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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. Carbon nanotube-mediated siRNA delivery for gene silencing in cancer cells

    NASA Astrophysics Data System (ADS)

    Hong, Tu; Guo, Honglian; Xu, Yaqiong

    2011-10-01

    Small interfering RNA (siRNA) is potentially a promising tool in influencing gene expression with a high degree of target specificity. However, its poor intracellular uptake, instability in vivo, and non-specific immune stimulations impeded its effect in clinical applications. In this study, carbon nanotubes (CNTs) functionalized with two types of phospholipid-polyethylene glycol (PEG) have shown capabilities to stabilize siRNA in cell culture medium during the transfection and efficiently deliver siRNA into neuroblastoma and breast cancer cells. Moreover, the intrinsic optical properties of CNTs have been investigated through absorption and fluorescence measurements. We have found that the directly-functionalized groups play an important role on the fluorescence imaging of functionalized CNTs. The unique fluorescence imaging and high delivery efficiency make CNTs a promising material to deliver drugs and evaluate the treatment effect simultaneously.

  3. 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. PMID:21654030

  4. A new family of folate-decorated and carbon nanotube-mediated drug delivery system: synthesis and drug delivery response.

    PubMed

    Huang, H; Yuan, Q; Shah, J S; Misra, R D K

    2011-11-01

    We describe here a new family of folate-decorated and carbon nanotube (CNT)-mediated drug delivery system that involves uniquely combining carbon nanotubes with anticancer drug (doxorubicin) for controlled drug release, which is gaining significant attention. The synthesis of nanocarrier involved attachment of doxorubicin (DOX) to CNT surface via π-π stacking interaction, followed by encapsulation of CNTs with folic acid-conjugated chitosan. The π-π stacking interaction, ascribed as a non-covalent type of functionalization, allows controlled release of drug. Furthermore, encapsulation of CNTs enhances the stability of the nanocarrier in aqueous medium because of the hydrophilicity and cationic charge of chitosan. The unique integration of drug targeting and visualization has high potential to address the current challenges in cancer therapy. Thus, it is attractive to consider the possibility of investigating a drug delivery system that combines the biodegradable chitosan and carbon nanotubes (CNTs). PMID:21514336

  5. Chitosan-functionalised single-walled carbon nanotube-mediated drug delivery of SNX-2112 in cancer cells.

    PubMed

    Zheng, Lixia; Wu, Shao; Tan, Li; Tan, Huo; Yu, Baodan

    2016-09-01

    Delivery of amphiphobic drugs (insoluble in both water and oil) has been a great challenge in drug delivery. SNX-2112, a novel inhibitor of Hsp90, is a promising drug candidate for treating various types of cancers; however, the insolubility greatly limits its clinical application. This study aimed to build a new type of drug delivery system using single-walled carbon nanotubes (SWNTs) for controllable release of SNX-2112; chitosan (CHI) was non-covalently added to SWNTs to improve their biocompatibility. SWNTs-CHI demonstrated high drug-loading capability; the release of SNX-2112 was pH triggered and time related. The intracellular reactive oxygen species of SWNTs-CHI increased, compared with that of SWNTs, leading to higher mitogen-activated protein kinase and cell apoptosis. The results of western-blotting, lactate dehydrogenase (LDH) release assay, and cell viability assay analyses indicated that apoptosis-related proteins were abundantly expressed in K562 cells and that the drug delivery system significantly inhibited K562 cells. Thus, SWNT-CHI/SNX-2112 shows great potential as a drug delivery system for cancer therapy. PMID:27231263

  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. Advances in cancer therapy through the use of carbon nanotube-mediated targeted hyperthermia

    PubMed Central

    Iancu, Cornel; Mocan, Lucian

    2011-01-01

    Carbon nanotubes (CNTs) are emerging versatile tools in nanomedicine applications, particularly in the field of cancer targeting. Due to diverse surface chemistry and unique thermal properties, CNTs can act as strong optical absorbers in near infrared light where biological systems prove to be highly transparent. The process of laser-mediated ablation of cancer cells marked with biofunctionalized CNTs is frequently termed “nanophotothermolysis.” This paper illustrates the potential of engineered CNTs as laser-activated photothermal agents for the selective nanophotothermolysis of cancer cells. PMID:21904457

  8. 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

  9. 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

  10. Carbon-Nanotube-Mediated Electrochemical Transition in a Redox-Active Supramolecular Hydrogel Derived from Viologen and an l-Alanine-Based Amphiphile.

    PubMed

    Datta, Sougata; Bhattacharya, Santanu

    2016-05-23

    A two-component hydrogelator (16-A)2 -V(2+) , comprising an l-alanine-based amphiphile (16-A) and a redox-active viologen based partner (V(2+) ), is reported. The formation the hydrogel depended, not only on the acid-to-amine stoichiometric ratio, but on the choice of the l-amino acid group and also on the hydrocarbon chain length of the amphiphilic component. The redox responsive property and the electrochemical behavior of this two-component system were further examined by step-wise chemical and electrochemical reduction of the viologen nucleus (V(2+) /V(+) and V(+) /V(0) ). The half-wave reduction potentials (E1/2 ) associated with the viologen ring shifted to more negative values with increasing amine component. This indicates that higher extent of salt formation hinders reduction of the viologen moiety. Interestingly, the incorporation of single-walled carbon nanotubes in the electrochemically irreversible hydrogel (16-A)2 -V(2+) transformed it into a quasi-reversible electrochemical system. PMID:27059107

  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. PMID:26692360

  14. 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

  15. 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.

  16. Size control of magnetic carbon nanoparticles for drug delivery.

    PubMed

    Oh, W-K; Yoon, H; Jang, J

    2010-02-01

    Carbonized polypyrrole nanoparticles with controlled diameters were readily fabricated by the pyrolysis of polypyrrole nanoparticles. The carbonized polypyrrole nanoparticles showed narrow size distribution, large micropore volume, and high surface area. Magnetic phases were introduced into the carbon nanoparticles during the pyrolysis without sophisticated process, which resulted in useful magnetic properties for selective nanoparticle separation. Field emission scanning electron microscopy, Raman spectrometer, N(2) adsorption/desorption, X-ray diffraction, and superconducting interference device were employed for characterizing the carbonized polypyrrole nanoparticles. Hydrophobic guest molecules were incorporated into the carbonized polypyrrole nanoparticles by surface adsorption, pore filling, and surface covalent coupling. The carbonized polypyrrole nanoparticles exhibited embedding capability using pyrene as a typical hydrophobic fluorescent molecule. In addition, ibuprofen was incorporated into the carbon nanoparticles, and drug-loaded carbon nanoparticles sustained release property. In addition, the carbonized polypyrrole nanoparticles revealed low toxicity at concentrations below 100 microg mL(-1) via cell viability test and were uptaken inside the cells. These results suggest a new platform for the drug delivery using carbonized polypyrrole nanoparticles. PMID:19878989

  17. Interactions between carbon nanotubes and bioactives: a drug delivery perspective.

    PubMed

    Mehra, Neelesh Kumar; Palakurthi, Srinath

    2016-04-01

    Applications of carbon nanotubes (CNTs) in the biomedical arena have gained increased attention over the past decade. Surface engineering of CNTs by covalent and noncovalent modifications enables site-specific drug delivery and targeting. CNTs are available as single-, double-, triple-, and multiwalled carbon nanotubes (SWCNTs, DWCNTs, TWCNTs, and MWCNTs, respectively) and have unique physicochemical properties, including a high surface area, high loading efficiency, good biocompatibility, low toxicity, ultra lightweight, rich surface chemistry, non-immunogenicity, and photoluminescence. In this review, we highlight current understanding of the different types of physical and chemical interaction that occur between therapeutics and CNTs, and the potential application of the latter in drug delivery and imaging. Such understanding will aid exploration of the utility of multifunctional CNTs as pharmaceutical nanocarriers, and potential safety and toxicity issues. PMID:26657088

  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. Design of biomaterials for intracellular delivery of carbon monoxide.

    PubMed

    Inaba, Hiroshi; Fujita, Kenta; Ueno, Takafumi

    2015-11-01

    Carbon monoxide (CO) is recognized as one of the most important gas signaling molecules involved in governing various therapeutic responses. Intracellular generation of CO is spatiotemporally controlled by catalytic reactions of heme oxygenases (HOs). Thus, the ability to control intracellular CO delivery with modulation of the CO-release rate in specific amounts and locations is expected to improve our fundamental understanding of the functions of CO and the development of clinical applications. For this purpose, CO-releasing molecules (CORMs) have been developed and investigated in vitro and in vivo. Most CORMs are based on transition metal carbonyl complexes. Recently, various biomaterials consisting of metal carbonyls with biomacromolecular scaffolds have been reported to improve the properties of bare metal carbonyls. In this mini-review, current progress in CO delivery, recent strategies for the development of CORMs, and future directions in this field are discussed. PMID:26252321

  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. Carbon Nanomaterials for Drug Delivery and Cancer Therapy.

    PubMed

    Chakrabarti, Mrinmay; Kiseleva, Raisa; Vertegel, Alexey; Ray, Swapan K

    2015-08-01

    Nanotechnology is one of the most exciting disciplines and it incorporates physics, chemistry, materials science, and biology. It can be applied to design cancer medicines with improved therapeutic indices. At the basic level, carbon nanotubes (CNTs) and graphene are sp2 carbon nanomaterials. Their unique physical and chemical properties make them interesting candidates of research in a wide range of areas including biological systems and different diseases. Recent research has been focused on exploring the potential of the CNTs as a carrier or vehicle for intracellular transport of drugs, proteins, and targeted genes in vitro and in vivo. Several research groups are actively involved to find out a functional CNT carrier capable of transporting targeted drug molecules in animal models with least toxicity. Current investigations are also focused on graphene, an allotrope of carbon, which appears to be a promising agent for successful delivery of biomolecules in various animal models. But potential clinical implementations of CNTs are still hampered by distinctive barriers such as poor bioavailability and intrinsic toxicity, which pose difficulties in tumor targeting and penetration as well as in improving therapeutic outcome. This article presents recent progresses in the design and evaluation of closely related CNTs for experimental cancer therapy and explores their implications in bringing nanomedicines into the clinics. PMID:26369109

  2. Single-Walled Carbon Nanotube Transporter for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Ke, Pu-Chun

    2005-03-01

    Recent studies have shown great promises in integrating nanomaterials in biomedicine. To explore the feasibility of using single-walled carbon nanotubes (SWNTs) as transporters for gene delivery, we have investigated the binding of SWNTs and RNA polymer poly(rU), and the diffusion and the translocation of the SWNT-poly(rU) complexes. Through single-molecule fluorescence imaging, we have found that the pi- stacking dominates the hydrophobic interactions between the carbon rings on tubes and the nitrogenous bases of RNA. Our diffusion study has further demonstrated the feasibility of tracking the motion of water soluble SWNT-poly(rU) complexes. The uptake of SWNT-poly(rU) by breast cancer cells MCF7 was observed using confocal scanning fluorescence microscopy. It was evident that the complexes could penetrate through cell membrane into cytoplasm and cell nucleus. Our cell culture, MTS assay, and radioisotope labeling showed the negligible cytotoxicity of surface modified SWNTs with RNA polymer and amino acids in cell growth medium. These studies have paved the way for gene transfection using SWNTs as transporters.

  3. Fabrication of carbon nanotube-polyimide composite hollow microneedles for transdermal drug delivery.

    PubMed

    Lyon, Bradley J; Aria, Adrianus I; Gharib, Morteza

    2014-12-01

    We introduce a novel method for fabricating hollow microneedles for transdermal drug delivery using a composite of vertically-aligned carbon nanotubes and polyimide. Patterned bundles of carbon nanotubes are used as a porous scaffold for defining the microneedle geometry. Polyimide resin is wicked through the carbon nanotube scaffold to reinforce the structure and provide the prerequisite strength for achieving skin penetration. The high aspect ratio and bottom-up assembly of carbon nanotubes allow the structure of the microneedles to be created in a single step of nanotube fabrication, providing a simple, scalable method for producing hollow microneedles. To demonstrate the utility of these microneedles, liquid delivery experiments are performed. Successful delivery of aqueous methylene blue dye into both hydrogel and swine skin in vitro is demonstrated. Electron microscopy images of the microneedles taken after delivery confirm that the microneedles do not sustain any structural damage during the delivery process. PMID:25095899

  4. Programmable Transdermal Clonidine Delivery through Voltage Gated Carbon Nanotube Membranes

    PubMed Central

    Strasinger, Caroline; Paudel, Kalpana S; Wu, Ji; Hammell, Dana; Pinninti, Raghotham R.; Hinds, Bruce; Stinchcomb, Audra

    2014-01-01

    Oral dosage forms and traditional transdermal patches are inadequate for complex clonidine therapy dosing schemes, because of the variable dose/flux requirement for the treatment of opioid withdrawal symptoms. The purpose of this study was to evaluate the in vitro transdermal flux changes of clonidine in response to alterations in carbon nanotube (CNT) delivery rates by applying various electrical bias. Additional skin diffusion studies were carried out to demonstrate the therapeutic feasibility of the system. This study demonstrated that application of a small electrical bias (-600mV) to the CNT membrane on the skin resulted in a 4.7-fold increase in clonidine flux as compared to no bias (0mV) application. The high and low clonidine flux values were very close to the desired variable flux of clonidine for the treatment of opioid withdrawal symptoms. Therapeutic feasibility studies demonstrated that CNT membrane served as the rate limiting step to clonidine diffusion and lag and transition times were suitable for the clonidine therapy. Skin elimination studies revealed that clonidine depletion from the skin would not negatively affect clonidine therapy. Overall, this study showed that clonidine administration difficulties associated with the treatment of opiate withdrawal symptoms can be reduced with the programmable CNT membrane transdermal system. PMID:24788096

  5. 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

  6. Delivery of molecules into cells using carbon nanoparticles activated by femtosecond laser pulses.

    PubMed

    Chakravarty, Prerona; Qian, Wei; El-Sayed, Mostafa A; Prausnitz, Mark R

    2010-08-01

    A major barrier to drug and gene delivery is crossing the cell's plasma membrane. Physical forces applied to cells via electroporation, ultrasound and laser irradiation generate nanoscale holes in the plasma membrane for direct delivery of drugs into the cytoplasm. Inspired by previous work showing that laser excitation of carbon nanoparticles can drive the carbon-steam reaction to generate highly controlled shock waves, we show that carbon black nanoparticles activated by femtosecond laser pulses can facilitate the delivery of small molecules, proteins and DNA into two types of cells. Our initial results suggest that interaction between the laser energy and carbon black nanoparticles may generate photoacoustic forces by chemical reaction to create transient holes in the membrane for intracellular delivery. PMID:20639882

  7. Synthesis of calcium carbonate nanocrystals and their potential application as vessels for drug delivery

    NASA Astrophysics Data System (ADS)

    Vergaro, Viviana; Carata, Elisabetta; Panzarini, Elisa; Baldassare, Francesca; Dini, Luciana; Ciccarella, Giuseppe

    2015-06-01

    Pure and stable calcium carbonate (CaCO3) nanocrystals were synthesized by spray drying method. We exploited the opportunity to use them as vessels for drug delivery studying the biocompatibility and the internalization in HeLa cells.

  8. Toward Carbon Monoxide-Based Therapeutics: Critical Drug Delivery and Developability Issues.

    PubMed

    Ji, Xingyue; Damera, Krishna; Zheng, Yueqin; Yu, Bingchen; Otterbein, Leo E; Wang, Binghe

    2016-02-01

    Carbon monoxide (CO) is an intrinsic signaling molecule with importance on par with that of nitric oxide. During the past decade, pharmacologic studies have amply demonstrated the therapeutic potential of carbon monoxide. However, such studies were mostly based on CO inhalation and metal-based CO-releasing molecules. The field is now at the stage that a major effort is needed to develop pharmaceutically acceptable forms of CO for delivery via various routes such as oral, injection, infusion, or topical applications. This review examines the state of the art, discusses the existing hurdles to overcome, and proposes developmental strategies necessary to address remaining drug delivery issues. PMID:26869408

  9. Multifunctional hybrid-carbon nanotubes: new horizon in drug delivery and targeting.

    PubMed

    Mehra, Neelesh Kumar; Jain, Narendra Kumar

    2016-01-01

    Carbon nanotubes (CNTs) have emerged as an intriguing nanotechnological tool for numerous biomedical applications including biocompatible modules for the bioactives delivery ascribed to their unique properties, such as greater loading efficiency, biocompatibility, non-immunogenicity, high surface area and photoluminescence, that make them ideal candidate in pharmaceutical and biomedical science. The design of multifunctional hybrid-CNTs for drug delivery and targeting may differ from the conventional drug delivery system. The conventional nanocarriers have few limitations, such as inappropriate availability of surface-chemical functional groups for conjugation, low entrapment/loading efficiency as well as stability as per ICH guidelines with generally regarded as safe (GRAS) prominences. The multifunctional hybrid-CNTs will sparked and open a new door for researchers, scientist of the pharmaceutical and biomedical arena. This review summarizes the vivid aspects of CNTs like characterization, supramolecular chemistry of CNTs-dendrimer, CNTs-nanoparticles, CNTs-quantum dots conjugate for delivery of bioactives, not discussed so far. PMID:26147085

  10. Delivery of siRNA to ovarian cancer cells using laser-activated carbon nanoparticles

    PubMed Central

    Sengupta, Aritra; Mezencev, Roman; McDonald, John F; Prausnitz, Mark R

    2015-01-01

    Aim The RNAi-mediated knockdown of gene expression is an attractive tool for research and therapeutic purposes but its implementation is challenging. Here we report on a new method based on photoacoustic delivery of siRNA developed to address some of these challenges. Materials & methods Physical properties and photoacoustic emission of carbon black (CB) particles upon near-infrared laser irradiation were characterized. Next, ovarian cancer cells Hey A8-F8 were exposed to near-infrared nanosecond laser pulses in the presence of siRNA targeting EGFR gene and CB particles. The intracellular delivery of siRNA and silencing of the target gene were determined by specific qPCR assays. Results & conclusion Laser-activated CB nanoparticles generated photoacoustic emission and enabled intracellular delivery of siRNA and significant knockdown of its target EGFR mRNA. This physical method represents a new promising approach to targeted therapeutic delivery of siRNA. PMID:26080699

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24870227

  17. 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.

  18. Polyethylene-Glycol-Modified Single-Walled Carbon Nanotubes for Intra-Articular Delivery to Chondrocytes

    PubMed Central

    Sacchetti, Cristiano; Liu-Bryan, Ru; Magrini, Andrea; Rosato, Nicola; Bottini, Nunzio; Bottini, Massimo

    2015-01-01

    Osteoarthritis (OA) is a common and debilitating degenerative disease of articular joints for which no disease-modifying medical therapy is currently available. Inefficient delivery of pharmacologic agents into cartilage-resident chondrocytes after systemic administration has been a limitation to the development of anti-OA medications. Direct intra-articular injection enables delivery of high concentrations of agents in close proximity to chondrocytes; however, the efficacy of this approach is limited by the fast clearance of small molecules and biomacromolecules after injection into the synovial cavity. Coupling of pharmacologic agents with drug delivery systems able to enhance their residence time and cartilage penetration can enhance the effectiveness of intra-articularly injected anti-OA medications. Herein we describe an efficient intra-articular delivery nanosystem based on single-walled carbon nanotubes (SWCNTs) modified with polyethylene glycol (PEG) chains (PEG-SWCNTs). We show that PEG-SWCNTs are capable to persist in the joint cavity for a prolonged time, enter the cartilage matrix, and deliver gene inhibitors into chondrocytes of both healthy and OA mice. PEG-SWCNT nanoparticles did not elicit systemic or local side effects. Our data suggest that PEG-SWCNTs represent a biocompatible and effective nanocarrier for intra-articular delivery of agents to chondrocytes. PMID:25415768

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

    PubMed

    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. PMID:27458235

  20. 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.

  1. 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.

  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. 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

  4. Oral drug delivery of therapeutic gases - carbon monoxide release for gastrointestinal diseases.

    PubMed

    Steiger, Christoph; Lühmann, Tessa; Meinel, Lorenz

    2014-09-10

    Deploying the therapeutic potential of carbon monoxide (CO) in various gastrointestinal diseases is challenged by inappropriate oral delivery modes. It is for this challenge, that we developed an easy to use tablet referred to as oral carbon monoxide release system (OCORS) providing precise, controlled, tunable and targeted CO delivery for the treatment of sequelae of gastrointestinal diseases. OCORS is an oral tablet based on sulfite induced CO release from the CO releasing molecule 2 (CORM-2). OCORS performance was detailed as a function of the presence of buffer within the tablet core and the composition of a semipermeable cellulose acetate coating, shielding the tablet core. OCORS delivered CO for up to 10h with a nearly linear release profile between approximately 30 to 240min. This controlled release system delivered the therapeutic gas independent of environmental pH for reliable CO generation at gastric, intestinal or colonic sites. In vivo experiments and toxicological assessments particularly with respect to observed ruthenium release of OCORS are required to demonstrate the pharmacokinetics and clinical potential of this oral delivery platform for therapeutic gases. PMID:24969354

  5. 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

  6. 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

  7. 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

  8. 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

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

    PubMed

    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. PMID:26901756

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Polyamidoamine-grafted multiwalled carbon nanotubes for gene delivery: synthesis, transfection and intracellular trafficking.

    PubMed

    Liu, Min; Chen, Biao; Xue, Yanan; Huang, Jie; Zhang, Liming; Huang, Shiwen; Li, Qingwen; Zhang, Zhijun

    2011-11-16

    Functionalized multiwalled carbon nanotubes (f-MWNTs) are of great interest and designed as a novel gene delivery system. In this paper, we presented synthesis of polyamidoamine-functionalized multiwalled carbon nanotubes (PAA-g-MWNTs) and their application as a novel gene delivery system. The PAA-g-MWNTs, obtained from amide formation between PAA and chemically oxidized MWNTs, were stable in aqueous solution and much less toxic to cells than PAA and PEI 25KDa. More importantly, PAA-g-MWNTs showed comparable or even higher transfection efficiency than PAA and PEI at optimal w/w ratio. Intracellular trafficking of Cy3-labeled pGL-3 indicated that a large number of Cy3-labeled pGL-3 were attached to nucleus membrane, the majority of which was localized in nucleus after incubation with cells for 24 h. We have demonstrated that PAA modification of MWNTs facilitate higher DNA uptake and gene expression in vitro. All these facts suggest potential application of PAA-g-MWNTs as a novel gene vector with high transfection efficiency and low cytotoxicity. PMID:21995530

  15. 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.

  16. Dual-Responsive Carbon Dots for Tumor Extracellular Microenvironment Triggered Targeting and Enhanced Anticancer Drug Delivery.

    PubMed

    Feng, Tao; Ai, Xiangzhao; Ong, Huimin; Zhao, Yanli

    2016-07-27

    In this work, pH/redox dual-responsive carbon dots (CDs-RGD-Pt(IV)-PEG) were fabricated for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. The system consists of fluorescent carbon dots as imaging-guided drug nanocarriers, cisplatin(IV) as prodrug, and RGD peptide as active targeting ligand, which is covered by monomethoxypolyethylene glycol (mPEG) through tumor extracellular pH (6.5-6.8) responsive benzoic-imine bond. The drug nanocarriers could be tracked by multicolor fluorescence of carbon dots. After the hydrolysis of benzoic-imine bond at the tumor extracellular pH to expose the inner targeting RGD peptide, the drug nanocarriers showed effective uptake by cancer cells through RGD-integrin αvβ3 (ligand-receptor) interaction. Upon the internalization, the loaded cisplatin(IV) prodrug was reduced to cytotoxic cisplatin in reductive cytosol of cancer cells to exhibit therapeutic effects. Confocal imaging, flow cytometry, and cell viability assays using CDs-RGD-Pt(IV)-PEG were performed to reveal the enhanced uptake and better therapeutic efficiency to cancer cells with high integrin αvβ3 expression at tumor extracellular pH than that in physiological condition. The developed CDs-RGD-Pt(IV)-PEG offers a new strategy to provide safe and effective therapeutic agents based on carbon dots for promising cancer therapy. PMID:27367152

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. Functionalized carbon nanomaterials as nanocarriers for loading and delivery of a poorly water-soluble anticancer drug: a comparative study.

    PubMed

    Sahoo, Nanda Gopal; Bao, Hongqian; Pan, Yongzheng; Pal, Mintu; Kakran, Mitali; Cheng, Henry Kuo Feng; Li, Lin; Tan, Lay Poh

    2011-05-14

    Carbon nanomaterials such as multiwalled carbon nanotubes (MWCNTs) and graphene oxide (GO) have been functionalized by highly hydrophilic and biocompatible poly(vinyl alcohol) (PVA) for loading and delivery of an anticancer drug, camptothecin (CPT). For the first time, CPT was loaded onto MWCNT-PVA and GO-PVA through π-π interactions and its capability to kill human breast and skin cancer cells was investigated. PMID:21451845

  3. 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.

  4. In vivo drug delivery of gemcitabine with PEGylated single-walled carbon nanotubes.

    PubMed

    Razzazan, Ali; Atyabi, Fatemeh; Kazemi, Bahram; Dinarvand, Rassoul

    2016-05-01

    Gemcitabine (GEM) is an anticancer agent widely used in non-small cell lung and pancreatic cancers. The clinical use of GEM has been limited by its rapid metabolism and short plasma half-life. These restrictions lead to frequent administration of high drug doses which can cause severe side effects. Therefore, new delivery strategies are needed aiming toward improved therapeutic effects. Single-walled carbon nanotubes (SWCNTs) are emerging as promising carriers for drug delivery due to their unique properties including high drug loading capacities, notable cell membrane penetrability and prolonged circulation times. In this work, pristine SWCNTs were functionalized through carboxylation, acylation, amination, PEGylation and finally GEM conjugation. The prepared SWCNT-GEM and SWCNT-PEG-GEM conjugates were characterized by FTIR, NMR, DSC and TEM to confirm the successful functionalization. The amount of GEM bound to the conjugates was 43.14% (w/w) for the SWCNT-GEM and 37.32% for the SWCNT-PEG-GEM, indicating high loading capacity. MTT assay on the human lung carcinoma cell line (A549) and the human pancreatic carcinoma cell line (MIA PaCa-2) demonstrated that the SWCNT-GEM was more cytotoxic than SWCNT-PEG-GEM and GEM. The SWCNT-PEG-GEM conjugates afford higher efficacy in suppressing tumor growth than SWCNT-GEM and GEM in B6 nude mice. The results demonstrate that the new formulation of GEM is useful strategy for improving the antitumor efficacy of GEM. PMID:26952465

  5. 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

  6. Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system.

    PubMed

    Cetin, Emel Oyku; Gundogdu, Evren; Baspinar, Yücel; Karasulu, Ercument; Kirilmaz, Levent

    2013-12-01

    The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system. PMID:22397637

  7. Highly efficient siRNA delivery system into human and murine cells using single-wall carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Ladeira, M. S.; Andrade, V. A.; Gomes, E. R. M.; Aguiar, C. J.; Moraes, E. R.; Soares, J. S.; Silva, E. E.; Lacerda, R. G.; Ladeira, L. O.; Jorio, A.; Lima, P.; Leite, M. Fatima; Resende, R. R.; Guatimosim, S.

    2010-09-01

    Development of RNA interference (RNAi) technology utilizing short interfering RNA sequences (siRNA) has focused on creating methods for delivering siRNAs to cells and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel approach for siRNA cellular delivery using siRNA coiling into carboxyl-functionalized single-wall carbon nanotubes (SWCNTs). The CNT-siRNA delivery system successfully demonstrates nonspecific toxicity and transfection efficiency greater than 95%. This approach offers the potential for siRNA delivery into different types of cells, including hard-to-transfect cells, such as neuronal cells and cardiomyocytes. We also tested the CNT-siRNA system in a non-metastatic human hepatocellular carcinoma cell line (SKHep1). In all types of cells used in this work the CNT-siRNA delivery system showed high efficiency and apparent no side effects for various in vitro applications.

  8. 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

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

    PubMed

    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

  10. 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

  11. 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.

  12. 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.

  13. Evaluation of beam delivery and ripple filter design for non-isocentric proton and carbon ion therapy

    NASA Astrophysics Data System (ADS)

    Grevillot, L.; Stock, M.; Vatnitsky, S.

    2015-10-01

    This study aims at selecting and evaluating a ripple filter design compatible with non-isocentric proton and carbon ion scanning beam treatment delivery for a compact nozzle. The use of non-isocentric treatments when the patient is shifted as close as possible towards the nozzle exit allows for a reduction in the air gap and thus an improvement in the quality of scanning proton beam treatment delivery. Reducing the air gap is less important for scanning carbon ions, but ripple filters are still necessary for scanning carbon ion beams to reduce the number of energy steps required to deliver homogeneous SOBP. The proper selection of ripple filters also allows a reduction in the possible transverse and depth-dose inhomogeneities that could appear in non-isocentric conditions in particular. A thorough review of existing ripple filter designs over the past 16 years is performed and a design for non-isocentric treatment delivery is presented. A unique ripple filter quality index (QIRiFi) independent of the particle type and energy and representative of the ratio between energy modulation and induced scattering is proposed. The Bragg peak width evaluated at the 80% dose level (BPW80) is proposed to relate the energy modulation of the delivered Bragg peaks and the energy layer step size allowing the production of homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for carbon ion and ripple filter simulations based on measurements performed at CNAO and subsequently used for a detailed analysis of the proposed ripple filter design. A combination of two ripple filters in a series has been validated for non-isocentric delivery and did not show significant transverse and depth-dose inhomogeneities. Non-isocentric conditions allow a significant reduction in the spot size at the patient entrance (up to 350% and 200% for protons and carbon ions with range shifter, respectively), and therefore in the lateral penumbra in the patients.

  14. Evaluation of beam delivery and ripple filter design for non-isocentric proton and carbon ion therapy.

    PubMed

    Grevillot, L; Stock, M; Vatnitsky, S

    2015-10-21

    This study aims at selecting and evaluating a ripple filter design compatible with non-isocentric proton and carbon ion scanning beam treatment delivery for a compact nozzle. The use of non-isocentric treatments when the patient is shifted as close as possible towards the nozzle exit allows for a reduction in the air gap and thus an improvement in the quality of scanning proton beam treatment delivery. Reducing the air gap is less important for scanning carbon ions, but ripple filters are still necessary for scanning carbon ion beams to reduce the number of energy steps required to deliver homogeneous SOBP. The proper selection of ripple filters also allows a reduction in the possible transverse and depth-dose inhomogeneities that could appear in non-isocentric conditions in particular. A thorough review of existing ripple filter designs over the past 16 years is performed and a design for non-isocentric treatment delivery is presented. A unique ripple filter quality index (QIRiFi) independent of the particle type and energy and representative of the ratio between energy modulation and induced scattering is proposed. The Bragg peak width evaluated at the 80% dose level (BPW80) is proposed to relate the energy modulation of the delivered Bragg peaks and the energy layer step size allowing the production of homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for carbon ion and ripple filter simulations based on measurements performed at CNAO and subsequently used for a detailed analysis of the proposed ripple filter design. A combination of two ripple filters in a series has been validated for non-isocentric delivery and did not show significant transverse and depth-dose inhomogeneities. Non-isocentric conditions allow a significant reduction in the spot size at the patient entrance (up to 350% and 200% for protons and carbon ions with range shifter, respectively), and therefore in the lateral penumbra in the patients. PMID:26418366

  15. Controlled delivery of dopamine hydrochloride using surface modified carbon dots for neuro diseases.

    PubMed

    Khan, M Shahnawaz; Pandey, Sunil; Talib, Abou; Bhaisare, Mukesh Lavkush; Wu, Hui-Fen

    2015-10-01

    Delivery of therapeutic agents using water-soluble, highly biocompatible Carbon dots (C-dots) is an efficient strategy to control drug release under physiological milieu. Dopamine hydrochloride (DA), the most important inotropic vasopressor agent used in neurological diseases. In our study DA is anchored to water-soluble carbon dots for controlled release under mimicked in vitro physiological conditions. The tenure of the DA release at pH 7.4 was greatly extended to 60 h for C-dots-DA, in comparison with the control DA alone. The statistical calculation was used to comprehend the release pattern of the DA, which exhibited the pattern of Hixson-Crowell model of release. In order to understand the impact of the C-dots-DA conjugate under physiological conditions, Neuro 2A cells were taken under consideration. The conjugate C-dots-DA was found to be biocompatible against Neuro 2A cells. The survival rate was found to be 74% at maximum concentration of 9 μg mL(-1). In vivo toxicity was studied using thin section of tissues after staining with Hematoxyline and Eosin Yellow (H&E). As per microscopic observations, conjugates did not inflict any anatomical distortions or hostile effects on tissues. Body weight of mice was also taken into consideration after injecting 20 μg mL(-1) of nano-conjugates via tail vein. The impact of nano-conjugate on body weight was found to be negligible after 45 days of observation. PMID:26186107

  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. 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

  18. 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

  19. One-step bulk preparation of calcium carbonate nanotubes and its application in anticancer drug delivery.

    PubMed

    Tang, Jing; Sun, Dong-Mei; Qian, Wen-Yu; Zhu, Rong-Rong; Sun, Xiao-Yu; Wang, Wen-Rui; Li, Kun; Wang, Shi-Long

    2012-06-01

    Bulk fabrication of ordered hollow structural particles (HSPs) with large surface area and high biocompatibility simultaneously is critical for the practical application of HSPs in biosensing and drug delivery. In this article, we describe a smart approach for batch synthesis of calcium carbonate nanotubes (CCNTs) based on supported liquid membrane (SLM) with large surface area, excellent structural stability, prominent biocompatibility, and acid degradability. The products were characterized by transmission electron micrograph, X-ray diffraction, Fourier transform infrared spectra, UV-vis spectroscopy, zeta potential, and particle size distribution. The results showed that the tube-like structure facilitated podophyllotoxin (PPT) diffusion into the cavity of hollow structure, and the drug loading and encapsulation efficiency of CCNTs for PPT are as high as 38.5 and 64.4 wt.%, respectively. In vitro drug release study showed that PPT was released from the CCNTs in a pH-controlled and time-dependent manner. The treatment of HEK 293T and SGC 7901 cells demonstrated that PPT-loaded CCNTs were less toxic to normal cells and more effective in antitumor potency compared with free drugs. In addition, PPT-loaded CCNTs also enhanced the apoptotic process on tumor cells compared with the free drugs. This study not only provides a new kind of biocompatible and pH-sensitive nanomaterial as the feasible drug container and carrier but more importantly establishes a facile approach to synthesize novel hollow structural particles on a large scale based on SLM technology. PMID:22351100

  20. Photoluminescent carbon nanotags from harmful cyanobacteria for drug delivery and imaging in cancer cells

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Uk; Park, So Young; Park, Eun Sik; Son, Byoungchul; Lee, Soon Chang; Lee, Jae Won; Lee, Young-Chul; Kang, Kyoung Suk; Kim, Moon Il; Park, Hyun Gyu; Choi, Saehae; Huh, Yun Suk; Lee, Seung-Yeul; Lee, Kyung-Bok; Oh, You-Kwan; Lee, Jouhahn

    2014-04-01

    Using a simple method of mass production of green carbon nanotags (G-tags) from harmful cyanobacteria, we developed an advanced and efficient imaging platform for the purpose of anticancer therapy. Approximately 100 grams of G-tags per 100 kilograms of harmful cyanobacteria were prepared using our eco-friendly approach. The G-tags possess high solubility, excellent photostability, and low cytotoxicity (<1.5 mg/mL for 24 h). Moreover, doxorubicin-conjugated G-tags (T-tags; >0.1 mg/mL) induced death in cancer cells (HepG2 and MCF-7) in-vitro at a higher rate than that of only G-tags while in-vivo mice experiment showed enhanced anticancer efficacy by T-tags at 0.01 mg/mL, indicating that the loaded doxorubicin retains its pharmaceutical activity. The cancer cell uptake and intracellular location of the G- and T-tags were observed. The results indicate that these multifunctional T-tags can deliver doxorubicin to the targeted cancer cells and sense the delivery of doxorubicin by activating the fluorescence of G-tags.

  1. Photoluminescent carbon nanotags from harmful cyanobacteria for drug delivery and imaging in cancer cells

    PubMed Central

    Lee, Hyun Uk; Park, So Young; Park, Eun Sik; Son, Byoungchul; Lee, Soon Chang; Lee, Jae Won; Lee, Young-Chul; Kang, Kyoung Suk; Kim, Moon Il; Park, Hyun Gyu; Choi, Saehae; Huh, Yun Suk; Lee, Seung-Yeul; Lee, Kyung-Bok; Oh, You-Kwan; Lee, Jouhahn

    2014-01-01

    Using a simple method of mass production of green carbon nanotags (G-tags) from harmful cyanobacteria, we developed an advanced and efficient imaging platform for the purpose of anticancer therapy. Approximately 100 grams of G-tags per 100 kilograms of harmful cyanobacteria were prepared using our eco-friendly approach. The G-tags possess high solubility, excellent photostability, and low cytotoxicity (<1.5 mg/mL for 24 h). Moreover, doxorubicin-conjugated G-tags (T-tags; >0.1 mg/mL) induced death in cancer cells (HepG2 and MCF-7) in-vitro at a higher rate than that of only G-tags while in-vivo mice experiment showed enhanced anticancer efficacy by T-tags at 0.01 mg/mL, indicating that the loaded doxorubicin retains its pharmaceutical activity. The cancer cell uptake and intracellular location of the G- and T-tags were observed. The results indicate that these multifunctional T-tags can deliver doxorubicin to the targeted cancer cells and sense the delivery of doxorubicin by activating the fluorescence of G-tags. PMID:24721805

  2. 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

  3. 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. PMID:26472449

  4. 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.

  5. 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

  6. 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.

  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. Measurement of neutron ambient dose equivalent in carbon-ion radiotherapy with an active scanned delivery system.

    PubMed

    Yonai, S; Furukawa, T; Inaniwa, T

    2014-10-01

    In ion beam radiotherapy, secondary neutrons contribute to an undesired dose outside the target volume, and consequently the increase of secondary cancer risk is a growing concern. In this study, neutron ambient dose equivalents in carbon-ion radiotherapy (CIRT) with an active beam delivery system were measured with a rem meter, WENDI-II, at National Institute of Radiological Sciences. When the same irradiation target was assumed, the measured neutron dose with an active beam was at most ∼15 % of that with a passive beam. This percentage became smaller as larger distances from the iso-centre. Also, when using an active beam delivery system, the neutron dose per treatment dose in CIRT was comparable with that in proton radiotherapy. Finally, it was experimentally demonstrated that the use of an active scanned beam in CIRT can greatly reduce the secondary neutron dose. PMID:24126486

  10. Phosphorus and Nitrogen Dual-Doped Hollow Carbon Dot as a Nanocarrier for Doxorubicin Delivery and Biological Imaging.

    PubMed

    Gong, Xiaojuan; Zhang, Qingyan; Gao, Yifang; Shuang, Shaomin; Choi, Martin M F; Dong, Chuan

    2016-05-11

    Innovative phosphorus and nitrogen dual-doped hollow carbon dots (PNHCDs) have been fabricated for anticancer drug delivery and biological imaging. The functional groups of PNHCDs are introduced by simply mixing glucose, 1,2-ethylenediamine, and concentrated phosphoric acid. This is an automatic method without external heat treatment to rapidly produce large quantities of PNHCDs, which avoid high temperature, complicated operations, and long reaction times. The as-prepared PNHCDs possess small particle size, hollow structure, and abundant phosphate/hydroxyl/pyridinic/pyrrolic-like N groups, endowing PNHCDs with fluorescent properties, improving the accuracy of PNHCDs as an optical monitoring code both in vitro and in vivo. The investigation of PNHCDs as an anticancer drug nanocarrier for doxorubicin (DOX) indicates a better antitumor efficacy than free DOX owing to its enhanced nuclear delivery in vitro and tumor accumulation in vivo, which results in highly effective tumor growth inhibition and improved targeted therapy for cancer in clinical medicine. PMID:27088972

  11. 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.

  12. Fatal respiratory thermal injury following accidental administration of carbon dioxide using the circle system for a cesarean delivery.

    PubMed

    Aghdashi, M M; Abbasivash, R; Hassani, E; Pirnejad, H

    2009-10-01

    A 37-year-old parturient underwent emergency cesarean delivery because of severe preeclampsia. After induction of general anesthesia, the oxygen saturation decreased. Volatile anesthetics were discontinued and examination of the anesthetic circuit and machine revealed a soda lime canister that was extremely hot. The patient was detached from the anesthetic machine and hand-ventilated with an external oxygen cylinder. The surgery was cancelled and the patient was extubated. Analysis of the cylinder connected to the anesthesia machine displayed 100% carbon dioxide. The patient developed progressive respiratory failure. Bronchoscopic examination revealed burn scars from the carina to the main bronchi. The patient died within four months of the incident. PMID:19734035

  13. 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. PMID:26646711

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

    DOEpatents

    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.

  15. 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

  16. Unzipping and binding of small interfering RNA with single walled carbon nanotube: A platform for small interfering RNA delivery

    NASA Astrophysics Data System (ADS)

    Santosh, Mogurampelly; Panigrahi, Swati; Bhattacharyya, Dhananjay; Sood, A. K.; Maiti, Prabal K.

    2012-02-01

    In an effort to design efficient platform for siRNA delivery, we combine all atom classical and quantum simulations to study the binding of small interfering RNA (siRNA) by pristine single wall carbon nanotube (SWCNT). Our results show that siRNA strongly binds to SWCNT surface via unzipping its base-pairs and the propensity of unzipping increases with the increase in the diameter of the SWCNTs. The unzipping and subsequent wrapping events are initiated and driven by van der Waals interactions between the aromatic rings of siRNA nucleobases and the SWCNT surface. However, molecular dynamics (MD) simulations of double strand DNA (dsDNA) of the same sequence show that the dsDNA undergoes much less unzipping and wrapping on the SWCNT in the simulation time scale of 70 ns. This interesting difference is due to smaller interaction energy of thymidine of dsDNA with the SWCNT compared to that of uridine of siRNA, as calculated by dispersion corrected density functional theory (DFT) methods. After the optimal binding of siRNA to SWCNT, the complex is very stable which serves as one of the major mechanisms of siRNA delivery for biomedical applications. Since siRNA has to undergo unwinding process with the effect of RNA-induced silencing complex, our proposed delivery mechanism by SWCNT possesses potential advantages in achieving RNA interference.

  17. 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

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

    PubMed

    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

    2016-06-01

    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

  19. The next generation cell-penetrating peptide and carbon dot conjugated nano-liposome for transdermal delivery of curcumin.

    PubMed

    Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K

    2016-03-01

    To overcome the problems associated with conventional liposomes in transdermal drug delivery like limited penetration ability and poor stability, in this article we report a new generation of cell penetrating peptide polyarginine containing nano-liposomes conjugated with carbon dots. The newly synthesized, cost-effective liposomic precursors were used for the fabrication of liposomes. The resulting liposomes have a bilayer structure like that of conventional liposomes with much smaller size, higher stability, and high penetration ability. The nano-liposomes show high stability at room temperature for three months without any change in size or encapsulation efficiency. The incorporation of carbon dots also opens up their application in fluorescence cell imaging studies, which is very well supported by the fluorescence microscopic analysis of the liposome skin penetration. The as-prepared nano-liposomes do not show any cytotoxicity for MCF-7 cells, even at high concentrations; however, when drug loaded liposomes are applied, they can kill the cancer cells with a high rate. The synthesized nano-liposomes have the potential to be used as an efficient, stable, biocompatible nanocarrier for transdermal drug delivery. PMID:26631310

  20. 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. PMID:24299837

  1. 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.

  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. 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

  4. Sustainable mesoporous carbons as storage and controlled-delivery media for functional molecules.

    PubMed

    Saha, Dipendu; Payzant, E Andrew; Kumbhar, Amar S; Naskar, Amit K

    2013-06-26

    Here, we report the synthesis of surfactant-templated mesoporous carbons from lignin, which is a biomass-derived polymeric precursor, and their potential use as a controlled-release medium for functional molecules such as pharmaceuticals. To the best of our knowledge, this is the first report on the use of lignin for chemical-activation-free synthesis of functional mesoporous carbon. The synthesized carbons possess the pore widths within the range of 2.5-12.0 nm. In this series of mesoporous carbons, our best result demonstrates a Brunauer-Emmett-Teller (BET) surface area of 418 m(2)/g and a mesopore volume of 0.34 cm(3)/g, which is twice the micropore volume in this carbon. Because of the dominant mesoporosity, this engineered carbon demonstrates adsorption and controlled release of a representative pharmaceutical drug, captopril, in simulated gastric fluid. Large-scale utilization of these sustainable mesoporous carbons in applications involving adsorption, transport, and controlled release of functional molecules is desired for industrial processes that yield lignin as a coproduct. PMID:23731336

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Nano-Carbon-Based Systems for the Delivery of Bioactive Agents:. Pros and Cons

    NASA Astrophysics Data System (ADS)

    Nayak, Tapas R.; Pastorin, Giorgia

    2013-09-01

    Nanotechnology has become a distinctive field of research, aimed to modernize the way scientists have addressed urgent needs and sophisticated problems, towards the achievement of unprecedented discoveries. Amidst the myriad of materials extensively used in the modern society, carbon-based systems seem to embody a significant role especially where endurance and strength are required: carbon nanoparticles, nanotubes, graphite, diamonds and fullerenes et al. In addition to the above advantages, this review also emphasizes some concerns on the carbonnanosystems and which are mainly attributable to the lack of an exhaustive characterization and to the potential hazardous effects deriving from their potential accumulation in the environment and inside the body.

  10. 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

  11. 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.

  12. 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

  13. Targeted Killing of Cancer Cells In vivo and In vitro with EGF-directed Carbon Nanotube-based Drug Delivery

    PubMed Central

    Bhirde, Ashwin A.; Patel, Vyomesh; Gavard, Julie; Zhang, Guofeng; Sousa, Alioscka A.; Masedunskas, Andrius; Leapman, Richard D.; Weigert, Roberto; Gutkind, J. Silvio

    2009-01-01

    Carbon nanotube-based drug delivery holds great promise for cancer therapy. Herein we report the first targeted, in vivo killing of cancer cells using a drug-single wall carbon nanotube (SWNT) bioconjugate, and demonstrate efficacy superior to non-targeted bioconjugates. First line anti-cancer agent cisplatin and epidermal growth factor (EGF) were attached to SWNTs to specifically target squamous cancer, and the non-targeted control was SWNT-cisplatin without EGF. Initialin vitro imaging studies with head and neck squamous carcinoma cells (HNSCC) overexpressing EGF receptors (EGFR) using Qdot luminescence and confocal microscopy showed that SWNT-Qdot-EGF bioconjugates internalized rapidly into the cancer cells. Limited uptake occurred for control cells without EGF, and uptake was blocked by siRNA knockdown of EGFR in cancer cells, revealing the importance of EGFEGFR binding. Three color, two-photon intra-vital video imagingin vivo showed that SWNT-Qdot-EGF injected into live mice was selectively taken up by HNSCC tumors, but SWNT-Qdot controls with no EGF were cleared from the tumor region in <20 min. HNSCC cells treated with SWNT-cisplatin-EGF were also killed selectively, while control systems that did not feature EGF-EGFR binding did not influence cell proliferation. Most significantly, regression of tumor growth was rapid in mice treated with targeted SWNT-cisplatin-EGF relative to non-targeted SWNT-cisplatin. PMID:19236065

  14. 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.

  15. In Vivo Delivery of Nitric Oxide-Sensing, Single-Walled Carbon Nanotubes

    PubMed Central

    Iverson, Nicole M; Strano, Michael S; Wogan, Gerald N

    2015-01-01

    Detection of nitric oxide (NO) in vivo by single walled carbon nanotubes (SWNT) is based on the fluorescent properties of SWNT and the ability of NO to quench the fluorescence signal. Alterations of the signal can be utilized to detect a small molecule in vivo that has not previously been possible by other assay techniques. The protocols described here explain the techniques used to prepare NO-detecting SWNTs and to administer them to mice by both intravenous and subcutaneous routes. These techniques can also be utilized with other SWNT sensors as well as non-SWNT sensors. PMID:26344235

  16. 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. PMID:27475727

  17. 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

  18. 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

  19. Regulation of angiogenesis through the efficient delivery of microRNAs into endothelial cells using polyamine-coated carbon nanotubes.

    PubMed

    Masotti, Andrea; Miller, Mark R; Celluzzi, Antonella; Rose, Lorraine; Micciulla, Federico; Hadoke, Patrick W F; Bellucci, Stefano; Caporali, Andrea

    2016-08-01

    MicroRNAs (miRNAs) directly regulate gene expression at a post-transcriptional level and represent an attractive therapeutic target for a wide range of diseases. Here, we report a novel strategy for delivering miRNAs to endothelial cells (ECs) to regulate angiogenesis, using polymer functionalized carbon nanotubes (CNTs). CNTs were coated with two different polymers, polyethyleneimine (PEI) or polyamidoamine dendrimer (PAMAM), followed by conjugation of miR-503 oligonucleotides as recognized regulators of angiogenesis. We demonstrated a reduced toxicity for both polymer-coated CNTs, compared with pristine CNTs or polymers alone. Moreover, polymer-coated CNT stabilized miR-503 oligonucleotides and allowed their efficient delivery to ECs. The functionality of PAMAM-CNT-miR-503 complexes was further demonstrated in ECs through regulation of target genes, cell proliferation and angiogenic sprouting and in a mouse model of angiogenesis. This comprehensive series of experiments demonstrates that the use of polyamine-functionalized CNTs to deliver miRNAs is a novel and effective means to regulate angiogenesis. PMID:27013131

  20. 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. PMID:26816656

  1. 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

  2. Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery.

    PubMed

    Singh, Rahul Pratap; Sharma, Gunjan; Sonali; Singh, Sanjay; Patne, Shashikant C U; Pandey, Bajarangprasad L; Koch, Biplob; Muthu, Madaswamy S

    2016-10-01

    The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). d-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC50 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P<0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™. PMID:27287127

  3. 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.

  4. 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

  5. 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

  6. Targeted killing of cancer cells in vivo and in vitro with IGF-IR antibody-directed carbon nanohorns based drug delivery.

    PubMed

    Li, Nannan; Zhao, Qian; Shu, Chang; Ma, Xiaona; Li, Ruixin; Shen, Hongjun; Zhong, Wenying

    2015-01-30

    Oxidized single-wall carbon nanohorns (oxSWNHs) have shown great potential in drug delivery. The purpose of this study was to design an effective targeted drug delivery system (DDS) based on oxSWNHs, which could carry high dose of drug to tumor sites and improve the therapeutic efficacy with less adverse effects. OxSWNHs incorporated the anticancer drug vincristine (VCR) via physical adsorption, then wrapped DSPE-PEG-IGF-IR monoclonal antibody (mAb) through an amide liker to obtain the drug delivery system, VCR@oxSWNHs-PEG-mAb. The in vitro release behavior study indicated that the DDS had good sustained release and the cumulative release of VCR was 80% at 144h. Compared with free VCR, the tumor targeting drug delivery efficiently enhanced the cytotoxicity in cultured MCF-7 cells in vitro, and afforded higher antitumor efficacy without obvious toxic effects to normal organs in tumor mice in vivo. In addition, the targeted DDS could reduce the toxicity of VCR to the living mice. This study demonstrated that VCR@oxSWNHs-PEG-mAb might be promising for high treatment efficacy with minimal side effects in future cancer therapy. PMID:25510600

  7. SINGLE-WALLED CARBON NANOTUBE–MEDIATED SMALL INTERFERING RNA DELIVERY AND SILENCING GASTRIN-RELEASING PEPTIDE RECEPTOR IN HUMAN NEUROBLASTOMA CELLS

    PubMed Central

    Qiao, Jingbo; Hong, Tu; Guo, Honglian; Xu, Ya-Qiong; Chung, Dai H.

    2015-01-01

    Small interfering RNA (siRNA) has the potential to influence expression with a high degree of target gene specificity. However, the clinical application of siRNA therapeutics has proven to be less promising as evidenced by poor intracellular uptake, instability in vivo, and non-specific immune stimulations. Recently, we have demonstrated that single-walled carbon nanotube (SWNT)-mediated siRNA delivery can enhance the efficiency of siRNA-mediated gastrin-releasing peptide receptor (GRP-R) gene silencing by stabilizing siRNA while selectively targeting tumor tissues. Based on our recent findings, we introduce a novel technique to silence specific gene(s) in human neuroblastoma through SWNT-mediated siRNA delivery in vitro and in vivo. PMID:23749575

  8. 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

  9. Tumor Acidity-Induced Sheddable Polyethylenimine-Poly(trimethylene carbonate)/DNA/Polyethylene Glycol-2,3-Dimethylmaleicanhydride Ternary Complex for Efficient and Safe Gene Delivery.

    PubMed

    Zhao, Caiyan; Shao, Leihou; Lu, Jianqing; Deng, Xiongwei; Wu, Yan

    2016-03-16

    Amphiphilic PEI derivatives/DNA complexes are widely used for DNA delivery, but they are unstable in vivo and have cytotoxicity due to the excess cationic charge. PEGylation of cationic complexes can improve sterical stability and biocompatibility. However, PEGylation significantly inhibits cellular uptake and endosomal escape. In this work, sheddable ternary complexes were developed by coating a tumor acidity-sensitive β-carboxylic amide functionalized PEG layer on the binary complexes of amphiphilic cationic polyethylenimine-poly(trimethylene carbonate) nanoparticles/DNA (PEI-PTMC/DNA). Such sheddable ternary complexes markedly reduced their nonspecific interactions with serum protein in the bloodstream and obtained minimal cytotoxicity due to the protection of the PEG shell. At the tumor site, the PEG layer was deshielded by responding to the tumor acidic microenvironment and the positively charged complexes re-exposed that had higher affinity with negatively charged cell membranes. Meanwhile the positively charged complexes facilitated endosomal escape. Accordingly, this delivery system improved the biocompatibility of gene-loaded complexes and enhanced the gene transfection efficiency. Such PEGylated complexes with the ability to deshield the PEG layer at the target tissues hold great promise for efficient and safe gene delivery in vivo. PMID:26904916

  10. 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

  11. Evidence for a plasma-accessible carbonic anhydrase in the lumen of salmon heart that may enhance oxygen delivery to the myocardium.

    PubMed

    Alderman, Sarah L; Harter, Till S; Wilson, Jonathan M; Supuran, Claudiu T; Farrell, Anthony P; Brauner, Colin J

    2016-03-01

    Oxygen supply to the heart of most teleosts, including salmonids, relies in part or in whole on oxygen-depleted venous blood. Given that plasma-accessible carbonic anhydrase (CA) in red muscle of rainbow trout has recently been shown to facilitate oxygen unloading from arterial blood under certain physiological conditions, we tested the hypothesis that plasma-accessible CA is present in the lumen of coho salmon (Oncorhynchus kisutch) hearts, and may therefore assist in the luminal oxygen supply to the spongy myocardium, which has no coronary circulation. We demonstrate a widespread distribution of CA throughout the heart chambers, including lumen-facing cells in the atrium, and confirm that the membrane-bound isoform ca4 is expressed in the atrium and ventricle of the heart. Further, we confirm that CA catalytic activity is available to blood in the atrial lumen using a modified electrometric ΔpH assay in intact atria in combination with either a membrane-impermeable CA inhibitor or specific cleavage of the Ca4 membrane anchor. Combined, these results support our hypothesis of the presence of an enhanced oxygen delivery system in the lumen of a salmonid heart, which could help support oxygen delivery when the oxygen content of venous blood becomes greatly reduced, such as after burst exercise and during environmental hypoxia. PMID:26936639

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    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

  14. 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

  15. Development of Novel Drug and Gene Delivery Carriers Composed of Single-Walled Carbon Nanotubes and Designed Peptides With PEGylation.

    PubMed

    Ohta, Takahisa; Hashida, Yasuhiko; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2016-09-01

    Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical applications including drug and gene delivery. In this study, we developed a novel delivery system using SWCNTs associated with designed polycationic and amphiphilic peptides. Wrapping of SWCNTs with H-(-Lys-Trp-Lys-Gly-)7-OH [(KWKG)7] resulted in stable dispersion in water, but the composite aggregated in the buffered solution. This dispersion instability was also evident in a cell culture medium with fetal bovine serum. To improve the aqueous dispersibility, the SWCNTs-(KWKG)7 composite was further modified with polyethylene glycol (PEG) at the lysine residues via amide bond formation and the highest modification extent of 13.3% of the amino groups which corresponded to 2 PEG chains in each peptide molecule was achieved with fluorescein isothiocyanate-labeled carboxyl-PEG12. The uptake of the SWCNTs composite by A549 human lung adenocarcinoma epithelial cells was evaluated by visual observation and fluorescence activated cell sorting analysis for SWCNTs wrapped with a mixture of (KWKG)7 with PEGylation and H-(-Cys-Trp-Lys-Gly-)-OH-(KWKG)6 [CWKG(KWKG)6] labeled with fluorescent boron-dipyrromethene tetramethylrhodamine and 7-fold higher uptake comparing with SWCNTs-peptide composite without PEGylation was obtained suggesting the importance of dispersibility in addition to a cationic charge. The superior potential of SWCNTs composites assisted by polycationic and amphiphilic peptides with PEGylation was thus demonstrated. PMID:27179670

  16. 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.

  17. 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

  18. Polycation-b-polyzwitterion copolymer grafted luminescent carbon dots as a multifunctional platform for serum-resistant gene delivery and bioimaging.

    PubMed

    Cheng, Lu; Li, Yongmao; Zhai, Xinyun; Xu, Bing; Cao, Zhiqiang; Liu, Wenguang

    2014-11-26

    Nanomaterials that integrate functions of imaging and gene delivery have been of great interest due to their potential use in simultaneous diagnosis and therapy. Herein, polycation-b-polysulfobetaine block copolymer, poly[2-(dimethylamino) ethyl methacrylate]-b-poly[N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide] (PDMAEMA-b-PMPDSAH) grafted luminescent carbon dots (CDs) were prepared via surface-initiated atom transfer radical polymerization (ATRP) and investigated as a multifunctional gene delivery system (denoted as CD-PDMA-PMPD) in which the CD cores acted as good multicolor cell imaging probes, the cationic PDMAEMA acted as a DNA condensing agent, and the outer shell of zwitterionic PMPDSAH block protected the vector against nonspecific interactions with serum components. As revealed by the fluorescent spectrum study, the photoluminescent attributes, especially the tunable emission property, were well inherited from the parent CDs. The CD-PDMA-PMPD could condense plasmid DNA into nanospheres with sizes of approximate 50 nm at a proper complex ratio, posing little cytotoxicity at higher ratios. It was shown that the hybrid vector exhibited significantly suppressed BSA protein adsorption and superior hemocompatibility compared to those of the widely used PEI25k. In the in vitro transfection assay, an increased serum concentration from 10 to 50% caused a dramatic drop in PEI25k transfection performance, whereas the transfection efficiency of CD-PDMA-PMPD was well maintained; CD-PDMA80-PMPD40 showed 13 and 28 times higher transfection efficiencies than PEI25k at 30 and 50% serum concentration, respectively. Intriguingly, the carbon dots in the transfected cells displayed excitation-dependent fluorescent emissions, portending that this polycation-polyzwitterion modified CD will be a promising theranostic vector with excellent stealth performance. PMID:25285670

  19. 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

  20. Coadsorption of Doxorubicin and Selected Dyes on Carbon Nanotubes. Theoretical Investigation of Potential Application as a pH-Controlled Drug Delivery System.

    PubMed

    Panczyk, Tomasz; Wolski, Pawel; Lajtar, Leszek

    2016-05-17

    This work shows results of a theoretical survey, based on molecular dynamics simulation, of potential applicability of doxorubicin coadsorption with various dyes molecules on/in carbon nanotubes as a drug delivery system. The central idea is to take advantage of the dyes charge distribution change upon switching the pH of the environment from neutral (physiological 7.4) to acidic one (∼5.5 which is typical for tumor tissues). This work discusses results obtained for four dye molecules revealing more or less interesting behavior. These were bromothymol blue, methyl red, neutral red, and p-phenylenediamine. All of them reveal pKa in the range 5-7 and thus will undergo protonation in that pH range. We considered coadsorption on external walls of carbon nanotubes and sequential filling of the nanotubes inner hollow space by drug and dyes. The latter approach, with the application of neutral red and p-phenylenediamine as blockers of doxorubicin, led to the most promising results. Closer analysis of these systems allowed us to state that neutral red can be particularly useful as a long-term blocker of doxorubicin encapsulated in the inner cavity of (30,0) carbon nanotube at neutral pH. At acidic pH we observed a spontaneous release of neutral red from the nanotube and unblocking of doxorubicin. We also confirmed, by analysis of free energy profiles, that unblocked doxorubicin can spontaneously leave the nanotube interior at the considered conditions. Thus, that system can realize pH controlled doxorubicin release in acidic environment of tumor tissues. PMID:27133585

  1. 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

  2. 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

  3. Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

    PubMed Central

    Jeyamohan, Prashanti; Hasumura, Takashi; Nagaoka, Yutaka; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

    2013-01-01

    The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy. PMID:23926428

  4. Pseudomonas fluorescens CHA0 maintains carbon delivery to Fusarium graminearum-infected roots and prevents reduction in biomass of barley shoots through systemic interactions

    PubMed Central

    Henkes, Gunnar J.; Jousset, Alexandre; Bonkowski, Michael; Thorpe, Michael R.; Scheu, Stefan; Lanoue, Arnaud; Schurr, Ulrich; Röse, Ursula S. R.

    2011-01-01

    Soil bacteria such as pseudomonads may reduce pathogen pressure for plants, both by activating plant defence mechanisms and by inhibiting pathogens directly due to the production of antibiotics. These effects are hard to distinguish under field conditions, impairing estimations of their relative contributions to plant health. A split-root system was set up with barley to quantify systemic and local effects of pre-inoculation with Pseudomonas fluorescens on the subsequent infection process by the fungal pathogen Fusarium graminearum. One root half was inoculated with F. graminearum in combination with P. fluorescens strain CHA0 or its isogenic antibiotic-deficient mutant CHA19. Bacteria were inoculated either together with the fungal pathogen or in separate halves of the root system to separate local and systemic effects. The short-term plant response to fungal infection was followed by using the short-lived isotopic tracer 11CO2 to track the delivery of recent photoassimilates to each root half. In the absence of bacteria, fungal infection diverted carbon from the shoot to healthy roots, rather than to infected roots, although the overall partitioning from the shoot to the entire root system was not modified. Both local and systemic pre-inoculation with P. fluorescens CHA0 prevented the diversion of carbon as well as preventing a reduction in plant biomass in response to F. graminearum infection, whereas the non-antibiotic-producing mutant CHA19 lacked this ability. The results suggest that the activation of plant defences is a central feature of biocontrol bacteria which may even surpass the effects of direct pathogen inhibition. PMID:21561952

  5. Synthesis and characterization of biodegradable poly(ethylene glycol)-block-poly(5-benzyloxy-trimethylene carbonate) copolymers for drug delivery.

    PubMed

    Zeng, Faquan; Liu, Jubo; Allen, Christine

    2004-01-01

    Amphiphilic diblock copolymers with various block compositions were synthesized with monomethoxy-terminated poly(ethylene glycol) (MePEG) as the hydrophilic block and poly(5-benzyloxy-trimethylene carbonate) (PBTMC) as the hydrophobic block. When the copolymerization was conducted using MePEG as a macroinitiator and stannous 2-ethylhexanoate (Sn(Oct)2) as a catalyst, the molecular weight of the second block was uncontrollable, and the method only afforded a mixture of homopolymer and copolymer with a broad molecular weight distribution. By contrast, the use of the triethylaluminum-MePEG initiator yielded block copolymers with controllable molecular weight and a more narrow molecular weight distribution than the copolymers obtained using Sn(Oct)2. GPC and 1H NMR studies confirmed that the macroinitiator was consumed and the copolymer composition was as predicted. Two of the newly synthesized MePEG-b-PBTMC copolymers were evaluated in terms of properties primarily relating to their use in micellar drug delivery. MePEG-b-PBTMC micelles with a narrow monomodal size distribution were prepared using a high-pressure extrusion technique. The MePEG-b-PBTMC copolymers were also confirmed to be biodegradable and noncytotoxic. PMID:15360292

  6. 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. PMID:26510313

  7. 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.

  8. The role of hydrologic variability in the delivery of dissolved organic carbon and nitrogen to surface water

    NASA Astrophysics Data System (ADS)

    Martin, R. A.; Harrison, J.

    2011-12-01

    Hydrologic connectivity expands and contracts within watersheds as moisture conditions change, with implications for in-stream water quality. Dissolved organic carbon (DOC) concentration has been shown to increase in streams during high flow events, presumably as sources of DOC in side-channels, riparian soils, and/or uplands are mobilized and transported to surface water. Dissolved organic nitrogen (DON) has been less well studied, but behavior of DON is often assumed to mirror that of DOC. However, because DOC- and DON-rich pools of organic matter may be mobilized at different times, and because DOC and DON may undergo unbalanced abiotic and biotic processing along flowpaths, there is reason to suspect that DOC and DON respond divergently to high flow events. We use a meta-analysis to address the following questions: 1) To what extent do high flow events affect in-stream DON concentration? And 2) To what extent are DOC and DON concentrations decoupled during these events? Across 47 systems that included 78 high flow events, flow-weighted mean DON concentration increased, on average, 1.58-fold from baseflow to high flow, with a maximum increase of 9.5-fold. DOC and DON exhibited a complex relationship, with DOC and DON concentrations peaking at different times in over half of the events, and molar DOC:DON ratios varying, on average, 4-fold during high flow. An intensive field investigation of a tile-drained agricultural system in eastern Washington indicates that DOC and DON concentrations increase in tile drain discharge during winter runoff relative to baseflow, consistent with the mobilization of novel sources of DOM. However, DOM characteristics, including DOC and DON concentrations, DOC:DON, and fluorescence indices, of tile drain discharge can vary widely from potential sources identified in the watershed (ground water, soil water). For example, during a base flow period, DOC:DON was 41 in ground water, 24 in water-extractable soil organic matter, but only 1

  9. Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment.

    PubMed

    Jiang, Xinyi; Xin, Hongliang; Ren, Qiuyue; Gu, Jijin; Zhu, Lingjun; Du, Fengyi; Feng, Chunlai; Xie, Yike; Sha, Xianyi; Fang, Xiaoling

    2014-01-01

    Based on the facilitative glucose transporter (GLUT) over-expression on both blood-brain barrier (BBB) and glioma cells, 2-deoxy-d-glucose modified poly(ethylene glycol)-co-poly(trimethylene carbonate) nanoparticles (dGlu-NP) were developed as a potential dual-targeted drug delivery system for enhancing the BBB penetration via GLUT-mediated transcytosis and improving the drug accumulation in the glioma via GLUT-mediated endocytosis. In vitro physicochemical characterization of the dual-targeted nanoparticulate system presented satisfactory size of 71 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of paclitaxel (PTX). Compared with non-glucosylated nanoparticles (NP), a significantly higher amount of dGlu-NP was internalized by RG-2 glioma cells through caveolae-mediated and clathrin-mediated endocytosis. Both of the transport ratios across the in vitro BBB model and the cytotoxicity of RG-2 cells after crossing the BBB were significantly greater of dGlu-NP/PTX than that of NP/PTX. In vivo fluorescent image indicated that dGlu-NP had high specificity and efficiency in intracranial tumor accumulation. The anti-glioblastoma efficacy of dGlu-NP/PTX was significantly enhanced in comparison with that of Taxol and NP/PTX. Preliminary safety tests showed no acute toxicity to hematological system, liver, kidney, heart, lung and spleen in mice after intravenous administration at a dose of 100 mg/kg blank dGlu-NP per day for a week. Therefore, these results indicated that dGlu-NP developed in this study could be a potential dual-targeted vehicle for brain glioma therapy. PMID:24125772

  10. Preparation and binding study of a complex made of DNA-treated single-walled carbon nanotubes and antibody for specific delivery of a “molecular heater” platform

    PubMed Central

    Kawaguchi, Minoru; Yamazaki, Jun; Ohno, Jun; Fukushima, Tadao

    2012-01-01

    Carbon nanotubes have been explored as heat-delivery vehicles for thermal ablation of tumors. To use single-walled carbon nanotubes (SWNT) as a “molecular heater” for hyperthermia therapy in cancer, stable dispersibility and smart-delivery potential will be needed, as well as lack of toxicity. This paper reports the preparation of a model complex comprising DNA-treated SWNT and anti-human IgG antibody and the specific binding ability of this model complex with the targeted protein, ie, human IgG. Treatment with double-stranded DNA enabled stable dispersibility of a complex composed of SWNT and the antibody under physiological conditions. Quartz crystal microbalance results suggest that there was one immobilized IgG molecule to every 21,700 carbon atoms in the complex containing DNA-treated SWNT and the antibody. The DNA-SWNT antibody complex showed good selectivity for binding to the targeted protein. Binding analysis revealed that treatment with DNA did not interfere with binding affinity or capacity between the immobilized antibody and the targeted protein. The results of this study demonstrate that the DNA-SWNT antibody complex is a useful tool for use as a smart “molecular heater” platform applicable to various types of antibodies targeting a specific antigen. PMID:22915857

  11. 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

  12. Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells.

    PubMed

    Taghavi, Sahar; HashemNia, Azadeh; Mosaffa, Fatemeh; Askarian, Saeedeh; Abnous, Khalil; Ramezani, Mohammad

    2016-04-01

    In this study, single-walled carbon nanotubes (SWCNTs) were covalently attached to poly(ethylene glycol) (PEG) and polyethylenimine (PEI) 10kDa, or its derivatives, to fabricate efficient carriers for gene delivery. PEI 10kDa was modified by alkylcarboxylation of its primary amines with a series of ω-bromo-alkylcarboxylic acids to provide a range of vectors with increased lipophilicity. PEI 10kDa or its alkylcarboxylate derivatives were conjugated to SWCNT-PEG to develop vectors possessing effective DNA condensation ability which can interact with cell membrane via both nano-needle mechanism and electrostatic interactions produced by SWCNT and PEI, respectively. The results demonstrated that SWCNT-PEG-PEI and SWCNT-PEG-derivatives of PEI could condense DNA into particle size less than 150nm with positive surface charges between 6.3-30.8mV. To improve the antitumor efficacy, we developed a targeted gene delivery system using a 5TR1 aptamer. The most efficient vector, which was prepared by attachment of SWCNT-PEG to modified PEI 10kDa with 10-bromodecanoic acid (10%), showed 8.5-10 folds enhancement in transfection activity at C/P ratio 6 as compared to the gold standard PEI 25kDa at C/P ratio of 0.8. We also showed that the selected polyplex could efficiently and selectively transfer plasmid shRNA to MUC1 positive cells. PMID:26731195

  13. 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

  14. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    A combination of data from ICP-MS, Raman spectroscopy, UV-vis spectrometry, atomic force microscopy, ζ-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.

  16. Targeted Drug Delivery in Pancreatic Cancer

    PubMed Central

    Yu, Xianjun; Zhang, Yuqing; Chen, Changyi; Yao, Qizhi; Li, Min

    2009-01-01

    Effective drug delivery in pancreatic cancer treatment remains a major challenge. Because of the high resistance to chemo and radiation therapy, the overall survival rate for pancreatic cancer is extremely low. Recent advances in drug delivery systems hold great promise for improving cancer therapy. Using liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule inhibitor and antibody has been a success in recent pre-clinical trials. However, how to improve the specificity and stability of the delivered drug using ligand or antibody directed delivery represent a major problem. Therefore, developing novel, specific, tumor-targeted drug delivery systems is urgently needed for this terrible disease. This review summarizes the current progress on targeted drug delivery in pancreatic cancer, and provides important information on potential therapeutic targets for pancreatic cancer treatment. PMID:19853645

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Glacial and tectonic influence on terrestrial organic carbon delivery to high latitude deep marine systems: IODP Site U1417, Surveyor Fan, Gulf of Alaska

    NASA Astrophysics Data System (ADS)

    Childress, L. B.; Ridgway, K. D.

    2014-12-01

    Glacial and tectonic processes on active margins are intrinsically coupled to the transport of sediment and associated organic carbon (OC). Glaciation/deglaciation and the formation of ice sheets can alter the quantity and composition of OC delivered to the marine environment. Over geologic time scales (>1 Ma), exhumation and mass wasting of sedimentary rock from uplifted accretionary wedges inject recycled OC (e.g. kerogen), along with modern OC into the marine environment. The sedimentary record of glacial and tectonic processes along the southern Alaska margin is particularly well preserved at Integrated Ocean Drilling Program (IODP) Site U1417. Lithofacies of Site U1417 can be divided into 3 sedimentary packages that we interpret as linked to the onset of tidewater glaciation along, and tectonic convergence of the Yakutat Terrane with, the continental margin of northwestern Canada and southern Alaska. Based on previous studies linking the development of the Cordilleran Ice Sheet and the movement of the Yakutat Terrane to the development of the Surveyor Fan System, we hypothesize biogeochemical variations in the deposited sediments as a result of changing provenance. Preservation of terrestrial OC that has been documented in sediments of the Alaskan continental shelf margin and sediment routing through the deep-sea Surveyor Channel from the Pleistocene to modern time implies a long-term conduit for this OC to reach the distal portion of the Surveyor Fan system. To correlate marine deposits with terrestrial formations, bulk geochemical and detailed biomarker analyses are used to delineate source material. Preliminary bulk OC content and stable carbon isotope analyses of the Yakataga, Poul Creek, and Kultheith Fms. reveal notable differences. Detailed biomarker analysis by pyrolysis-gas chromatograph-mass spectrometry has revealed further differences between the three primary formations. Using the biogeochemical fingerprints of the Yakataga, Poul Creek, and coal

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Molecular aptamers for drug delivery.

    PubMed

    Tan, Weihong; Wang, Hui; Chen, Yan; Zhang, Xiaobing; Zhu, Haizhen; Yang, Chaoyong; Yang, Ronghua; Liu, Chen

    2011-12-01

    The active targeting of drugs in a cell-, tissue- or disease-specific manner represents a potentially powerful technology with widespread applications in medicine, including the treatment of cancers. Aptamers have properties such as high affinity and specificity for targets, easy chemical synthesis and modification, and rapid tissue penetration. They have become attractive molecules in diagnostics and therapeutics rivaling and, in some cases, surpassing other molecular probes, such as antibodies. In this review, we highlight the recent progress in aptamer-mediated delivery for therapeutics and disease-targeting based on aptamer integration with a variety of nanomaterials, such as gold nanorods, DNA micelles, DNA hydrogels and carbon nanotubes. PMID:21821299

  9. 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

  10. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

  11. 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

  12. Antibiotic delivery by nanobioceramics.

    PubMed

    Kumar, Ts Sampath; Madhumathi, K

    2016-08-01

    The role of nanotechnology has evinced remarkable interest in the field of drug delivery. Bioceramics are inorganic biomaterials which are frequently used as bone substitutes. They have been explored in drug delivery as carriers for antibiotics, anti-osteoporotic drugs and anticancer drugs. Bioceramic nanoparticles are excellent alternatives to polymers due to their bioactivity, pH and temperature stability, multifunctionality, biocompatibility and tunable biodegradability. The use of bioceramics for local drug delivery in the field of orthopedics offer an efficient, safe mode of drug delivery directly to the surgical site thereby overcoming the limitations of systemic drug delivery. This review focuses on the development and applications of various nanobioceramics employed as drug delivery systems for the treatment of bone infections. PMID:27444496

  13. 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.

  14. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

    New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

  15. 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

  16. 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

  17. 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 ...

  18. Molecular aptamers for drug delivery

    PubMed Central

    Tan, Weihong; Wang, Hui; Chen, Yan; Zhang, Xiaobing; Zhu, Haizhen; Yang, Chaoyong; Yang, Ronghua

    2011-01-01

    The active targeting of drugs in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology with widespread applications in medicine, including the treatment of cancers. Aptamers, with properties such as high affinity and specificity to their targets, easy chemical synthesis and modification, as well as rapid tissue penetration, have become attractive molecules in diagnostics and therapeutics. They rival and, in some cases, surpass other molecular probes, such as antibodies. In this review, we highlight the recent progress in aptamer-mediated delivery for therapeutics and disease-targeting based on aptamer integration with a variety of nanomaterials, such as gold nanorods, DNA-micelles, DNA-hydrogels and carbon nanotubes. PMID:21821299

  19. Delivery by Cesarean Section

    MedlinePlus

    ... Español Text Size Email Print Share Delivery by Cesarean Section Page Content Article Body More than one mother in three gives birth by Cesarean section in the United States (it is also called ...

  20. 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)

  1. 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 ...

  2. [Transdermal Delivery of NSAIDs].

    PubMed

    Nakajima, Takehisa; Makino, Kimiko

    2015-11-01

    Skin has been studied as administration site of drug for its systemic effects, since systemic therapeutic agents can be delivered for long time with a controlled ratio, escaping from the first pass effect by liver by the transdermal delivery, which can decrease the dosage form. The low permeability of drug molecules through stratum corneum has been the limiting factor for developing transdermal delivery system of therapeutic agents. To enhance the permeability of drug molecules, many studies have been reported. PMID:26689064

  3. 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. PMID:26773302

  4. 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

  5. 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

  6. Metrology for drug delivery.

    PubMed

    Lucas, Peter; Klein, Stephan

    2015-08-01

    In various recently published studies, it is argued that there are underestimated risks with infusion technology, i.e., adverse incidents believed to be caused by inadequate administration of the drugs. This is particularly the case for applications involving very low-flow rates, i.e., <1 ml/h and applications involving drug delivery by means of multiple pumps. The risks in infusing are caused by a lack of awareness, incompletely understood properties of the complete drug delivery system and a lack of a proper metrological infrastructure for low-flow rates. Technical challenges such as these were the reason a European research project "Metrology for Drug Delivery" was started in 2011. In this special issue of Biomedical Engineering, the results of that project are discussed. PMID:25879307

  7. 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

  8. 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

  9. 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

  10. Technological Delivery Systems.

    ERIC Educational Resources Information Center

    Kennedy, Don; And Others

    A section on technological delivery systems, presented as part of the second Australian National Workshop on Distance Education (Perth, 1983), contains four papers on using technological resources to provide educational services to persons in isolated locations. The first paper, by Don Kennedy, covers the use of satellite broadcasting of course…

  11. Fluid delivery control system

    SciTech Connect

    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.

  12. 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…

  13. Nanotopography applications in drug delivery.

    PubMed

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2015-01-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  14. 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. PMID:25703045

  15. 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.

  16. Continuing Professional Education Delivery Systems.

    ERIC Educational Resources Information Center

    Weeks, James P.

    This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

  17. PECTIN IN CONTROLLED DRUG DELIVERY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drug delivery systems for site-specific drug delivery. Sev...

  18. Peptide and protein delivery using new drug delivery systems.

    PubMed

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

  19. Terplex Gene Delivery System.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16243067

  20. Terplex gene delivery system.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16240997

  1. 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

  2. Delivery strategies for antiparasitics.

    PubMed

    Kayser, Oliver; Kiderlen, Albrecht F

    2003-02-01

    Optimisation of drug carrier systems and drug delivery strategies that take into account the peculiarities of individual infectious agents and diseases are key elements of modern drug development. In the following, different aspects of a rational design for antiparasitic drug formulation will be reviewed, covering delivery systems such as nano- and microparticles, liposomes, emulsions and microemulsions, cochleates and bioadhesive macromolecules. Functional properties for each carrier system will be discussed as well as their therapeutic efficacy for parasitic diseases, including leishmaniasis, human African trypanosomiasis, human cryptosporidiosis, malaria and schistosomiasis. Critical issues for the application of drug carrier systems will be discussed, focusing on biopharmaceutical and pathophysiological parameters such as routes of application, improvement of body distribution and targeting intracellularly persisting pathogens. PMID:12556214

  3. Compact SPS - Power delivery

    NASA Astrophysics Data System (ADS)

    Pospisil, M.; Pospisilova, L.

    1982-09-01

    The power deliverable by a compact solar Space Power Station (SPS) is a function of its outer surface shape. Methods of fitting the power delivery curve of such a system to different patterns of daily power demand are considered that involve the appropriate choice of the number of satellites, their maximal power, height to width ratio and the shift of longitude with respect to the receiving station. Changes in the daily delivery curve can be made by altering the longitudes and orientations of the satellites. Certain limitations to the choice of parameters exist, such as: the height to width ratio should be near 1.2, and the sum of longitude and orientation changes will probably not be greater than 50 deg. The optimization of the peak to average power ratio is also discussed.

  4. Monitoring and delivery of sedation.

    PubMed

    Sheahan, C G; Mathews, D M

    2014-12-01

    Sedation for medical procedures is provided in a variety of clinical settings by medical personnel with differing levels of education and training. Although generally a safe practice, there is a degree of morbidity and mortality associated with sedation practice. Monitoring standards continue to be refined by professional societies with the goal of improving care. The depth of sedation should be monitored with clinical criteria. Processed electroencephalographic monitors currently do not contribute significantly to sedation care. Monitoring ventilation using pulse oximetry should be abandoned for more direct methods, such as capnography-transcutaneous carbon dioxide, respiratory acoustical and thoracic impedance monitoring could also play a role. Propofol has become widely utilized for sedation, although there are concerns about its margin of safety and synergistic interactions with other agents. Dexmedetomidine and propofol/ketamine also have utility. Patient-controlled sedation pumps and target-controlled infusion devices have been developed to improve patient care and satisfaction. A computer-assisted propofol sedation device to be used by non-anaesthesiologists has been approved in the USA by the Food and Drug Administration. More computer-assisted sedation delivery devices are likely to be developed, but their clinical utility is unclear. PMID:25498581

  5. Reproductive health care delivery.

    PubMed

    Lindgren, Mark C; Ross, Lawrence S

    2014-02-01

    Most patients in the United States with reproductive health disorders are not covered by their health insurance for these problems. Health insurance plans consider reproductive care as a lifestyle choice not as a disease. If coverage is provided it is, most often, directed to female factor infertility and advanced reproductive techniques, ignoring male factor reproductive disorders. This article reviews the history of reproductive health care delivery and its present state, and considers its possible future direction. PMID:24286778

  6. Mucosal delivery of vaccines.

    PubMed

    Del Giudice, G; Pizza, M; Rappuoli, R

    1999-09-01

    Oral delivery represents one of the most pursued approaches for large-scale human vaccination. Due to the different characteristics of mucosal immune response, as compared with systemic response, oral immunization requires particular methods of antigen preparation and selective strategies of adjuvanticity. In this paper, we describe the preparation and use of genetically detoxified bacterial toxins as mucosal adjuvants and envisage the possibility of their future exploitation for human oral vaccines. PMID:10525451

  7. 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

  8. 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

  9. Nanovehicular intracellular delivery systems.

    PubMed

    Prokop, Ales; Davidson, Jeffrey M

    2008-09-01

    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

  10. Transmembrane heme delivery systems

    PubMed Central

    Goldman, Barry S.; Beck, David L.; Monika, Elizabeth M.; Kranz, Robert G.

    1998-01-01

    Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins. PMID:9560218

  11. Novel antigen delivery systems.

    PubMed

    Trovato, Maria; De Berardinis, Piergiuseppe

    2015-08-12

    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

  12. Revolutionary impact of nanodrug delivery on neuroscience.

    PubMed

    Khanbabaie, Reza; Jahanshahi, Mohsen

    2012-12-01

    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

  13. 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

  14. Rationale for the selection of an aerosol delivery system for gene delivery.

    PubMed

    Lentz, Yvonne K; Anchordoquy, Thomas J; Lengsfeld, Corinne S

    2006-01-01

    Genetic therapeutics show great promise toward the treatment of illnesses associated with the lungs; however, current methods of delivery such as jet and ultrasonic nebulization decrease the activity and effectiveness of these treatments. Extremely low transfection rates exhibited by non-complexed plasmid DNA in these nebulizers have been primarily attributed to poor translocation and loss of molecular integrity as a consequence of shear-induced degradation. Current research focusing on methods to increase transfection rates via the pulmonary delivery route has largely concentrated on the incorporation of carbon dioxide in the air stream to increase breath depth as well as the addition of cationic agents that condense DNA into compact, ordered complexes. The purpose of this study was to examine the impact of several classic as well as the latest atomization devices on the structure of non-complexed DNA. Various sizes of plasmid and cosmid DNA were processed through an electrostatic spray, ultrasonic nebulizer, vibrating mesh nebulizer, and jet nebulizer. Results varied dramatically based upon atomization device as well as DNA size. This may explain the inefficiency experienced by genetic therapeutics during pulmonary delivery. More importantly, this suggests that the selection of an atomization device should consider DNA size in order to achieve optimal gene delivery to the lungs. PMID:17034312

  15. 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

  16. Hierarchical self-assembled structures based on nitrogen-doped carbon nanotubes as advanced negative electrodes for Li-ion batteries and 3D microbatteries

    NASA Astrophysics Data System (ADS)

    Sharifi, Tiva; Valvo, Mario; Gracia-Espino, Eduardo; Sandström, Robin; Edström, Kristina; Wågberg, Thomas

    2015-04-01

    Hierarchical structures based on carbon paper and multi-walled nitrogen-doped carbon nanotubes were fabricated and subsequently decorated with hematite nanorods to obtain advanced 3D architectures for Li-ion battery negative electrodes. The carbon paper provides a versatile metal-free 3D current collector ensuring a good electrical contact of the active materials to its carbon fiber network. Firstly, the nitrogen-doped carbon nanotubes onto the carbon paper were studied and a high footprint area capacity of 2.1 mAh cm-2 at 0.1 mA cm-2 was obtained. The Li can be stored in the inter-wall regions of the nanotubes, mediated by the defects formed on their walls by the nitrogen atoms. Secondly, the incorporation of hematite nanorods raised the footprint area capacity to 2.25 mAh cm-2 at 0.1 mA cm-2. However, the repeated conversion/de-conversion of Fe2O3 limited both coulombic and energy efficiencies for these electrodes, which did not perform as well as those including only the N-doped carbon nanotubes at higher current densities. Thirdly, long-cycling tests showed the robust Li insertion mechanism in these N-doped carbonaceous structures, which yielded an unmatched footprint area capacity enhancement up to 1.95 mAh cm-2 after 60 cycles at 0.3 mA cm-2 and an overall capacity of 204 mAh g-1 referred to the mass of the entire electrode.

  17. Anemia and Oxygen Delivery.

    PubMed

    Bliss, Stuart

    2015-09-01

    Clinical assessment of tissue oxygenation is challenging. Anemia reflects a decreased oxygen carrying capacity of the blood and its significance in the perioperative setting relates largely to the associated risk of insufficient oxygen delivery and cellular hypoxia. Until meaningful clinical measures of tissue oxygenation are available in veterinary practice, clinicians must rely on evaluation of a patient's hemodynamic and ventilatory performance, along with biochemical and hemogasometric measurements. Blood transfusion is used commonly for treatment of perioperative anemia, and may improve tissue oxygenation by normalizing the rheologic properties of blood and enhancing perfusion, independent of increases in oxygen carrying capacity. PMID:26033442

  18. 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

  19. Vaporization as a smokeless cannabis delivery system: a pilot study.

    PubMed

    Abrams, D I; Vizoso, H P; Shade, S B; Jay, C; Kelly, M E; Benowitz, N L

    2007-11-01

    Although cannabis may have potential therapeutic value, inhalation of a combustion product is an undesirable delivery system. The aim of the study was to investigate vaporization using the Volcano((R)) device as an alternative means of delivery of inhaled Cannabis sativa. Eighteen healthy inpatient subjects enrolled to compare the delivery of cannabinoids by vaporization to marijuana smoked in a standard cigarette. One strength (1.7, 3.4, or 6.8% tetrahydrocannabinol (THC)) and delivery system was randomly assigned for each of the 6 study days. Plasma concentrations of Delta-9-THC, expired carbon monoxide (CO), physiologic and neuropsychologic effects were the main outcome measures. Peak plasma concentrations and 6-h area under the plasma concentration-time curve of THC were similar. CO levels were reduced with vaporization. No adverse events occurred. Vaporization of cannabis is a safe and effective mode of delivery of THC. Further trials of clinical effectiveness of cannabis could utilize vaporization as a smokeless delivery system. PMID:17429350

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Intrathecal delivery of analgesics.

    PubMed

    De Andres, Jose; Asensio-Samper, Juan Marcos; Fabregat-Cid, Gustavo

    2014-01-01

    Targeted intrathecal (IT) drug delivery systems (IDDS) are an option in algorithms for the treatment of patients with moderate to severe chronic refractory pain when more conservative options fail. This therapy is well established and supported by several publications. It has shown efficacy and is an important tool for the treatment of spasticity, and both cancer and nonmalignant pain. Recent technological advances, new therapeutic applications, reported complications, and the costs as well as maintenance required for this therapy require the need to stay up-to-date about new recommendations that may improve outcomes. This chapter reviews all technological issues regarding IDDS implantation with follow-up, and pharmacological recommendations published during recent years that provide evidence-based decision making process in the management of chronic pain and spasticity in patients. PMID:24567144

  8. Topical delivery of hexamidine.

    PubMed

    Parisi, Nicola; Paz-Alvarez, Miguel; Matts, Paul J; Lever, Rebecca; Hadgraft, Jonathan; Lane, Majella E

    2016-06-15

    Hexamidine diisethionate (HEX D) has been used for its biocidal actions in topical preparations since the 1950s. Recent data also suggest that it plays a beneficial role in skin homeostasis. To date, the extent to which this compound penetrates the epidermis has not been reported nor how its topical delivery may be modulated. In the present work we set out to characterise the interaction of HEX D with the skin and to develop a range of simple formulations for topical targeting of the active. A further objective was to compare the skin penetration of HEX D with its corresponding dihydrochloride salt (HEX H) as the latter has more favourable physicochemical properties for skin uptake. Candidate vehicles were evaluated by in vitro Franz cell permeation studies using porcine skin. Initially, neat solvents were investigated and subsequently binary systems were examined. The solvents and chemical penetration enhancers investigated included glycerol, dimethyl isosorbide (DMI), isopropyl alcohol (IPA), 1,2-pentanol (1,2-PENT), polyethylene glycol (PEG) 200, propylene glycol (PG), propylene glycol monolaurate (PGML) and Transcutol(®)P (TC). Of a total of 30 binary solvent systems evaluated only 10 delivered higher amounts of active into the skin compared with the neat solvents. In terms of topical efficacy, formulations containing PGML far surpassed all other solvents or binary combinations. More than 70% of HEX H was extracted from the skin following application in PG:PGML (50:50). Interestingly, the same vehicle effectively promoted skin penetration of HEX D but demonstrated significantly lower uptake into and through the skin (30%). The findings confirm the unpredictable nature of excipients on delivery of actives with reference to skin even where there are minor differences in molecular structures. We also believe that they underline the ongoing necessity for fundamental studies on the interaction of topical excipients with the skin. PMID:27130367

  9. 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.

  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. The Bankruptcy of Service Delivery.

    ERIC Educational Resources Information Center

    Seeley, David S.

    The dominant concept of public education at present can be described as a "service delivery" model. The public wants its children educated, delegates the job to a government agency (the schools), and holds that agency responsible for the delivery of educational services. The problems in public education, however, will not be solved by holding the…

  12. Chemical Abstracts' Document Delivery Service.

    ERIC Educational Resources Information Center

    Rollins, Stephen

    1984-01-01

    The Document Delivery Service offered by Chemical Abstracts is described in terms of the DIALORDER option on the Dialog information retrieval system, mail requests, and requests transmitted through OCLC's Interlibrary Loan system. Transmission costs, success rates, delivery rates, and other considerations in utilizing the service are included.…

  13. Novel Delivery Strategies for Glioblastoma

    PubMed Central

    Zhou, Jiangbing; Atsina, Kofi-Buaku; Himes, Benjamin T.; Strohbehn, Garth W.; Saltzman, W. Mark

    2012-01-01

    Brain tumors—particularly glioblastoma multiforme (GBM)—pose an important public health problem in the US. Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim: current therapy for is insufficient with nearly universal recurrence. A major reason for this failure is the difficulty of delivering therapeutic agents to the brain: better delivery approaches are needed to improve treatment. In this article, we summarize recent progress in drug delivery to the brain, with an emphasis on convection-enhanced delivery of nanocarriers. We examine the potential of new delivery methods to permit novel drug- and gene-based therapies that target brain cancer stem cells (BCSCs) and discuss the use of nanomaterials for imaging of tumors and drug delivery. PMID:22290262

  14. Polymer Particulates in Drug Delivery.

    PubMed

    Kaur, Harmeet; Kumar, Virender; Kumar, Krishan; Rathor, Sandeep; Kumari, Parveen; Singh, Jasbir

    2016-01-01

    Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily tuned by precisely engineering the constituent blocks of polymers for improving drug loading, release rate, pharmacokinetics, targeting, etc. The end-groups of various polymers can be readily modified with ligands making them suitable for recognizing by cell-specific receptors, providing cellular specificity, and superior intracellular delivery. This review will mainly cover delivery of many potential drugs and biomolecules by means of polymeric microparticles, nanoparticles and copolymer micelles or assemblies. An overview about formulation methods of polymer particulates has also been addressed. Attempt has been made to cover all the potential polymers that are well known in pharmaceutical history. PMID:26898740

  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. Laser-power delivery using chalcogenide glass fibers

    NASA Astrophysics Data System (ADS)

    Hilton, Albert R., Sr.; Hilton, A. R., Jr.; McCord, James; Loretz, Thomas J.

    1997-04-01

    During the last 15 years, numerous programs have been carried out in the U.S., UK, France, Japan, Israel and Russia aimed at providing a flexible chalcogenide glass fiber suited for delivery of power from a carbon dioxide laser emitting at 10.6 micrometer. The success of these programs has been modest at best with output power limited to 10 watts or less. The purpose of this paper is to examine chalcogenide glasses used for fiber from a thermal lensing standpoint.

  17. 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

  18. Mineralized cyclodextrin nanoparticles for sustained protein delivery.

    PubMed

    Sivasubramanian, Maharajan; Thambi, Thavasyappan; Park, Jae Hyung

    2013-09-12

    The extensive therapeutic potential of protein drugs has been severely limited by their instability and short biological half-lives in vivo. To prolong their therapeutic effects, a sustained delivery system is required. In this study, cyclodextrin-based polymeric nanoparticles (CD-NPs), mineralized by calcium phosphate as the diffusion barrier, were developed as a carrier for sustained protein delivery. Spherical CD-NPs were readily prepared by a conjugate, composed of β-CD as the protein-binding moiety and carboxymethyl dextran as the substrate for mineralization in a physiological solution. Owing to the presence of carboxylic acids in CD-NPs, they were effectively mineralized by sequential addition of calcium nitrate and ammonium phosphate. The physicochemical characteristics of mineralized CD-NPs were characterized using FT-IR, thermogravimetric analysis, transmission electron microscopy and energy dispersive X-ray photoelectron spectroscopy. Mineralization reduced CD-NP particle size from 310 nm to 121 nm in PBS (pH 7.4) indicating the formation of compact nanoparticles. Carbonic anhydrase B (CAB), chosen as the model protein, was loaded into the mineralized CD-NPs with a high loading efficiency (80%) by a simple dialysis method. In vitro release tests showed that CAB was completely released from bare CD-NPs in 3 days. Interestingly, the mineralized CD-NPs released CAB in a sustained manner for 21 days, which was due to the stable calcium phosphate barrier inhibiting CAB release. The enzymatic activity of CAB, which was released from the nanoparticles, did not significantly deteriorate compared to native CAB. Overall, mineralized CD-NPs could be a promising carrier for sustained protein delivery. PMID:23911496

  19. 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

  20. 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.

  1. Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers in breast cancer murine model: noninvasive monitoring using diffusion-weighted magnetic resonance imaging as sensitive imaging biomarker

    PubMed Central

    Al Faraj, Achraf; Shaik, Abjal Pasha; Shaik, Asma Sultana

    2015-01-01

    Purpose Targeting doxorubicin (DOX) by means of single-walled carbon nanotube (SWCNT) nanocarriers may help improve the clinical utility of this highly active therapeutic agent. Active targeting of SWCNTs using tumor-specific antibody and magnetic attraction by tagging the nanotubes with iron oxide nanoparticles can potentially reduce the unnecessary side effects and provide enhanced theranostics. In the current study, the in vitro and in vivo efficacy of DOX-loaded SWCNTs as theranostic nanoprobes was evaluated in a murine breast cancer model. Methods Iron-tagged SWCNTs conjugated with Endoglin/CD105 antibody with or without DOX were synthetized and extensively characterized. Their biocompatibility was assessed in vitro in luciferase (Luc2)-expressing 4T1 (4T1-Luc2) murine breast cancer cells using TiterTACS™ Colorimetric Apoptosis Detection Kit (apoptosis induction), poly (ADP-ribose) polymerase (marker for DNA damage), and thiobarbituric acid-reactive substances (oxidative stress generation) assays, and the efficacy of DOX-loaded SWCNTs was evaluated by measuring the radiance efficiency using bioluminescence imaging (BLI). Tumor progression and growth were monitored after 4T1-Luc2 cells inoculation using noninvasive BLI and magnetic resonance imaging (MRI) before and after subsequent injection of SWCNT complexes actively and magnetically targeted to tumor sites. Results Significant increases in apoptosis, DNA damage, and oxidative stress were induced by DOX-loaded SWCNTs. In addition, a tremendous decrease in bioluminescence was observed in a dose- and time-dependent manner. Noninvasive BLI and MRI revealed successful tumor growth and subsequent attenuation along with metastasis inhibition following DOX-loaded SWCNTs injection. Magnetic tagging of SWCNTs was found to produce significant discrepancies in apparent diffusion coefficient values providing a higher contrast to detect treatment-induced variations as noninvasive imaging biomarker. In addition, it

  2. 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

  3. Variable delivery, fixed displacement pump

    SciTech Connect

    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.

  4. 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

  5. The delivery of therapeutic oligonucleotides.

    PubMed

    Juliano, Rudolph L

    2016-08-19

    The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology. PMID:27084936

  6. 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.

  7. 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

  8. Development of insulin delivery systems.

    PubMed

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A

    2008-01-01

    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems. PMID:18285745

  9. Electronic Nicotine Delivery Systems

    PubMed Central

    Adkison, Sarah E.; O’Connor, Richard J.; Bansal-Travers, Maansi; Hyland, Andrew; Borland, Ron; Yong, Hua-Hie; Cummings, K. Michael; McNeill, Ann; Thrasher, James F.; Hammond, David; Fong, Geoffrey T.

    2013-01-01

    Background Electronic nicotine delivery systems (ENDS) initially emerged in 2003 and have since become widely available globally, particularly over the Internet. Purpose Data on ENDS usage patterns are limited. The current paper examines patterns of ENDS awareness, use, and product-associated beliefs among current and former smokers in four countries. Methods Data come from Wave 8 of the International Tobacco Control Four-Country Survey, collected July 2010 to June 2011 and analyzed through June 2012. Respondents included 5939 current and former smokers in Canada (n=1581); the U.S. (n=1520); the United Kingdom (UK; n=1325); and Australia (n=1513). Results Overall, 46.6% were aware of ENDS (U.S.: 73%, UK: 54%, Canada: 40%, Australia: 20%); 7.6% had tried ENDS (16% of those aware of ENDS); and 2.9% were current users (39% of triers). Awareness of ENDS was higher among younger, non-minority smokers with higher incomes who were heavier smokers. Prevalence of trying ENDS was higher among younger, nondaily smokers with a high income and among those who perceived ENDS as less harmful than traditional cigarettes. Current use was higher among both nondaily and heavy (≥20 cigarettes per day) smokers. In all, 79.8% reported using ENDS because they were considered less harmful than traditional cigarettes; 75.4% stated that they used ENDS to help them reduce their smoking; and 85.1% reported using ENDS to help them quit smoking. Conclusions Awareness of ENDS is high, especially in countries where they are legal (i.e., the U.S. and UK). Because trial was associated with nondaily smoking and a desire to quit smoking, ENDS may have potential to serve as a cessation aid. PMID:23415116

  10. Advances in Gene Delivery Systems

    PubMed Central

    Kamimura, Kenya; Suda, Takeshi; Zhang, Guisheng; Liu, Dexi

    2011-01-01

    The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral- and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives. PMID:22200988