Eclipse can dramatically

  14. Organic Carbon Delivery to a High Arctic Watershed over the Late Holocene: Insights from Plant Biomarkers and Compound Specific δ13C and Δ14C Measurements

    NASA Astrophysics Data System (ADS)

    Schreiner, K. M.; Bianchi, T. S.; Eglinton, T. I.; Allison, M. A.

    2012-12-01

    The Colville River in Alaska is the largest river in North America which has a drainage basin that is exclusively underlain by permafrost, and as such provides a unique signal of historical changes in one of the world's most vulnerable areas to climate changes. Additionally, the Colville flows into Simpson's Lagoon, an area of the Alaskan Beaufort coast protected by a barrier island chain, lessening the impacts of Arctic storms and ice grounding on sediment mixing. Cores collected from the Colville river delta in August of 2010 were found to be composed of muddy, organic-rich, well-laminated sediments. The 2.5 to 3 meter length of each core spans about one to two thousand years of Holocene history, including the entire Anthropocene and much of the late Holocene. Two cores were sampled for this data set - one from close to the river mouth, and one from farther east in Simpson's Lagoon. Samples were taken every 2 cm for the entire length of both cores. In order to determine how the amount of terrestrial organic matter input changed over the Holocene, bulk analyses including percent organic carbon, percent nitrogen, and stable carbon isotopic analysis were performed, and biomarkers including lignin-phenols and fatty acids were measured. It was shown that lignin-phenol input is positively correlated with Alaskan North Slope temperature reconstructions. To determine whether the source of this increased terrestrial organic matter input was from fresh vegetation (for example, shrub encroachment onto tundra areas) or aged soil organic matter (potentially due to permafrost thawing and breakdown), selected samples were analyzed for compound-specific δ13C and Δ14C of fatty acids and lignin-phenols. These analyses show significant changes in carbon storage and in terrestrial carbon delivery to the Lagoon over time. These results represent the first fine-scale organic biomarker study in a high Arctic North American Lagoon, and have many implications for the future of carbon

  15. Fractional carbon dioxide laser-assisted drug delivery of topical timolol solution for the treatment of deep infantile hemangioma: a pilot study.

    PubMed

    Ma, Gang; Wu, Pinru; Lin, Xiaoxi; Chen, Hui; Hu, Xiaojie; Jin, Yunbo; Qiu, Yajing

    2014-01-01

    Infantile hemangiomas (IHs) are benign vascular tumors of infancy. Topical timolol has recently been reported to be an effective treatment for superficial IHs, although it failed to have an effect on deep IHs. This prospective study was aimed at evaluating the feasibility of ablative fractional laser-assisted drug delivery for enhancing topical timolol permeation into deep IHs. Nine patients ages 1 to 6 months with deep IHs were enrolled. A fractional carbon dioxide (CO2 ) laser system was applied to the skin surface of deep IHs using the DeepFx mode (25-30 mJ/pulse, 5% density, single pulse) at 1-week intervals. Topical timolol maleate 0.5% ophthalmic solution was applied under occlusion for 30 minutes four to five times per day for an average treatment duration of 14.2 weeks. Clinical improvement was evaluated according to a global score and the Hemangioma Activity Score (HAS). Four patients (44.4%) demonstrated excellent regression, four (44.4%) showed good response, and one (11.1%) experienced moderate regression. The HAS declined from 4.1 ± 0.7 at baseline to 1.7 ± 0.7 at 1 week (p < 0.001) and 1.4 ± 0.7 at 3 months (p = 0.03) after the last treatment procedure. Plasma timolol concentration was not detected in any of the patients after the first administration of topical timolol. No systemic complication or skin side effects were observed in any of the patients. Ablative fractional laser-assisted transdermal delivery of topical timolol is a safe and effective method for the treatment of deep IHs.

  16. Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchison, Betty

    This paper on delivery systems for preparing and training early childhood educators focuses on three main topics: (1) adequacy of delivery systems and access; (2) market influences on delivery systems; and (3) linking preparation and professional development components. Questions addressed include the following: Would the current preparation and…

  17. Iron metal-organic frameworks MIL-88B and NH2-MIL-88B for the loading and delivery of the gasotransmitter carbon monoxide.

    PubMed

    Ma, Mingyan; Noei, Heshmat; Mienert, Bernd; Niesel, Johanna; Bill, Eckhard; Muhler, Martin; Fischer, Roland A; Wang, Yuemin; Schatzschneider, Ulrich; Metzler-Nolte, Nils

    2013-05-17

    Crystals of MIL-88B-Fe and NH2-MIL-88B-Fe were prepared by a new rapid microwave-assisted solvothermal method. High-purity, spindle-shaped crystals of MIL-88B-Fe with a length of about 2 μm and a diameter of 1 μm and needle-shaped crystals of NH2-MIL-88B-Fe with a length of about 1.5 μm and a diameter of 300 nm were produced with uniform size and excellent crystallinity. The possibility to reduce the as-prepared frameworks and the chemical capture of carbon monoxide in these materials was studied by in situ ultrahigh vacuum Fourier-transform infrared (UHV-FTIR) spectroscopy and Mössbauer spectroscopy. CO binding occurs to unsaturated coordination sites (CUS). The release of CO from the as-prepared materials was studied by a myoglobin assay in physiological buffer. The release of CO from crystals of MIL-88B-Fe with t(1/2) = 38 min and from crystals of NH2-MIL-88B-Fe with t(1/2) = 76 min were found to be controlled by the degradation of the MIL materials under physiological conditions. These MIL-88B-Fe and NH2-MIL-88B-Fe materials show good biocompatibility and have the potential to be used in pharmacological and therapeutic applications as carriers and delivery vehicles for the gasotransmitter carbon monoxide. PMID:23536364

  18. Conversion of sustained release omeprazole loaded buccal films into fast dissolving strips using supercritical carbon dioxide (scCO2) processing, for potential paediatric drug delivery.

    PubMed

    Khan, Sajjad; Trivedi, Vivek; Mitchell, John; Boateng, Joshua S

    2016-10-10

    This study involves the development of thin oral solvent cast films for the potential delivery of the proton pump inhibitor, omeprazole (OME) via the buccal mucosa for paediatric patients. OME containing films were prepared from ethanolic gels (1% w/w) of metolose (MET) with polyethylene glycol (PEG 400) (0.5% w/w) as plasticiser, and L-arginine (l-arg) (0.2% w/w) as a stabilizer and dried in an oven at 40°C. The blank and drug loaded films were divided into two groups, one group was subjected to supercritical carbon dioxide (scCO2) treatment and the other group untreated. The untreated and scCO2 treated films were then characterised using differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, hydration (swelling), mucoadhesion and in vitro drug dissolution studies. Treatment of the solvent cast films with scCO2 caused significant changes to the functional and physical properties of the MET films. The original drug loaded MET films showed a sustained release of OME (1h), whereas scCO2 treatment of the formulations resulted in fast dissolving films with >90% drug release within 15min.

  19. Conversion of sustained release omeprazole loaded buccal films into fast dissolving strips using supercritical carbon dioxide (scCO2) processing, for potential paediatric drug delivery.

    PubMed

    Khan, Sajjad; Trivedi, Vivek; Mitchell, John; Boateng, Joshua S

    2016-10-10

    This study involves the development of thin oral solvent cast films for the potential delivery of the proton pump inhibitor, omeprazole (OME) via the buccal mucosa for paediatric patients. OME containing films were prepared from ethanolic gels (1% w/w) of metolose (MET) with polyethylene glycol (PEG 400) (0.5% w/w) as plasticiser, and L-arginine (l-arg) (0.2% w/w) as a stabilizer and dried in an oven at 40°C. The blank and drug loaded films were divided into two groups, one group was subjected to supercritical carbon dioxide (scCO2) treatment and the other group untreated. The untreated and scCO2 treated films were then characterised using differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, hydration (swelling), mucoadhesion and in vitro drug dissolution studies. Treatment of the solvent cast films with scCO2 caused significant changes to the functional and physical properties of the MET films. The original drug loaded MET films showed a sustained release of OME (1h), whereas scCO2 treatment of the formulations resulted in fast dissolving films with >90% drug release within 15min. PMID:27497613

  20. Negatively Charged Carbon Nanohorn Supported Cationic Liposome Nanoparticles: A Novel Delivery Vehicle for Anti-Nicotine Vaccine.

    PubMed

    Zheng, Hong; Hu, Yun; Huang, Wei; de Villiers, Sabina; Pentel, Paul; Zhang, Jianfei; Dorn, Harry; Ehrich, Marion; Zhang, Chenming

    2015-12-01

    Tobacco addiction is the second-leading cause of death in the world. Due to the nature of nicotine (a small molecule), finding ways to combat nicotine's deleterious effects has been a constant challenge to the society and the medical field. In the present work, a novel anti-nicotine vaccine based on nanohorn supported liposome nanoparticles (NsL NPs) was developed. The nano-vaccine was constructed by using negatively charged carbon nanohorns as a scaffold for the assembly of cationic liposomes, which allow the conjugation of hapten conjugated carrier proteins. The assembled bio-nanoparticles are stable. Mice were immunized subcutaneously with the nano-vaccine, which induced high titer and high affinity of nicotine specific antibodies in mice. Furthermore, no evidence of clinical signs or systemic toxicity followed multiple administrations of NsL-based anti-nicotine vaccine. These results suggest that NsL-based anti-nicotine vaccine is a promising candidate in treating nicotine dependence and could have potential to significantly contribute to smoking cessation.

  1. The role of effective discharge in the ocean delivery of particulate organic carbon by small, mountainous river systems

    USGS Publications Warehouse

    Wheatcroft, R.A.; Goni, M.A.; Hatten, J.A.; Pasternack, G.B.; Warrick, J.A.

    2010-01-01

    Recent research has shown that small, mountainous river systems (SMRS) account for a significant fraction of the global flux of sediment and particulate organic carbon (POC) to the ocean. The enormous number of SMRS precludes intensive studies of the sort conducted on large systems, necessitating development of a conceptual framework that permits cross-system comparison and scaling up. Herein, we introduce the geomorphic concept of effective discharge to the problem of source-to-sink POC transport. This idea recognizes that transport effectiveness is the product of discharge frequency and magnitude, wherein the latter is quantified as a power-law relationship between discharge and load (the 'rating curve'). An analytical solution for effective discharge (Qe) identifies two key variables: the standard deviation of the natural logarithm of discharge (??q), and the rating exponent of constituent i (bi Data from selected SMRS are used to show that for a given river Qe-POC < Qesediment, Qe for different POC constituents (e.g., POCfossil vs. POC(modern) differs in predictable ways, and Qe for a particular constituent can vary seasonally. When coupled with the idea that discharge peaks of small rivers may be coincident with specific oceanic conditions (e.g., large waves, wind from a certain direction) that determine dispersal and burial, these findings have potentially important implications for POC fate on continental margins. Future studies of POC transport in SMRS should exploit the conceptual framework provided herein and seek to identify how constituent-specific effective discharges vary between rivers and respond to perturbations. ?? 2010, by the American Society of Limnology and Oceanography, Inc.

  2. Submicrometer particle removal indoors by a novel electrostatic precipitator with high clean air delivery rate, low ozone emissions, and carbon fiber ionizer.

    PubMed

    Kim, H-J; Han, B; Kim, Y-J; Oda, T; Won, H

    2013-10-01

    A novel positive-polarity electrostatic precipitator (ESP) was developed using an ionization stage (0.4 × 0.4 × 0.14 m(3) ) with 16 carbon fiber ionizers in each channel and a collection stage (0.4 × 0.4 × 0.21 m(3) ) with parallel metallic plates. The single-pass collection efficiency and clean air delivery rate (CADR) were measured by standard tests using KCl particles in 0.25-0.35 μm. Performance was determined using the Deutsch equation and established diffusion and field charging theories and also compared with the commercialized HEPA filter-type air cleaner. Experimental results showed that the single-pass collection efficiency of the ESP ranged from 50 to 95% and decreased with the flow rate (10-20 m(3) /min), but increased with the voltage applied to the ionizers (6 to 8 kV) and collection plates (-5 to -7 kV). The ESP with 18 m(3) /min achieved a CADR of 12.1 m(3) /min with a voltage of 8 kV applied to the ionization stage and with a voltage of -6 kV applied to the collection stage. The concentration of ozone in the test chamber (30.4 m(3) ), a maximum value of 5.4 ppb over 12 h of continuous operation, was much lower than the current indoor regulation (50 ppb).

  3. Submicrometer particle removal indoors by a novel electrostatic precipitator with high clean air delivery rate, low ozone emissions, and carbon fiber ionizer.

    PubMed

    Kim, H-J; Han, B; Kim, Y-J; Oda, T; Won, H

    2013-10-01

    A novel positive-polarity electrostatic precipitator (ESP) was developed using an ionization stage (0.4 × 0.4 × 0.14 m(3) ) with 16 carbon fiber ionizers in each channel and a collection stage (0.4 × 0.4 × 0.21 m(3) ) with parallel metallic plates. The single-pass collection efficiency and clean air delivery rate (CADR) were measured by standard tests using KCl particles in 0.25-0.35 μm. Performance was determined using the Deutsch equation and established diffusion and field charging theories and also compared with the commercialized HEPA filter-type air cleaner. Experimental results showed that the single-pass collection efficiency of the ESP ranged from 50 to 95% and decreased with the flow rate (10-20 m(3) /min), but increased with the voltage applied to the ionizers (6 to 8 kV) and collection plates (-5 to -7 kV). The ESP with 18 m(3) /min achieved a CADR of 12.1 m(3) /min with a voltage of 8 kV applied to the ionization stage and with a voltage of -6 kV applied to the collection stage. The concentration of ozone in the test chamber (30.4 m(3) ), a maximum value of 5.4 ppb over 12 h of continuous operation, was much lower than the current indoor regulation (50 ppb). PMID:23418721

  4. Facile one-pot synthesis of carbon/calcium phosphate/Fe3O4 composite nanoparticles for simultaneous imaging and pH/NIR-responsive drug delivery.

    PubMed

    Gou, Mingyu; Li, Shengnan; Zhang, Lingyu; Li, Lu; Wang, Chungang; Su, Zhongmin

    2016-09-25

    A facile one-pot synthetic strategy was explored to synthesize carbon/calcium phosphate/Fe3O4 composite nanoparticles (carbon/CaP/Fe3O4 composite NPs). Taking advantage of the unique structure including mesoporous, small CaP and Fe3O4 subunits homogeneously distributed in a carbon matrix, carbon/CaP/Fe3O4 NPs integrate high drug loading, pH/NIR-sensitive, photothermal and magnetic properties into one nanoplatform for cancer theranostics.

  5. Impact delivery of organic matter on the acapulcoite-lodranite parent-body deduced from C, N isotopes and nanostructures of carbon phases in Acapulco and Lodran

    NASA Astrophysics Data System (ADS)

    Charon, E.; Aléon, J.; Rouzaud, J.-N.

    2014-10-01

    The structure and nanostructures of carbon phases from the Acapulco and Lodran meteorites and their carbon and nitrogen isotopic composition were investigated at the nanometer and micrometer scale using a systematic combination of Raman microspectrometry, high-resolution transmission electron microscopy and secondary ion mass spectrometry to determine their origin and thermal evolution. Several morphological types were recognized belonging to roughly two isotopic and structural families: coarse carbon grains and rosettes, only found in Acapulco, and vein-like carbon occurrences present in both Acapulco and Lodran. Carbon phases in Acapulco are highly graphitized, and show a genetic relationship with metal indicative of metal-assisted graphitization. By contrast, carbon phases in Lodran are exclusively disordered mesoporous turbostratic carbons, in spite of their inclusion in metal and the higher peak temperature experienced by the Lodran parent body. δ13C values range between -59‰ and +37‰ in Acapulco and between -38‰ and -1‰ in Lodran and show in both cases a peak in their distribution at the value of chondritic insoluble organic matter (IOM, -10‰ to -15‰). N concentrations together with δ15N values indicate a mixing between a component akin to chondritic IOM in Lodran with a δ15N value around +10‰ to +20‰ and a component akin to that in the most N-poor Acapulco graphites. The latter are systematically depleted in 15N with a δ15N value constant at ∼-140‰ for N concentrations below ∼1.4 wt%. These observations can be explained if carbon phases in Acapulco and Lodran result from the late impact introduction of CI-CM like IOM, after significant cooling of the parent-body, and subsequent carbonization and graphitization of IOM by interaction with FeNi metal by the heat wave induced by the impact. Temperatures probably reached 900 °C in Acapulco, enough to achieve metal-assisted graphitization but were not significantly higher than 650 °C in

  6. Enriched Seawater Delivery System to Support In Situ Ocean Acidification Experiments using Carbon Dioxide for pH Adjustment of Seawater

    NASA Astrophysics Data System (ADS)

    Kirkwood, W. J.; Peltzer, E. T.; Walz, P. M.; Shane, F.; Kecy, C.; Headley, K. L.; Herlien, B.; Maughan, T.; Scholfield, J.; Salamy, K. A.; O'Reilly, T.; Brewer, P. G.

    2011-12-01

    A series of Free Ocean CO2 Enrichment (FOCE) experiments are underway or are in planning to perform in situ ocean acidification research at a number of locations around the world. One of the most challenging locations is in Monterey Bay at the site of the Monterey Accelerated Research System, the United States test facility for cabled observatories. This site is located at 890 m deep and 4 0C within the local oxygen minimum zone and approximately 50 kilometers from shore. At this depth and temperature the behavior of liquid CO2 presents various challenges that had to be addressed in order to provide the low pH seawater needed for the FOCE apparatus to perform as desired. To solve this challenge a team of engineers and scientists at the Monterey Bay Aquarium Research Institute (MBARI) have developed a standalone device referred to as the Enriched Seawater Delivery System. Simple injections of seawater saturated at one atmosphere with CO2 demonstrated that the FOCE unit itself performs as designed. However, providing a consistent source of CO2 enriched pH altered seawater within the design criteria proved to be an imposing problem which when solved could have a broader impact in the oceanographic community. The decision was made to build a stand-alone device separate from the FOCE flume to perform in situ CO2 experiments in conditions where CO2 hydrate can form. Challenges to be over-come by this work included: (1) liquid CO2 is buoyant at the prescribed depth; (2) minimizing the formation of hydrates while manufacturing the CO2 enriched seawater. Because CO2 hydrate is denser than seawater, management of the phases and stability of liquid CO2 was necessary to prevent clogging within the delivery system. Our earliest field experiments demonstrated that containing and controlling the CO2 and the CO2-enriched seawater is difficult and makes the metering of the enriched fluid with on demand milliliter per second precision an extremely challenging problem. The Enriched

  7. Erosion of soil organic carbon at high latitudes and its delivery to Arctic Ocean sediments: New source to sink insight from radiocarbon dating

    NASA Astrophysics Data System (ADS)

    Hilton, Robert; Galy, Valier; Gaillardet, Jerome; Dellinger, Mathieu; Bryant, Charlotte; O'Regan, Matt; Grocke, Darren; Coxall, Helen

    2016-04-01

    Soils of the northern high latitudes store carbon over thousands of years and contain almost double the carbon stock of the atmosphere. Erosion processes can mobilise this pre-aged soil organic carbon from the landscape and supply it to rivers. If it escapes degradation during river transport and is delivered to the coastal ocean, this carbon may be sequestered for much longer periods of time (>104 yr) as a geological CO2 sink. Despite this recognition, the erosional flux and fate of particulate organic carbon (POC) in large rivers draining the high latitudes remains poorly constrained. Using radiocarbon activity, we quantify POC source, flux and fate in the Mackenzie River, the main sediment supplier to the Arctic Ocean. When combined with stable carbon isotopes and element ratios, the radiocarbon activity of POC allows us to distinguish inputs of POC from sedimentary rocks and quantify the average age of biospheric POC (from vegetation and soil) transported through the river system. We find that the eroded biospheric POC has resided in the basin for millennia, with a mean radiocarbon age of 5800±800 years. This is much older than large tropical rivers where we have equivalent data (Amazon River, Ganges River), and likely reflects the longer residence time of organic matter in cold, wet, high latitude soils. Based on the measured biospheric POC content and annual sediment flux, we calculate a biospheric POC flux of 2.2 (+1.3/-0.9) TgC yr-1 from the Mackenzie River. This is the largest input of aged organic carbon to the Arctic Ocean, more than the combined POC flux from the Eurasian Rivers. Offshore, we use a marine core to investigate organic carbon burial over the Holocene period. Radiocarbon measurements of bulk organic carbon reveal a significant offset from benthic foraminifera radiocarbon ages throughout the core, which is dependent upon the grain size of the sediments. Organic matter in sediments >63μm are offset from foraminifera by ˜ 6,000 14C years

  8. Physisorbed o-carborane onto lyso-phosphatidylcholine-functionalized, single-walled carbon nanotubes: a potential carrier system for the therapeutic delivery of boron.

    PubMed

    Yannopoulos, S N; Zouganelis, G D; Nurmohamed, S; Smith, J R; Bouropoulos, N; Calabrese, G; Fatouros, D G; Tsibouklis, J

    2010-02-26

    A combination of data from ICP-MS, Raman spectroscopy, UV-vis spectrometry, atomic force microscopy, zeta-potential measurements and gel electorphoresis studies has shown that o-carborane may be immobilized on stable aqueous dispersions of lyso-phosphatidylcholine-functionalized single-walled carbon nanotubes, which in turn indicates the potential of such structures for deployment as carrier vehicles in boron neutron capture therapy.

  9. Synthetic nanocarriers for intracellular protein delivery.

    PubMed

    Du, Juanjuan; Jin, Jing; Yan, Ming; Lu, Yunfeng

    2012-01-01

    Introducing exogenous proteins intracellularly presents tremendous chances in scientific research and clinical applications. The effectiveness of this method, however, has been limited by lack of efficient ways to achieve intracellular protein delivery and poor stability of the delivered proteins. Over the years, a variety of nanomaterials have been explored as intracellular protein delivery vectors, including liposomes, polymers, gold nanoparticles, mesoporous silica particles, and carbon nanotubes. Nanomaterials stand out in various protein delivery systems due to various advantages, such as efficient intracellular delivery, long circulation time, and passive tumor targeting. Additionally, chemistry behind these nanomaterials provides readily engineered materials, enabling versatile designs of delivery agents. Intracellular delivery mediated by such nanocarriers achieved varying degrees of success. Different problems associated with these nanocarriers, however, still hamper their real-world applications. Developing new delivery methods or vectors remains essential but challenging. This review surveys the current developments in protein delivery based on synthetic nanocarriers, including liposomes, polymers and inorganic nanocarriers; Prospects for future development of protein delivery nanocarriers are also provided.

  10. A facile Friedel-Crafts acylation for the synthesis of polyethylenimine-grafted multi-walled carbon nanotubes as efficient gene delivery vectors.

    PubMed

    Nia, Azadeh Hashem; Amini, Abbas; Taghavi, Sahar; Eshghi, Hossein; Abnous, Khalil; Ramezani, Mohammad

    2016-04-11

    Low chemical reactivity of carbon nanotubes is one of the major obstacles in their functionalization via chemical reactions. As a non-destructive method, Friedel-Crafts acylation was suggested among the explored reactions for which only a few methods have been reported under harsh reaction conditions, e.g., high temperature all leading to low yields. In this study, we propose a novel method for the acylation of multi-walled carbon nanotubes (MWCNTs) at a low temperature (i.e., 42°C), using SiO2-Al2O3 as a catalyst and 6-bromohexanoic acid as the acylating agent to produce high yield functionalized MWCNTs. After acylation, MWCNTs are conjugated with polyethylenimines (PEIs) with three molecular weights (1.8, 10 and 25kDa). Three different MWCNT-PEI conjugates are synthesized and evaluated for their condensation ability, viability, size and zeta potential properties. The transfection efficiency of the functionalized MWCNTs is evaluated using luciferase assay and flow cytometry in a Neuroblastoma cell line. MWCNT-PEI (10 kDa) conjugate shows the highest transfection efficacy compared to others. For this carrier transfection efficacy exceeds the amount of PEI 25 kDa at similar carrier to plasmid weight ratio (C/P) and is around 3 times higher compared to PEI 25 kDa at C/P=0.8 as positive control regarding its high transfection efficiency and low cytotoxicity. PMID:26906459

  11. Carbon nanotubes: Fibrillar pharmacology

    NASA Astrophysics Data System (ADS)

    Kostarelos, Kostas

    2010-10-01

    The mechanisms by which chemically functionalized carbon nanotubes flow in blood and are excreted through the kidneys illustrate the unconventional behaviour of these fibrillar nanostructures, and the opportunities they offer as components for the design of advanced delivery vehicles.

  12. The Interaction of CORM-2 with Block Copolymers Containing Poly(4-vinylpyridine): Macromolecular Scaffolds for Carbon Monoxide Delivery in Biological Systems.

    PubMed

    Nguyen, Diep; Adnan, Nik Nik M; Oliver, Susan; Boyer, Cyrille

    2016-05-01

    CORM-2, tricarbonyldichlororuthenium(II) dimer (Ru2 Cl4 (CO)6 ), is a common carbon monoxide releasing molecule (CORM) studied both in vitro and in vivo, but this compound possesses poor water solubility and a short half-life, which hinders its clinical development. Herein, for the first time the conjugation of CORM-2 is reported with a copolymer containing poly(4-vinylpyridine) to yield water-soluble CO-releasing polymeric nanoparticles. CORM-2 is rapidly conjugated to copolymers through pyridine groups as confirmed by inductively coupled plasma-optical emission spectroscopy and infrared spectroscopy. In comparison with free CORM-2, the copolymers functionalized with CORM-2 display better water solubility and the CO release from the polymer-based CORM is slow and sustained. This study paves the way for the potential use of a copolymer encapsulating CORM-2 as a therapeutic agent. PMID:26945898

  13. Therapeutic gas delivery via microbubbles and liposomes.

    PubMed

    Fix, Samantha M; Borden, Mark A; Dayton, Paul A

    2015-07-10

    Gaseous molecules including nitric oxide, hydrogen sulfide, carbon monoxide and oxygen mediate numerous cell signaling pathways and have important physiological roles. Several noble gasses have been shown to elicit biological responses. These bioactive gasses hold great therapeutic potential, however, their controlled delivery remains a significant challenge. Recently, researchers have begun using microbubbles and liposomes to encapsulate such gasses for parenteral delivery. The resultant particles are acoustically active, and ultrasound can be used to stimulate and/or image gas release in a targeted region. This review provides a summary of recent advances in therapeutic gas delivery using microbubbles and liposomes.

  14. Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin.

    PubMed

    Iancu, Cornel; Mocan, Lucian; Bele, Constantin; Orza, Anamaria Ioana; Tabaran, Flaviu A; Catoi, Cornel; Stiufiuc, Rares; Stir, Ariana; Matea, Cristian; Iancu, Dana; Agoston-Coldea, Lucia; Zaharie, Florin; Mocan, Teodora

    2011-01-17

    The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

  15. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

  16. Mapping the intracellular distribution of carbon nanotubes after targeted delivery to carcinoma cells using confocal Raman imaging as a label-free technique

    NASA Astrophysics Data System (ADS)

    Lamprecht, C.; Gierlinger, N.; Heister, E.; Unterauer, B.; Plochberger, B.; Brameshuber, M.; Hinterdorfer, P.; Hild, S.; Ebner, A.

    2012-04-01

    The uptake of carbon nanotubes (CNTs) by mammalian cells and their distribution within cells is being widely studied in recent years due to their increasing use for biomedical purposes. The two main imaging techniques used are confocal fluorescence microscopy and transmission electron microscopy (TEM). The former, however, requires labeling of the CNTs with fluorescent dyes, while the latter is a work-intensive technique that is unsuitable for in situ bio-imaging. Raman spectroscopy, on the other hand, presents a direct, straightforward and label-free alternative. Confocal Raman microscopy can be used to image the CNTs inside cells, exploiting the strong Raman signal connected to different vibrational modes of the nanotubes. In addition, cellular components, such as the endoplasmic reticulum and the nucleus, can be mapped. We first validate our method by showing that only when using the CNTs’ G band for intracellular mapping accurate results can be obtained, as mapping of the radial breathing mode (RBM) only shows a small fraction of CNTs. We then take a closer look at the exact localization of the nanotubes inside cells after folate receptor-mediated endocytosis and show that, after 8-10 h incubation, the majority of CNTs are localized around the nucleus. In summary, Raman imaging has enormous potential for imaging CNTs inside cells, which is yet to be fully realized. The authors declare no conflict of interest.

  17. Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

    PubMed

    Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo

    2015-01-01

    The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-β-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-β-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-β-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (C max) and the area under the mean plasma concentration-time curve (AUC[0→48]) of IRB-loaded HP-β-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-β-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-β-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB. PMID:25995635

  18. Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs

    PubMed Central

    Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo

    2015-01-01

    The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-β-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-β-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-β-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (Cmax) and the area under the mean plasma concentration–time curve (AUC[0→48]) of IRB-loaded HP-β-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-β-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-β-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB. PMID:25995635

  19. Combined and sequential delivery of bioactive VEGF165 and HGF from poly(trimethylene carbonate) based photo-cross-linked elastomers.

    PubMed

    Chapanian, R; Amsden, B G

    2010-04-01

    The ability of trimethylene carbonate (TMC) based elastomers to release bioactive vascular endothelial growth factor (VEGF(165)) and hepatocyte growth factor (HGF) separately and in combined and sequential fashions using an osmotic release mechanism was investigated. A TMC-based elastomer was chosen since TMC degrades without producing potentially harmful acidic degradation products, and its mechanical properties can be tailored by copolymerizing with D,L-lactide (DLLA) and epsilon-caprolactone (epsilon-CL) and by controlling the cross-link density. The bioactivities of released VEGF(165) and HGF were assessed using the proliferation of human aortic endothelial (HAEC) and CCL 208 monkey lung epithelial cell lines. VEGF(165) and HGF were lyophilized separately or together with trehalose, rat serum albumin (RSA) and NaCl. No significant elastomer degradation occurred over the initial 8 weeks, during which the bulk of the embedded growth factors were released. The presence of a low concentration of NaCl in the release media did not affect the viability of HAEC and CCL 208 cells. The TMC-based elastomer was able to provide a sustained release of highly bioactive VEGF(165) and HGF for more than 10 days. When released in combination from the same device, VEGF(165) and HGF were released at similar rates. By preparing a dual-layered cylinder, in which VEGF(165) was in the outer layer and HGF in the inner layer, a constant release of VEGF alone was first obtained, followed by overlapping and constant release of the two growth factors after a period of 4days. This study demonstrates the potential of TMC-based elastomers combined with an osmotic mechanism to release acid-sensitive growth factors in bioactive form alone and in combination, in controlled rates and sequences. PMID:19961885

  20. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  1. Articulating feedstock delivery device

    DOEpatents

    Jordan, Kevin

    2013-11-05

    A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

  2. Immunosuppressive agent leflunomide: a SWNTs-immobilized dihydroortate dehydrogenase inhibitory effect and computational study of its adsorption properties on zigzag single walled (6,0) carbon and boron nitride nanotubes as controlled drug delivery devices.

    PubMed

    Raissi, Heidar; Mollania, Fariba

    2014-06-01

    Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4trifluoromethylphenyl)-4-isoxazole carboximide] is an immunosuppressive agent effective in the treatment of rheumatoid arthritis. Dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) immobilization on the nanotubes was carried out and biochemical characterization of free and immobilized enzyme was determined. In comparison with free enzyme, the immobilized DHODH showed improved stability and reusability for investigation of inhibition pattern of drugs such as leflunomide. The experimental data showed that, DHODH was inhibited by the active metabolite of leflunomide (RS-61980) with a Ki and KI of 0.82 and 0.06 mM, respectively. Results exhibited mixed-type inhibition kinetics towards dihydroorotate as a substrate in the free and immobilized enzyme. Furthermore, the behavior of anticancer drug leflunomide adsorbed on the external surface of zigzag single walled (6,0) carbon and boron nitride nanotubes (SWCNT and SWBNNT) was studied by means of DFT calculations at the B3LYP/6-31G(*) level of theory. The larger adsorption energies and charges transfer showed that the adsorption of leflunomide onto SWBNNT is more stable than that the adsorption of leflunomide onto SWCNT. Frontier molecular orbitals (HOMO and LUMO) suggest that adsorption of leflunomide onto SWBNNT behave as charge transfer compounds with leflunomide as an electron donor and SWBNNT as an electron acceptor. Thus, nanotubes (NTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic application. The AIM theory has been also applied to analyze the properties of the bond critical points: their electron densities and their laplacians. Also, the natural bond orbital (NBO) calculations were performed to derive natural atomic orbital occupancies, and partial charges of the interacting atoms in the equilibrium tube-molecule distance. PMID:24566615

  3. Immunosuppressive agent leflunomide: a SWNTs-immobilized dihydroortate dehydrogenase inhibitory effect and computational study of its adsorption properties on zigzag single walled (6,0) carbon and boron nitride nanotubes as controlled drug delivery devices.

    PubMed

    Raissi, Heidar; Mollania, Fariba

    2014-06-01

    Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4trifluoromethylphenyl)-4-isoxazole carboximide] is an immunosuppressive agent effective in the treatment of rheumatoid arthritis. Dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) immobilization on the nanotubes was carried out and biochemical characterization of free and immobilized enzyme was determined. In comparison with free enzyme, the immobilized DHODH showed improved stability and reusability for investigation of inhibition pattern of drugs such as leflunomide. The experimental data showed that, DHODH was inhibited by the active metabolite of leflunomide (RS-61980) with a Ki and KI of 0.82 and 0.06 mM, respectively. Results exhibited mixed-type inhibition kinetics towards dihydroorotate as a substrate in the free and immobilized enzyme. Furthermore, the behavior of anticancer drug leflunomide adsorbed on the external surface of zigzag single walled (6,0) carbon and boron nitride nanotubes (SWCNT and SWBNNT) was studied by means of DFT calculations at the B3LYP/6-31G(*) level of theory. The larger adsorption energies and charges transfer showed that the adsorption of leflunomide onto SWBNNT is more stable than that the adsorption of leflunomide onto SWCNT. Frontier molecular orbitals (HOMO and LUMO) suggest that adsorption of leflunomide onto SWBNNT behave as charge transfer compounds with leflunomide as an electron donor and SWBNNT as an electron acceptor. Thus, nanotubes (NTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic application. The AIM theory has been also applied to analyze the properties of the bond critical points: their electron densities and their laplacians. Also, the natural bond orbital (NBO) calculations were performed to derive natural atomic orbital occupancies, and partial charges of the interacting atoms in the equilibrium tube-molecule distance.

  4. Hydrogen storage and delivery system development

    SciTech Connect

    Handrock, J.L.; Wally, K.; Raber, T.N.

    1995-09-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. The purpose of this project is to develop a platform for the engineering evaluation of hydrogen storage and delivery systems with an added focus on lightweight hydride utilization. Hybrid vehicles represent the primary application area of interest, with secondary interests including such items as existing vehicles and stationary uses. The near term goal is the demonstration of an internal combustion engine/storage/delivery subsystem. The long term goal is optimization of storage technologies for both vehicular and industrial stationary uses. In this project an integrated approach is being used to couple system operating characteristics to hardware development. A model has been developed which integrates engine and storage material characteristics into the design of hydride storage and delivery systems. By specifying engine operating parameters, as well as a variety of storage/delivery design features, hydride bed sizing calculations are completed. The model allows engineering trade-off studies to be completed on various hydride material/delivery system configurations. A more generalized model is also being developed to allow the performance characteristics of various hydrogen storage and delivery systems to be compared (liquid, activated carbon, etc.). Many of the features of the hydride storage model are applicable to the development of this more generalized model.

  5. Microcapsule carbon nanotube devices for therapeutic applications

    NASA Astrophysics Data System (ADS)

    Kulamarva, Arun; Raja, Pavan M. V.; Bhathena, Jasmine; Chen, Hongmei; Talapatra, Saikat; Ajayan, Pulickel M.; Nalamasu, Omkaram; Prakash, Satya

    2009-01-01

    Carbon nanotubes are a new class of nanomaterials that have immense potential in the field of biomedicine. Their ability to carry large quantities of therapeutic molecules makes them prime candidates for providing targeted delivery of therapeutics for use in various diseases. However, their utility is limited due to the problems faced during their delivery to target sites. This article for the first time describes the design of a novel microcapsule carbon nanotube targeted delivery device. This device has potential in the targeted delivery of carbon nanotubes in suitable membranes along with their cargo, safely and effectively to the target loci.

  6. Transdermal delivery of contraceptives.

    PubMed

    Friend, D R

    1990-01-01

    Contraceptive agents are administered to the body through a variety of routes. Research has recently been directed at examining the transdermal route for systemic delivery of contraceptive agents, including estrogens and progestins. The transdermal route has several potential advantages over the other routes of administration: (1) improved compliance, (2) once-weekly administration, (3) delivery is easily terminated, and (4) some side effects can be alleviated based on more constant delivery rates. This article reviews the permeability of skin toward contraceptive steroids and how skin permeability is evaluated. The metabolism of contraceptive steroids is also considered. Transdermal delivery systems used to deliver contraceptives are presented, followed by a detailed discussion of several delivery systems for specific contraceptive agents such as levonorgestrel and estradiol. The potential problem of skin irritation is presented as it relates to transdermal contraceptive delivery systems, all of which will be worn chronically. PMID:2272099

  7. Activated carbon to the rescue

    SciTech Connect

    Sen, S.

    1996-03-01

    This article describes the response to pipeline spill of ethylene dichloride (EDC) on the property of an oil company. Activated carbon cleanup proceedure was used. During delivery, changeout, transport, storage, thermal reactivation, and return delivery to the site, the carbon never came into direct contact with operating personnel or the atmosphere. More than 10,000 tones of dredge soil and 50 million gallons of surface water were processed during the emergency response.

  8. [The moon and delivery].

    PubMed

    Romero Martínez, Jorge; Guerrero Guijo, Inmaculada; Artura Serrano, Antonio

    2004-11-01

    In different cultures and mythologies, the moon is related with fertility, pregnancy and delivery. Professional obstetricians also notice an increase in care demands on the days when the moon is full. Many studies have been made which try to correlate delivery processes to the phases of the moon with contradictory results. The authors plan to try to find any basis in fact which support these popular beliefs and to discover if lunar phases bear an influence on the distribution of deliveries. They carried out a descriptive transversal study on a total of 1715 unassisted deliveries over the course of ten complete lunar cycles. The authors have carried out a descriptive and inferential analysis, a one way ANOVA and a Kruskal Wallis test on their three data bases which are general, primipara and multipara in which they contemplated the total number of deliveries per phase, the mean of each phase, as well as the central day in each phase of the lunar cycle. The differences found in the distribution of deliveries over the four lunar phases, along with the comparison of the means and the comparison of the number of deliveries on the central day in each phase are not statistically significant. The different phases in the lunar cycle and especially the full moon do not appear to have any influence over the distribution of deliveries in this study.

  9. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  10. Document Delivery Update.

    ERIC Educational Resources Information Center

    Computers in Libraries, 1992

    1992-01-01

    Describes new products that relate to document delivery, including a wireless electronic mail connection; multivendor office integration software to exchange electronic mail; analog film recorders; an electronic messaging system for personal computer local area networks; software for transferring data files; voice message delivery systems; and…

  11. Staff Development Content Delivery.

    ERIC Educational Resources Information Center

    Dillon, Elizabeth A.

    1979-01-01

    Question clusters related to staff development content delivery are used to develop programs that will result in more productive professional development. The questions determine the focus of programs, analyze the target audience, discuss the selection of delivery modes, and identify future directions. (JMF)

  12. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

  13. Inorganic Nanomaterials as Carriers for Drug Delivery.

    PubMed

    Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

    2016-01-01

    For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study. PMID:27301169

  14. Elective Delivery Before 39 Weeks

    MedlinePlus

    ... Delivery, and Postpartum Care Elective Delivery Before 39 Weeks • What is a “medically indicated” delivery? • What is ... the baby grow and develop during the last weeks of pregnancy? • What are the risks for babies ...

  15. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  16. Nanomedicine-nanoscale drugs and delivery systems.

    PubMed

    Singh, Surya

    2010-12-01

    Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and release from the human body. The biocompatible nanomaterials have been used in biological markers, contrast agents for biological imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. Nanomedicines offer delivery of potential drugs to human organs which were previously beyond reach of microscale drugs due to specific biological barriers. The nanoscale systems work as nanocarriers for the delivery of drugs. The nanocarriers are made of biocompatible and biodegradable materials such as synthetic proteins, peptides, lipids, polysaccharides, biodegradable polymers and fibers. This review article reports the recent developments in the field of nanomedicine covering biodegradable polymers, nanoparticles, cyclodextrin, dendrimeres, liposomes and lipid-based nanocarriers, nanofibers, nanowires and carbon nanotubes and their chemical functionalization for distribution to different organs, their solubility, surface, chemical and biological properties, stability and release systems. The toxicity and safety of nanomaterials on human health is also briefly discussed.

  17. Project Delivery Methods.

    ERIC Educational Resources Information Center

    Dolan, Thomas G.

    2003-01-01

    Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)

  18. Assisted Vaginal Delivery

    MedlinePlus

    ... having a repeat assisted vaginal delivery in a future pregnancy? If you have had one assisted vaginal ... a vacuum device. Vacuum Device: A metal or plastic cup that is applied to the fetus’ head ...

  19. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  20. Microneedle-mediated transdermal bacteriophage delivery

    PubMed Central

    Ryan, Elizabeth; Garland, Martin J.; Singh, Thakur Raghu Raj; Bambury, Eoin; O’Dea, John; Migalska, Katarzyna; Gorman, Sean P.; McCarthy, Helen O.; Gilmore, Brendan F.; Donnelly, Ryan F.

    2012-01-01

    Interest in bacteriophages as therapeutic agents has recently been reawakened. Parenteral delivery is the most routinely-employed method of administration. However, injection of phages has numerous disadvantages, such as the requirement of a health professional for administration and the possibility of cross-contamination. Transdermal delivery offers one potential means of overcoming many of these problems. The present study utilized a novel poly (carbonate) (PC) hollow microneedle (MN) device for the transdermal delivery of Escherichia coli-specific T4 bacteriophages both in vitro and in vivo. MN successfully achieved bacteriophage delivery in vitro across dermatomed and full thickness skin. A concentration of 2.67 × 106 PFU/ml (plaque forming units per ml) was detected in the receiver compartment when delivered across dermatomed skin and 4.0 × 103 PFU/ml was detected in the receiver compartment when delivered across full thickness skin. An in vivo study resulted in 4.13 × 103 PFU/ml being detected in blood 30 min following initial MN-mediated phage administration. Clearance occurred rapidly, with phages being completely cleared from the systemic circulation within 24 h, which was expected in the absence of infection. We have shown here that MN-mediated delivery allows successful systemic phage absorption. Accordingly, bacteriophage-based therapeutics may now have an alternative route for systemic delivery. Once fully-investigated, this could lead to more widespread investigation of these interesting therapeutic viruses. PMID:22750416

  1. Nanomedicine in pulmonary delivery

    PubMed Central

    Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

    2009-01-01

    The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

  2. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  3. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  4. Polymers in Small-Interfering RNA Delivery

    PubMed Central

    Singha, Kaushik; Namgung, Ran

    2011-01-01

    This review will cover the current strategies that are being adopted to efficiently deliver small interfering RNA using nonviral vectors, including the use of polymers such as polyethylenimine, poly(lactic-co-glycolic acid), polypeptides, chitosan, cyclodextrin, dendrimers, and polymers-containing different nanoparticles. The article will provide a brief and concise account of underlying principle of these polymeric vectors and their structural and functional modifications which were intended to serve different purposes to affect efficient therapeutic outcome of small-interfering RNA delivery. The modifications of these polymeric vectors will be discussed with reference to stimuli-responsiveness, target specific delivery, and incorporation of nanoconstructs such as carbon nanotubes, gold nanoparticles, and silica nanoparticles. The emergence of small-interfering RNA as the potential therapeutic agent and its mode of action will also be mentioned in a nutshell. PMID:21749290

  5. Document Delivery Update.

    ERIC Educational Resources Information Center

    Nelson, Nancy Melin

    1992-01-01

    Presents highlights of research that used industrywide surveys, focus groups, personal interviews, and industry-published data to explore the future of electronic information delivery in libraries. Topics discussed include CD-ROMs; prices; full-text products; magnetic tape leasing; engineering and technical literature; connections between online…

  6. Fluid delivery control system

    DOEpatents

    Hoff, Brian D.; Johnson, Kris William; Algrain, Marcelo C.; Akasam, Sivaprasad

    2006-06-06

    A method of controlling the delivery of fluid to an engine includes receiving a fuel flow rate signal. An electric pump is arranged to deliver fluid to the engine. The speed of the electric pump is controlled based on the fuel flow rate signal.

  7. Vaccine delivery using nanoparticles

    PubMed Central

    Gregory, Anthony E.; Titball, Richard; Williamson, Diane

    2013-01-01

    Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens. PMID:23532930

  8. Caesarean delivery: conflicting interests.

    PubMed

    Osuna, Eduardo; Pérez Cárceles, Maria Dolores; Sánchez Ferrer, Maria Luisa; Machado, Francisco

    2015-12-01

    Within the maternal-fetal relationship, interests may sometimes diverge. In this paper, a pregnant woman's refusal to undergo a caesarean delivery, which was recommended both to save the life of the fetus and to minimize risks to her, is described. The legal aspects involved in the conflict between maternal autonomy and fetal well-being are analysed. The patient requested an abortion because of the poor condition of the fetus; however, according to Spanish legislation, the possibility of abortion was rejected as the pregnancy was in its 27th week. The woman still persisted in her refusal to accept a caesarian delivery. After the medical team sought guidance on the course to follow, the Duty Court authorized a caesarean delivery against the wishes of the patient. From a legal point of view, at stake were the freedom of the woman - expressed by the decision to reject a caesarean delivery - and the life of the unborn child. In clinical treatment, the interests of the fetus are generally aligned with those of the pregnant woman. When they are not, it is the pregnant woman's autonomy that should be respected, and coercion should form no part of treatment, contrary to the decision of this court.

  9. Educational Telecommunications Delivery Systems.

    ERIC Educational Resources Information Center

    Curtis, John A., Ed.; Biedenbach, Joseph M., Ed.

    This monograph is a single volume reference manual providing an overall review of the current status and likely near future application of six major educational telecommunications delivery technologies. The introduction provides an overview to the usage and potential for these systems in the context of the major educational issues involved. Each…

  10. Toxicity induced enhanced extracellular matrix production in osteoblastic cells cultured on single-walled carbon nanotube networks.

    PubMed

    Tutak, Wojtek; Park, Ki Ho; Vasilov, Anatoly; Starovoytov, Valentin; Fanchini, Giovanni; Cai, Shi-Qing; Partridge, Nicola C; Sesti, Federico; Chhowalla, Manish

    2009-06-24

    A central effort in biomedical research concerns the development of materials for sustaining and controlling cell growth. Carbon nanotube based substrates have been shown to support the growth of different kinds of cells (Hu et al 2004 Nano Lett. 4 507-11; Kalbacova et al 2006 Phys. Status Solidi b 13 243; Zanello et al 2006 Nano Lett. 6 562-7); however the underlying molecular mechanisms remain poorly defined. To address the fundamental question of mechanisms by which nanotubes promote bone mitosis and histogenesis, primary calvariae osteoblastic cells were grown on single-walled carbon nanotube thin film (SWNT) substrates. Using a combination of biochemical and optical techniques we demonstrate here that SWNT networks promote cell development through two distinct steps. Initially, SWNTs are absorbed in a process that resembles endocytosis, inducing acute toxicity. Nanotube-mediated cell destruction, however, induces a release of endogenous factors that act to boost the activity of the surviving cells by stimulating the synthesis of extracellular matrix.

  11. Microprocessor controlled transdermal drug delivery.

    PubMed

    Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

    2006-07-01

    Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

  12. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.

  13. Nanotube-assisted protein deactivation

    NASA Astrophysics Data System (ADS)

    Joshi, Amit; Punyani, Supriya; Bale, Shyam Sundhar; Yang, Hoichang; Borca-Tasciuc, Theodorian; Kane, Ravi S.

    2008-01-01

    Conjugating proteins onto carbon nanotubes has numerous applications in biosensing, imaging and cellular delivery. However, remotely controlling the activity of proteins in these conjugates has never been demonstrated. Here we show that upon near-infrared irradiation, carbon nanotubes mediate the selective deactivation of proteins in situ by photochemical effects. We designed nanotube-peptide conjugates to selectively destroy the anthrax toxin, and also optically transparent coatings that can self-clean following either visible or near-infrared irradiation. Nanotube-assisted protein deactivation may be broadly applicable to the selective destruction of pathogens and cells, and will have applications ranging from antifouling coatings to functional proteomics.

  14. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  15. Delivery of Chlamydia vaccines.

    PubMed

    Igietseme, Joseph; Eko, Francis; He, Qing; Bandea, Claudiu; Lubitz, Werner; Garcia-Sastre, Adolfo; Black, Carolyn

    2005-05-01

    The plethora of ocular, genital and respiratory diseases of Chlamydia, including nongonococcal urethritis, cervicitis pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, conjunctivitis, blinding trachoma and interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult onset asthma and Alzheimer's disease, still pose a considerable public health challenge to many nations. Although antibiotics are effective against Chlamydia when effectively diagnosed, asymptomatic infections are rampart, making clinical presentation of complications often the first evidence of an infection. Consequently, the current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections. Clinical and experimental studies have demonstration that Chlamydia immunity in animals and humans is mediated by T cells and a complementary antibody response, and the completion of the genome sequencing of several isolates of Chlamydia is broadening our knowledge of the immunogenic antigens with potential vaccine value. Thus, major advances have been made in defining the essential elements of a potentially effective subunit vaccine design and parameters for evaluation. However, the challenge to develop effective delivery systems and human compatible adjuvants that would boost the immune response to achieve long-lasting protective immunity remains an elusive objective in chlamydial vaccine research. In response to evolving molecular and cellular technologies and novel vaccinology approaches, considerable progress is being made in the construction of novel delivery systems, such as DNA and plasmid expression systems, viral vectors, living and nonliving bacterial delivery systems, the use of chemical adjuvants, lipoprotein constructs and the codelivery of vaccines and specific immuno-modulatory biological agonists targeting

  16. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

    This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

  17. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  18. Revolutionary Impact of Nanodrug Delivery on Neuroscience

    PubMed Central

    Khanbabaie, Reza; Jahanshahi, Mohsen

    2012-01-01

    Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders. PMID:23730260

  19. Interactions between Carbon Nanomaterials and Biomolecules.

    PubMed

    Han, Xu; Li, Shanghao; Peng, Zhili; Al-Yuobi, Abdulrahman Obaid; Omar Bashammakh, Abdulaziz Saleh; El-Shahawi, M S; Leblanc, Roger M

    2016-01-01

    Interactions between carbon nanomaterials, including carbon dots, fullerene, carbon nanotube, graphene, and graphene oxide, and biomolecules play an important role in the field of nanobiotechnology. Due to the unique properties of carbon nanomaterials and the magnificent features of their colloids, it shows high potential in fibrillation inhibition, high sensitivity sensor fabrication, bioimaging, drug delivery, and other areas. Hereby, we will go over different families of carbon nanomaterials regarding to the interaction between carbon nanomaterials and biomolecules at the interface, and their applications will be reviewed as well.

  20. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  1. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  2. Studying Different Binding and Intracellular Delivery Efficiency of ssDNA Single-Walled Carbon Nanotubes and Their Effects on LC3-Related Autophagy in Renal Mesangial Cells via miRNA-382.

    PubMed

    Wang, Guobao; Zhao, Tingting; Wang, Leyu; Hu, Bianxiang; Darabi, Ali; Lin, Jiansheng; Xing, Malcolm M Q; Qiu, Xiaozhong

    2015-11-25

    Single-walled carbon nanotubes (SWCNTs) have been used to deliver single-stranded (ssDNA). ssDNA in oligonucleotide can act as an inhibitor of microRNA to regulate cellular functions. However, these ssDNA are difficult to bind carbon nanotubes with low transferring efficiency to cells. To this end, we designed ssDNA with regulatory and functional units to form ssDNA-SWCNT hybrids to study their binding effects and transferring efficiency. The functional unit on ssDNA mimics the inhibitor (MI) of miRNA-382, which plays a crucial role in the progress of many diseases such as renal interstitial fibrosis. After verification of overexpression of miRNA-382 in a coculture system, we designed oligonucleotide sequences (GCG)5-MI, (TAT)5-MI, and N23-MI as regulatory units added to the 5'-terminal end of the functional DNA fragment, respectively. These regulatory units lead to different secondary structures and thus exhibit different affinity ability to SWCNTs, and finally decide their deliver efficacy to cells. Autophagy, apoptosis and necrosis were observed in renal mesangial cells.

  3. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  4. Recent developments in protein and peptide parenteral delivery approaches

    PubMed Central

    Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K

    2014-01-01

    Discovery of insulin in the early 1900s initiated the research and development to improve the means of therapeutic protein delivery in patients. In the past decade, great emphasis has been placed on bringing protein and peptide therapeutics to market. Despite tremendous efforts, parenteral delivery still remains the major mode of administration for protein and peptide therapeutics. Other routes such as oral, nasal, pulmonary and buccal are considered more opportunistic rather than routine application. Improving biological half-life, stability and therapeutic efficacy is central to protein and peptide delivery. Several approaches have been tried in the past to improve protein and peptide in vitro/in vivo stability and performance. Approaches may be broadly categorized as chemical modification and colloidal delivery systems. In this review we have discussed various chemical approaches such as PEGylation, hyperglycosylation, mannosylation, and colloidal carriers including microparticles, nanoparticles, liposomes, carbon nanotubes and micelles for improving protein and peptide delivery. Recent developments on in situ thermosensitive gel-based protein and peptide delivery have also been described. This review summarizes recent developments on some currently existing approaches to improve stability, bioavailability and bioactivity of peptide and protein therapeutics following parenteral administration. PMID:24592957

  5. Photomechanical drug delivery

    NASA Astrophysics Data System (ADS)

    Doukas, Apostolos G.; Lee, Shun

    2000-05-01

    Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

  6. Delivery methods for LVSD systems

    NASA Astrophysics Data System (ADS)

    Kasner, James H.; Brower, Bernard V.

    2011-06-01

    In this paper we present formats and delivery methods of Large Volume Streaming Data (LVSD) systems. LVSD systems collect TBs of data per mission with aggregate camera sizes in the 100 Mpixel to several Gpixel range at temporal rates of 2 - 60 Hz. We present options and recommendations for the different stages of LVSD data collection and delivery, to include the raw (multi-camera) data, delivery of processed (stabilized mosaic) data, and delivery of user-defined region of interest windows. Many LVSD systems use JPEG 2000 for the compression of raw and processed data. We explore the use of the JPEG 2000 Interactive Protocol (JPIP) for interactive client/server delivery to thick-clients (desktops and laptops) and MPEG-2 and H.264 to handheld thin-clients (tablets, cell phones). We also explore the use of 3D JPEG 2000 compression, defined in ISO 15444-2, for storage and delivery as well. The delivery of raw, processed, and region of interest data requires different metadata delivery techniques and metadata content. Beyond the format and delivery of data and metadata we discuss the requirements for a client/server protocol that provides data discovery and retrieval. Finally, we look into the future as LVSD systems perform automated processing to produce "information" from the original data. This information may include tracks of moving targets, changes of the background, snap shots of targets, fusion of multiple sensors, and information about "events" that have happened.

  7. Photosensitized Singlet Oxygen Production upon Two-Photon Excitation of Single-Walled Carbon Nanotubes and Their Functionalized Analogs

    PubMed Central

    Gandra, Naveen; Chiu, Pui Lam; Li, Wenbing; Anderson, Yolanda R.; Mitra, Somenath; He, Huixin; Gao, Ruomei

    2009-01-01

    Single-walled carbon nanotubes (SWNTs) functionalized with -COOH (along with some sulphonation and nitration), and/or modified with chitosan were prepared and tested for their singlet oxygen (1O2) production. The emission from 1O2 observed upon SWNT irradiation at 532 nm was due to a two-photon process, while 1O2 production via excitation at 355 nm occurred through a conventional one-photon pathway. The relative quantum yield of 1O2 production at excitation wavelength of 532 nm was found to be 0.00, 0.07-0.13 and 0.24-0.54 for highly-functionalized, partially-functionalized and non-functionalized SWNT samples respectively. The nanotube-mediated generation of 1O2 may find applications in both targeted destruction of tumor cells and selective degradation of drug molecules. Our research provides a practical approach to modulate the production of reactive oxygen species from SWNTs via surface functionalization/modification. PMID:20046942

  8. Economical ground data delivery

    NASA Technical Reports Server (NTRS)

    Markley, Richard W.; Byrne, Russell H.; Bromberg, Daniel E.

    1994-01-01

    Data delivery in the Deep Space Network (DSN) involves transmission of a small amount of constant, high-priority traffic and a large amount of bursty, low priority data. The bursty traffic may be initially buffered and then metered back slowly as bandwidth becomes available. Today both types of data are transmitted over dedicated leased circuits. The authors investigated the potential of saving money by designing a hybrid communications architecture that uses leased circuits for high-priority network communications and dial-up circuits for low-priority traffic. Such an architecture may significantly reduce costs and provide an emergency backup. The architecture presented here may also be applied to any ground station-to-customer network within the range of a common carrier. The authors compare estimated costs for various scenarios and suggest security safeguards that should be considered.

  9. Secondary fuel delivery system

    DOEpatents

    Parker, David M.; Cai, Weidong; Garan, Daniel W.; Harris, Arthur J.

    2010-02-23

    A secondary fuel delivery system for delivering a secondary stream of fuel and/or diluent to a secondary combustion zone located in the transition piece of a combustion engine, downstream of the engine primary combustion region is disclosed. The system includes a manifold formed integral to, and surrounding a portion of, the transition piece, a manifold inlet port, and a collection of injection nozzles. A flowsleeve augments fuel/diluent flow velocity and improves the system cooling effectiveness. Passive cooling elements, including effusion cooling holes located within the transition boundary and thermal-stress-dissipating gaps that resist thermal stress accumulation, provide supplemental heat dissipation in key areas. The system delivers a secondary fuel/diluent mixture to a secondary combustion zone located along the length of the transition piece, while reducing the impact of elevated vibration levels found within the transition piece and avoiding the heat dissipation difficulties often associated with traditional vibration reduction methods.

  10. Hydrogen Delivery Technical Team Roadmap

    SciTech Connect

    2013-06-01

    The mission of the Hydrogen Delivery Technical Team (HDTT) is to enable the development of hydrogen delivery technologies, which will allow for fuel cell competitiveness with gasoline and hybrid technologies by achieving an as-produced, delivered, and dispensed hydrogen cost of $2-$4 per gallon of gasoline equivalent of hydrogen.

  11. Emerging Frontiers in Drug Delivery.

    PubMed

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  12. Hydrogen Distribution and Delivery Infrastructure

    SciTech Connect

    2008-11-01

    This 2-page fact sheet provides a brief introduction to hydrogen delivery technologies. Intended for a non-technical audience, it explains how hydrogen is transported and delivered today, the challenges to delivering hydrogen for use as a widespread energy carrier, and the research goals for hydrogen delivery.

  13. Computer Assisted Rehabilitation Service Delivery.

    ERIC Educational Resources Information Center

    West Virginia Rehabilitation Research and Training Center, Dunbar.

    This volume consisting of state of the art reviews, suggestions and guidelines for practitioners, and program descriptions deals with the current and potential applications of computers in the delivery of services for vocational rehabilitation (VR). Discussed first are current applications of computer technology in rehabilitative service delivery.…

  14. Birth delivery trauma and malocclusion.

    PubMed

    Cattaneo, Ruggero; Monaco, Annalisa; Streni, Oriana; Serafino, Vittorio; Giannoni, Mario

    2005-01-01

    The aim of the investigation was to determine the dynamic of birth delivery and relate to dental occlusion among a group of adult subjects. The group studied was made up of 106 subjects (57 females and 49 males) referred for dental diagnosis and treatment. The average age was 26 with a range 22 to 30 years. In data collection and analysis the following were used as measures: dental occlusion (Angle Class I, II div 1, II div 2 and III) and type of delivery (normal, short, long, caesarean and other). Results showed that among 106 subjects 72 (68%) had malocclusion versus 34 (32%) with normal occlusion; 24 subjects (22.6%) have been normal delivery versus 82 (77.4%) with non-normal delivery. Class I is present in 34 subjects (32%), class II division 1 in 26 (24%), class II division 2 in 22. (20%), class III in 16 (14%), and 8 subjects (6%) fall in the section "other". Among 24 subjects with normal delivery 100% presented class I occlusion. However, among 82 subjects with non-normal delivery 10 subjects had a class I (12.2%) and the 72 (87.8%) had in the other classes, are distributed in the various subgroups of non-normal labor/delivery. None of the subjects with a malocclusion have a normal labor/delivery. Better understanding of the connections among osteopathic theory, craniosacral treatment and the outcomes upon dental occlusion, more rigorous evaluations are warranted.

  15. Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment

    PubMed Central

    Spencer, David S.; Puranik, Amey S.; Peppas, Nicholas A.

    2015-01-01

    Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes. PMID:25621200

  16. Transmucosal macromolecular drug delivery.

    PubMed

    Prego, C; García, M; Torres, D; Alonso, M J

    2005-01-01

    Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the

  17. Cell-Mediated Drugs Delivery

    PubMed Central

    Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

    2011-01-01

    INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

  18. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  19. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

  20. Drug delivery systems, CNS protection, and the blood brain barrier.

    PubMed

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  1. Why new delivery systems?

    PubMed

    Calkins, J M

    1984-01-01

    Although anesthetists have accomplished a remarkable safety record with commercially available anesthetic machines, these results have been obtained in spite of machine design, which could best be described as a nonsystem. In cases involving severely compromised patients, surgical procedures that severely alter patient physiology, and untoward events during "routine" anesthesia, it is a tribute to the flexibility and resourcefulness of anesthetists that more incidents do not occur. Industry has long sought precision, reliability, automatic control, and human-factors engineering in nonmedical applications, such as aircraft cockpit design, word-processing stations, and manufacturing processes. The relentless accretion of more and more nonintegrated gadgets onto an antiquated technology has exceeded the boundaries of proper function. Neither the patient nor the anesthetist is being served well by failure to implement state-of-the-art technology in anesthesic delivery systems. Anesthesiologists and others who are vitally interested in the welfare of their patients must insist that development of radically new integrated modular systems proceed at full speed. Their checkbooks can speak as loudly as the facts; it is time the manufacturers are aware that deep concern will be translated into purchasing decisions.

  2. Space age health care delivery

    NASA Technical Reports Server (NTRS)

    Jones, W. L.

    1977-01-01

    Space age health care delivery is being delivered to both NASA astronauts and employees with primary emphasis on preventive medicine. The program relies heavily on comprehensive health physical exams, health education, screening programs and physical fitness programs. Medical data from the program is stored in a computer bank so epidemiological significance can be established and better procedures can be obtained. Besides health care delivery to the NASA population, NASA is working with HEW on a telemedicine project STARPAHC, applying space technology to provide health care delivery to remotely located populations.

  3. Click chemistry for drug delivery nanosystems.

    PubMed

    Lallana, Enrique; Sousa-Herves, Ana; Fernandez-Trillo, Francisco; Riguera, Ricardo; Fernandez-Megia, Eduardo

    2012-01-01

    The purpose of this Expert Review is to discuss the impact of click chemistry in nanosized drug delivery systems. Since the introduction of the click concept by Sharpless and coworkers in 2001, numerous examples of click reactions have been reported for the preparation and functionalization of polymeric micelles and nanoparticles, liposomes and polymersomes, capsules, microspheres, metal and silica nanoparticles, carbon nanotubes and fullerenes, or bionanoparticles. Among these click processes, Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has attracted most attention based on its high orthogonality, reliability, and experimental simplicity for non-specialists. A renewed interest in the use of efficient classical transformations has been also observed (e.g., thiol-ene coupling, Michael addition, Diels-Alder). Special emphasis is also devoted to critically discuss the click concept, as well as practical aspects of application of CuAAC to ensure efficient and harmless bioconjugation.

  4. Photocrosslinked poly(ester anhydride)s for peptide delivery: Effect of oligomer hydrophobicity on PYY3-36 delivery.

    PubMed

    Mönkäre, Juha; Hakala, Risto A; Kovalainen, Miia; Korhonen, Harri; Herzig, Karl-Heinz; Seppälä, Jukka V; Järvinen, Kristiina

    2012-01-01

    The treatment for many diseases can be improved by developing more efficient peptide delivery technologies, for example, biodegradable polymers. In this work, photocrosslinked poly(ester anhydride)s based on functionalized poly(ε-caprolactone) oligomers were investigated for their abilities to achieve controlled peptide delivery. The effect of oligomer hydrophobicity on erosion and peptide release from poly(ester anhydride)s was evaluated by developing a sustained subcutaneous delivery system for an antiobesity drug candidate, peptide YY3-36 (PYY3-36). Oligomer hydrophobicity was modified with alkenylsuccinic anhydrides containing a 12-carbon alkenyl chain. PYY3-36 was mixed as a solid powder with methacrylated poly(ester anhydride) precursors, and this mixture was photocrosslinked at room temperature to form an implant for subcutaneous administration in rats. The oligomer hydrophobicity controlled the polymer erosion and PYY3-36 release as the increased hydrophobicity via the alkenyl chain prolonged polymer erosion in vitro and sustained in vivo release of PYY3-36. In addition, photocrosslinked poly(ester anhydride)s increased the bioavailability of PYY3-36 by up to 20-fold in comparison with subcutaneous administration of solution, evidence of remarkably improved delivery. In conclusion, this work demonstrates the suitability of photocrosslinked poly(ester anhydride)s for use in peptide delivery.

  5. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

    For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

  6. Drug delivery to the ear.

    PubMed

    Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

    2013-01-01

    Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions.

  7. Variable delivery, fixed displacement pump

    DOEpatents

    Sommars, Mark F.

    2001-01-01

    A variable delivery, fixed displacement pump comprises a plurality of pistons reciprocated within corresponding cylinders in a cylinder block. The pistons are reciprocated by rotation of a fixed angle swash plate connected to the pistons. The pistons and cylinders cooperate to define a plurality of fluid compression chambers each have a delivery outlet. A vent port is provided from each fluid compression chamber to vent fluid therefrom during at least a portion of the reciprocal stroke of the piston. Each piston and cylinder combination cooperates to close the associated vent port during another portion of the reciprocal stroke so that fluid is then pumped through the associated delivery outlet. The delivery rate of the pump is varied by adjusting the axial position of the swash plate relative to the cylinder block, which varies the duration of the piston stroke during which the vent port is closed.

  8. Adenosine-Associated Delivery Systems

    PubMed Central

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  9. Electroporation-mediated gene delivery.

    PubMed

    Young, Jennifer L; Dean, David A

    2015-01-01

    Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models. PMID:25620008

  10. Photoresponsive nanoparticles for drug delivery

    PubMed Central

    Rwei, Alina Y.; Wang, Weiping; Kohane, Daniel S.

    2015-01-01

    Summary Externally triggerable drug delivery systems provide a strategy for the delivery of therapeutic agents preferentially to a target site, presenting the ability to enhance therapeutic efficacy while reducing side effects. Light is a versatile and easily tuned external stimulus that can provide spatiotemporal control. Here we will review the use of nanoparticles in which light triggers drug release or induces particle binding to tissues (phototargeting). PMID:26644797

  11. Radiation delivery system and method

    DOEpatents

    Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

    2002-01-01

    A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

  12. Electroporation-mediated gene delivery.

    PubMed

    Young, Jennifer L; Dean, David A

    2015-01-01

    Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models.

  13. Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases.

    PubMed

    Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

    2014-01-01

    Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.

  14. Gold nanoparticles for nucleic acid delivery.

    PubMed

    Ding, Ya; Jiang, Ziwen; Saha, Krishnendu; Kim, Chang Soo; Kim, Sung Tae; Landis, Ryan F; Rotello, Vincent M

    2014-06-01

    Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell. PMID:24599278

  15. Carbon-carbon cylinder block

    NASA Technical Reports Server (NTRS)

    Ransone, Philip O. (Inventor)

    1998-01-01

    A lightweight cylinder block composed of carbon-carbon is disclosed. The use of carbon-carbon over conventional materials, such as cast iron or aluminum, reduces the weight of the cylinder block and improves thermal efficiency of the internal combustion reciprocating engine. Due to the negligible coefficient of thermal expansion and unique strength at elevated temperatures of carbon-carbon, the piston-to-cylinder wall clearance can be small, especially when the carbon-carbon cylinder block is used in conjunction with a carbon-carbon piston. Use of the carbon-carbon cylinder block has the effect of reducing the weight of other reciprocating engine components allowing the piston to run at higher speeds and improving specific engine performance.

  16. Delivery systems for intradermal vaccination.

    PubMed

    Kim, Y C; Jarrahian, C; Zehrung, D; Mitragotri, S; Prausnitz, M R

    2012-01-01

    Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development.

  17. Bladder Injury During Cesarean Delivery

    PubMed Central

    Tarney, Christopher M.

    2013-01-01

    Cesarean section is the most common surgery performed in the United States with over 30% of deliveries occurring via this route. This number is likely to increase given decreasing rates of vaginal birth after cesarean section (VBAC) and primary cesarean delivery on maternal request, which carries the inherent risk for intraoperative complications. Urologic injury is the most common injury at the time of either obstetric or gynecologic surgery, with the bladder being the most frequent organ damaged. Risk factors for bladder injury during cesarean section include previous cesarean delivery, adhesions, emergent cesarean delivery, and cesarean section performed at the time of the second stage of labor. Fortunately, most bladder injuries are recognized at the time of surgery, which is important, as quick recognition and repair are associated with a significant reduction in patient mortality. Although cesarean delivery is a cornerstone of obstetrics, there is a paucity of data in the literature either supporting or refuting specific techniques that are performed today. There is evidence to support double-layer closure of the hysterotomy, the routine use of adhesive barriers, and performing a Pfannenstiel skin incision versus a vertical midline subumbilical incision to decrease the risk for bladder injury during cesarean section. There is also no evidence that supports the creation of a bladder flap, although routinely performed during cesarean section, as a method to reduce the risk of bladder injury. Finally, more research is needed to determine if indwelling catheterization, exteriorization of the uterus, and methods to extend hysterotomy incision lead to bladder injury. PMID:24876830

  18. Optimised transdermal delivery of pravastatin.

    PubMed

    Burger, Cornel; Gerber, Minja; du Preez, Jan L; du Plessis, Jeanetta

    2015-12-30

    Wiechers' programme "Formulating for Efficacy" initiated a new strategy to optimise the oil phase of topical formulations in order to achieve optimal transdermal drug delivery. This new approach uses the "Delivery Gap Theory" on any active pharmaceutical ingredients (APIs) to test if it could enhance transdermal drug delivery. The aim of the study was to formulate six different semi-solid formulations (three creams and three emulgels) with 2% pravastatin as the API in order to investigate the "Delivery Gap Principle", by determining which formulation would deliver pravastatin best to the target-site (system circulation). The three cream- and three emulgel formulations had different polarities, i.e. a formulation with polarity equal to that of the stratum corneum (optimised), a non-polar (lipophilic)- and a polar (hydrophilic)-formulation. Franz cell diffusion studies were executed over 12h and the optimised emulgel (2.578μg/cm(2)) had the highest median amount per area obtained. Tape stripping followed the diffusion studies and in the stratum corneum-epidermis, the hydrophilic emulgel (1.448μg/ml) contained the highest median pravastatin concentration and the epidermis-dermis the optimised emulgel (0.849μg/ml) depicted the highest pravastatin concentration. During this study, it was observed that when both emulgel and cream formulations were compared; the emulgels enhanced the delivery of pravastatin more than the creams. PMID:26505148

  19. Responsive foams for nanoparticle delivery.

    PubMed

    Tang, Christina; Xiao, Edward; Sinko, Patrick J; Szekely, Zoltan; Prud'homme, Robert K

    2015-09-01

    We have developed responsive foam systems for nanoparticle delivery. The foams are easy to make, stable at room temperature, and can be engineered to break in response to temperature or moisture. Temperature-responsive foams are based on the phase transition of long chain alcohols and could be produced using medical grade nitrous oxide as a propellant. These temperature-sensitive foams could be used for polyacrylic acid (PAA)-based nanoparticle delivery. We also discuss moisture-responsive foams made with soap pump dispensers. Polyethylene glycol (PEG)-based nanoparticles or PMMA latex nanoparticles were loaded into Tween 20 foams and the particle size was not affected by the foam formulation or foam break. Using biocompatible detergents, we anticipate this will be a versatile and simple approach to producing foams for nanoparticle delivery with many potential pharmaceutical and personal care applications. PMID:26091943

  20. Composite Nanoparticles for Gene Delivery

    PubMed Central

    Wang, Yuhua; Huang, Leaf

    2016-01-01

    Nanoparticle-mediated gene and siRNA delivery has been an appealing area to gene therapists when they attempt to treat the diseases by manipulating the genetic information in the target cells. However, the advances in materials science could not keep up with the demand for multifunctional nanomaterials to achieve desired delivery efficiency. Researchers have thus taken an alternative approach to incorporate various materials into single composite nanoparticle using different fabrication methods. This approach allows nanoparticles to possess defined nanostructures as well as multiple functionalities to overcome the critical extracellular and intracellular barriers to successful gene delivery. This chapter will highlight the advances of fabrication methods that have the most potential to translate nanoparticles from bench to bedside. Furthermore, a major class of composite nanoparticle–lipid-based composite nanoparticles will be classified based on the components and reviewed in details. PMID:25409605

  1. Nanoparticulate systems for polynucleotide delivery

    PubMed Central

    Basarkar, Ashwin; Singh, Jagdish

    2007-01-01

    Nanotechnology has tremendously influenced gene therapy research in recent years. Nanometer-size systems have been extensively investigated for delivering genes at both local and systemic levels. These systems offer several advantages in terms of tissue penetrability, cellular uptake, systemic circulation, and cell targeting as compared to larger systems. They can protect the polynucleotide from a variety of degradative and destabilizing factors and enhance delivery efficiency to the cells. A variety of polymeric and non-polymeric nanoparticles have been investigated in an effort to maximize the delivery efficiency while minimizing the toxic effects. This article provides a review on the most commonly used nanoparticulate systems for gene delivery. We have discussed frequently used polymers, such as, polyethyleneimine, poly (lactide-co-glycolide), chitosan, as well as non-polymeric materials such as cationic lipids and metallic nanoparticles. The advantages and limitations of each system have been elaborated. PMID:18019834

  2. Microchip technology in drug delivery.

    PubMed

    Santini, J T; Richards, A C; Scheidt, R A; Cima, M J; Langer, R S

    2000-09-01

    The realization that the therapeutic efficacy of certain drugs can be affected dramatically by the way in which they are delivered has created immense interest in controlled drug delivery systems. Much previous work in drug delivery focused on achieving sustained drug release rates over time, while a more recent trend is to make devices that allow the release rate to be varied over time. Advances in microfabrication technology have made an entirely new type of drug delivery device possible. Proof-of-principle experiments have shown that silicon microchips have the ability to store and release multiple chemicals on demand. Future integration of active control electronics, such as microprocessors, remote control units, or biosensors, could lead to the development of a 'pharmacy on a chip,' ie 'smart' microchip implants or tablets that release drugs into the body automatically when needed.

  3. Advances in ophthalmic drug delivery.

    PubMed

    Morrison, Peter W J; Khutoryanskiy, Vitaliy V

    2014-12-01

    Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long-term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient's lifetime.

  4. Carbon Smackdown: Carbon Capture

    ScienceCinema

    Jeffrey Long

    2016-07-12

    In this July 9, 2010 Berkeley Lab summer lecture, Lab scientists Jeff Long of the Materials Sciences and Nancy Brown of the Environmental Energy Technologies Division discuss their efforts to fight climate change by capturing carbon from the flue gas of power plants, as well as directly from the air

  5. Carbon Smackdown: Carbon Capture

    SciTech Connect

    Jeffrey Long

    2010-07-12

    In this July 9, 2010 Berkeley Lab summer lecture, Lab scientists Jeff Long of the Materials Sciences and Nancy Brown of the Environmental Energy Technologies Division discuss their efforts to fight climate change by capturing carbon from the flue gas of power plants, as well as directly from the air

  6. Multi-protein delivery by nanodiamonds promotes bone formation.

    PubMed

    Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

    2013-11-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

  7. Multi-protein Delivery by Nanodiamonds Promotes Bone Formation

    PubMed Central

    Moore, L.; Gatica, M.; Kim, H.; Osawa, E.; Ho, D.

    2013-01-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE® for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

  8. Effect of Carbon Nanotubes on Mammalian Cells

    NASA Astrophysics Data System (ADS)

    Chen, Michelle; Ahmed, Asma; Black, Melanie; Kawamoto, Nicole; Lucas, Jessica; Pagala, Armie; Pham, Tram; Stankiewicz, Sara; Chen, Howard

    2010-03-01

    Carbon Nanotubes possess extraordinary electrical, mechanical, and thermal properties. Research on applying the carbon nanotubes for ultrasensitive detection, disease diagnosis, and drug delivery is rapidly developing. While the fundamental and technological findings on carbon nanotubes show great promise, it is extremely important to investigate the effect of the carbon nanotubes on human health. In our experiments, we introduce purified carbon nanotubes in suspension to ovary cells cultured from Hamsters. These cells are chosen since they show robust morphological changes associated with cytotoxicity that can easily be observed under a light microscope. We will discuss the toxicity of carbon nanotubes by characterizing the cell morphology and viability as a function of time and the concentration of carbon nanotube suspension.

  9. Histologic chorioamnionitis and preterm delivery.

    PubMed

    Holzman, Claudia; Lin, Ximin; Senagore, Patricia; Chung, Hwan

    2007-10-01

    Inconsistent findings linking placental histologic chorioamnionitis (HCA) and preterm delivery may result from variations in HCA definition, population studied, and exclusion criteria. This analysis from the 1998-2004 Pregnancy Outcomes and Community Health Study (five Michigan communities) includes the first 1,053 subcohort women (239 preterm, 814 term) with completed placental assessments. Multiple HCA definitions were constructed by 1) varying polymorphonuclear leukocytes/high-powered field thresholds and placenta components included and 2) using polymorphonuclear leukocyte characteristics to assign low/high maternal, fetal inflammation stage and grade. In African Americans, HCA was associated with preterm delivery before 35 weeks. The effect size was modest for polymorphonuclear leukocytes/high-powered field thresholds of greater than 10 and greater than 30 (odds ratios (ORs) = 0.8 and 2.0); larger for greater than 100 (OR = 3.2, 95% confidence interval (CI): 1.4, 7.1); strengthened after excluding medically indicated preterm deliveries (OR = 4.9, 95% CI: 2.0, 11.8); and strongest for high maternal/high fetal HCA (OR = 5.6, 95% CI: 1.4, 22.1). These latter HCA criteria also produced the largest effect size in Whites/others (OR = 2.7, 95% CI: 0.3, 26.9). Among preterm deliveries before 35 weeks excluding those medically indicated, 12% of Whites/others and 55% of African Americans had high maternal HCA. The authors conclude that HCA definition, exclusion criteria, and race/ethnicity influence the HCA-preterm delivery association and that HCA contributes to preterm delivery-related ethnic disparity. PMID:17625222

  10. Active Targeted Drug Delivery for Microbes Using Nano-Carriers

    PubMed Central

    Lin, Yung-Sheng; Lee, Ming-Yuan; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced. PMID:25877093

  11. Trojan-horse nanotube on-command intracellular drug delivery.

    PubMed

    Wu, Chia-Hsuan; Cao, Cong; Kim, Jin Ho; Hsu, Chih-Hsun; Wanebo, Harold J; Bowen, Wayne D; Xu, Jimmy; Marshall, John

    2012-11-14

    A major challenge to nanomaterial-based medicine is the ability to release drugs on-command. Here, we describe an innovative drug delivery system based on carbon nanotubes (CNTs), in which compounds can be released inside cells from within the nanotube "on-command" by inductive heating with an external alternating current or pulsed magnetic field. Without inductive heating the drug remains safely inside the CNTs, showing no toxicity in cell viability tests. Similar to the "Trojan-Horse" in function, we demonstrate the delivery of a combination of chemotherapeutic agents with low aqueous solubility, paclitaxel (Taxol), and C6-ceramide, to multidrug resistant pancreatic cancer cells. Nanotube encapsulation permitted the drugs to be used at a 100-fold lower concentration compared to exogenous treatment yet achieve a comparable ~70% cancer kill rate.

  12. Carbon-carbon piston development

    NASA Technical Reports Server (NTRS)

    Gorton, Mark P.

    1994-01-01

    A new piston concept, made of carbon-carbon refractory-composite material, has been developed that overcomes a number of the shortcomings of aluminum pistons. Carbon-carbon material, developed in the early 1960's, is lighter in weight than aluminum, has higher strength and stiffness than aluminum and maintains these properties at temperatures over 2500 F. In addition, carbon-carbon material has a low coefficient of thermal expansion and excellent resistance to thermal shock. An effort, called the Advanced Carbon-Carbon Piston Program was started in 1986 to develop and test carbon-carbon pistons for use in spark ignition engines. The carbon-carbon pistons were designed to be replacements for existing aluminum pistons, using standard piston pin assemblies and using standard rings. Carbon-carbon pistons can potentially enable engines to be more reliable, more efficient and have greater power output. By utilizing the unique characteristics of carbon-carbon material a piston can: (1) have greater resistance to structural damage caused by overheating, lean air-fuel mixture conditions and detonation; (2) be designed to be lighter than an aluminum piston thus, reducing the reciprocating mass of an engine, and (3) be operated in a higher combustion temperature environment without failure.

  13. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  14. Document Delivery over the Internet.

    ERIC Educational Resources Information Center

    Jackson, Mary E.

    1993-01-01

    Discusses three innovative Internet-based electronic document delivery systems: Ariel, developed by the Research Libraries Group; Digitized Document Transmission Project, developed by North Carolina State University; and Network Fax Project, developed by Ohio State University. System are compared in terms of equipment, operation, advantages and…

  15. Nanoparticles for Brain Drug Delivery

    PubMed Central

    Masserini, Massimo

    2013-01-01

    The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments. PMID:25937958

  16. Delivery System, 2003-2004.

    ERIC Educational Resources Information Center

    Office of Federal Student Aid (ED), Washington, DC.

    This workshop guide for financial aid administrators provides training in the federal student financial aid delivery system. An introduction enables the participant to share some information about his or her responsibilities and to reflect on the relevance of the training to the job. Session 1, "Application Systems," identifies methods of applying…

  17. Teleteach Expanded Delivery System: Evaluation.

    ERIC Educational Resources Information Center

    Christopher, G. Ronald; Milam, Alvin L.

    In order to meet the demand for Air Force Institute of Technology (AFIT) professional continuing education (PCE) courses within the School of Systems and Logistics and the School of Engineering, the Teleteach Expanded Delivery System (TEDS) for instruction of Air Force personnel at remote locations was developed and evaluated. TEDS uses a device…

  18. Perispinal Delivery of CNS Drugs.

    PubMed

    Tobinick, Edward Lewis

    2016-06-01

    Perispinal injection is a novel emerging method of drug delivery to the central nervous system (CNS). Physiological barriers prevent macromolecules from efficiently penetrating into the CNS after systemic administration. Perispinal injection is designed to use the cerebrospinal venous system (CSVS) to enhance delivery of drugs to the CNS. It delivers a substance into the anatomic area posterior to the ligamentum flavum, an anatomic region drained by the external vertebral venous plexus (EVVP), a division of the CSVS. Blood within the EVVP communicates with the deeper venous plexuses of the CSVS. The anatomical basis for this method originates in the detailed studies of the CSVS published in 1819 by the French anatomist Gilbert Breschet. By the turn of the century, Breschet's findings were nearly forgotten, until rediscovered by American anatomist Oscar Batson in 1940. Batson confirmed the unique, linear, bidirectional and retrograde flow of blood between the spinal and cerebral divisions of the CSVS, made possible by the absence of venous valves. Recently, additional supporting evidence was discovered in the publications of American neurologist Corning. Analysis suggests that Corning's famous first use of cocaine for spinal anesthesia in 1885 was in fact based on Breschet's anatomical findings, and accomplished by perispinal injection. The therapeutic potential of perispinal injection for CNS disorders is highlighted by the rapid neurological improvement in patients with otherwise intractable neuroinflammatory disorders that may ensue following perispinal etanercept administration. Perispinal delivery merits intense investigation as a new method of enhanced delivery of macromolecules to the CNS and related structures.

  19. Career Information Delivery Systems Inventory.

    ERIC Educational Resources Information Center

    Olson, Gerald T.; Whitman, Patricia D.

    This inventory highlights similarities and differences between 19 computerized career information delivery systems (CIDS) so practitioners may make more informed choices concerning the adoption of such systems, and policymakers may monitor the developing scope of system features and costs. It was developed through a survey of computer products…

  20. Cesarean delivery: counseling issues and complication management.

    PubMed

    Quinlan, Jeffrey D; Murphy, Neil J

    2015-02-01

    Nearly one-third of all deliveries in the United States are cesarean deliveries. Compared with spontaneous vaginal delivery, cesarean delivery is associated with increased maternal and neonatal morbidity and mortality. Interventions that decrease the chance of a cesarean delivery include avoiding non-medically indicated induction of labor, avoiding amniotomy, and having a doula present. In North America, the most common reasons for cesarean delivery include elective repeat cesarean delivery, dystocia or failure to progress, malpresentation, and fetal heart rate tracings that suggest fetal distress. Post-cesarean delivery complications include pain, endomyometritis, wound separation/infection, urinary tract infection, gastrointestinal problems, deep venous thrombosis, and septic thrombophlebitis. Women with no risk factors for deep venous thrombosis other than the postpartum state and the operative delivery do not require thromboembolism prophylaxis other than early ambulation. A pregnant woman's decision to attempt a trial of labor after cesarean delivery or have a planned repeat cesarean delivery involves a balancing of maternal and neonatal risks, as well as personal preference after counseling by her physician. Approximately 75% of attempted trials of labor after cesarean delivery are successful. Provision of advanced maternity care practices by family physicians, including serving as primary surgeons for cesarean deliveries, is consistent with the goals of the patient-centered medical home. PMID:25822271

  1. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology. PMID:26891564

  2. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

  3. Nitrogen-doped, carbon-rich, highly photoluminescent carbon dots from ammonium citrate.

    PubMed

    Yang, Zhi; Xu, Minghan; Liu, Yun; He, Fengjiao; Gao, Feng; Su, Yanjie; Wei, Hao; Zhang, Yafei

    2014-01-01

    The synthesis of water-soluble nitrogen-doped carbon dots has received great attention, due to their wide applications in oxygen reduction reaction, cell imaging, sensors, and drug delivery. Herein, nitrogen-doped, carbon-rich, highly photoluminescent carbon dots have been synthesized for the first time from ammonium citrate under hydrothermal conditions. The obtained nitrogen-doped carbon dots possess bright blue luminescence, short fluorescence lifetime, pH-sensitivity and excellent stability at a high salt concentration. They have potential to be used for pH sensors, cell imaging, solar cells, and photocatalysis.

  4. 38 CFR 21.4505 - Check delivery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... surviving spouse and shall be mailed promptly to the educational institution in which the eligible spouse or surviving spouse is enrolled for delivery by the educational institution. (b) Delivery and certification. (1... check to the eligible spouse or surviving spouse and shall certify the fact of delivery to...

  5. Teletex Based Electronic Document Delivery (Project HERMES).

    ERIC Educational Resources Information Center

    Amy, Susan J.

    1985-01-01

    Project HERMES is characterized by participation of publishers, industrial and public libraries, and national government, and by use of Teletex for both document ordering and delivery. Provision of three facilities (electronic document ordering and delivery, automatic document delivery, electronic mail) to pilot group of 60 organizations is…

  6. Viral and nonviral delivery systems for gene delivery.

    PubMed

    Nayerossadat, Nouri; Maedeh, Talebi; Ali, Palizban Abas

    2012-01-01

    Gene therapy is the process of introducing foreign genomic materials into host cells to elicit a therapeutic benefit. Although initially the main focus of gene therapy was on special genetic disorders, now diverse diseases with different patterns of inheritance and acquired diseases are targets of gene therapy. There are 2 major categories of gene therapy, including germline gene therapy and somatic gene therapy. Although germline gene therapy may have great potential, because it is currently ethically forbidden, it cannot be used; however, to date human gene therapy has been limited to somatic cells. Although numerous viral and nonviral gene delivery systems have been developed in the last 3 decades, no delivery system has been designed that can be applied in gene therapy of all kinds of cell types in vitro and in vivo with no limitation and side effects. In this review we explain about the history of gene therapy, all types of gene delivery systems for germline (nuclei, egg cells, embryonic stem cells, pronuclear, microinjection, sperm cells) and somatic cells by viral [retroviral, adenoviral, adeno association, helper-dependent adenoviral systems, hybrid adenoviral systems, herpes simplex, pox virus, lentivirus, Epstein-Barr virus)] and nonviral systems (physical: Naked DNA, DNA bombardant, electroporation, hydrodynamic, ultrasound, magnetofection) and (chemical: Cationic lipids, different cationic polymers, lipid polymers). In addition to the above-mentioned, advantages, disadvantages, and practical use of each system are discussed. PMID:23210086

  7. Polymeric Nanoparticle Drug Delivery Technologies for Oral Delivery Applications

    PubMed Central

    Pridgen, Eric M.; Alexis, Frank; Farokhzad, Omid C.

    2016-01-01

    Introduction Many therapeutics are limited to parenteral administration. Oral administration is a desirable alternative because of the convenience and increased compliance by patients, especially for chronic diseases that require frequent administration. Polymeric nanoparticles are one technology being developed to enable clinically feasible oral delivery. Areas covered This review discusses the challenges associated with oral delivery. Strategies used to overcome gastrointestinal barriers using polymeric nanoparticles will be considered, including mucoadhesive biomaterials and targeting of nanoparticles to transcytosis pathways associated with M cells and enterocytes. Applications of oral delivery technologies will also be discussed, such as oral chemotherapies, oral insulin, treatment of inflammatory bowel disease, and mucosal vaccinations. Expert opinion There have been many approaches used to overcome the transport barriers presented by the gastrointestinal tract, but most have been limited by low bioavailability. Recent strategies targeting nanoparticles to transcytosis pathways present in the intestines have demonstrated that it is feasible to efficiently transport both therapeutics and nanoparticles across the intestines and into systemic circulation after oral administration. Further understanding of the physiology and pathophysiology of the intestines could lead to additional improvements in oral polymeric nanoparticle technologies and enable the translation of these technologies to clinical practice. PMID:25813361

  8. Nanoparticle delivery for transdermal HRT.

    PubMed

    Valenzuela, Pilar; Simon, James A

    2012-09-01

    Nanomedicine is an emerging technology and the first nano-engineered medical products have come to light in the last decade. Transdermal drug delivery has significant advantages compared to other routes of drug administration. Nanoparticles unique physical and chemical properties enable transport of substances directly into the skin. The objective of this paper is to review different aspects of nanoparticle delivery, generally, and discuss its current use for transdermal hormone therapy. Transdermal estrogen therapy remains the most effective treatment for bothersome menopausal symptoms, particularly in those women for whom the potential adverse effects associated with "first pass" hepatic metabolism are to be avoided. Available alternatives for transdermal estrogen delivery include patches, gels, sprays and lotions. Other non-oral therapies which likewise avoid "first pass" hepatic metabolism include: subcutaneous implants and vaginal rings. Some of the transdermal products are associated with mild adverse skin effects such as redness and irritation, but more severe and bothersome consequences include blistering and tattooing. Even the mild adverse skin effects are frequently cited as reasons for discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion-like therapy which constitutes an alternative transdermal delivery system not requiring the permeation enhancers or temporary skin digestion, both of which increase the possibility of irritation. MNPEE's advantages include low fluctuation of plasma estradiol concentrations, infrequent skin related adverse effects, and pleasant cosmetic-like moisturizing properties. The efficacy of MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a randomized placebo controlled trial, and the product is FDA approved for management of moderate to severe vasomotor symptoms. None of the observed adverse effects in the MNPEE group were statistically different from the placebo group

  9. Nanoparticle delivery for transdermal HRT.

    PubMed

    Valenzuela, Pilar; Simon, James A

    2012-09-01

    Nanomedicine is an emerging technology and the first nano-engineered medical products have come to light in the last decade. Transdermal drug delivery has significant advantages compared to other routes of drug administration. Nanoparticles unique physical and chemical properties enable transport of substances directly into the skin. The objective of this paper is to review different aspects of nanoparticle delivery, generally, and discuss its current use for transdermal hormone therapy. Transdermal estrogen therapy remains the most effective treatment for bothersome menopausal symptoms, particularly in those women for whom the potential adverse effects associated with "first pass" hepatic metabolism are to be avoided. Available alternatives for transdermal estrogen delivery include patches, gels, sprays and lotions. Other non-oral therapies which likewise avoid "first pass" hepatic metabolism include: subcutaneous implants and vaginal rings. Some of the transdermal products are associated with mild adverse skin effects such as redness and irritation, but more severe and bothersome consequences include blistering and tattooing. Even the mild adverse skin effects are frequently cited as reasons for discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion-like therapy which constitutes an alternative transdermal delivery system not requiring the permeation enhancers or temporary skin digestion, both of which increase the possibility of irritation. MNPEE's advantages include low fluctuation of plasma estradiol concentrations, infrequent skin related adverse effects, and pleasant cosmetic-like moisturizing properties. The efficacy of MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a randomized placebo controlled trial,(1) and the product is FDA approved for management of moderate to severe vasomotor symptoms. None of the observed adverse effects in the MNPEE group were statistically different from the placebo group.(1

  10. Nonviral Vectors for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Baoum, Abdulgader Ahmed

    2011-12-01

    The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was

  11. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  12. RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis

    NASA Astrophysics Data System (ADS)

    Jiang, Xinglu; Wang, Guobao; Liu, Ru; Wang, Yaling; Wang, Yongkui; Qiu, Xiaozhong; Gao, Xueyun

    2013-07-01

    To date, RNase degradation and endosome/lysosome trapping are still serious problems for siRNA-based molecular therapy, although different kinds of delivery formulations have been tried. In this report, a cell penetrating peptide (CPP, including a positively charged segment, a linear segment, and a hydrophobic segment) and a single wall carbon nanotube (SWCNT) are applied together by a simple method to act as a siRNA delivery system. The siRNAs first form a complex with the positively charged segment of CPP via electrostatic forces, and the siRNA-CPP further coats the surface of the SWCNT via hydrophobic interactions. This siRNA delivery system is non-sensitive to RNase and can avoid endosome/lysosome trapping in vitro. When this siRNA delivery system is studied in Hela cells, siRNA uptake was observed in 98% Hela cells, and over 70% mRNA of mammalian target of rapamycin (mTOR) is knocked down, triggering cell apoptosis on a significant scale. Our siRNA delivery system is easy to handle and benign to cultured cells, providing a very efficient approach for the delivery of siRNA into the cell cytosol and cleaving the target mRNA therein.

  13. Calcium Carbonate

    MedlinePlus

    Calcium carbonate is a dietary supplement used when the amount of calcium taken in the diet is not ... for healthy bones, muscles, nervous system, and heart. Calcium carbonate also is used as an antacid to relieve ...

  14. Carbon photonics

    NASA Astrophysics Data System (ADS)

    Konov, V. I.

    2015-11-01

    The properties of new carbon materials (single-crystal and polycrystalline CVD diamond films and wafers, single-wall carbon nanotubes and graphene) and the prospects of their use as optical elements and devices are discussed.

  15. Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity

    PubMed Central

    Galagudza, Michael M; Korolev, Dmitry V; Sonin, Dmitry L; Postnov, Viktor N; Papayan, Garry V; Uskov, Ivan S; Belozertseva, Anastasia V; Shlyakhto, Eugene V

    2010-01-01

    The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry. PMID:20463939

  16. [Fetal macrosomia: mode of delivery].

    PubMed

    Tatarova, S; Popov, I; Khristova, P

    2004-01-01

    This study was provided among 1847 deliveries from January, 1 to December, 31, 2003. The aim of the study was to examine the correlation between antenatal diagnosis "fetal macrosomia" and the mode of delivery. We found that among the cases with birth weight > or = 4000 g and antenatal diagnosis "fetal macrosomia" the rate of cesarean section was fourfold higher than among the cases without such a diagnosis. There weren't statistically significant correlation between the cases with antenatal diagnosis "fetal macrosomia " and the cases with estimated birth weight < or = 3999g in reference to the mother's age and weight, parity, fundal height and abdominal circumference. There are insignificant differences between both of groups in reference to gestacional age and birth.

  17. [CAESAREAN DELIVERY: STANDARDIZING THE PRACTICES].

    PubMed

    Thellier, Élise; Benhamou, Dan

    2016-06-01

    Caesarean delivery was performed in 20% of all deliveries in France in 2010 and this rate has remained unchanged during the last 10 years. Indications to perform this procedure are well defined, especially in case of scarred uterus, twin pregnancies, macrosomia or breech presentation. Surgical (haemorrhage, urinary or intestinal tract injury) and anaesthetic (hypotension after regional anaesthesia, difficult intubation and aspiration after general anaesthesia) complications may occur during the procedure. Complications may also be encountered in the early postoperative period (haemorrhage, infection, venous thromboembolism) but also on the long-term, such as placenta accreta or uterine rupture which may significantly impact obstetric outcomes. Enhanced recovery after surgery promotes early recovery and rapid convalescence. It simplifies nursing practice after surgery and is the first important step toward a patient- and family-centred care. PMID:27538322

  18. Cellular Delivery of RNA Nanoparticles.

    PubMed

    Parlea, Lorena; Puri, Anu; Kasprzak, Wojciech; Bindewald, Eckart; Zakrevsky, Paul; Satterwhite, Emily; Joseph, Kenya; Afonin, Kirill A; Shapiro, Bruce A

    2016-09-12

    RNA nanostructures can be programmed to exhibit defined sizes, shapes and stoichiometries from naturally occurring or de novo designed RNA motifs. These constructs can be used as scaffolds to attach functional moieties, such as ligand binding motifs or gene expression regulators, for nanobiology applications. This review is focused on four areas of importance to RNA nanotechnology: the types of RNAs of particular interest for nanobiology, the assembly of RNA nanoconstructs, the challenges of cellular delivery of RNAs in vivo, and the delivery carriers that aid in the matter. The available strategies for the design of nucleic acid nanostructures, as well as for formulation of their carriers, make RNA nanotechnology an important tool in both basic research and applied biomedical science.

  19. Nanoparticle-Mediated Gene Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Sha; Leach, John C.; Ye, Kaiming

    Nonviral gene delivery has been gaining considerable attention recently. Although the efficacy of DNA transfection, which is a major concern, is low in nonviral vector-mediated gene transfer compared with viral ones, nonviral vectors are relatively easy to prepare, less immunogenic and oncogenic, and have no potential of virus recombination and no limitation on the size of a transferred gene. The ability to incorporate genetic materials such as plasmid DNA, RNA, and siRNA into functionalized nanoparticles with little toxicity demonstrates a new era in pharmacotherapy for delivering genes selectively to tissues and cells. In this chapter, we highlight the basic concepts and applications of nonviral gene delivery using super paramagnetic iron oxide nanoparticles and functionalized silica nanoparticles. The experimental protocols related to these topics are described in the chapter.

  20. Cellular Delivery of RNA Nanoparticles.

    PubMed

    Parlea, Lorena; Puri, Anu; Kasprzak, Wojciech; Bindewald, Eckart; Zakrevsky, Paul; Satterwhite, Emily; Joseph, Kenya; Afonin, Kirill A; Shapiro, Bruce A

    2016-09-12

    RNA nanostructures can be programmed to exhibit defined sizes, shapes and stoichiometries from naturally occurring or de novo designed RNA motifs. These constructs can be used as scaffolds to attach functional moieties, such as ligand binding motifs or gene expression regulators, for nanobiology applications. This review is focused on four areas of importance to RNA nanotechnology: the types of RNAs of particular interest for nanobiology, the assembly of RNA nanoconstructs, the challenges of cellular delivery of RNAs in vivo, and the delivery carriers that aid in the matter. The available strategies for the design of nucleic acid nanostructures, as well as for formulation of their carriers, make RNA nanotechnology an important tool in both basic research and applied biomedical science. PMID:27509068

  1. Vaginal birth after cesarean delivery.

    PubMed

    Martins, M E

    1996-03-01

    The rate of vaginal birth after a previous cesarean delivery continues to rise due to both national organization recommendations and trials spanning 10 years of experience demonstrating its effectiveness and general safety. Broadening eligibility criteria and investigation of the clinical and nonclinical factors influencing this rate should place us on the glide path to reduction of the overall cesarean rate by the year 2000. Remaining controversies and management strategy will be discussed.

  2. Cyclodextrins in delivery systems: Applications

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Rai, Awani K.

    2010-01-01

    Cyclodextrins (CDs) are a family of cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic central cavity. CD molecules are relatively large with a number of hydrogen donors and acceptors and, thus in general, they do not permeate lipophilic membranes. In the pharmaceutical industry, CDs have mainly been used as complexing agents to increase aqueous solubility of poorly soluble drugs and to increase their bioavailability and stability. CDs are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current CD-based therapeutics is described and possible future applications are discussed. CD-containing polymers are reviewed and their use in drug delivery is presented. Of specific interest is the use of CD-containing polymers to provide unique capabilities for the delivery of nucleic acids. Studies in both humans and animals have shown that CDs can be used to improve drug delivery from almost any type of drug formulation. Currently, there are approximately 30 different pharmaceutical products worldwide containing drug/CD complexes in the market. PMID:21814436

  3. A review on protein functionalized carbon nanotubes.

    PubMed

    Nagaraju, Kathyayini; Reddy, Roopa; Reddy, Narendra

    2015-01-01

    Carbon nanotubes (CNTs) have been widely recognized and used for controlled drug delivery and in various other fields due to their unique properties and distinct advantages. Both single-walled carbon nanotubes (SWCNTs) and multiwalled (MWCNTs) carbon nanotubes are used and/or studied for potential applications in medical, energy, textile, composite, and other areas. Since CNTs are chemically inert and are insoluble in water or other organic solvents, they are functionalized or modified to carry payloads or interact with biological molecules. CNTs have been preferably functionalized with proteins because CNTs are predominantly used for medical applications such as delivery of drugs, DNA and genes, and also for biosensing. Extensive studies have been conducted to understand the interactions, cytotoxicity, and potential applications of protein functionalized CNTs but contradicting results have been published on the cytotoxicity of the functionalized CNTs. This paper provides a brief review of CNTs functionalized with proteins, methods used to functionalize the CNTs, and their potential applications. PMID:26660626

  4. A review on protein functionalized carbon nanotubes.

    PubMed

    Nagaraju, Kathyayini; Reddy, Roopa; Reddy, Narendra

    2015-12-18

    Carbon nanotubes (CNTs) have been widely recognized and used for controlled drug delivery and in various other fields due to their unique properties and distinct advantages. Both single-walled carbon nanotubes (SWCNTs) and multiwalled (MWCNTs) carbon nanotubes are used and/or studied for potential applications in medical, energy, textile, composite, and other areas. Since CNTs are chemically inert and are insoluble in water or other organic solvents, they are functionalized or modified to carry payloads or interact with biological molecules. CNTs have been preferably functionalized with proteins because CNTs are predominantly used for medical applications such as delivery of drugs, DNA and genes, and also for biosensing. Extensive studies have been conducted to understand the interactions, cytotoxicity, and potential applications of protein functionalized CNTs but contradicting results have been published on the cytotoxicity of the functionalized CNTs. This paper provides a brief review of CNTs functionalized with proteins, methods used to functionalize the CNTs, and their potential applications.

  5. Injectable nanomaterials for drug delivery: carriers, targeting moieties, and therapeutics.

    PubMed

    Webster, David M; Sundaram, Padma; Byrne, Mark E

    2013-05-01

    Therapeutics such as nucleic acids, proteins/peptides, vaccines, anti-cancer, and other drugs have disadvantages of low bio-availability, rapid clearance, and high toxicity. Thus, there is a significant need for the development of efficient delivery methods and carriers. Injectable nanocarriers have received much attention due to their vast range of structures and ability to contain multiple functional groups, both within the bulk material and on the surface of the particles. Nanocarriers may be tailored to control drug release and/or increase selective cell targeting, cellular uptake, drug solubility, and circulation time, all of which lead to a more efficacious delivery and action of therapeutics. The focus of this review is injectable, targeted nanoparticle drug delivery carriers highlighting the diversity of nanoparticle materials and structures as well as highlighting current therapeutics and targeting moieties. Structures and materials discussed include liposomes, polymersomes, dendrimers, cyclodextrin-containing polymers (CDPs), carbon nanotubes (CNTs), and gold nanoparticles. Additionally, current clinical trial information and details such as trial phase, treatment, active drug, carrier sponsor, and clinical trial identifier for different materials and structures are presented and discussed.

  6. Paclitaxel Nano-Delivery Systems: A Comprehensive Review.

    PubMed

    Ma, Ping; Mumper, Russell J

    2013-02-18

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.

  7. Delivery

    MedlinePlus

    > Find Us On Facebook Twitter Pinterest Youtube Instagram Diabetes Stops Here Blog Online Community Site Menu Are You at Risk? Diagnosis Lower Your Risk Risk Test Alert Day Prediabetes My Health Advisor Tools to ...

  8. Use and influence of Delivery and Birth Plans in the humanizing delivery process1

    PubMed Central

    Suárez-Cortés, María; Armero-Barranco, David; Canteras-Jordana, Manuel; Martínez-Roche, María Emilia

    2015-01-01

    OBJECTIVES: get to know, analyze and describe the current situation of the Delivery and Birth Plans in our context, comparing the delivery and birth process between women who presented a Delivery and Birth Plan and those who did not. METHOD: quantitative and cross-sectional, observational, descriptive and comparative cohort study, carried out over two years. All women who gave birth during the study period were selected, including 9303 women in the study. RESULTS: 132 Delivery and Birth Plans were presented during the first year of study and 108 during the second. Among the variables analyzed, a significant difference was found in "skin to skin contact", "choice of dilation and delivery posture", "use of enema", "intake of foods or fluids", "eutocic deliveries", "late clamping of the umbilical cord" and "perineal shaving". CONCLUSIONS: the Delivery and Birth Plans positively influence the delivery process and its outcome. Health policies are needed to increase the number of Delivery and Birth Plans in our hospitals. PMID:26155015

  9. Glycosylated carriers for cell-selective and nuclear delivery of nucleic acids.

    PubMed

    Wijagkanalan, Wassana; Kawakami, Shigeru; Hashida, Mitsuru

    2011-06-01

    Targeted gene delivery via selective cellular receptors has been realized as a crucial strategy for successful gene therapy by maximizing therapeutic efficiency in target cells and minimizing systemic toxicity. The membrane carbohydrate-binding proteins (membrane lectins) with different carbohydrate specificities are differentially expressed on the cellular and intracellular membranes of a number of cells. Their multiplicity, high affinity, and effective endocytosis after receptor binding as well as the biocompatibility of carbohydrate ligands endow them as potential ligands for glycosylated carriers in cell-selective delivery of nucleic acids. To achieve the in vivo application, glycosylated carriers/nucleic acid complexes have to fulfill certain conditions, including having a suitable size, minimal nonspecific interactions, low immunogenicity, and high uptake in target cells. Accordingly, the effective nuclear delivery of nucleic acids is the paramount important step for efficient gene transfer. This review summarizes the recent progress regarding application of glycosylated carriers for cell-selective and nuclear delivery of nucleic acids and their critical factors for efficient gene transfer. In addition, the development of new materials, such as carbon nanotubes, carbon nanospheres, and gold nanoparticles, as innovative carriers will be discussed with regards to glycosylation-mediated delivery of nucleic acids.

  10. Carbon-Carbon Piston Architectures

    NASA Technical Reports Server (NTRS)

    Rivers, H. Kevin (Inventor); Ransone, Philip O. (Inventor); Northam, G. Burton (Inventor); Schwind, Francis A. (Inventor)

    1999-01-01

    An improved structure for carbon-carbon composite piston architectures consists of replacing the knitted fiber, three-dimensional piston preform architecture described in U.S. Pat. No. 4.909,133 (Taylor et al.) with a two-dimensional lay-up or molding of carbon fiber fabric or tape. Initially. the carbon fabric or tape layers are prepregged with carbonaceous organic resins and/or pitches and are laid up or molded about a mandrel. to form a carbon-fiber reinforced organic-matrix composite part shaped like a "U" channel, a "T"-bar. or a combination of the two. The molded carbon-fiber reinforced organic-matrix composite part is then pyrolized in an inert atmosphere, to convert the organic matrix materials to carbon. At this point, cylindrical piston blanks are cored from the "U" channel, "T"-bar, or combination part. These blanks are then densified by reimpregnation with resins or pitches which are subsequently carbonized. Densification is also be accomplished by direct infiltration with carbon by vapor deposition processes. Once the desired density has been achieved, the piston billets are machined to final piston dimensions; coated with oxidation sealants; and/or coated with a catalyst. When compared to conventional steel or aluminum-alloy pistons, the use of carbon-carbon composite pistons reduces the overall weight of the engine; allows for operation at higher temperatures without a loss of strength; allows for quieter operation; reduces the heat loss; and reduces the level of hydrocarbon emissions.

  11. Sediment delivery after a wildfire

    USGS Publications Warehouse

    Reneau, S.L.; Katzman, D.; Kuyumjian, G.A.; Lavine, A.; Malmon, D.V.

    2007-01-01

    We use a record of sedimentation a small reservoir within the Cerro Grande burn area, New Mexico, to document postfire delivery of ash, other fine-grained sediment carried in suspension within floods, and coarse-grained sediment transported as bedload over a five-year period. Ash content of sediment layers is estimated using fallout 137Cs as a tracer, and ash concentrations are shown to rapidly decrease through a series of moderate-intensity convective storms in the first rainy season after the fire. Over 90% of the ash was delivered to the reservoir in the first year, and ash concentrations in suspended sediment were negligible after the second year. Delivery of the remainder of the fine sediment also declined rapidly after the first year despite the occurrence of higher-intensity storms in the second year. Fine sediment loads after five years remained significantly above prefire averages. Deposition of coarse-grained sediment was irregular in time and was associated with transport by snowmelt runoff of sediment stored along the upstream channel during short-duration summer floods. Coarse sediment delivery in the first four years was strongly correlated with snowmelt volume, suggesting a transport-limited system with abundant available sediment. Transport rates of coarse sediment declined in the fifth year, consistent with a transition to a more stable channel as the accessible sediment supply was depleted and the channel bed coarsened. Maximum impacts from ash and other fine-grained sediment therefore occurred soon after the fire, whereas the downstream impacts from coarse-grained sediment were attenuated by the more gradual process of bedload sediment transport. ?? 2007 Geological Society of America.

  12. Functionalized nanomaterials: are they effective to perform gene delivery to difficult-to-transfect cells with no cytotoxicity?

    NASA Astrophysics Data System (ADS)

    Tonelli, F. M. P.; Lacerda, S. M. S. N.; Paiva, N. C. O.; Pacheco, F. G.; Scalzo Junior, S. R. A.; de Macedo, F. H. P.; Cruz, J. S.; Pinto, M. C. X.; Junior, J. D. Corrêa; Ladeira, L. O.; França, L. R.; Guatimosim, S.; Resende, R. R.

    2015-10-01

    Nanodiamonds (NDs), multiwalled carbon nanotubes (MWCNTs) and gold nanorods (NRs) can be functionalized to promote gene delivery to hard-to-transfect cells with higher transfection efficiency than cationic lipids, and inducing less cell death.Nanodiamonds (NDs), multiwalled carbon nanotubes (MWCNTs) and gold nanorods (NRs) can be functionalized to promote gene delivery to hard-to-transfect cells with higher transfection efficiency than cationic lipids, and inducing less cell death. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04173b

  13. Medical care delivery in space

    NASA Technical Reports Server (NTRS)

    Stewart, Don F.

    1989-01-01

    Consideration is given to the delivery of medical care in space. The history of aviation medicine is reviewed. Medical support for the early space programs is discussed, including the Mercury, Gemini, Apollo, and Skylab programs. The process of training crew members for basic medical procedures for the Space Shuttle program is briefly described and medical problems during the Shuttle program are noted. Plans for inflight medical care on the Space Station are examined, including the equipment planned for the Health Maintenance Facility, the use of exercise to help prevent medical problems.

  14. Targeting delivery in Parkinson's disease.

    PubMed

    Newland, Ben; Dunnett, Stephen B; Dowd, Eilís

    2016-08-01

    Disease-modifying therapies for Parkinson's disease (PD), with the potential to halt the neurodegenerative process and to stimulate the protection, repair, and regeneration of dopaminergic neurons, remain a vital but unmet clinical need. Targeting the delivery of current and new therapeutics directly to the diseased brain region (in particular the nigrostriatal pathway) could result in greater improvements in the motor functions that characterise PD. Here, we highlight some of the opportunities and challenges facing the development of the next generation of therapies for patients with PD. PMID:27312875

  15. Evaluation of Retrofit Delivery Packages

    SciTech Connect

    Berman, M.; Smith, P.; Porse, E.

    2013-07-01

    Residential energy retrofit activities are a critical component of efforts to increase energy efficiency in the U.S. building stock; however, retrofits account for a small percentage of aggregate energy savings at relatively high per unit costs. This report by Building America research team, Alliance for Residential Building Innovation (ARBI), describes barriers to widespread retrofits and evaluates opportunities to improve delivery of home retrofit measures by identifying economies of scale in marketing, energy assessments, and bulk purchasing through pilot programs in portions of Sonoma, Los Angeles, and San Joaquin Counties, CA. These targeted communities show potential and have revealed key strategies for program design, as outlined in the report.

  16. Innovation in Health Care Delivery.

    PubMed

    Sharan, Alok D; Schroeder, Gregory D; West, Michael E; Vaccaro, Alexander R

    2016-02-01

    As reimbursement transitions from a volume-based to a value-based system, innovation in health care delivery will be needed. The process of innovation begins with framing the problem that needs to be solved along with the strategic vision that has to be achieved. Similar to scientific testing, a hypothesis is generated for a new solution to a problem. Innovation requires conducting a disciplined form of experimentation and then learning from the process. This manuscript will discuss the different types of innovation, and the key steps necessary for successful innovation in the health care field.

  17. Soil Delivery to Phoenix Oven

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This image shows a view from NASA's Phoenix Mars Lander's Stereo Surface Imager's left eye after delivery of soil to the Thermal and Evolved-Gas Analyzer (TEGA), taken on the 12th Martian day after landing (Sol 12, June $6, 2008).

    Soil is visible on both sides of the open doors of TEGA's #4 oven. Sensors inside the device indicate no soil passed through the screen and into the oven.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  18. Infection, antibiotics, and preterm delivery.

    PubMed

    Locksmith, G; Duff, P

    2001-10-01

    The relationship between genital tract infection and preterm delivery has been established on the basis of biochemical, microbiological, and clinical evidence. In theory, pathogenic bacteria may ascend from the lower reproductive tract into the uterus, and the resulting inflammation leads to preterm labor, rupture of the membranes, and birth. A growing body of evidence suggests that preterm labor and/rupture of the membranes are triggered by micro-organisms in the genital tract and by the host response to these organisms, ie, elaboration of cytokines and proteolytic enzymes. Epidemiologic and in vitro studies do not prove a cause-and-effect relationship between infection and preterm birth. However, the preponderance of evidence indicates that treatment of asymptomatic bacteriuria and symptomatic lower genital tract infections such as bacterial vaginosis (BV), trichomoniasis, gonorrhea, and chlamydia will lower the risk of preterm delivery. Based on current evidence, pregnant women who note an abnormal vaginal discharge should be tested for BV, trichomonas, gonorrhea, and chlamydia. Those who test positive should be treated appropriately. A 3- to 7-day course of antibiotic treatment for asymptomatic bacteriuria during pregnancy is clinically indicated to reduce the risk of pyelonephritis and preterm delivery. Routine screening for chlamydia and gonorrhea should be performed for women at high risk of acquiring sexually transmitted diseases. The practice of routine screening for BV in asymptomatic women who are at low risk for preterm delivery cannot be supported based on evidence from the literature. Routine screening for asymptomatic bacteriuria during pregnancy is cost-effective, particularly in high-prevalence populations. The results of antibiotic trials for the treatment of preterm labor have been inconsistent. In the absence of reasonable evidence that antimicrobial therapy leads to significant prolongation of pregnancy in the setting of preterm labor

  19. Opportunities in respiratory drug delivery.

    PubMed

    Pritchard, John N; Giles, Rachael D

    2014-12-01

    A wide range of asthma and chronic obstructive pulmonary disease products are soon to be released onto the inhaled therapies market and differentiation between these devices will help them to gain market share over their competitors. Current legislation is directing healthcare towards being more efficient and cost-effective in order to continually provide quality care despite the challenges of aging populations and fewer resources. Devices and drugs that can be differentiated by producing improved patient outcomes would, therefore, be likely to win market share. In this perspective article, the current and potential opportunities for the successful delivery and differentiation of new inhaled drug products are discussed.

  20. Parallel macromolecular delivery and biochemical/electrochemical interface to cells employing nanostructures

    SciTech Connect

    McKnight, Timothy E; Melechko, Anatoli V; Griffin, Guy D; Guillorn, Michael A; Merkulov, Vladimir L; Simpson, Michael L

    2015-03-31

    Systems and methods are described for parallel macromolecular delivery and biochemical/electrochemical interface to whole cells employing carbon nanostructures including nanofibers and nanotubes. A method includes providing a first material on at least a first portion of a first surface of a first tip of a first elongated carbon nanostructure; providing a second material on at least a second portion of a second surface of a second tip of a second elongated carbon nanostructure, the second elongated carbon nanostructure coupled to, and substantially parallel to, the first elongated carbon nanostructure; and penetrating a boundary of a biological sample with at least one member selected from the group consisting of the first tip and the second tip.

  1. Carbonate aquifers

    USGS Publications Warehouse

    Cunningham, Kevin J.; Sukop, Michael; Curran, H. Allen

    2012-01-01

    Only limited hydrogeological research has been conducted using ichnology in carbonate aquifer characterization. Regardless, important applications of ichnology to carbonate aquifer characterization include its use to distinguish and delineate depositional cycles, correlate mappable biogenically altered surfaces, identify zones of preferential groundwater flow and paleogroundwater flow, and better understand the origin of ichnofabric-related karst features. Three case studies, which include Pleistocene carbonate rocks of the Biscayne aquifer in southern Florida and Cretaceous carbonate strata of the Edwards–Trinity aquifer system in central Texas, demonstrate that (1) there can be a strong relation between ichnofabrics and groundwater flow in carbonate aquifers and (2) ichnology can offer a useful methodology for carbonate aquifer characterization. In these examples, zones of extremely permeable, ichnofabric-related macroporosity are mappable stratiform geobodies and as such can be represented in groundwater flow and transport simulations.

  2. Molecular Diagnostic and Drug Delivery Agents based on Aptamer-Nanomaterial Conjugates

    PubMed Central

    Lee, Jung Heon; Yigit, Mehmet V.; Mazumdar, Debapriya; Lu, Yi

    2010-01-01

    Recent progress in an emerging area of designing aptamer and nanomaterial conjugates as molecular diagnostic and drug delivery agents in biomedical applications is summarized. Aptamers specific for a wide range of targets are first introduced and compared to antibodies. Methods of integrating these aptamers with a variety of nanomaterials, such as gold nanoparticles, quantum dots, carbon nanotubes, and superparamagnetic iron oxide nanoparticles, each with unique optical, magnetic, and electrochemical properties, are reviewed. Applications of these systems as fluorescent, colorimetric, magnetic resonance imaging, and electrochemical sensors in medical diagnostics are given, along with new applications as smart drug delivery agents. PMID:20338204

  3. Mobilization of Aquatic Carbon from Permafrost: Tracking the Ancient Carbon Signal.

    NASA Astrophysics Data System (ADS)

    Striegl, R. G.; Walvoord, M. A.; Minsley, B. J.; Drake, T.; Aiken, G.; Wickland, K.

    2015-12-01

    Hydrological and carbon biogeochemical responses to permafrost thaw are well recognized and documented for arctic and subarctic river systems and include increased infiltration, groundwater flow, stream base flow, and yield of mineralized dissolved inorganic carbon (DIC). However, the anticipated concomitant signal of increased export of aged dissolved organic carbon (14C depleted DOC) is conspicuously small or absent at the river basin scale. Delivery of permafrost-derived DOC to stream and river networks is controlled by combinations of the amount of carbon stored in permafrost soils; hydrologic connectivity; subsurface physical conditions, including the potential for rapid thaw; and the chemical composition and degradability of the DOC released from permafrost. We examine these conditions in the discontinuous permafrost region of Yukon Flats, Alaska. Results indicate variable coupling among the factors controlling carbon release from permafrost, with greatest aged DOC source and biodegradability in regions that have low potential for immediate thaw or development of well-connected hydrologic networks. Conversely, regions having high potential for impending thaw and enhanced hydrologic connectivity tend to have smaller aged DOC sources and/or are dominated by modern DOC sources. This emphasizes the importance of the water-surface to atmosphere emission of permafrost carbon, with a majority of thawed permafrost organic carbon mineralizing to carbon gases in isolated thaw depressions, wetlands, and upland lakes and limited downstream delivery to river networks.

  4. Nitrogen-doped, carbon-rich, highly photoluminescent carbon dots from ammonium citrate

    NASA Astrophysics Data System (ADS)

    Yang, Zhi; Xu, Minghan; Liu, Yun; He, Fengjiao; Gao, Feng; Su, Yanjie; Wei, Hao; Zhang, Yafei

    2014-01-01

    The synthesis of water-soluble nitrogen-doped carbon dots has received great attention, due to their wide applications in oxygen reduction reaction, cell imaging, sensors, and drug delivery. Herein, nitrogen-doped, carbon-rich, highly photoluminescent carbon dots have been synthesized for the first time from ammonium citrate under hydrothermal conditions. The obtained nitrogen-doped carbon dots possess bright blue luminescence, short fluorescence lifetime, pH-sensitivity and excellent stability at a high salt concentration. They have potential to be used for pH sensors, cell imaging, solar cells, and photocatalysis.The synthesis of water-soluble nitrogen-doped carbon dots has received great attention, due to their wide applications in oxygen reduction reaction, cell imaging, sensors, and drug delivery. Herein, nitrogen-doped, carbon-rich, highly photoluminescent carbon dots have been synthesized for the first time from ammonium citrate under hydrothermal conditions. The obtained nitrogen-doped carbon dots possess bright blue luminescence, short fluorescence lifetime, pH-sensitivity and excellent stability at a high salt concentration. They have potential to be used for pH sensors, cell imaging, solar cells, and photocatalysis. Electronic supplementary information (ESI) available: The curve of photoluminescence and absorbance of N-doped CDs and quinine sulfate, and the table showing XPS detailed information. See DOI: 10.1039/c3nr05380f

  5. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. PMID:26501994

  6. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.

  7. Drug delivery systems: An updated review

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

    2012-01-01

    Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

  8. Fiber coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

    A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

  9. Nanoparticles for drug delivery to the lungs.

    PubMed

    Sung, Jean C; Pulliam, Brian L; Edwards, David A

    2007-12-01

    The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers additional degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders have been developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles.

  10. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  11. Hydrogen production and delivery analysis in US markets : cost, energy and greenhouse gas emissions.

    SciTech Connect

    Mintz, M.; Gillette, J.; Elgowainy, A.

    2009-01-01

    Hydrogen production cost conclusions are: (1) Steam Methane Reforming (SMR) is the least-cost production option at current natural gas prices and for initial hydrogen vehicle penetration rates, at high production rates, SMR may not be the least-cost option; (2) Unlike coal and nuclear technologies, the cost of natural gas feedstock is the largest contributor to SMR production cost; (3) Coal- and nuclear-based hydrogen production have significant penalties at small production rates (and benefits at large rates); (4) Nuclear production of hydrogen is likely to have large economies of scale, but because fixed O&M costs are uncertain, the magnitude of these effects may be understated; and (5) Given H2A default assumptions for fuel prices, process efficiencies and labor costs, nuclear-based hydrogen is likely to be more expensive to produce than coal-based hydrogen. Carbon taxes and caps can narrow the gap. Hydrogen delivery cost conclusions are: (1) For smaller urban markets, compressed gas delivery appears most economic, although cost inputs for high-pressure gas trucks are uncertain; (2) For larger urban markets, pipeline delivery is least costly; (3) Distance from hydrogen production plant to city gate may change relative costs (all results shown assume 100 km); (4) Pipeline costs may be reduced with system 'rationalization', primarily reductions in service pipeline mileage; and (5) Liquefier and pipeline capital costs are a hurdle, particularly at small market sizes. Some energy and greenhouse gas Observations: (1) Energy use (per kg of H2) declines slightly with increasing production or delivery rate for most components (unless energy efficiency varies appreciably with scale, e.g., liquefaction); (2) Energy use is a strong function of production technology and delivery mode; (3) GHG emissions reflect the energy efficiency and carbon content of each component in a production-delivery pathway; (4) Coal and natural gas production pathways have high energy consumption

  12. Targeting carbon nanotubes against cancer.

    PubMed

    Fabbro, Chiara; Ali-Boucetta, Hanene; Da Ros, Tatiana; Kostarelos, Kostas; Bianco, Alberto; Prato, Maurizio

    2012-04-25

    The use of carbon nanotubes (CNTs) as polyvalent tools for cancer treatment is progressing at a very fast pace. The most promising approach is the targeted delivery of drugs, designed to selectively direct the therapeutic treatment towards the tumours. CNTs may offer several advantages to overcome one of the main limitations of most existing anticancer therapies, namely the lack of selectivity. Herein, an account of the existing literature on CNT-based nanomedicine for cancer treatment is given. The most significant results obtained so far in the field of drug delivery are presented for many anticancer chemotherapeutics (doxorubicin, methotrexate, taxanes, platinum analogues, camptothecine and gemcitabine), but also for immunotherapeutics and nucleic acids. Moreover, the alternative anticancer therapies based on thermal ablation and radiotherapy are discussed. The attention throughout the review is focused on the different targeting strategies proposed so far, mainly based on antibodies, but also on other specifically recognised molecules or on the application of an external magnetic field.

  13. Double layered hydroxides as potential anti-cancer drug delivery agents.

    PubMed

    Riaz, Ufana; Ashraf, S M

    2013-04-01

    The emergence of nanotechnology has changed the scenario of the medical world by revolutionizing the diagnosis, monitoring and treatment of cancer. This nanotechnology has been proved miraculous in detecting cancer cells, delivering chemotherapeutic agents and monitoring treatment from non-specific to highly targeted killing of tumor cells. In the past few decades, a number of inorganic materials have been investigated such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for examining their efficacy in targeting drug delivery. The reason behind the selection of these inorganic materials was their versatile and unique features efficient in drug delivery, such as wide availability, rich surface functionality, good biocompatibility, potential for target delivery, and controlled release of the drug from these inorganic nanomaterials. Although, the drug-LDH hybrids are found to be quite instrumental because of their application as advanced anti-cancer drug delivery systems, there has not been much research on them. This mini review is set to highlight the advancement made in the use of layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with the advantages of LDHs as anti-cancer drug delivery agents, the process of interaction of some of the common anti-cancer drugs with LDH has also been discussed.

  14. Ocular drug delivery systems: An overview

    PubMed Central

    Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

    2014-01-01

    The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

  15. Gene delivery by functional inorganic nanocarriers.

    PubMed

    Loh, Xian Jun; Lee, Tung-Chun

    2012-08-01

    Gene delivery into cells to elicit cellular response has received a great attention recently. Viruses, lipids, peptides, cationic polymers and certain inorganic nanomaterials have been reported as gene delivery vectors. In this review, we focus on the recent literature on gene delivery using inorganic nanoparticles. This emerging field of study is concisely summarized and illustrated by selected examples and recent patents. New approaches and directions towards the practical use of multifunctional nanocarriers are highlighted.

  16. Ungual and transungual drug delivery.

    PubMed

    Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha

    2012-08-01

    Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate. PMID:22149347

  17. Transungual delivery: deliberations and creeds.

    PubMed

    Thatai, P; Sapra, B

    2014-10-01

    Although considered as trifling illness, nail diseases have a reasonably high occurrence and a noteworthy impact on the patients' quality of life. Furthermore, there is a need to improve the topical treatment for nail diseases to avoid drug interactions and to reduce side effects associated with oral therapy. Topical drug delivery to the nails has established amplified consideration lately. Strategies (such as chemical enhancers, formulation strategies, physical and mechanical methods) are being investigated in order to improve drug permeability across the nail plate. The rationale of this review is to present contemporary information on the structure of human nail along with its comparison with animal hooves. Precincts of nail permeability have been briefly discussed with respect to factors like permeant's molecular size, hydrophilicity, charge and the nature of the vehicle. These factors affect drug uptake and permeation through the nail. Formulations like nail lacquers which mimic cosmetic varnish and colloidal carriers along with nail substitutes that can be utilized for transungual delivery have also been discussed. PMID:24888698

  18. Aptamers for Targeted Drug Delivery

    PubMed Central

    Ray, Partha; White, Rebekah R.

    2010-01-01

    Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery. PMID:27713328

  19. Aptamers for Targeted Drug Delivery

    PubMed Central

    Ray, Partha; White, Rebekah R.

    2010-01-01

    Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  20. Carbohydrate Nanoparticles for Brain Delivery.

    PubMed

    Lalatsa, A; Barbu, E

    2016-01-01

    Many brain tumors and neurological diseases can greatly benefit from the use of emerging nanotechnologies based on targeted nanomedicines that are able to noninvasively transport highly potent and specific pharmaceuticals across the blood-brain barrier. Carbohydrates have received considerable interest as materials for drug carriers due to their natural origin and inherent biodegradability and biocompatibility, as well as due to their hydrophilic character and ease of chemical modification combined with low cost and the possibility for large-scale manufacturing. This chapter provides an overview of the latest research involving the use of carbohydrate-based nanoparticles for drug delivery to the central nervous system. After reviewing the challenges posed by delivering drugs into the brain, the current state-of-the-art approaches for delivery of actives across the blood-brain barrier, including invasive and noninvasive strategies, are presented. A particular focus has been placed on chitosan polymers as they are among the most promising carbohydrate nanocarriers for the preparation and testing of chitosan-based nanomedicines that led, in preclinical proof-of-concept studies, to enhanced brain drug levels and increased pharmacodynamics responses after intravenous, nasal, and oral administration. While chitosan nanoparticles are to date among the most studied and most promising carriers, approaches based on other polysaccharides such as dextran, pullulan, and cellulose warrant further research in the attempt to advance the existing technologies for overcoming the blood-brain barrier. PMID:27678176

  1. Episodic transdermal delivery of testosterone.

    PubMed

    Malik, Ritu; Venkatesh, K S; Dwivedi, Anil Kumar; Misra, Amit

    2012-06-01

    Film-forming lotions, precast films and adhesive patches containing testosterone (T) were prepared by compounding vinylic, acrylic and cellulosic polymers with a variety of excipients in order to achieve distribution of T in domains of heterogeneity within multicomponent matrices. The feasibility of this approach in achieving episodic transdermal delivery of testosterone (T) was investigated. Composition-dependent differences in extent of in vitro drug release and periodicity were observed. Representative formulations showing the most pronounced episodic T release in vitro were tested in female rats. Whereas intravenously administered T decayed exponentially, three maxima of T in serum were observed upon application of selected formulations. Thus, peak serum concentrations of 240, 36, and 29 ng/dL were observed at 0.2, 5, and 16.8 h after application of the preferred lotion formulation, and 89, 65, and 64 ng/dL at 1, 16.4, and 48.8 h after patches. Deconvolution, noncompartment pharmacokinetic analysis and multiple peak fitting also indicated episodicity. These results suggest the feasibility of using transdermal systems for pulsatile T delivery in a variety of clinical applications, including hormone supplementation and male contraception.

  2. Immunization delivery in British Columbia

    PubMed Central

    Omura, John; Buxton, Jane; Kaczorowski, Janusz; Catterson, Jason; Li, Jane; Derban, Andrea; Hasselback, Paul; Machin, Shelagh; Linekin, Michelle; Morgana, Tamsin; O’Briain, Barra; Scheifele, David; Dawar, Meena

    2014-01-01

    Abstract Objective To explore the experiences of family physicians and pediatricians delivering immunizations, including perceived barriers and supports. Design Qualitative study using focus groups. Setting Ten cities throughout British Columbia. Participants A total of 46 family physicians or general practitioners, 10 pediatricians, and 2 residents. Methods A semistructured dialogue guide was used by a trained facilitator to explore participants’ experiences and views related to immunization delivery in British Columbia. Verbatim transcriptions were independently coded by 2 researchers. Key themes were analyzed and identified in an iterative manner using interpretive description. Main findings Physicians highly valued vaccine delivery. Factors facilitating physician-delivered immunizations included strong beliefs in the value of vaccines and having adequate information. Identified barriers included the large time commitment and insufficient communication about program changes, new vaccines, and the adult immunization program in general. Some physicians reported good relationships with local public health, while others reported the opposite experience, and this varied by geographic location. Conclusion These findings suggest that physicians are supportive of delivering vaccines. However, there are opportunities to improve the sustainability of physician-delivered immunizations. While compensation schemes remain under the purview of the provincial governments, local public health authorities can address the information needs of physicians. PMID:24627403

  3. Transungual delivery: deliberations and creeds.

    PubMed

    Thatai, P; Sapra, B

    2014-10-01

    Although considered as trifling illness, nail diseases have a reasonably high occurrence and a noteworthy impact on the patients' quality of life. Furthermore, there is a need to improve the topical treatment for nail diseases to avoid drug interactions and to reduce side effects associated with oral therapy. Topical drug delivery to the nails has established amplified consideration lately. Strategies (such as chemical enhancers, formulation strategies, physical and mechanical methods) are being investigated in order to improve drug permeability across the nail plate. The rationale of this review is to present contemporary information on the structure of human nail along with its comparison with animal hooves. Precincts of nail permeability have been briefly discussed with respect to factors like permeant's molecular size, hydrophilicity, charge and the nature of the vehicle. These factors affect drug uptake and permeation through the nail. Formulations like nail lacquers which mimic cosmetic varnish and colloidal carriers along with nail substitutes that can be utilized for transungual delivery have also been discussed.

  4. Ungual and transungual drug delivery.

    PubMed

    Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha

    2012-08-01

    Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.

  5. "Programmed packaging" for gene delivery.

    PubMed

    Hyodo, M; Sakurai, Y; Akita, H; Harashima, H

    2014-11-10

    We report on the development of a multifunctional envelope-type nano device (MEND) based on our packaging concept "Programmed packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept. PMID:24780263

  6. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

    Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.

  7. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension

  8. Recent Patents in Pulmonary Delivery of Macromolecules.

    PubMed

    Ray, Animikh; Mandal, Abhirup; Mitra, Ashim K

    2015-01-01

    Pulmonary delivery is a non-invasive form of delivery that holds tremendous therapeutic promise for topical and systemic administration of several macromolecules. Oral administration of macromolecules has several limitations such as low bioavailability, degradation of drug before reaching circulation and insufficient absorption across intestinal membrane. Administration of macromolecules such as proteins, peptides and nucleic acids via inhalation offers great potential due to the avoidance of first pass metabolism, higher surface area and rapid clinical response. However, delivery of reproducible, uniform and safe doses of inhaled particles remains a major challenge for clinical translation. Recent advances in the fields of biotechnology and particle engineering led to progress in novel pulmonary drug delivery systems. Moreover, significant developments in carriers and delivery devices prevent denaturation of macromolecules and control their release within the lungs. This article reviews the advances in pulmonary drug delivery systems by focusing on the recent patents in delivery of macromolecules. Furthermore, recent patents in gene delivery to the lungs have also been discussed. List of patents included in this review is comprehensive in terms of pulmonary delivery of therapeutics. It includes inventions related to proteins and peptides, DNA therapeutics, siRNA and other genetic materials with therapeutic applications. The diseases targeted by these therapeutic molecules are varied including but not limited to different forms of cancer, respiratory diseases etc.

  9. Payment for deliveries in Sierra Leone.

    PubMed Central

    Edwards, N. C.; Birkett, N. J.; Sengeh, P. A.

    1989-01-01

    The type and amount of payment for deliveries were investigated in 1982 during a survey on health status in two districts. Data on the payments made for 83.5% of the 2591 deliveries in 535 randomly selected study villages showed that the most common method of payment was in cash only. Payments in kind were mostly given to trained traditional birth attendants (TBAs) (for 38.1% of their deliveries) and rare for professional staff (2.9% of deliveries). The total amount paid for a delivery differed significantly with the type of birth attendant (P less than 0.00001) and the place of delivery (hospital, peripheral health unit or home) (P less than 0.00001). The total average payment for a delivery was highest for professional birth attendants (Le 16.60) and lowest for untrained TBAs (Le 4.85) (Le 2 = approx. US+ 1 at the time of the study). The outcome of a delivery had a significant effect on the amount paid. Payments were significantly higher for stillbirths than for live births among professional and auxiliary birth attendants (P less than 0.0001). However, the trained and untrained TBAs received less payment for stillbirths (Le 2.25) than for live births (Le 4.89) (P = 0.0146). The results show that there are several levels of financial disincentives for pregnant women requiring the services of trained auxiliary or professional health workers at the time of delivery. PMID:2787215

  10. Vaccine Delivery Methods into the Future

    PubMed Central

    Apostolopoulos, Vasso

    2016-01-01

    Several modes of vaccine delivery have been developed in the last 25 years, which induce strong immune responses in pre-clinical models and in human clinical trials. Some modes of delivery include, adjuvants (aluminum hydroxide, Ribi formulation, QS21), liposomes, nanoparticles, virus like particles, immunostimulatory complexes (ISCOMs), dendrimers, viral vectors, DNA delivery via gene gun, electroporation or Biojector 2000, cell penetrating peptides, dendritic cell receptor targeting, toll-like receptors, chemokine receptors and bacterial toxins. There is an enormous amount of information and vaccine delivery methods available for guiding vaccine and immunotherapeutics development against diseases. PMID:27043641

  11. Dendrimers as Nanovectors for Nucleic Acid Delivery

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoxuan; Wang, Qi; Peng, Ling

    2013-09-01

    Nucleic acid based gene therapy holds great promise in the treatment of various diseases. However, the success of both DNA- and siRNAbased gene therapies depends critically on safe and efficient nucleic acid delivery systems. Owing to their well-defined structure and multivalent cooperativity, dendrimers have attracted particular attention as ideal nanocarriers for nucleic acid delivery. The present chapter highlights the current status of dendrimers as non-viral nanovectors for both DNA and siRNA delivery, focusing on the different dendrimers investigated for their delivery efficiency with respect to structural alterations in the view to developing safe and efficient nanovectors for gene therapy application.

  12. Integrated delivery systems focus on service delivery after capitation efforts stall.

    PubMed

    2005-03-01

    Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver.

  13. Integrated delivery systems focus on service delivery after capitation efforts stall.

    PubMed

    2005-03-01

    Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver. PMID:15889632

  14. Carbon-Carbon Piston Architectures

    NASA Technical Reports Server (NTRS)

    Rivers, H. Kevin (Inventor); Ransone, Philip O. (Inventor); Northam, G. Burton (Inventor); Schwind, Francis A. (Inventor)

    2000-01-01

    An improved structure for carbon-carbon composite piston architectures is disclosed. The improvement consists of replacing the knitted fiber, three-dimensional piston preform architecture described in U.S. Pat.No. 4,909,133 (Taylor et al.) with a two-dimensional lay-up or molding of carbon fiber fabric or tape. Initially, the carbon fabric of tape layers are prepregged with carbonaceous organic resins and/or pitches and are laid up or molded about a mandrel, to form a carbon-fiber reinforced organic-matrix composite part shaped like a "U" channel, a "T"-bar, or a combination of the two. The molded carbon-fiber reinforced organic-matrix composite part is then pyrolized in an inert atmosphere, to convert the organic matrix materials to carbon. At this point, cylindrical piston blanks are cored from the "U"-channel, "T"-bar, or combination part. These blanks are then densified by reimpregnation with resins or pitches which are subsequently carbonized. Densification is also accomplished by direct infiltration with carbon by vapor deposition processes. Once the desired density has been achieved, the piston billets are machined to final piston dimensions; coated with oxidation sealants; and/or coated with a catalyst. When compared to conventional steel or aluminum alloy pistons, the use of carbon-carbon composite pistons reduces the overall weight of the engine; allows for operation at higher temperatures without a loss of strength; allows for quieter operation; reduces the heat loss; and reduces the level of hydrocarbon emissions.

  15. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  16. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  17. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  18. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  19. 49 CFR 663.39 - Post-delivery audit review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Post-delivery audit review. 663.39 Section 663.39..., DEPARTMENT OF TRANSPORTATION PRE-AWARD AND POST-DELIVERY AUDITS OF ROLLING STOCK PURCHASES Post-Delivery Audits § 663.39 Post-delivery audit review. (a) If a recipient cannot complete a post-delivery...

  20. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t{sup {1/2}} and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and {sup 14}C-inulin release rates were evaluated subcutaneously in rats.

  1. Rapid Data Delivery System (RDDS)

    USGS Publications Warehouse

    Cress, Jill J.; Goplen, Susan E.

    2007-01-01

    Since the start of the active 2000 summer fire season, the U. S. Geological Survey (USGS) Rocky Mountain Geographic Science Center (RMGSC) has been actively engaged in providing crucial and timely support to Federal, State, and local natural hazards monitoring, analysis, response, and recovery activities. As part of this support, RMGSC has developed the Rapid Data Delivery System (RDDS) to provide emergency and incident response teams with timely access to geospatial data. The RDDS meets these needs by combining a simple web-enabled data viewer for the selection and preview of vector and raster geospatial data with an easy to use data ordering form. The RDDS viewer also incorporates geospatial locations for current natural hazard incidents, including wildfires, earthquakes, hurricanes, and volcanoes, allowing incident responders to quickly focus on their area of interest for data selection.

  2. Suborbital freight delivery concept exploration

    SciTech Connect

    Andrews, D.; Paris, S.; Rubeck, M.

    1997-01-01

    Suborbital Freight, sometimes called Fast Freight, is delivery of high priority packages over intercontinental distances in periods of approximately one hour. The vehicles required are usually rocket-powered and have total ideal velocities of around 7.5 km/second. Analysis of this market indicates that there are niches where commercial operations are possible and might even be profitable using today{close_quote}s state-of-the-art technologies. The key requirements to capture this market are low nonrecurring costs, quick turnaround ({lt}9hours), and high reliability (0.999). This draft is a report on work in progress. The Fast Freight study will be completed before the STAIF-97 conference and results will be presented at that time. {copyright} {ital 1997 American Institute of Physics.}

  3. Oxygen in the delivery room.

    PubMed

    Cernada, María; Cubells, Elena; Torres-Cuevas, Isabel; Kuligowski, Julia; Escobar, Javier; Aguar, Marta; Escrig, Raquel; Vento, Maximo

    2013-06-01

    Immediately after birth the newly born infant aerates the lungs, diminishes pulmonary vascular resistance, and initiates gas exchange. However, under certain circumstances this process will not be adequately accomplished. Asphyxia is characterized by periods of hypoxia and ischemia leading frequently to hypoxic ischemic encephalopathy. The mainstay of newborn resuscitation resides in the establishment of a functional residual capacity and an adequate oxygenation. Recent guidelines have established guidelines which provide counsel on the use of oxygen in term infants. However, preterm oxygenation in the delivery room (DR) has only been defined very vaguely. Herewith, we will address available information regarding the use of oxygen supplementation in the DR both in term and preterm babies for a satisfactory postnatal adaptation. PMID:23809339

  4. Cubosomes: remarkable drug delivery potential.

    PubMed

    Karami, Zahra; Hamidi, Mehrdad

    2016-05-01

    Cubosomes are nanostructured liquid crystalline particles, made of certain amphiphilic lipids in definite proportions, known as biocompatible carriers in drug delivery. Cubosomes comprise curved bicontinuous lipid bilayers that are organized in three dimensions as honeycombed structures and divided into two internal aqueous channels that can be exploited by various bioactive ingredients, such as chemical drugs, peptides and proteins. Owing to unique properties such as thermodynamic stability, bioadhesion, the ability of encapsulating hydrophilic, hydrophobic and amphiphilic substances, and the potential for controlled release through functionalization, cubosomes are regarded as promising vehicles for different routes of administration. Based on the most recent reports, this review introduces cubosomes focusing on their structure, preparation methods, mechanism of release and potential routes of administration. PMID:26780385

  5. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  6. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

    A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

  7. Nanocarriers for Nitric Oxide Delivery

    PubMed Central

    Saraiva, Juliana; Marotta-Oliveira, Samantha S.; Cicillini, Simone Aparecida; Eloy, Josimar de Oliveira; Marchetti, Juliana Maldonado

    2011-01-01

    Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology. PMID:21869934

  8. Nanodisks: hydrophobic drug delivery vehicles.

    PubMed

    Ryan, Robert O

    2008-03-01

    Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells.

  9. Tax exemption and integrated delivery systems.

    PubMed

    Aseltyne, W J; Peters, G R

    1994-01-01

    This chapter discusses tax exemption of integrated delivery systems, including the requirements for exemption, the charitable purposes test, the private inurement and private benefit tests, and an application to integrated delivery systems. It also discusses the structure of the Friendly Hills and Facey Nonprofit Medical Foundations, including the analysis of the Internal Revenue Service. Finally, it discusses the process for obtaining tax exemption.

  10. Puerperal endometritis after abdominal twin delivery.

    PubMed

    Suonio, S; Huttunen, M

    1994-04-01

    The infectious complications of 122 consecutive abdominal twin deliveries over the period 1984-1989 were analyzed in a prospective clinical study, comparing them with 761 singleton abdominal deliveries over the period 1984-1986. The incidence of endometritis was nearly three-fold after twin deliveries and the incidence of abdominal wound infections nearly two-fold compared with singleton abdominal pregnancies (13.1/4.7% and 5.6/3.0%). The risk of amnionitis was increased ten-fold, 6 hours after rupture of the membranes in abdominal twin delivery, but no connection was found between amnionitis and endometritis, as in singleton abdominal deliveries. Multiple regression analysis indicated only two risk factors as regards puerperal endometritis after abdominal twin delivery: age under 25 years (odds ratio 6.9, 95% confidence limits 1.9-24.8), an association also seen in singleton abdominal deliveries, and a period of more than 6 hours from rupture of membranes to delivery (odds ratio 7.8, 95% confidence limits 2.1-28.5). Multiple pregnancy appears to be associated with an increased risk of endometritis. The etiological factors remain unknown, but a large placental bed and/or immunological factors may be implicated. PMID:8160537

  11. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  12. Organized Athletics as a Leisure Delivery System.

    ERIC Educational Resources Information Center

    Kidd, Thomas R.; Mendell, Ron

    1980-01-01

    Athletic programs are leisure time delivery systems for the athletes, spectators, and the local community as long as scholarships and extensive media coverage are not involved. College administration should make sure that sports and athletics do not become a delivery sytem for public relations and finance. (CJ)

  13. Preparing a Course for Distance Education Delivery.

    ERIC Educational Resources Information Center

    Pollack, Thomas A.

    Duquesne University (Pennsylvania) has committed to the electronic delivery of an MBA (Masters in Business Administration) program to Northern Jiaotong University in Beijing, China. This paper describes the process of preparing a course for electronic delivery, along with related course preparation issues. The university's partnership with…

  14. Applications of Important Polysaccharides in Drug Delivery.

    PubMed

    Huang, Gangliang; Mei, Xinya; Xiao, Feng; Chen, Xin; Tang, Qilin; Peng, Daquan

    2015-01-01

    Polysaccharide is a kind of biological material, which has good biocompatibility, non-toxicity, and non-immunogenicity. So, the polysaccharide has widely been applied in drug delivery system. The applications of chitosan, hyaluronic acid and dextran in drug delivery have been summarized herein. PMID:25578889

  15. Toward Effective Science Delivery among Recreation Personnel

    ERIC Educational Resources Information Center

    Courtney, Arielle; Schneider, Ingrid E.

    2016-01-01

    Effective science delivery to practitioners can improve recreation experiences and environmental educational outcomes. This project explored U.S. Department of Agriculture-Forest Service recreation personnel's research-based information sources, constraints to access and use of research, and opinions about how to improve science delivery to…

  16. 18 CFR 157.211 - Delivery points.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Delivery points. 157.211 Section 157.211 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... supporting data, of the impact of the service rendered through the proposed delivery tap upon the...

  17. 18 CFR 157.211 - Delivery points.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Delivery points. 157.211 Section 157.211 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... supporting data, of the impact of the service rendered through the proposed delivery tap upon the...

  18. 18 CFR 157.211 - Delivery points.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Delivery points. 157.211 Section 157.211 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... supporting data, of the impact of the service rendered through the proposed delivery tap upon the...

  19. Automated Management and Delivery of Distance Courseware.

    ERIC Educational Resources Information Center

    Johnson, W. Lewis; Blake, Tyler; Shaw, Erin

    This paper describes a system called ANDES, designed for the management and delivery of distance education courses. ANDES enables students to study at home at their own pace, as well as interact with instructors and other students in virtual classrooms. It uses World Wide Web technology for transmission and delivery, with extensions relevant to…

  20. International Document Delivery: The ADONIS Project.

    ERIC Educational Resources Information Center

    Stern, Barrie; Campbell, Robert

    1989-01-01

    Describes the development of a project to test whether publishers can gain copyright revenue by supplying their journals in machine readable form for document delivery centers. Areas discussed include technical considerations; document delivery centers involved; workstation development; and statistical analyses to be reported at the end of the…

  1. Evaluating Student Perceptions of Course Delivery Platforms

    ERIC Educational Resources Information Center

    Bramorski, Tom; Madan, Manu S.

    2016-01-01

    In this paper we evaluate effectiveness of course delivery mode on three dimensions: values, networking opportunities and learning. While students and their future employers are two important customers for the business program, we focus on the perception of students regarding the effectiveness of course delivery mode on program performance. The…

  2. Development of the Choctaw Health Delivery System.

    ERIC Educational Resources Information Center

    Nguyen, Binh N.

    The Choctaw Tribe is the first and only tribe to develop a health delivery system to take over an existing Indian Health Service inpatient facility. The takeover was accomplished in January 1984 under the Indian Self-Determination Act through a contract with the Indian Health Service. The Choctaw Health Delivery System includes a 35-bed general…

  3. 78 FR 15797 - Service Delivery Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... objectives laid out in our Agency Strategic Plan. DATES: To ensure that we consider your comments, we must... ADMINISTRATION Service Delivery Plan AGENCY: Social Security Administration (SSA). ACTION: Notice; request for comments. SUMMARY: We are requesting public input as we finalize our Service Delivery Plan (SDP)....

  4. 77 FR 44306 - Service Delivery Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ... ADMINISTRATION Service Delivery Plan AGENCY: Social Security Administration (SSA). ACTION: Notice; request for comments. SUMMARY: We are requesting public input as we develop our Service Delivery Plan (SDP). We recently completed our Agency Strategic Plan (ASP) for 2013-2016. The ASP identifies four goals:...

  5. Health Service Delivery in Developing Countries

    ERIC Educational Resources Information Center

    Benyoussef, Amor

    1977-01-01

    Reviews recent work dealing with methodological and technical issues in health and development; presents examples of the application of social sciences, including health demography and economics, in questions of health services delivery; and analyzes delivery of health services to rural and nomadic populations in Africa, Asia, and Latin America.…

  6. Information Delivery Options over Three Decades.

    ERIC Educational Resources Information Center

    Kennedy, H. Edward

    1986-01-01

    The rate of new technology-driven innovations for information delivery has accelerated over the past three decades. New information delivery formats in the 1950s and 1960s included microforms and, in response to demands from librarians, indexing and abstracting services began to make their publications available on this medium. Electronic…

  7. 18 CFR 157.211 - Delivery points.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Delivery points. 157.211 Section 157.211 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... supporting data, of the impact of the service rendered through the proposed delivery tap upon the...

  8. 18 CFR 157.211 - Delivery points.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Delivery points. 157.211 Section 157.211 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... supporting data, of the impact of the service rendered through the proposed delivery tap upon the...

  9. Consumer Choice, Consumer Control in Service Delivery

    ERIC Educational Resources Information Center

    Meenaghan, Thomas M.; Mascari, Michael

    1971-01-01

    This article discusses patterns in the delivery of social welfare services, with reference to the specific service area of mental retardation. The authors propose a model that adds two vital elements to present service delivery patterns, a benefit system and a plan for consumer organization. (Author)

  10. Delivery system for laser medical instrument

    NASA Astrophysics Data System (ADS)

    Jelinkova, Helena; Nemec, Michal; Sulc, Jan; Cerny, Pavel; Miyagi, Mitsunobu; Shi, Yi-Wei; Matsuura, Yuji

    2003-10-01

    Investigation of the special constructed hollow glass waveguides was realized. Maximum mean power transmitted via this delivery system was 5.8 W (for alexandrite radiation) or 5.1 W (for mid infrared Er.YAG light). Maximum output intensity 173 GW/cm2 was reached for delivery of 55 psec long Nd:YAG pulses.

  11. Nanomeniscus-induced delivery of liquid solutions for diverse nanofiber fabrication

    NASA Astrophysics Data System (ADS)

    An, Sangmin; Kim, Bongsu; Kwon, Soyoung; Lee, Kunyoung; Kim, Jongwoo; Ahn, Heejoon; Jhe, Wonho

    2015-07-01

    Nanomaterial-delivery fabrication expects high-potential impacts on nanoscience, technology and industry, but still faces limited applicability mainly due to high-field requirement for liquid delivery, complicated intermediate processes, and narrow ink selectivity. Here, we demonstrates a simple, non-template, non-contact and electric field-free fabrication of diverse nanofibers. The process consists of continuous, meniscus-assisted delivery of liquid solutions through a nanoapertured nozzle in ambient conditions, followed by subsequent evaporation of liquid and aggregation of nanoparticle residues. For example, the carbon-nanotube nanofibers of 500 nm diameter exhibit a high shear modulus of ~1.5 GPa and current density up to 104 A/cm2. The results provide a unique, universal and versatile tool with wide selectivity in both ink and substrate.

  12. Towards erythropoietin equations that estimate oxygen delivery rather than static hemoglobin targets.

    PubMed

    Diskin, Charles J

    2012-01-01

    Although we have known since the 19th century that oxygen tension affects erythrocyte production, we have only recently begun to understand many subtleties of erythropoietin physiology. The unanticipated increase in mortality associated with erythropoietin use found in recent randomized studies is prompting a reassessment of static hemoglobin targets. Hemoglobin levels in dialysis patients do not correlate with endogenous erythropoietin production and may be related to differences in oxygen delivery resulting from shifts in the oxygen-hemoglobin dissociation curve. The time may have arrived to develop more physiologic targets such as oxygen delivery that would mimic the natural response to hypoxia. There are several equations that already exist that can compensate for the effects of the concentration of inorganic and organic phosphates as well as pH, carbon dioxide, and temperature on the delivery of oxygen. However, since the shape and dispersion of the oxygen-hemoglobin dissociation curve may actually change in different disease states, more work is needed.

  13. [Carbon monoxide poisoning].

    PubMed

    Jaeger, K; Ruschulte, H; Heine, J; Piepenbrock, S

    2000-01-01

    Carbon monoxide (CO) is a product of incomplete burning of coals and carbon compounds and is a gas without any typical taste, colour or smell. Defective radiators or gas pipes, open fireplaces, fires and explosions are sources of unintended CO production and inhalation. CO bonds with haemoglobin much more readily than oxygen does. CO toxicity causes impaired oxygen delivery and utilisation at cellular level. It affects different sites within the body, but has its most profound impact on the organs with the highest oxygen requirement. CO concentration and the intensity and duration of inhalation determine the extent of intoxication. Following basic life support, assisted or controlled ventilation with 100% oxygen is essential during emergency care. Hyperbaric oxygenation (HBO) is the preferred therapeutic option for releasing CO from its binding to haemoglobin. It has been shown that CO may cause lipid peroxidation and leukocyte-mediated inflammatory changes in the brain, a process that may be inhibited by HBO. Patients with neurological symptoms including loss of consciousness and expectant mothers should undergo HBO treatment, no matter how high their CO levels are. Neonates and in-utero fetuses are more vulnerable due to the natural leftward shift of the dissociation curve of fetal haemoglobin, a lower baseline pO2 and carboxyhaemoglobin levels at equilibration that are 10-15% higher than maternal levels. Physicians need to be aware of the potential occurrence of this life threatening hazard so that appropriate emergency treatment can be administered and fatalities prevented. PMID:10920484

  14. Nanoparticles for intracellular-targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Paulo, Cristiana S. O.; Pires das Neves, Ricardo; Ferreira, Lino S.

    2011-12-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  15. Heart-targeted nanoscale drug delivery systems.

    PubMed

    Liu, Meifang; Li, Minghui; Wang, Guangtian; Liu, Xiaoying; Liu, Daming; Peng, Haisheng; Wang, Qun

    2014-09-01

    The efficacious delivery of drugs to the heart is an important treatment strategy for various heart diseases. Nanocarriers have shown increasing promise in targeted drug delivery systems. The success of nanocarriers for delivering drugs to therapeutic sites in the heart mainly depends on specific target sites, appropriate drug delivery carriers and effective targeting ligands. Successful targeted drug delivery suggests the specific deposition of a drug in the heart with minimal effects on other organs after administration. This review discusses the pathological manifestations, pathogenesis, therapeutic limitations and new therapeutic advances in various heart diseases. In particular, we summarize the recent advances in heart-targeted nanoscale drug delivery systems, including dendrimers, liposomes, polymer-drug conjugates, microparticles, nanostents, nanoparticles, micelles and microbubbles. Current clinical trials, the commercial market and future perspective are further discussed in the conclusions.

  16. Multi-channel gas-delivery system

    DOEpatents

    Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

    2016-09-13

    One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gases to a corresponding gas channel.

  17. Cyclodextrins in non-viral gene delivery.

    PubMed

    Lai, Wing-Fu

    2014-01-01

    Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an "inner-outer" amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades. PMID:24103652

  18. Lunar Cycle Influences Spontaneous Delivery in Cows.

    PubMed

    Yonezawa, Tomohiro; Uchida, Mona; Tomioka, Michiko; Matsuki, Naoaki

    2016-01-01

    There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition. PMID:27580019

  19. Lunar Cycle Influences Spontaneous Delivery in Cows

    PubMed Central

    Yonezawa, Tomohiro; Uchida, Mona; Tomioka, Michiko; Matsuki, Naoaki

    2016-01-01

    There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition. PMID:27580019

  20. Controlled delivery of antibodies from injectable hydrogels.

    PubMed

    Fletcher, Nathan A; Babcock, Lyndsey R; Murray, Ellen A; Krebs, Melissa D

    2016-02-01

    Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invasive potential for controlled release in a localized area. Here, alginate-chitosan hydrogels are demonstrated to provide controlled delivery of IgG model antibodies and also of Fab antibody fragments. Also, an alternate delivery system comprised of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with antibodies and encapsulated in alginate was shown to successfully provide another level of control over release. These biopolymer systems that offer controlled delivery for antibodies and antibody fragments will be promising for many applications in drug delivery and regenerative medicine.

  1. Delivery materials for siRNA therapeutics

    NASA Astrophysics Data System (ADS)

    Kanasty, Rosemary; Dorkin, Joseph Robert; Vegas, Arturo; Anderson, Daniel

    2013-11-01

    RNA interference (RNAi) has broad potential as a therapeutic to reversibly silence any gene. To achieve the clinical potential of RNAi, delivery materials are required to transport short interfering RNA (siRNA) to the site of action in the cells of target tissues. This Review provides an introduction to the biological challenges that siRNA delivery materials aim to overcome, as well as a discussion of the way that the most effective and clinically advanced classes of siRNA delivery systems, including lipid nanoparticles and siRNA conjugates, are designed to surmount these challenges. The systems that we discuss are diverse in their approaches to the delivery problem, and provide valuable insight to guide the design of future siRNA delivery materials.

  2. Fiber laser coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam

    2008-03-04

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  3. Natural Carriers for siRNA Delivery.

    PubMed

    Karunaratne, D Nedra; Jafari, Mousa; Ranatunga, R J K Udayana; Siriwardhana, Asitha

    2015-01-01

    This review is based on carriers of natural origin such as polysaccharides, proteins, and cell derived entities which have been used for delivery of siRNA. To realize the therapeutic potential of a delivery system, the role of the carrier is of utmost importance. Historical aspects of viral vectors, the first carriers of genes are briefly outlined. Chitosan, one of the extensively experimented carriers, alginates and other polysaccharides have shown success in siRNA delivery. Peptides of natural origin and mimics thereof have emerged as another versatile carrier. Exosomes and mini cells of cellular origin are the newest entrants to the area of siRNA delivery and probably the closest one can get to a natural carrier. In many of the carriers, modifications have provided better efficiency in delivery. The salient features of the carriers and their advantages and disadvantages are also reviewed.

  4. Cell Nucleus-Targeting Zwitterionic Carbon Dots

    PubMed Central

    Jung, Yun Kyung; Shin, Eeseul; Kim, Byeong-Su

    2015-01-01

    An innovative nucleus-targeting zwitterionic carbon dot (CD) vehicle has been developed for anticancer drug delivery and optical monitoring. The zwitterionic functional groups of the CDs introduced by a simple one-step synthesis using β-alanine as a passivating and zwitterionic ligand allow cytoplasmic uptake and subsequent nuclear translocation of the CDs. Moreover, multicolor fluorescence improves the accuracy of the CDs as an optical code. The CD-based drug delivery system constructed by non-covalent grafting of doxorubicin, exhibits superior antitumor efficacy owing to enhanced nuclear delivery in vitro and tumor accumulation in vivo, resulting in highly effective tumor growth inhibition. Since the zwitterionic CDs are highly biocompatible and effectively translocated into the nucleus, it provides a compelling solution to a multifunctional nanoparticle for substantially enhanced nuclear uptake of drugs and optical monitoring of translocation. PMID:26689549

  5. Cell Nucleus-Targeting Zwitterionic Carbon Dots.

    PubMed

    Jung, Yun Kyung; Shin, Eeseul; Kim, Byeong-Su

    2015-12-22

    An innovative nucleus-targeting zwitterionic carbon dot (CD) vehicle has been developed for anticancer drug delivery and optical monitoring. The zwitterionic functional groups of the CDs introduced by a simple one-step synthesis using β-alanine as a passivating and zwitterionic ligand allow cytoplasmic uptake and subsequent nuclear translocation of the CDs. Moreover, multicolor fluorescence improves the accuracy of the CDs as an optical code. The CD-based drug delivery system constructed by non-covalent grafting of doxorubicin, exhibits superior antitumor efficacy owing to enhanced nuclear delivery in vitro and tumor accumulation in vivo, resulting in highly effective tumor growth inhibition. Since the zwitterionic CDs are highly biocompatible and effectively translocated into the nucleus, it provides a compelling solution to a multifunctional nanoparticle for substantially enhanced nuclear uptake of drugs and optical monitoring of translocation.

  6. Carbon cyclist

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    A satellite launched in early August as part of NASA's Mission to Planet Earth could dramatically increase understanding of how carbon cycles through the Earth's biosphere and living organisms and how this process influences global climate. The Sea-viewing Wide Field-of-View Sensor (SeaWiFS) will measure the color of the oceans with a radiometer to determine the concentration of chlorophyll found in oceanic phytoplankton. The single-celled plants, at the base of food chains around the world, remove carbon dioxide from seawater through photosynthesis, which allows oceans to absorb more carbon dioxide from the atmosphere.

  7. Primary Cesarean Delivery in the United States

    PubMed Central

    Boyle, Annelee; Reddy, Uma M.; Landy, Helain J.; Huang, Chun-Chih; Driggers, Rita W.; Laughon, S. Katherine

    2013-01-01

    OBJECTIVES To characterize the indications for primary cesarean delivery in a large national cohort and to identify opportunities to lower the U.S. primary cesarean rate. METHODS A retrospective cohort study of the 38,484 primary cesarean deliveries among the 228,562 deliveries at sites participating in the Consortium on Safe Labor from 2002 to 2008. RESULTS The primary cesarean rate was 30.8% for primiparous women and 11.5% for multiparous women. The most common indications for primary cesarean delivery were failure to progress (35.4%), nonreassuring fetal heart rate tracing (27.3%), and fetal malpresentation (18.5%), although frequencies for each indication varied by parity. Among women with failure to progress, 42.6% of primiparous women and 33.5% of multiparous women never progressed beyond 5cm of dilation prior to delivery. Among women who reached the second stage of labor, 17.3% underwent cesarean delivery for arrest of descent before 2 hours and only 1.1% were given a trial of operative vaginal delivery. Of all primary cesarean deliveries, 45.6% were performed on primiparous women at term with a singleton fetus in cephalic presentation. CONCLUSION Using 6 cm as the cutoff for active labor, allowing adequate time for the second stage of labor, and encouraging operative vaginal delivery, when appropriate, may be important strategies to reduce the primary cesarean delivery rate. These actions may be particularly important in the primiparous woman at term with a singleton fetus in cephalic presentation. PMID:23743454

  8. Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

    PubMed

    Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-01-01

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects. PMID:27483234

  9. From Lab to Fab: Developing a Nanoscale Delivery Tool for Scalable Nanomanufacturing

    NASA Astrophysics Data System (ADS)

    Safi, Asmahan A.

    The emergence of nanomaterials with unique properties at the nanoscale over the past two decades carries a capacity to impact society and transform or create new industries ranging from nanoelectronics to nanomedicine. However, a gap in nanomanufacturing technologies has prevented the translation of nanomaterial into real-world commercialized products. Bridging this gap requires a paradigm shift in methods for fabricating structured devices with a nanoscale resolution in a repeatable fashion. This thesis explores the new paradigms for fabricating nanoscale structures devices and systems for high throughput high registration applications. We present a robust and scalable nanoscale delivery platform, the Nanofountain Probe (NFP), for parallel direct-write of functional materials. The design and microfabrication of NFP is presented. The new generation addresses the challenges of throughput, resolution and ink replenishment characterizing tip-based nanomanufacturing. To achieve these goals, optimized probe geometry is integrated to the process along with channel sealing and cantilever bending. The capabilities of the newly fabricated probes are demonstrated through two type of delivery: protein nanopatterning and single cell nanoinjection. The broad applications of the NFP for single cell delivery are investigated. An external microfluidic packaging is developed to enable delivery in liquid environment. The system is integrated to a combined atomic force microscope and inverted fluorescence microscope. Intracellular delivery is demonstrated by injecting a fluorescent dextran into Hela cells in vitro while monitoring the injection forces. Such developments enable in vitro cellular delivery for single cell studies and high throughput gene expression. The nanomanufacturing capabilities of NFPs are explored. Nanofabrication of carbon nanotube-based electronics presents all the manufacturing challenges characterizing of assembling nanomaterials precisely onto devices. The

  10. Graphene and graphene oxide as a docking station for modern drug delivery system.

    PubMed

    Muthoosamy, Kasturi; Bai, Renu G; Manickam, Sivakumar

    2014-01-01

    Motivated by the success and exhaustive research on carbon nanotubes (CNTs) based drug delivery, graphene, a two-dimensional; honey-comb crystal lattice has emerged as the rising star in recent years. Graphene is a flat monolayer of carbon atoms that holds many promising properties such as unparalleled thermal conductivity, remarkable electronic properties, and most intriguingly higher planar surface and superlative mechanical strength, which are attractive in biotechnological applications. Delivery of anti-cancer drugs using graphene and its derivatives has sparked major interest in this emerging field. The anti-cancer therapies often pose a limitation of insolubility, administration problems and cell penetration ability. In addition, systemic toxicity caused by lack of selective targeting towards cancer cells and inefficient distribution limits its clinical applications. Graphene nanocomposite is a promising tool to address these drawbacks. This review will focus on various synthesis and functionalization of graphene and graphene oxide for providing better solubility and targeted drug delivery at cancer cells. A more advanced and 'smart' graphene hybrid nanostructures that have several functionalities such as stimulus-response mediated delivery, imaging at release sites as well as transfection into cancer cells are also presented. A brief description on the challenges and perspectives for future research in this field is also discussed. PMID:24909150

  11. Leveraging socially networked mobile ICT platforms for the last-mile delivery problem.

    PubMed

    Suh, Kyo; Smith, Timothy; Linhoff, Michelle

    2012-09-01

    Increasing numbers of people are managing their social networks on mobile information and communication technology (ICT) platforms. This study materializes these social relationships by leveraging spatial and networked information for sharing excess capacity to reduce the environmental impacts associated with "last-mile" package delivery systems from online purchases, particularly in low population density settings. Alternative package pickup location systems (PLS), such as a kiosk on a public transit platform or in a grocery store, have been suggested as effective strategies for reducing package travel miles and greenhouse gas emissions, compared to current door-to-door delivery models (CDS). However, our results suggest that a pickup location delivery system operating in a suburban setting may actually increase travel miles and emissions. Only once a social network is employed to assist in package pickup (SPLS) are significant reductions in the last-mile delivery distance and carbon emissions observed across both urban and suburban settings. Implications for logistics management's decades-long focus on improving efficiencies of dedicated distribution systems through specialization, as well as for public policy targeting carbon emissions of the transport sector are discussed.

  12. Calcium Carbonate.

    PubMed

    Al Omari, M M H; Rashid, I S; Qinna, N A; Jaber, A M; Badwan, A A

    2016-01-01

    Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables.

  13. Calcium Carbonate.

    PubMed

    Al Omari, M M H; Rashid, I S; Qinna, N A; Jaber, A M; Badwan, A A

    2016-01-01

    Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables. PMID:26940168

  14. Developments in carbon materials

    NASA Technical Reports Server (NTRS)

    Burchell, Timothy D.

    1994-01-01

    The following carbon-based materials are reviewed and their applications discussed: fullerenes; graphite (synthetic and manufactured); activated carbon fibers; and carbon-carbon composites. Carbon R&D activities at ORNL are emphasized.

  15. TOPICAL REVIEW: Carbon nanomaterials in biological systems

    NASA Astrophysics Data System (ADS)

    Ke, Pu Chun; Qiao, Rui

    2007-09-01

    This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment.

  16. Infiltrated carbon foam composites

    NASA Technical Reports Server (NTRS)

    Lucas, Rick D. (Inventor); Danford, Harry E. (Inventor); Plucinski, Janusz W. (Inventor); Merriman, Douglas J. (Inventor); Blacker, Jesse M. (Inventor)

    2012-01-01

    An infiltrated carbon foam composite and method for making the composite is described. The infiltrated carbon foam composite may include a carbonized carbon aerogel in cells of a carbon foam body and a resin is infiltrated into the carbon foam body filling the cells of the carbon foam body and spaces around the carbonized carbon aerogel. The infiltrated carbon foam composites may be useful for mid-density ablative thermal protection systems.

  17. Lipid nanoparticles for dermal drug delivery.

    PubMed

    Kakadia, Pratibha G; Conway, Barbara R

    2015-01-01

    Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles. The extent and ability of nanoparticles to penetrate into the underlying viable tissue is still the subject of debate although recent studies have identified the follicular route as the most likely route of entry; this influences the potential applications of these dosage forms as a drug delivery strategy. This paper reviews present state of art of lipid-based nanocarriers focussing on solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, their production methods, potential advantages and applications in dermal drug delivery. PMID:25925115

  18. Oral Insulin Delivery: How Far Are We?

    PubMed Central

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  19. Development of Protein Mimics for Intracellular Delivery

    PubMed Central

    deRonde, Brittany M.; Tew, Gregory N.

    2015-01-01

    Designing delivery agents for therapeutics is an ongoing challenge. As treatments and desired cargoes become more complex, the need for improved delivery vehicles becomes critical. Excellent delivery vehicles must ensure the stability of the cargo, maintain the cargo’s solubility, and promote efficient delivery and release. In order to address these issues, many research groups have looked to nature for design inspiration. Proteins, such as HIV-1 TAT and Antennapedia homeodomain protein, are capable of crossing cellular membranes. However, due to the complexities of their structures, they are synthetically challenging to reproduce in the laboratory setting. Being able to incorporate the key features of these proteins that enable cell entry into simpler scaffolds opens up a wide range of opportunities for the development of new delivery reagents with improved performance. This review charts the development of protein mimics based on cell-penetrating peptides and how structure-activity relationships with these molecules and their protein counterparts ultimately led to the use of polymeric scaffolds. These scaffolds deviate from the normal peptide backbone, allowing for simpler, synthetic procedures to make carriers and tune chemical compositions for application specific needs. Successful design of polymeric protein mimics would allow researchers to further understand the key features in proteins and peptides necessary for efficient delivery and to design the next generation of more efficient delivery reagents. PMID:25858701

  20. Magnetizable implants for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Forbes, Zachary Graham

    The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. This project proposes a method for targeted drug delivery by applying high magnetic field gradients within the body to an injected superparamagnetic colloidal fluid carrying a drug, with the aid of modest uniform magnetic field. The design involves patterning of endovascular implants, such as coronary stents, with soft magnetic coatings capable of applying high local magnetic field gradients within the body. Examination of the feasibility of the design has been focused around the treatment of coronary restenosis following angioplasty. Drug-eluting stents, which have debuted in hospitals over the past two years, have thus far reduced restenosis rates to below 10%. Our local drug delivery system is a viable alternative or enhancement to drug-eluting stents, offering increased clinician control of dose size, the ability to treat a site repeatedly, and a wide array of applications for treatment of other pathologies. The theoretical models, parallel plate and pipe flow analysis, and cell culture models presented give insight into the use of micron and sub-micron scale magnetic particles for site-specific delivery of pharmaceuticals and magnetically labeled cells.

  1. Carbon Dioxide Laser Fiber Optics In Endoscopy

    NASA Astrophysics Data System (ADS)

    Fuller, Terry A.

    1982-12-01

    Carbon dioxide laser surgery has been limited to a great extent to surgical application on the integument and accessible cavities such as the cervix, vagina, oral cavities, etc. This limitation has been due to the rigid delivery systems available to all carbon dioxide lasers. Articulating arms (series of hollow tubes connected by articulating mirrors) have provided an effective means of delivery of laser energy to the patient as long as the lesion was within the direct line of sight. Even direct line-of-sight applications were restricted to physical dimension of the articulating arm or associated hand probes, manipulators and hollow tubes. The many attempts at providing straight endoscopic systems to the laser only stressed the need for a fiber optic capable of carrying the carbon dioxide laser wavelength. Rectangular and circular hollow metal waveguides, hollow dielectric waveguides have proven ineffective to the stringent requirements of a flexible surgical delivery system. One large diameter (1 cm) fiber optic delivery system, incorporates a toxic thalliumAbased fiber optic material. The device is an effective alternative to an articulating arm for external or conventional laser surgery, but is too large and stiff to use as a flexible endoscopic tool. The author describes the first highly flexible inexpensive series of fiber optic systems suitable for either conventional or endoscopic carbon dioxide laser surgery. One system (IRFLEX 3) has been manufactured by Medlase, Inc. for surgical uses capable of delivering 2000w, 100 mJ pulsed energy and 15w continuous wave. The system diameter is 0.035 inches in diameter. Surgically suitable fibers as small as 120 um have been manufactured. Other fibers (IRFLEX 142,447) have a variety of transmission characteristics, bend radii, etc.

  2. Recent advances in ocular drug delivery.

    PubMed

    Achouri, Djamila; Alhanout, Kamel; Piccerelle, Philippe; Andrieu, Véronique

    2013-11-01

    Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable

  3. Assembly of single-walled carbon nanohorn supported liposome particles.

    PubMed

    Huang, Wei; Zhang, Jianfei; Dorn, Harry C; Geohegan, David; Zhang, Chenming

    2011-06-15

    Nanoparticle-supported liposomes can be a promising platform for drug delivery, vaccine development, and biomedical imaging. Single-walled carbon nanohorns are a relatively new carbon nanomaterial, and they could be used as carriers of drug and imaging reagents. Assembling lipids around carbon nanohorns would confer this nanomaterial much broader applications such as vaccine development and targeted drug delivery by embedding a target protein or immunogenic protein into the lipid bilayer structure. Here, we show the assembly of functionalized single-walled carbon nanohorns (-CH(2)-CH(2)-COOH(x), ~100 nm) with positively charged lipids through a freeze and thaw cycle. The assembled complex particles can be readily separated from individual nanohorns or liposomes under specific centrifugation conditions. The results from transmission electronic microscopy, flow cytometry through nitrobenzoxadiazole labeled lipids, and zeta potential analysis clearly show that the nanohorns are encapsulated by liposomes with a median size of ca. 120 nm.

  4. Paclitaxel Nano-Delivery Systems: A Comprehensive Review

    PubMed Central

    Ma, Ping; Mumper, Russell J.

    2013-01-01

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

  5. Microvesicle and tunneling nanotube mediated intercellular transfer of g-protein coupled receptors in cell cultures

    SciTech Connect

    Guescini, M.; Leo, G.; Genedani, S.; Carone, C.; Pederzoli, F.; Ciruela, F.; Guidolin, D.; Stocchi, V.; Mantuano, M.; Borroto-Escuela, D.O.; Fuxe, K.; Agnati, L.F.

    2012-03-10

    Recent evidence shows that cells exchange collections of signals via microvesicles (MVs) and tunneling nano-tubes (TNTs). In this paper we have investigated whether in cell cultures GPCRs can be transferred by means of MVs and TNTs from a source cell to target cells. Western blot, transmission electron microscopy and gene expression analyses demonstrate that A{sub 2A} and D{sub 2} receptors are present in released MVs. In order to further demonstrate the involvement of MVs in cell-to-cell communication we created two populations of cells (HEK293T and COS-7) transiently transfected with D{sub 2}R-CFP or A{sub 2A}R-YFP. These two types of cells were co-cultured, and FRET analysis demonstrated simultaneously positive cells to the D{sub 2}R-CFP and A{sub 2A}R-YFP. Fluorescence microscopy analysis also showed that GPCRs can move from one cell to another also by means of TNTs. Finally, recipient cells pre-incubated for 24 h with A{sub 2A}R positive MVs were treated with the adenosine A{sub 2A} receptor agonist CGS-21680. The significant increase in cAMP accumulation clearly demonstrated that A{sub 2A}Rs were functionally competent in target cells. These findings demonstrate that A{sub 2A} receptors capable of recognizing and decoding extracellular signals can be safely transferred via MVs from source to target cells.

  6. Nanotubes mediate niche-stem cell signaling in the Drosophila testis

    PubMed Central

    Inaba, Mayu; Buszczak, Michael; Yamashita, Yukiko M.

    2015-01-01

    Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short-range such that only stem cells but not their differentiating progeny receive the self-renewing signals1. However, the cellular mechanisms that limit niche signaling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells (GSCs) form previously unrecognized structures, microtubule-based (MT)-nanotubes, which extend into the hub, a major niche component. MT-nanotubes are observed specifically within GSC populations, and require IFT (intraflagellar transport) proteins for their formation. The BMP receptor Tkv localizes to MT-nanotubes. Perturbation of MT-nanotubes compromises activation of Dpp signaling within GSCs, leading to GSC loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for MT-nanotube formation. We propose that MT-nanotubes provide a novel mechanism for selective receptor-ligand interaction, contributing to the short-range nature of niche-stem cell signaling. PMID:26131929

  7. Boron Nitride Nanotube-Mediated Stimulation of Cell Co-Culture on Micro-Engineered Hydrogels

    PubMed Central

    Ricotti, Leonardo; Fujie, Toshinori; Vazão, Helena; Ciofani, Gianni; Marotta, Roberto; Brescia, Rosaria; Filippeschi, Carlo; Corradini, Irene; Matteoli, Michela; Mattoli, Virgilio; Ferreira, Lino; Menciassi, Arianna

    2013-01-01

    In this paper, we describe the effects of the combination of topographical, mechanical, chemical and intracellular electrical stimuli on a co-culture of fibroblasts and skeletal muscle cells. The co-culture was anisotropically grown onto an engineered micro-grooved (10 µm-wide grooves) polyacrylamide substrate, showing a precisely tuned Young’s modulus (∼ 14 kPa) and a small thickness (∼ 12 µm). We enhanced the co-culture properties through intracellular stimulation produced by piezoelectric nanostructures (i.e., boron nitride nanotubes) activated by ultrasounds, thus exploiting the ability of boron nitride nanotubes to convert outer mechanical waves (such as ultrasounds) in intracellular electrical stimuli, by exploiting the direct piezoelectric effect. We demonstrated that nanotubes were internalized by muscle cells and localized in both early and late endosomes, while they were not internalized by the underneath fibroblast layer. Muscle cell differentiation benefited from the synergic combination of topographical, mechanical, chemical and nanoparticle-based stimuli, showing good myotube development and alignment towards a preferential direction, as well as high expression of genes encoding key proteins for muscle contraction (i.e., actin and myosin). We also clarified the possible role of fibroblasts in this process, highlighting their response to the above mentioned physical stimuli in terms of gene expression and cytokine production. Finally, calcium imaging-based experiments demonstrated a higher functionality of the stimulated co-cultures. PMID:23977119

  8. Nanotubes mediate niche-stem-cell signalling in the Drosophila testis.

    PubMed

    Inaba, Mayu; Buszczak, Michael; Yamashita, Yukiko M

    2015-07-16

    Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short range such that only stem cells but not their differentiating progeny receive the self-renewing signals. However, the cellular mechanisms that limit niche signalling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells form previously unrecognized structures, microtubule-based nanotubes, which extend into the hub, a major niche component. Microtubule-based nanotubes are observed specifically within germline stem cell populations, and require intraflagellar transport proteins for their formation. The bone morphogenetic protein (BMP) receptor Tkv localizes to microtubule-based nanotubes. Perturbation of microtubule-based nanotubes compromises activation of Dpp signalling within germline stem cells, leading to germline stem cell loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for microtubule-based nanotube formation. We propose that microtubule-based nanotubes provide a novel mechanism for selective receptor-ligand interaction, contributing to the short-range nature of niche-stem-cell signalling.

  9. Synthesis of CaCO3 Nanobelts for Drug Delivery in Cancer Therapy.

    PubMed

    Sun, Dongmei; Peng, Haibao; Wang, Shilong; Zhu, Dazhang

    2015-12-01

    Nanobelt carriers have demonstrated some advantages such as good biocompatibility, biodegradability, and strain-accommodating properties. We prepared an optimized nanobelt carrier formulation for drug (etoposide) as an oral delivery system and estimated the potential of calcium carbonate (CaCO3) nanobelts. The nanobelts were prepared by the method of binary solvent approach and were characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), and ultraviolet-visible (UV-vis) spectra. MTT (3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide) assay test exhibited that etoposide-loaded calcium carbonate nanobelts (ECCNBs) showed a higher cell kill ratio against SGC-7901 cells compared with free drug. The apoptosis test and cell cycle test analysis revealed that etoposide entrapped in calcium carbonate nanobelts (CCNBs) could enhance the delivery efficiencies of drug and improved inhibition effect. The present findings demonstrated that ECCNBs might induce cell cycle arrest at G2/M phase and cell apoptosis in a p53-related manner. It can be foreseen that CCNBs are a promising drug carrier to store the anti-cancer drug for cancer therapy and drug delivery. PMID:26055480

  10. Synthesis of CaCO3 Nanobelts for Drug Delivery in Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Sun, Dongmei; Peng, Haibao; Wang, Shilong; Zhu, Dazhang

    2015-05-01

    Nanobelt carriers have demonstrated some advantages such as good biocompatibility, biodegradability, and strain-accommodating properties. We prepared an optimized nanobelt carrier formulation for drug (etoposide) as an oral delivery system and estimated the potential of calcium carbonate (CaCO3) nanobelts. The nanobelts were prepared by the method of binary solvent approach and were characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), and ultraviolet-visible (UV-vis) spectra. MTT (3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide) assay test exhibited that etoposide-loaded calcium carbonate nanobelts (ECCNBs) showed a higher cell kill ratio against SGC-7901 cells compared with free drug. The apoptosis test and cell cycle test analysis revealed that etoposide entrapped in calcium carbonate nanobelts (CCNBs) could enhance the delivery efficiencies of drug and improved inhibition effect. The present findings demonstrated that ECCNBs might induce cell cycle arrest at G2/M phase and cell apoptosis in a p53-related manner. It can be foreseen that CCNBs are a promising drug carrier to store the anti-cancer drug for cancer therapy and drug delivery.

  11. Race, genes and preterm delivery.

    PubMed Central

    Fiscella, Kevin

    2005-01-01

    High rates of preterm delivery (PTD) among African Americans are the leading cause of excess infant mortality among African Americans. Failure to fully explain racial disparity in PTD has led to speculation that genetic factors might contribute to this disparity. Current evidence suggests that genetic factors contribute to PTD, but this does not imply that genetic factors contribute to racial disparity in PTD. Environmental factors clearly contribute to PTD. Many of these factors acting over a women's life prior to pregnancy disproportionately affect African Americans and contribute significantly to racial disparity in PTD. Thus, inferring genetic contribution to racial disparity in PTD by attempting to control for environmental factors measured at a single point in time is flawed. There is emerging evidence of gene-environment interactions for PTD, some of which disproportionately affect African Americans. There is also evidence of racial differences in the prevalence of polymorphisms potentially related to PTD. However, to date there is no direct evidence that these differences contribute significantly to racial disparity in PTD. Given the complexity of polygenic conditions such as PTD, the possibility of any single gene contributing substantially to racial disparity in PTD seems remote. PMID:16334498

  12. Cationic Bolaamphiphiles for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  13. Delivery of testosterone replacement therapy.

    PubMed

    Hameed, Asjad; Brothwood, Theresa; Bouloux, Pierre

    2003-10-01

    Optimal testosterone replacement therapy remains a considerable challenge for the estimated five out of 1000 men in the general community with androgen deficiency. Oral delivery is not possible due to rapid first pass metabolism and short half-life. Testosterone derivatives have been developed to enhance intrinsic androgenic potency, prolong duration of action, or improve oral bioavailability of synthetic androgens. Structural modification of testosterone include 17 beta-esterification, 17 alpha-alkylation, 1-methylation, addition of a 19-normethyl group, and 7 alpha-methylation. Currently, oral (testosterone undecanoate), transcutaneous (Andropatch, Virormone, Testoderm (ALZA Corp), Testogel), sublingual (testosterone cyclodextrin), intramuscular (Sustanon, Primoteston Depot), and fused crystalline testosterone pellet preparations are available for clinical use. Transbuccal testosterone systems have also been developed for clinical use and require twice daily application. Suspensions of biodegradable microspheres consisting of a polyglycolide-lactide matrix laden with testosterone can deliver stable, physiological levels of testosterone for 2 to 3 months. Micronized testosterone has low oral bioavailability requiring high daily doses. 7 alpha-Methyl 19-nortestosterone, a potent, synthetic androgen free of hepatotoxicity, has tissue-specific selectivity, being susceptible to aromatization but not 5 alpha-reduction, thereby potentially avoiding intraprostatic androgen amplification. PMID:14649214

  14. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

    Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

    2003-12-01

    Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

  15. Polymeric conjugates for drug delivery

    PubMed Central

    Larson, Nate; Ghandehari, Hamidreza

    2012-01-01

    The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both “see and treat” patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status. PMID:22707853

  16. Perfluorocarbon-based oxygen delivery.

    PubMed

    Riess, Jean G

    2006-01-01

    The basic properties of perfluorocarbons (PFCs) and PFC emulsions relevant to their use as oxygen delivery systems are briefly reviewed. The key issues related to the selection of an appropriate, readily excretable PFC and the engineering of a stable injectable PFC emulsion are discussed. Oxygent, a terminally heat-sterilized, injectable 60% w/v PFC emulsion made primarily of F-octyl bromide and a few percent of F-decyl bromide, with egg phospholipids as an emulsifier, has been developed. Its efficacy in avoiding and reducing red cell transfusion during surgery has been established during a Phase III clinical evaluation. Another Phase III clinical trial in cardiopulmonary bypass surgery, with a protocol that included both augmented-acute normovolemic hemodilution and intraoperative autologous donation, has, however, been interrupted following the observation of adverse events. Data analysis assigned these events to an inappropriate study protocol. A search for possible interactions between Oxygent and fluids present during cardiopulmonary bypass surgery detected no effect of the emulsion on hemostasis, hemolysis and blood rheology. PMID:17090429

  17. Coated microneedles for transdermal delivery

    PubMed Central

    Gill, Harvinder S.; Prausnitz, Mark R.

    2007-01-01

    Coated microneedles have been shown to deliver proteins and DNA into the skin in a minimally invasive manner. However, detailed studies examining coating methods and their breadth of applicability are lacking. This study’s goal was to develop a simple, versatile and controlled microneedle coating process to make uniform coatings on microneedles and establish the breadth of molecules and particles that can be coated onto microneedles. First, microneedles were fabricated from stainless steel sheets as single microneedles or arrays of microneedles. Next, a novel micron-scale dip-coating process and a GRAS coating formulation were designed to reliably produce uniform coatings on both individual and arrays of microneedles. This process was used to coat compounds including calcein, vitamin B, bovine serum albumin and plasmid DNA. Modified vaccinia virus and microparticles of 1 to 20 μm diameter were also coated. Coatings could be localized just to the needle shafts and formulated to dissolve within 20 s in porcine cadaver skin. Histological examination validated that microneedle coatings were delivered into the skin and did not wipe off during insertion. In conclusion, this study presents a simple, versatile, and controllable method to coat microneedles with proteins, DNA, viruses and microparticles for rapid delivery into the skin. PMID:17169459

  18. Starch Applications for Delivery Systems

    NASA Astrophysics Data System (ADS)

    Li, Jason

    2013-03-01

    Starch is one of the most abundant and economical renewable biopolymers in nature. Starch molecules are high molecular weight polymers of D-glucose linked by α-(1,4) and α-(1,6) glycosidic bonds, forming linear (amylose) and branched (amylopectin) structures. Octenyl succinic anhydride modified starches (OSA-starch) are designed by carefully choosing a proper starch source, path and degree of modification. This enables emulsion and micro-encapsulation delivery systems for oil based flavors, micronutrients, fragrance, and pharmaceutical actives. A large percentage of flavors are encapsulated by spray drying in today's industry due to its high throughput. However, spray drying encapsulation faces constant challenges with retention of volatile compounds, oxidation of sensitive compound, and manufacturing yield. Specialty OSA-starches were developed suitable for the complex dynamics in spray drying and to provide high encapsulation efficiency and high microcapsule quality. The OSA starch surface activity, low viscosity and film forming capability contribute to high volatile retention and low active oxidation. OSA starches exhibit superior performance, especially in high solids and high oil load encapsulations compared with other hydrocolloids. The submission is based on research and development of Ingredion

  19. Transorbital therapy delivery: phantom testing

    NASA Astrophysics Data System (ADS)

    Ingram, Martha-Conley; Atuegwu, Nkiruka; Mawn, Louise; Galloway, Robert L.

    2011-03-01

    We have developed a combined image-guided and minimally invasive system for the delivery of therapy to the back of the eye. It is composed of a short 4.5 mm diameter endoscope with a magnetic tracker embedded in the tip. In previous work we have defined an optimized fiducial placement for accurate guidance to the back of the eye and are now moving to system testing. The fundamental difficulty in testing performance is establishing a target in a manner which closely mimics the physiological task. We have to have a penetrable material which obscures line of sight, similar to the orbital fat. In addition we need to have some independent measure of knowing when a target has been reached to compare to the ideal performance. Lastly, the target cannot be rigidly attached to the skull phantom since the optic nerve lies buried in the orbital fat. We have developed a skull phantom with white cloth stellate balls supporting a correctly sized globe. Placed in the white balls are red, blue, orange and yellow balls. One of the colored balls has been soaked in barium to make it bright on CT. The user guides the tracked endoscope to the target as defined by the images and tells us its color. We record task accuracy and time to target. We have tested this with 28 residents, fellows and attending physicians. Each physician performs the task twice guided and twice unguided. Results will be presented.

  20. Economical oxygen-delivery system.

    PubMed

    Olson, R M

    1976-04-01

    The conservation of aircraft oxygen supplies is becoming of considerable interest to the Air Force. Onboard oxygen-generating systems are being developed which could support an aircrew if oxygen produced by these systems were used conservatively. These experiments studied the conservation potential of a rebreather bag placed in a vented container near the regulator in an oxygen-delivery system. The bag's volume was close to that of the subject's physiologic dead space. When the subject exhaled, oxygen in the mouth, trachea, and mask dead space went to the rebreather bag, to be rebreathed with the next breath. The CO2-contaminated oxygen from the alveoli was vented to the cabin. The dead-space oxygen could be separated from contaminated oxygen because dead-space air is exhaled first with each breath. When the rebreather-bag volume matched the subject's physiologic dead space so that no CO2 accumulated, a 30% oxygen savings was realized. When the bag was large enough to realize a 50% savings, CO2 accumulation was only 2%.

  1. Antimicrobial Activity of Carbon-Based Nanoparticles

    PubMed Central

    Maleki Dizaj, Solmaz; Mennati, Afsaneh; Jafari, Samira; Khezri, Khadejeh; Adibkia, Khosro

    2015-01-01

    Due to the vast and inappropriate use of the antibiotics, microorganisms have begun to develop resistance to the commonly used antimicrobial agents. So therefore, development of the new and effective antimicrobial agents seems to be necessary. According to some recent reports, carbon-based nanomaterials such as fullerenes, carbon nanotubes (CNTs) (especially single-walled carbon nanotubes (SWCNTs)) and graphene oxide (GO) nanoparticles show potent antimicrobial properties. In present review, we have briefly summarized the antimicrobial activity of carbon-based nanoparticles together with their mechanism of action. Reviewed literature show that the size of carbon nanoparticles plays an important role in the inactivation of the microorganisms. As major mechanism, direct contact of microorganisms with carbon nanostructures seriously affects their cellular membrane integrity, metabolic processes and morphology. The antimicrobial activity of carbon-based nanostructures may interestingly be investigated in the near future owing to their high surface/volume ratio, large inner volume and other unique chemical and physical properties. In addition, application of functionalized carbon nanomaterials as carriers for the ordinary antibiotics possibly will decrease the associated resistance, enhance their bioavailability and provide their targeted delivery. PMID:25789215

  2. [Delivery of multiples, particularly of twins].

    PubMed

    Hasenöhrl, Gottfried; Maier, Barbara; Steiner, Horst

    2007-01-01

    Multiples run various risks. While for triplets and higher-grade multiples caesarean section is the first-line mode of delivery, the method is still under discussion in the case of twins. Evidence-based data in favour of a general elective caesarean section are lacking but prospective randomized study results on this subject are expected. The organization of the clinic is essential for the safety of twins during vaginal delivery. The prerequisites for the vaginal delivery of twins and its management under various conditions are discussed in light of the literature.

  3. Implantable Devices for Sustained, Intravesical Drug Delivery

    PubMed Central

    2016-01-01

    In clinical settings, intravesical instillation of a drug bolus is often performed for the treatment of bladder diseases. However, it requires repeated instillations to extend drug efficacy, which may result in poor patient compliance. To alleviate this challenge, implantable devices have been developed for the purpose of sustained, intravesical drug delivery. In this review, we briefly summarize the current trend in the development of intravesical drug-delivery devices. We also introduce the most recently developed devices with strong potential for intravesical drug-delivery applications. PMID:27377941

  4. Cytotoxicity assessment of porous silicon microparticles for ocular drug delivery.

    PubMed

    Korhonen, Eveliina; Rönkkö, Seppo; Hillebrand, Satu; Riikonen, Joakim; Xu, Wujun; Järvinen, Kristiina; Lehto, Vesa-Pekka; Kauppinen, Anu

    2016-03-01

    Porous silicon (PSi) is a promising material for the delivery and sustained release of therapeutic molecules in various tissues. Due to the constant rinsing of cornea by tear solution as well as the short half-life of intravitreal drugs, the eye is an attractive target for controlled drug delivery systems, such as PSi microparticles. Inherent barriers ensure that PSi particles are retained in the eye, releasing drugs at the desired speed until they slowly break down into harmless silicic acid. Here, we have examined the in vitro cytotoxicity of positively and negatively charged thermally oxidized (TOPSi) and thermally carbonized (TCPSi) porous silicon microparticles on human corneal epithelial (HCE) and retinal pigment epithelial (ARPE-19) cells. In addition to ocular assessment under an inverted microscope, cellular viability was evaluated using the CellTiter Blue™, CellTiter Fluor™, and lactate dehydrogenase (LDH) assays. CellTiter Fluor proved to be a suitable assay but due to non-specific and interfering responses, neither CellTiter Blue nor LDH assays should be used when evaluating PSi particles. Our results suggest that the toxicity of PSi particles is concentration-dependent, but at least at concentrations less than 200μg/ml, both positively and negatively charged PSi particles are well tolerated by human corneal and retinal epithelial cells and therefore applicable for delivering drug molecules into ocular tissues.

  5. Excipient-free nanoporous microparticles of budesonide for pulmonary delivery.

    PubMed

    Nolan, Lorraine M; Tajber, Lidia; McDonald, Bernard F; Barham, Ahmad S; Corrigan, Owen I; Healy, Anne Marie

    2009-07-12

    The aim of this study was to investigate the application of a spray-drying process for the production of nanoporous microparticles (NPMPs) to budesonide, and to characterise the particles produced in terms of their suitability for pulmonary delivery. Budesonide was spray dried with and without ammonium carbonate from ethanol/water or methanol/water solutions. The solid-state characteristics and micromeritic (particle size, density, surface area) properties of spray dried powders were assessed. In vitro deposition studies were performed to assess aerosol performance. The densities of the NPMPs were significantly lower and the surface areas significantly higher than for non-porous spray dried or micronised material. NPMPs of budesonide demonstrated improved aerosolisation properties compared to spray dried non-porous, micronised material and two budesonide commercial products. All spray dried materials were amorphous in nature. The glass transition temperature (approximately 90 degrees C) was sufficiently high to suggest good physical stability at room temperature. When stored at 25 degrees C/60% RH NPMPs showed a reduced tendency to recrystallise compared to the equivalent non-porous spray dried powder. The physical stability and amorphous nature of NPMPs was retained, under these storage conditions for at least one year and the in vitro aerosolisation properties were not affected by the storage conditions. Excipient-free porous microparticles, prepared by the novel process described, show good potential for drug delivery by oral inhalation with improved in vitro deposition properties compared to non-porous particles. PMID:19463948

  6. Cytotoxicity assessment of porous silicon microparticles for ocular drug delivery.

    PubMed

    Korhonen, Eveliina; Rönkkö, Seppo; Hillebrand, Satu; Riikonen, Joakim; Xu, Wujun; Järvinen, Kristiina; Lehto, Vesa-Pekka; Kauppinen, Anu

    2016-03-01

    Porous silicon (PSi) is a promising material for the delivery and sustained release of therapeutic molecules in various tissues. Due to the constant rinsing of cornea by tear solution as well as the short half-life of intravitreal drugs, the eye is an attractive target for controlled drug delivery systems, such as PSi microparticles. Inherent barriers ensure that PSi particles are retained in the eye, releasing drugs at the desired speed until they slowly break down into harmless silicic acid. Here, we have examined the in vitro cytotoxicity of positively and negatively charged thermally oxidized (TOPSi) and thermally carbonized (TCPSi) porous silicon microparticles on human corneal epithelial (HCE) and retinal pigment epithelial (ARPE-19) cells. In addition to ocular assessment under an inverted microscope, cellular viability was evaluated using the CellTiter Blue™, CellTiter Fluor™, and lactate dehydrogenase (LDH) assays. CellTiter Fluor proved to be a suitable assay but due to non-specific and interfering responses, neither CellTiter Blue nor LDH assays should be used when evaluating PSi particles. Our results suggest that the toxicity of PSi particles is concentration-dependent, but at least at concentrations less than 200μg/ml, both positively and negatively charged PSi particles are well tolerated by human corneal and retinal epithelial cells and therefore applicable for delivering drug molecules into ocular tissues. PMID:26686646

  7. Spatiotemporal drug delivery using laser-generated-focused ultrasound system.

    PubMed

    Di, Jin; Kim, Jinwook; Hu, Quanyin; Jiang, Xiaoning; Gu, Zhen

    2015-12-28

    Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation.

  8. Controlled growth of carbon nanotubes.

    PubMed

    Vajtai, R; Wei, B Q; Ajayan, P M

    2004-10-15

    Carbon nanotubes have extraordinary mechanical and electronic properties and hold great promise for future applications. The most important aspects of this structure are its low density, high aspect ratio, one dimensionality, high mechanical strength and high electrical and thermal conductivity. We present a short, state-of-the-art account of tailored nanotube growth. To provide these properties in real devices there exists a need for producing nanotubes on substrates. The challenge in the creation of mesoscale nanotube-based architectures and tailored nanotube networks consisting of thousands of tubes in a predefined order is obviously great. Currently, chemical vapour deposition (CVD) appears to be the most powerful method for achieving such required structures. We describe our work on a new synthesis method, based on catalytic CVD using mainly gas-phase catalyst delivery. Gas-phase catalyst delivery allows us to assemble single-walled and multi-walled carbon nanotubes in predetermined multiple orientations on substrates to build one- to three-dimensional architectures. We are able to control, to a large extent, the types of nanotubes produced, their lengths, locations and their orientations. The ability to make mesoscale architectures with nanotubes should lead us to develop applications in areas such as nano-electromechanical systems.

  9. Carbon sequestration.

    PubMed

    Lal, Rattan

    2008-02-27

    Developing technologies to reduce the rate of increase of atmospheric concentration of carbon dioxide (CO2) from annual emissions of 8.6PgCyr-1 from energy, process industry, land-use conversion and soil cultivation is an important issue of the twenty-first century. Of the three options of reducing the global energy use, developing low or no-carbon fuel and sequestering emissions, this manuscript describes processes for carbon (CO2) sequestration and discusses abiotic and biotic technologies. Carbon sequestration implies transfer of atmospheric CO2 into other long-lived global pools including oceanic, pedologic, biotic and geological strata to reduce the net rate of increase in atmospheric CO2. Engineering techniques of CO2 injection in deep ocean, geological strata, old coal mines and oil wells, and saline aquifers along with mineral carbonation of CO2 constitute abiotic techniques. These techniques have a large potential of thousands of Pg, are expensive, have leakage risks and may be available for routine use by 2025 and beyond. In comparison, biotic techniques are natural and cost-effective processes, have numerous ancillary benefits, are immediately applicable but have finite sink capacity. Biotic and abiotic C sequestration options have specific nitches, are complementary, and have potential to mitigate the climate change risks. PMID:17761468

  10. Nanospearing - Biomolecule Delivery and Its Biocompatibility

    NASA Astrophysics Data System (ADS)

    Cai, Dong; Kempa, Krzysztof; Ren, Zhifeng; Carnahan, David; Chiles, Thomas C.

    Introduction of exogenous DNA into mammalian cells represents a powerful approach for manipulating signal transduction. However, the currently available techniques have serious limits in terms of either low transduction efficiency or low cell viability. It is found that carbon nanotubes (CNTs) can mediate molecule transportations via various mechanisms. We have reported a highly efficient molecular delivery technique, called nanotube spearing, based on the penetration of Ni-particle-embedded nanotubes into cell membranes by magnetic field driving. DNA was immobilized onto the nanotubes and subsequently speared into targeted cells. We have achieved a high transduction efficiency in Bal 17 B-lymphoma cell line, ex vivo B cells, and primary neurons with high viability. This technique may provide a powerful tool for highly efficient gene transfer in a variety of cells, especially, in the hard-to-transfect cells. However, CNTs have been associated with environmental and public health concerns which arose in the course of research on possible biomedical applications. The disturbances CNTs cause in the immune system have been met with particular interest because any ideal in vivo application of CNTs should not trigger any undesirable bodily responses. It is imperative to unravel the effects of CNTs on B cells, which represent the humoral component of acquired immunity, so that the potential risk of CNTs to public health can be thoroughly understood and advanced strategies can be employed to develop safe applications. We investigated the compatibility of the PECVD nanotubes and the nanospearing procedure in terms of cell viability, growth, and intracellular signal pathways by means of flow cytometry and biochemical analysis. No additional cell death was observed after the spearing treatment, nor had B cell activation been indicated by changes in cell size, growth, CD69 expression, and kinase phosphorylation. The post-spearing cells preserve the ability to respond to

  11. WEDDS: The WITS Encrypted Data Delivery System

    NASA Technical Reports Server (NTRS)

    Norris, J.; Backes, P.

    1999-01-01

    WEDDS, the WITS Encrypted Data Delivery System, is a framework for supporting distributed mission operations by automatically transferring sensitive mission data in a secure and efficient manner to and from remote mission participants over the internet.

  12. Functional Cyclodextrin Polyrotaxanes for Drug Delivery

    NASA Astrophysics Data System (ADS)

    Yui, Nobuhiko; Katoono, Ryo; Yamashita, Atsushi

    The mobility of cyclodextrins (CDs) threaded onto a linear polymeric chain and the dethreading of the CDs from the chain are the most fascinating features seen in polyrotaxanes. These structural characteristics are very promising for their possible applications in drug delivery. Enhanced multivalent interaction between ligand-receptor systems by using ligand-conjugated polyrotaxanes would be just one of the excellent properties related to the CD mobility. Gene delivery using cytocleavable polyrotaxanes is a more practical but highly crucial issue in drug delivery. Complexation of the polyrotaxanes with DNA and its intracellular DNA release ingeniously utilizes both CD mobility and polyrotaxane dissociation to achieve effective gene delivery. Such a supramolecular approach using CD-containing polyrotaxanes is expected to exploit a new paradigm of biomaterials.

  13. Polymers for Colon Targeted Drug Delivery

    PubMed Central

    Rajpurohit, H.; Sharma, P.; Sharma, S.; Bhandari, A.

    2010-01-01

    The colon targeted drug delivery has a number of important implications in the field of pharmacotherapy. Oral colon targeted drug delivery systems have recently gained importance for delivering a variety of therapeutic agents for both local and systemic administration. Targeting of drugs to the colon via oral administration protect the drug from degradation or release in the stomach and small intestine. It also ensures abrupt or controlled release of the drug in the proximal colon. Various drug delivery systems have been designed that deliver the drug quantitatively to the colon and then trigger the release of drug. This review will cover different types of polymers which can be used in formulation of colon targeted drug delivery systems. PMID:21969739

  14. Synthetic micro/nanomotors in drug delivery

    NASA Astrophysics Data System (ADS)

    Gao, Wei; Wang, Joseph

    2014-08-01

    Nanomachines offer considerable promise for the treatment of diseases. The ability of man-made nanomotors to rapidly deliver therapeutic payloads to their target destination represents a novel nanomedicine approach. Synthetic nanomotors, based on a multitude of propulsion mechanisms, have been developed over the past decade toward diverse biomedical applications. In this review article, we journey from the use of chemically powered drug-delivery nanovehicles to externally actuated (fuel-free) drug-delivery nanomachine platforms, and conclude with future prospects and challenges for such practical propelling drug-delivery systems. As future micro/nanomachines become more powerful and functional, these tiny devices are expected to perform more demanding biomedical tasks and benefit different drug delivery applications.

  15. FastStats: Births -- Method of Delivery

    MedlinePlus

    ... MB] More data Birth Data Births in the United States, 2014 Maternal Morbidity for Vaginal and Cesarean Deliveries, According to Previous Cesarean History: New Data From the Birth Certificate, 2013 [PDF - ...

  16. Web Portal for Multicast Delivery Management.

    ERIC Educational Resources Information Center

    Mannaert, H.; De Gruyter, B.; Adriaenssens, P.

    2003-01-01

    Presents a Web portal for multicast communication management, which provides fully automatic service management with integrated provisioning of hardware equipment. Describes the software architecture, the implementation, and the application usage of the Web portal for multicast delivery. (Author/AEF)

  17. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation. PMID:24936306

  18. Adaptations and innovations in drug delivery.

    PubMed

    Cavalla, D

    2001-10-01

    The most recent meeting organized by the Society for Medicines Research, entitled Improving Medicines Through Drug Delivery, was held at the National Heart and Lung Institute in London on July 5, 2001. Drug delivery is increasingly becoming a central technology in the research and development of better medicines. This is so for at least three reasons. First, new drugs are being derived from complex biological molecules that are not readily amenable to oral delivery. Second, improved medicine is recognized as requiring better dosing regimens for the patient. Both compliance and preference are improved by reduced dosing frequency, and it is rare for new products to require three-times-daily administration. Lastly, drug delivery technology has come a long way in the past 20 years, beyond controlled-release pharmaceuticals to polymer conjugates and dry powder-inhaled proteins. PMID:12806435

  19. Controlling subcellular delivery to optimize therapeutic effect

    PubMed Central

    Mossalam, Mohanad; Dixon, Andrew S; Lim, Carol S

    2010-01-01

    This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy. PMID:21113240

  20. Quantitative theory of adsorptive separation for the electronic sorting of single-walled carbon nanotubes.

    PubMed

    Jain, Rishabh M; Tvrdy, Kevin; Han, Rebecca; Ulissi, Zachary; Strano, Michael S

    2014-04-22

    Recently, several important advances in techniques for the separation of single-walled carbon nanotubes (SWNTs) by chiral index have been developed. These new methods allow for the separation of SWNTs through selective adsorption and desorption of different (n,m) chiral indices to and from a specific hydrogel. Our group has previously developed a kinetic model for the chiral elution order of separation; however, the underlying mechanism that allows for this separation remains unknown. In this work, we develop a quantitative theory that provides the first mechanistic insights for the separation order and binding kinetics of each SWNT chirality (n,m) based on the surfactant-induced, linear charge density, which we find ranges from 0.41 e(-)/nm for (7,3) SWNTs in 17 mM sodium dodecyl sulfate (SDS) to 3.32 e(-)/nm for (6,5) SWNTs in 105 mM SDS. Adsorption onto the hydrogel support is balanced by short-distance hard-surface and long-distance electrostatic repulsive SWNT/substrate forces, the latter of which we postulate is strongly dependent on surfactant concentration and ultimately leads to gel-based single-chirality semiconducting SWNT separation. These molecular-scale properties are derived using bulk-phase, forward adsorption rate constants for each SWNT chirality in accordance with our previously published model. The theory developed here quantitatively describes the experimental elution profiles of 15 unique SWNT chiralities as a function of anionic surfactant concentration between 17 and 105 mM, as well as phenomenological observations of the impact of varying preparatory conditions such as extent of ultrasonication and ultracentrifugation. We find that SWNT elution order and separation efficiency are primarily driven by the morphological change of SDS surfactant wrapping on the surface of the nanotube, mediated by SWNT chirality and the ionic strength of the surrounding medium. This work provides a foundational understanding for high-purity, preparative

  1. Carbon particles

    DOEpatents

    Hunt, Arlon J.

    1984-01-01

    A method and apparatus whereby small carbon particles are made by pyrolysis of a mixture of acetylene carried in argon. The mixture is injected through a nozzle into a heated tube. A small amount of air is added to the mixture. In order to prevent carbon build-up at the nozzle, the nozzle tip is externally cooled. The tube is also elongated sufficiently to assure efficient pyrolysis at the desired flow rates. A key feature of the method is that the acetylene and argon, for example, are premixed in a dilute ratio, and such mixture is injected while cool to minimize the agglomeration of the particles, which produces carbon particles with desired optical properties for use as a solar radiant heat absorber.

  2. New delivery systems and propellants.

    PubMed

    Dolovich, M

    1999-01-01

    The removal of chlorofluorocarbon (CFC) propellants from industrial and household products has been agreed to by over 165 countries of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs) for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs) are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth) of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada - Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.

  3. Polymeric Gene Delivery for Diabetic Treatment

    PubMed Central

    2011-01-01

    Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD) mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD) MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4) were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal. PMID:21977450

  4. Innate hypothermia after hypoxic ischaemic delivery.

    PubMed

    Jayasinghe, Dulip

    2015-01-01

    The focus of this review is to collate the literature on the phenomenon of impaired thermal adaptation after hypoxic ischaemic (HI) delivery often culminating in hypothermia. This phenomenon appears different in severity and duration to a spontaneous postnatal fall in temperature observed after normal delivery. The original observation and contemporary descriptions of the temperature response to HI are described and a mechanism of action is proposed that may be utilised as a novel biomarker for HI. PMID:25675993

  5. Toward the redesign of nutrition delivery.

    PubMed

    Lamppa, John W; Horn, Greg; Edwards, David

    2014-09-28

    In the facilitation of widespread access to low-cost, good tasting food, the global food system has relied on the use of fat, sugar, chemical processing aids and plastics, among other elements potentially detrimental to human health and the environment. This contrasts starkly with the strategies of natural nutrition delivery systems. Rich in vitamins, minerals, and other substances of functional benefit to human health, natural delivery systems, such as fruits and vegetables, retain their physical and chemical stability in a range of conditions over relatively long times through protective skins and shells that can either be eaten or degrade rapidly and fully in nature. Frequently natural foods can be delivered in small (even extremely small) portions, as with berries, insects, plankton and krill, permitting portion control and the rapid and efficient delivery of functional nutrition in inherently mobile circumstances. These and other qualities, which have insured the sustainable and healthy nourishment of animals and humans for at least tens of thousands of years, are often absent from today's man-made food and beverage delivery systems. With growing awareness of the liabilities to maintaining the food system of today, efforts are now underway to redesign nutrition delivery so as to provide the contemporary benefits of global access while retrieving the health and environmental benefits associated with natural delivery systems. We review these here, with special attention to recently commercialized nutritional delivery systems emerging from the drug delivery field aimed at reducing waste in food and beverage (nutritional aerosols) and eliminating waste in food and beverage packaging (edible skins). We briefly discuss the potential ramifications to how we will eat tomorrow. PMID:24878187

  6. Role of microemuslsions in advanced drug delivery.

    PubMed

    Sharma, Aman Kumar; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-06-01

    Microemulsions have gained significant attention from formulation scientists since the time they have been discovered, because of their excellent properties related to their stability, solubility, simplicity, and formulation aspects. The application of microemulsions is not limited to drug delivery via the oral, topical or ocular routes, but may also be seen in cosmetics, immunology, sensor devices, coating, textiles, analytical chemistry, and spermicide. Finally, the objective of this review is to discuss briefly the applications of microemulsions in advanced drug delivery. PMID:25711493

  7. Innate hypothermia after hypoxic ischaemic delivery.

    PubMed

    Jayasinghe, Dulip

    2015-01-01

    The focus of this review is to collate the literature on the phenomenon of impaired thermal adaptation after hypoxic ischaemic (HI) delivery often culminating in hypothermia. This phenomenon appears different in severity and duration to a spontaneous postnatal fall in temperature observed after normal delivery. The original observation and contemporary descriptions of the temperature response to HI are described and a mechanism of action is proposed that may be utilised as a novel biomarker for HI.

  8. Magnetic nanoparticles for gene and drug delivery

    PubMed Central

    McBain, Stuart C; Yiu, Humphrey HP; Dobson, Jon

    2008-01-01

    Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting. PMID:18686777

  9. Nanomedicine and drug delivery: a mini review

    NASA Astrophysics Data System (ADS)

    Mirza, Agha Zeeshan; Siddiqui, Farhan Ahmed

    2014-02-01

    The field of nanotechnology now has pivotal roles in electronics, biology and medicine. Its application can be appraised, as it involves the materials to be designed at atomic and molecular level. Due to the advantage of their size, nanospheres have been shown to be robust drug delivery systems and may be useful for encapsulating drugs and enabling more precise targeting with a controlled release. In this review specifically, we highlight the recent advances of this technology for medicine and drug delivery systems.

  10. Biologically responsive polymeric nanoparticles for drug delivery.

    PubMed

    Colson, Yolonda L; Grinstaff, Mark W

    2012-07-24

    Responsive nanoparticles that release their drug cargo in accordance with a change in pH or oxidative stress are of significant clinical interest as this approach offers the opportunity to link drug delivery to a specific location or disease state. This research news article reviews the current state of this field by examining a series of published articles that highlight the novelty and benefits of using responsive polymeric particles to achieve functionally-targeted drug delivery. PMID:22988558

  11. HYDROGEN DELIVERY: INFRASTRUCTURE, CHALLENGES, AND MATERIALS NEEDS

    SciTech Connect

    Pawel, Steven J; Gardiner, Monterey

    2009-01-01

    Current domestic energy policy is aimed at encouraging the development of alternative fuels such as hydrogen for use as a renewable and environmentally-friendly alternative to traditional petroleum-based fuels for transportation and stationary power. The purpose of the Hydrogen Delivery Technical Team is to provide insight and input on hydrogen delivery infrastructure research. Ongoing research has identified materials R&D challenges required to support this infrastructure. A few of these challenges are summarized with emphasis placed on materials.

  12. Manual of carbonate sedimentology

    SciTech Connect

    Reijers, T.J.; Hsu, K.S.

    1986-01-01

    This manual, organised along encycolopaedic/lexicographic lines, summarizes information on the properties and characteristics of carbonates and their environments. Part 1 deals with the elements of carbonates; Part 2 with environments, settings, and carbonate bodies; Part 3 with carbonate diagenesis, and Part 4 with carbonate reservoirs. Contents include: Elements of carbonates; Carbonate Environments, Settings and Bodies; Carbonate diagenesis; Carbonate reservoirs; Alphabetical Indices; English, Dutch, German, Spanish, French Computer Compatible Codes; Commonly Used (Informal) abbreviations.

  13. Tank Farms and Waste Feed Delivery - 12507

    SciTech Connect

    Fletcher, Thomas; Charboneau, Stacy; Olds, Erik

    2012-07-01

    The mission of the Department of Energy's Office of River Protection (ORP) is to safely retrieve and treat the 56 million gallons of Hanford's tank waste and close the Tank Farms to protect the Columbia River. Our discussion of the Tank Farms and Waste Feed Delivery will cover progress made to date with Base and Recovery Act funding in reducing the risk posed by tank waste and in preparing for the initiation of waste treatment at Hanford. The millions of gallons of waste are a by-product of decades of plutonium production. After irradiated fuel rods were taken from the nuclear reactors to the processing facilities at Hanford they were exposed to a series of chemicals designed to dissolve away the rod, which enabled workers to retrieve the plutonium. Once those chemicals were exposed to the fuel rods they became radioactive and extremely hot. They also couldn't be used in this process more than once. Because the chemicals are caustic and extremely hazardous to humans and the environment, underground storage tanks were built to hold these chemicals until a more permanent solution could be found. The underground storage tanks range in capacity from 55,000 gallons to more than 1 million gallons. The tanks were constructed with carbon steel and reinforced concrete. There are eighteen groups of tanks, called 'tank farms', some having as few as two tanks and others up to sixteen tanks. Between 1943 and 1964, 149 single-shell tanks were built at Hanford in the 200 West and East Areas. Heat generated by the waste and the composition of the waste caused an estimated 67 of these single-shell tanks to leak into the ground. Washington River Protection Solutions is the prime contractor responsible for the safe management of this waste. WRPS' mission is to reduce the risk to the environment that is posed by the waste. All of the pumpable liquids have been removed from the single-shell tanks and transferred to the double-shell tanks. What remains in the single-shell tanks are

  14. Nanotechnology-based drug delivery systems

    PubMed Central

    Suri, Sarabjeet Singh; Fenniri, Hicham; Singh, Baljit

    2007-01-01

    Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA) and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF) receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression. PMID:18053152

  15. Nanoparticulate devices for brain drug delivery.

    PubMed

    Celia, Christian; Cosco, Donato; Paolino, Donatella; Fresta, Massimo

    2011-09-01

    The blood-brain barrier (BBB) limits the transport of therapeutic molecules from the blood compartment into the brain, thus greatly reducing the species of therapeutic compounds that can be efficiently accumulated in the central nervous system (CNS). Various strategies have been proposed for improving the delivery of drugs to this tissue, and numerous invasive and noninvasive methods have been proposed by different scientists in an attempt to circumvent the BBB and to increase the delivery of drug compounds into the brain. An interesting alternative, in the solution of this problem and also that of reaching a suitable target in the CNS, has recently been provided through the use of nanoparticulate colloidal devices as a noninvasive technique for brain drug delivery. These systems offer diverse advantages over invasive strategies, because (1) they are designed using biocompatible and biodegradable materials; (2) they avoid the disruption and/or modification of the BBB; and (3) they modulate the biopharmaceutical properties of the entrapped drugs. Moreover, the possibility of targeting specific brain tissue, thanks to ligands linked to the surface of the nanoparticulate colloidal devices, confers the necessary characteristics for the treatment of CNS pathologies to these drug carriers. The aim of this review is to focus on describing the main strategies in use for designing nanoparticulate colloidal devices for CNS delivery, their potentiality as noninvasive strategies in the delivery of drugs to the cerebral tissues, and their biological and clinical applications in cerebral drug delivery.

  16. Recent advances in ophthalmic drug delivery

    PubMed Central

    Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

    2011-01-01

    Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

  17. Agile Delivery of Protein Therapeutics to CNS

    PubMed Central

    Yi, Xiang; Manickam, Devika S.; Brynskikh, Anna; Kabanov, Alexander V.

    2014-01-01

    A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics. PMID:24956489

  18. Agile delivery of protein therapeutics to CNS.

    PubMed

    Yi, Xiang; Manickam, Devika S; Brynskikh, Anna; Kabanov, Alexander V

    2014-09-28

    A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics.

  19. Alternative delivery systems in rural areas.

    PubMed Central

    Christianson, J B

    1989-01-01

    Alternative delivery systems, such as HMOs, PPOs, and primary care case-management programs, have a long history in rural America despite significant impediments to their development. However, little is known about the effect of these systems on rural communities and their medical care delivery systems. Existing studies, which focus on rural HMOs, are qualitative in nature and generally are directed at identifying factors that facilitate or retard HMO development. Despite their limitations, the studies do raise a variety of issues deserving of quantitative analysis. Research is now needed that (1) investigates the effect of rural alternative delivery systems on the cost and quality of care received by rural residents, (2) assesses the effectiveness of different mechanisms used by these systems to contain costs, (3) estimates the effect of alternative delivery systems on rural providers, (4) determines the extent to which the presence or absence of alternative delivery systems influences physician decisions to locate in rural areas, (5) identifies factors that are important in consumer decisions to enroll or not enroll in a rural alternative delivery system, and (6) analyzes the diffusion patterns of these systems in rural areas. PMID:2645250

  20. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.