WorldWideScience

Sample records for cell delivery system

  1. Drug delivery system and breast cancer cells

    Science.gov (United States)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  2. Detonation nanodiamonds are promising nontoxic delivery system for urothelial cells.

    Science.gov (United States)

    Zupančič, Daša; Kreft, Mateja Erdani; Grdadolnik, Maja; Mitev, Dimitar; Iglič, Aleš; Veranič, Peter

    2018-01-01

    Detonation nanodiamonds (DNDs) are carbon-based nanomaterials that are among the most promising nanoparticles available for biomedical applications so far. This is due to their biocompatibility, which could be contributed to their inert core and conformable surface nature. However, DNDs cytotoxicity for urothelial cells and the routes of their internalization remains an open question in the aspect of nanodiamond surface. We therefore analyzed four types of DNDs for cytotoxicity and internalization with normal urothelial cells and two types of cancer urothelial cell lines in vitro. Viability of any of the cell types we used was not compromised with any of four DNDs we evaluated after 24-, 48- and 72-h incubation in three different concentrations of DNDs. Transmission electron microscopy revealed that all four types of DNDs were endocytosed into all three types of urothelial cells tested here. We observed DNDs in endosomes, as well as in multivesicular bodies and multilamellar bodies. These results propose using of DNDs as a delivery system for urological applications in human nanomedicine.

  3. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

    Science.gov (United States)

    Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

    2014-09-28

    Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

    Science.gov (United States)

    Kang, Ting; Gao, Xiaoling; Chen, Jun

    2014-01-01

    The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

  5. Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems : A Cost-Effective Alternative

    NARCIS (Netherlands)

    Goh, Wei Jiang; Zou, Shui; Ong, Wei Yi; Torta, Federico; Alexandra, Alvarez Fernandez; Schiffelers, Raymond M.; Storm, Gert; Wang, Jiong-Wei; Czarny, Bertrand M S; Pastorin, Giorgia

    2017-01-01

    Cell Derived Nanovesicles (CDNs) have been developed from the rapidly expanding field of exosomes, representing a class of bioinspired Drug Delivery Systems (DDS). However, translation to clinical applications is limited by the low yield and multi-step approach in isolating naturally secreted

  6. Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems : a Cost-Effective Alternative

    NARCIS (Netherlands)

    Goh, Wei Jiang; Zou, Shui; Ong, Wei Yi; Torta, Federico; Alexandra, Alvarez Fernandez; Schiffelers, Raymond M; Storm, G; Wang, Jiong Wei; Czarny, Bertrand; Pastorin, Giorgia

    2017-01-01

    Cell Derived Nanovesicles (CDNs) have been developed from the rapidly expanding field of exosomes, representing a class of bioinspired Drug Delivery Systems (DDS). However, translation to clinical applications is limited by the low yield and multi-step approach in isolating naturally secreted

  7. Immune cells: more than simple carriers for systemic delivery of oncolytic viruses

    Directory of Open Access Journals (Sweden)

    Eisenstein S

    2014-11-01

    Full Text Available Samuel Eisenstein,1 Shu-Hsia Chen,2 Ping-Ying Pan21Department of Surgery, 2Department of Oncological Sciences and Tisch Cancer Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, USAAbstract: Oncolytic virotherapy on its own has numerous drawbacks, including an inability of the virus to actively target tumor cells and systemic toxicities at the high doses necessary to effectively treat tumors. Addition of immune cell-based carriers of oncolytic viruses holds promise as a technique in which oncolytic virus can be delivered directly to tumors in smaller and less toxic doses. Interestingly, the cell carriers themselves have also demonstrated antitumor effects, which can be augmented further by tailoring the appropriate oncolytic virus to the appropriate cell type. This review discusses the multiple factors that go into devising an effective, cell-based delivery system for oncolytic viruses.Keywords: oncolytic virus, cell carrier, immune cells, cancer therapy, myeloid-derived suppressor cells

  8. New perspectives in cell delivery systems for tissue regeneration: natural-derived injectable hydrogels.

    Science.gov (United States)

    Munarin, Fabiola; Petrini, Paola; Bozzini, Sabrina; Tanzi, Maria Cristina

    2012-09-27

    Natural polymers, because of their biocompatibility, availability, and physico-chemical properties have been the materials of choice for the fabrication of injectable hydrogels for regenerative medicine. In particular, they are appealing materials for delivery systems and provide sustained and controlled release of drugs, proteins, gene, cells, and other active biomolecules immobilized.In this work, the use of hydrogels obtained from natural source polymers as cell delivery systems is discussed. These materials were investigated for the repair of cartilage, bone, adipose tissue, intervertebral disc, neural, and cardiac tissue. Papers from the last ten years were considered, with a particular focus on the advances of the last five years. A critical discussion is centered on new perspectives and challenges in the regeneration of specific tissues, with the aim of highlighting the limits of current systems and possible future advancements.

  9. A prosurvival and proangiogenic stem cell delivery system to promote ischemic limb regeneration.

    Science.gov (United States)

    Xu, Yanyi; Fu, Minghuan; Li, Zhihong; Fan, Zhaobo; Li, Xiaofei; Liu, Ying; Anderson, Peter M; Xie, Xiaoyun; Liu, Zhenguo; Guan, Jianjun

    2016-02-01

    Stem cell therapy is one of the most promising strategies to restore blood perfusion and promote muscle regeneration in ischemic limbs. Yet its therapeutic efficacy remains low owing to the inferior cell survival under the low oxygen and nutrient environment of the injured limbs. To increase therapeutic efficacy, high rates of both short- and long-term cell survival are essential, which current approaches do not support. In this work, we hypothesized that a high rate of short-term cell survival can be achieved by introducing a prosurvival environment into the stem cell delivery system to enhance cell survival before vascularization is established; and that a high rate of long-term cell survival can be attained by building a proangiogenic environment in the system to quickly vascularize the limbs. The system was based on a biodegradable and thermosensitive poly(N-Isopropylacrylamide)-based hydrogel, a prosurvival and proangiogenic growth factor bFGF, and bone marrow-derived mesenchymal stem cells (MSCs). bFGF can be continuously released from the system for 4weeks. The released bFGF significantly improved MSC survival and paracrine effects under low nutrient and oxygen conditions (0% FBS and 1% O2) in vitro. The prosurvival effect of the bFGF on MSCs was resulted from activating cell Kruppel-like factor 4 (KLF4) pathway. When transplanted into the ischemic limbs, the system dramatically improved MSC survival. Some of the engrafted cells were differentiated into skeletal muscle and endothelial cells, respectively. The system also promoted the proliferation of host cells. After only 2weeks of implantation, tissue blood perfusion was completely recovered; and after 4weeks, the muscle fiber diameter was restored similarly to that of the normal limbs. These pronounced results demonstrate that the developed stem cell delivery system has a potential for ischemic limb regeneration. Stem cell therapy is a promising strategy to restore blood perfusion and promote muscle

  10. Functionalized Carbon Nano-scale Drug Delivery Systems From Biowaste Sago Bark For Cancer Cell Imaging.

    Science.gov (United States)

    Abdul Manaf, Shoriya Aruni; Hegde, Gurumurthy; Mandal, Uttam Kumar; Wui, Tin Wong; Roy, Partha

    2017-01-01

    Nano-scale carbon systems are emerging alternatives in drug delivery and bioimaging applications of which they gradually replace the quantum dots characterized by toxic heavy metal content in the latter application. The work intended to use carbon nanospheres synthesized from biowaste Sago bark for cancer cell imaging applications. This study synthesised carbon nanospheres from biowaste Sago bark using a catalyst-free pyrolysis technique. The nanospheres were functionalized with fluorescent dye coumarin-6 for cell imaging. Fluorescent nanosytems were characterized by field emission scanning electron microscopy-energy dispersive X ray, photon correlation spectroscopy and fourier transform infrared spectroscopy techniques. The average size of carbon nanospheres ranged between 30 and 40 nm with zeta potential of -26.8 ± 1.87 mV. The percentage viability of cancer cells on exposure to nanospheres varied from 91- 89 % for N2a cells and 90-85 % for A-375 cells respectively. Speedy uptake of the fluorescent nanospheres in both N2a and A-375 cells was observed within two hours of exposure. Novel fluorescent carbon nanosystem design following waste-to-wealth approach exhibited promising potential in cancer cell imaging applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Dental mesenchymal stem cells encapsulated in alginate hydrogel co-delivery microencapsulation system for cartilage regeneration

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

    2013-01-01

    Dental-derived MSCs are promising candidates for cartilage regeneration, with high chondrogenic differentiation capacity. This property contributes to making dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating Periodontal Ligament Stem Cells (PDLSCs) or Gingival Mesenchymal Stem Cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs, GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSC) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by toluidine blue and safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (Palginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. PMID:23891740

  12. UAV Delivery Monitoring System

    Directory of Open Access Journals (Sweden)

    San Khin Thida

    2018-01-01

    Full Text Available UAV-based delivery systems are increasingly being used in the logistics field, particularly to achieve faster last-mile delivery. This study develops a UAV delivery system that manages delivery order assignments, autonomous flight operation, real time control for UAV flights, and delivery status tracking. To manage the delivery item assignments, we apply the concurrent scheduler approach with a genetic algorithm. The present paper describes real time flight data based on a micro air vehicle communication protocol (MAVLink. It also presents the detailed hardware components used for the field tests. Finally, we provide UAV component analysis to choose the suitable components for delivery in terms of battery capacity, flight time, payload weight and motor thrust ratio.

  13. Project delivery system (PDS)

    CERN Document Server

    2001-01-01

    As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

  14. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy

    Science.gov (United States)

    Kranz, Lena M.; Diken, Mustafa; Haas, Heinrich; Kreiter, Sebastian; Loquai, Carmen; Reuter, Kerstin C.; Meng, Martin; Fritz, Daniel; Vascotto, Fulvia; Hefesha, Hossam; Grunwitz, Christian; Vormehr, Mathias; Hüsemann, Yves; Selmi, Abderraouf; Kuhn, Andreas N.; Buck, Janina; Derhovanessian, Evelyna; Rae, Richard; Attig, Sebastian; Diekmann, Jan; Jabulowsky, Robert A.; Heesch, Sandra; Hassel, Jessica; Langguth, Peter; Grabbe, Stephan; Huber, Christoph; Türeci, Özlem; Sahin, Ugur

    2016-06-01

    Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

  15. Vapor Delivery Systems for the Study of the Effects of Reformate Gas Impurities in HT-PEM Fuel Cells

    DEFF Research Database (Denmark)

    Araya, Samuel Simon; Kær, Søren Knudsen; Andreasen, Søren Juhl

    2011-01-01

    , impurities in the reformate gas produced from methanol steam reforming can affect the performance and durability of fuel cells. In this paper different vapor delivery systems, intended to assist in the study of the effects of some of the impurities, are described and compared with each other. A system based...... on a pump and electrically heated evaporator was found to be more suitable for the typical flow rates involved in the anode feed of an H3PO4/PBI based HT-PEMFC unit cell assembly. Test stations composed of vapor delivery systems and mass flow controllers for testing the effects of methanol slip, water vapor...

  16. Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery.

    Science.gov (United States)

    Katz, S C; Point, G R; Cunetta, M; Thorn, M; Guha, P; Espat, N J; Boutros, C; Hanna, N; Junghans, R P

    2016-05-01

    Metastatic spread of colorectal cancer (CRC) to the peritoneal cavity is common and difficult to treat, with many patients dying from malignant bowel obstruction. Chimeric antigen receptor T cell (CAR-T) immunotherapy has shown great promise, and we previously reported murine and phase I clinical studies on regional intrahepatic CAR-T infusion for CRC liver metastases. We are now studying intraperitoneal (IP) delivery of CAR-Ts for peritoneal carcinomatosis. Regional IP infusion of CAR-T resulted in superior protection against carcinoembryonic antigen (CEA+) peritoneal tumors, when compared with systemically infused CAR-Ts. IP CAR-Ts also provided prolonged protection against IP tumor re-challenges and demonstrated an increase in effector memory phenotype over time. IP CAR-Ts provided protection against tumor growth at distant subcutaneous (SC) sites in association with increases in serum IFNγ levels. Given the challenges posed by immunoinhibitory pathways in solid tumors, we combined IP CAR-T treatment with suppressor cell targeting. High frequencies of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) were found within the IP tumors, with MDSC expressing high levels of immunosuppressive PD-L1. Combinatorial IP CAR-T treatment with depleting antibodies against MDSC and Treg further improved efficacy against peritoneal metastases. Our data support further development of combinatorial IP CAR-T immunotherapy for peritoneal malignancies.

  17. Health care delivery systems.

    NARCIS (Netherlands)

    Stevens, F.; Zee, J. van der

    2007-01-01

    A health care delivery system is the organized response of a society to the health problems of its inhabitants. Societies choose from alternative health care delivery models and, in doing so, they organize and set goals and priorities in such a way that the actions of different actors are effective,

  18. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  19. Towards increased selectivity of drug delivery to cancer cells: development of a LDL-based nanodelivery system for hydrophobic photosensitizers

    Science.gov (United States)

    Buzova, Diana; Huntosova, Veronika; Kasak, Peter; Petrovajova, Dana; Joniova, Jaroslava; Dzurova, Lenka; Nadova, Zuzana; Sureau, Franck; Midkovsky, Pavol; Jancura, Daniel

    2012-10-01

    Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic photosensitizers (pts) to tumor cells in photodynamic therapy (PDT) of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by polyethylene glycol (PEG) and dextran. Fluorescence spectroscopy and confocal fluorescence imaging were used to characterize redistribution of hypericin (Hyp), a natural potent pts, loaded in LDL/PEG and LDL/dextran complexes to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It was shown than the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. On the other hand, PEG does not significantly influence this process. The modification of LDL molecules by the polymers does not inhibit their recognition by cellular LDL receptors. U-87 MG cellular uptake of Hyp loaded in LDL/PEG and LDL/dextran complexes appears to be similar to that one observed for Hyp transported by unmodified LDL particles. It is proposed that by polymers modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic drugs to cancer cells expressing high level of LDL receptors.

  20. Development of a new LDL-based transport system for hydrophobic/amphiphilic drug delivery to cancer cells.

    Science.gov (United States)

    Huntosova, Veronika; Buzova, Diana; Petrovajova, Dana; Kasak, Peter; Nadova, Zuzana; Jancura, Daniel; Sureau, Franck; Miskovsky, Pavol

    2012-10-15

    Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic/amphiphilic photosensitizers to tumor cells in photodynamic therapy of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by dextran. Fluorescence spectroscopy, confocal fluorescence imaging, stopped-flow experiments and flow-cytometry were used to characterize redistribution of hypericin (Hyp), a natural occurring potent photosensitizer, loaded in LDL/dextran complex to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It is shown that the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. The modification of LDL molecules by dextran does not inhibit their recognition by cellular LDL receptors and U-87 MG cellular uptake of Hyp loaded in LDL/dextran complex appears to be similar to that one observed for Hyp transported by unmodified LDL particles. Thus, it is proposed that dextran modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic/amphiphilic drugs to cancer cells expressing high level of LDL receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement.

    Science.gov (United States)

    Wang, Yong; Yuan, Fan

    2006-01-01

    It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

  2. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  3. Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.

    Science.gov (United States)

    Maran, Avudaiappan; Dadsetan, Mahrokh; Buenz, Colleen M; Shogren, Kristen L; Lu, Lichun; Yaszemski, Michael J

    2013-09-01

    Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. Copyright © 2012 Wiley Periodicals, Inc.

  4. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Talaei F

    2011-09-01

    Full Text Available Fatemeh Talaei1, Ebrahim Azizi2, Rassoul Dinarvand3, Fatemeh Atyabi31Novel Drug Delivery Systems Lab, 2Molecular Research Lab, Department of Pharmacology and Toxicology, 3Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan and NAP-C (N-acetyl penicillamine-chitosan in anticancer drug delivery targeting epidermal growth factor receptor (EGFR. Doxorubicin (DOX and antisense oligonucleotide (ASOND-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo

  6. An Intelligent Neural Stem Cell Delivery System for Neurodegenerative Diseases Treatment.

    Science.gov (United States)

    Qiao, Shupei; Liu, Yi; Han, Fengtong; Guo, Mian; Hou, Xiaolu; Ye, Kangruo; Deng, Shuai; Shen, Yijun; Zhao, Yufang; Wei, Haiying; Song, Bing; Yao, Lifen; Tian, Weiming

    2018-05-02

    Transplanted stem cells constitute a new therapeutic strategy for the treatment of neurological disorders. Emerging evidence indicates that a negative microenvironment, particularly one characterized by the acute inflammation/immune response caused by physical injuries or transplanted stem cells, severely impacts the survival of transplanted stem cells. In this study, to avoid the influence of the increased inflammation following physical injuries, an intelligent, double-layer, alginate hydrogel system is designed. This system fosters the matrix metalloproeinases (MMP) secreted by transplanted stem cell reactions with MMP peptide grafted on the inner layer and destroys the structure of the inner hydrogel layer during the inflammatory storm. Meanwhile, the optimum concentration of the arginine-glycine-aspartate (RGD) peptide is also immobilized to the inner hydrogels to obtain more stem cells before arriving to the outer hydrogel layer. It is found that blocking Cripto-1, which promotes embryonic stem cell differentiation to dopamine neurons, also accelerates this process in neural stem cells. More interesting is the fact that neural stem cell differentiation can be conducted in astrocyte-differentiation medium without other treatments. In addition, the system can be adjusted according to the different parameters of transplanted stem cells and can expand on the clinical application of stem cells in the treatment of this neurological disorder. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Secondary fuel delivery system

    Science.gov (United States)

    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.

  8. Delivery systems for antimicrobial peptides

    DEFF Research Database (Denmark)

    Nordström, Randi; Malmsten, Martin

    2017-01-01

    Due to rapidly increasing resistance development against conventional antibiotics, finding novel approaches for the treatment of infections has emerged as a key health issue. Antimicrobial peptides (AMPs) have attracted interest in this context, and there is by now a considerable literature...... on the identification such peptides, as well as on their optimization to reach potent antimicrobial and anti-inflammatory effects at simultaneously low toxicity against human cells. In comparison, delivery systems for antimicrobial peptides have attracted considerably less interest. However, such delivery systems...... are likely to play a key role in the development of potent and safe AMP-based therapeutics, e.g., through reducing chemical or biological degradation of AMPs either in the formulation or after administration, by reducing adverse side-effects, by controlling AMP release rate, by promoting biofilm penetration...

  9. Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration.

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

    2013-12-01

    Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (palginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. Copyright © 2013 Acta Materialia Inc. All rights reserved.

  10. Content Delivery in Fog-Aided Small-Cell Systems with Offline and Online Caching: An Information—Theoretic Analysis

    Directory of Open Access Journals (Sweden)

    Seyyed Mohammadreza Azimi

    2017-07-01

    Full Text Available The storage of frequently requested multimedia content at small-cell base stations (BSs can reduce the load of macro-BSs without relying on high-speed backhaul links. In this work, the optimal operation of a system consisting of a cache-aided small-cell BS and a macro-BS is investigated for both offline and online caching settings. In particular, a binary fading one-sided interference channel is considered in which the small-cell BS, whose transmission is interfered by the macro-BS, has a limited-capacity cache. The delivery time per bit (DTB is adopted as a measure of the coding latency, that is, the duration of the transmission block, required for reliable delivery. For offline caching, assuming a static set of popular contents, the minimum achievable DTB is characterized through information-theoretic achievability and converse arguments as a function of the cache capacity and of the capacity of the backhaul link connecting cloud and small-cell BS. For online caching, under a time-varying set of popular contents, the long-term (average DTB is evaluated for both proactive and reactive caching policies. Furthermore, a converse argument is developed to characterize the minimum achievable long-term DTB for online caching in terms of the minimum achievable DTB for offline caching. The performance of both online and offline caching is finally compared using numerical results.

  11. Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury.

    Science.gov (United States)

    Badner, Anna; Vawda, Reaz; Laliberte, Alex; Hong, James; Mikhail, Mirriam; Jose, Alejandro; Dragas, Rachel; Fehlings, Michael

    2016-08-01

    : Spinal cord injury (SCI) is a life-threatening condition with multifaceted complications and limited treatment options. In SCI, the initial physical trauma is closely followed by a series of secondary events, including inflammation and blood spinal cord barrier (BSCB) disruption, which further exacerbate injury. This secondary pathology is partially mediated by the systemic immune response to trauma, in which cytokine production leads to the recruitment/activation of inflammatory cells. Because early intravenous delivery of mesenchymal stromal cells (MSCs) has been shown to mitigate inflammation in various models of neurologic disease, this study aimed to assess these effects in a rat model of SCI (C7-T1, 35-gram clip compression) using human brain-derived stromal cells. Quantitative polymerase chain reaction for a human-specific DNA sequence was used to assess cell biodistribution/clearance and confirmed that only a small proportion (approximately 0.001%-0.002%) of cells are delivered to the spinal cord, with the majority residing in the lung, liver, and spleen. Intriguingly, although cell populations drastically declined in all aforementioned organs, there remained a persistent population in the spleen at 7 days. Furthermore, the cell infusion significantly increased splenic and circulating levels of interleukin-10-a potent anti-inflammatory cytokine. Through this suppression of the systemic inflammatory response, the cells also reduced acute spinal cord BSCB permeability, hemorrhage, and lesion volume. These early effects further translated into enhanced functional recovery and tissue sparing 10 weeks after SCI. This work demonstrates an exciting therapeutic approach whereby a minimally invasive cell-transplantation procedure can effectively reduce secondary damage after SCI through systemic immunomodulation. Central nervous system pericytes (perivascular stromal cells) have recently gained significant attention within the scientific community. In addition to

  12. [Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy].

    Science.gov (United States)

    Tan, Jiao; Wang, Ya-Ping; Wang, Hui-Xin; Liang, Jian-Ming; Zhang, Meng; Sun, Xun; Huang, Yong-Zhuo

    2014-12-01

    To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

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

    Science.gov (United States)

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

    2011-01-01

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

  14. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

  15. Novel Peptide/Protein Delivery System Targeting erbB2-Overexpressing Breast Cancer Cells

    National Research Council Canada - National Science Library

    Yu, Dihua

    2002-01-01

    .... During this funding year, we focused on the delivery of erbB2 signal-blocking ESP peptides (objective 2) . Because of the complexity of biotin-penetratin-AHNP-ESP, the synthesis was unsuccessful...

  16. Electronic Nicotine Delivery Systems.

    Science.gov (United States)

    Walley, Susan C; Jenssen, Brian P

    2015-11-01

    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. Copyright © 2015 by the American Academy of Pediatrics.

  17. In vitro and in vivo delivery of siRNA via VIPER polymer system to lung cells.

    Science.gov (United States)

    Feldmann, Daniel P; Cheng, Yilong; Kandil, Rima; Xie, Yuran; Mohammadi, Mariam; Harz, Hartmann; Sharma, Akhil; Peeler, David J; Moszczynska, Anna; Leonhardt, Heinrich; Pun, Suzie H; Merkel, Olivia M

    2018-04-28

    The block copolymer VIPER (virus-inspired polymer for endosomal release) has been reported to be a promising novel delivery system of DNA plasmids both in vitro and in vivo. VIPER is comprised of a polycation segment for condensation of nucleic acids as well as a pH-sensitive segment that exposes the membrane lytic peptide melittin in acidic environments to facilitate endosomal escape. The objective of this study was to investigate VIPER/siRNA polyplex characteristics, and compare their in vitro and in vivo performance with commercially available transfection reagents and a control version of VIPER lacking melittin. VIPER/siRNA polyplexes were formulated and characterized at various charge ratios and shown to be efficiently internalized in cultured cells. Target mRNA knockdown was confirmed by both flow cytometry and qRT-PCR and the kinetics of knockdown was monitored by live cell spinning disk microscopy, revealing knockdown starting by 4 h post-delivery. Intratracheal instillation of VIPER particles formulated with sequence specific siRNA to the lung of mice resulted in a significantly more efficient knockdown of GAPDH compared to treatment with VIPER particles formulated with scrambled sequence siRNA. We also demonstrated using pH-sensitive labels that VIPER particles experience less acidic environments compared to control polyplexes. In summary, VIPER/siRNA polyplexes efficiently deliver siRNA in vivo resulting in robust gene silencing (>75% knockdown) within the lung. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. In vitro-ex vivo correlations between a cell-laden hydrogel and mucosal tissue for screening composite delivery systems.

    Science.gov (United States)

    Blakney, Anna K; Little, Adam B; Jiang, Yonghou; Woodrow, Kim A

    2016-11-01

    Composite delivery systems where drugs are electrospun in different layers and vary the drug stacking-order are posited to affect bioavailability. We evaluated how the formulation characteristics of both burst- and sustained-release electrospun fibers containing three physicochemically diverse drugs: dapivirine (DPV), maraviroc (MVC) and tenofovir (TFV) affect in vitro and ex vivo release. We developed a poly(hydroxyethyl methacrylate) (pHEMA) hydrogel release platform for the rapid, inexpensive in vitro evaluation of burst- and sustained-release topical or dermal drug delivery systems with varying microarchitecture. We investigated properties of the hydrogel that could recapitulate ex vivo release into nonhuman primate vaginal tissue. Using a dimethyl sulfoxide extraction protocol and high-performance liquid chromatography analysis, we achieved >93% recovery from the hydrogels and >88% recovery from tissue explants for all three drugs. We found that DPV loading, but not stacking order (layers of fiber containing a single drug) or microarchitecture (layers with isolated drug compared to all drugs in the same layer) impacted the burst release in vitro and ex vivo. Our burst-release formulations showed a correlation for DPV accumulation between the hydrogel and tissue (R 2 =   0.80), but the correlation was not significant for MVC or TFV. For the sustained-release formulations, the PLGA/PCL content did not affect TFV release in vitro or ex vivo. Incorporation of cells into the hydrogel matrix improved the correlation between hydrogel and tissue explant release for TFV. We expect that this hydrogel-tissue mimic may be a promising preclinical model to evaluate topical or transdermal drug delivery systems with complex microarchitectures.

  19. Cellular interaction of a layer-by-layer based drug delivery system depending on material properties and cell types.

    Science.gov (United States)

    Brueckner, Mandy; Jankuhn, Steffen; Jülke, Eva-Maria; Reibetanz, Uta

    2018-01-01

    Drug delivery systems (DDS) and their interaction with cells are a controversial topic in the development of therapeutic concepts and approaches. On one hand, DDS are very useful for protected and targeted transport of defined dosages of active agents. On the other hand, their physicochemical properties such as material, size, shape, charge, or stiffness have a huge impact on cellular uptake and intracellular processing. Additionally, even identical DDS can undergo a completely diverse interaction with different cell types. However, quite often in in vitro DDS/cell interaction experiments, those aspects are not considered and DDS and cells are randomly chosen. Hence, our investigations provide an insight into layer-by-layer designed microcarriers with modifications of only some of the most important parameters (surface charge, stiffness, and applied microcarrier/cell ratio) and their influence on cellular uptake and viability. We also considered the interaction of these differently equipped DDS with several cell types and investigated professional phagocytes (neutrophil granulocytes; macrophages) as well as non-professional phagocytes (epithelial cells) under comparable conditions. We found that even small modifications such as layer-by-layer (LbL)-microcarriers with positive or negative surface charge, or LbL-microcarriers with solid core or as hollow capsules but equipped with the same surface properties, show significant differences in interaction and viability, and several cell types react very differently to the offered DDS. As a consequence, the properties of the DDS have to be carefully chosen with respect to the addressed cell type with the aim to efficiently transport a desired agent.

  20. Synthetic sustained gene delivery systems.

    Science.gov (United States)

    Agarwal, Ankit; Mallapragada, Surya K

    2008-01-01

    Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

  1. Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Villadsen, Klaus; Østrem, Ragnhild Garborg

    2017-01-01

    constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells...... and macrophages. There was unaltered secretion of cytokines following exposure of peptide-conjugated liposomes to endothelial cells, indicating that the materials were not inflammogenic. Liposomes with a peptide targeting the fibronectin receptor (integrin α5β1) were more effective in targeting of activated....... Therefore, this study demonstrates the feasibility of constructing a peptide-conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells....

  2. A nanoengineered peptidic delivery system with specificity for human brain capillary endothelial cells

    DEFF Research Database (Denmark)

    Wu, Linping; Moghimi, Seyed Moein

    2016-01-01

    , without manipulating the integrity of the BBB. This may be achieved by simultaneous and appropriate nanoparticle surface decoration with polymers that protect nanoparticles against rapid interception by body's defenses and ligands specific for cerebral capillary endothelial cells. To date, the binding...... avidity of the majority of the so-called ‘brain-specific’ nanoparticles to the brain capillary endothelial cells has been poor, even during in vitro conditions. We have addressed this issue and designed a versatile peptidic nanoplatform with high binding avidity to the human cerebral capillary endothelial...... cells. This was achieved by selecting an appropriate phage-derived peptide with high specificity for human brain capillary endothelial cells, which following careful structural modifications spontaneously formed a nanoparticle-fiber network. The peptidic network was characterized fully and its uptake...

  3. Nanotechnology-based drug delivery systems

    Directory of Open Access Journals (Sweden)

    Singh Baljit

    2007-12-01

    Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.

  4. Self-nanoemulsifying drug delivery systems for oral insulin delivery

    DEFF Research Database (Denmark)

    Li, Ping; Tan, Angel; Prestidge, Clive A

    2014-01-01

    This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

  5. Cell culture models of biological barriers: in vitro test systems for drug absorption and delivery

    National Research Council Canada - National Science Library

    Lehr, Claus-Michael

    2002-01-01

    ... may be reprinted or reproduced or utilized in any form or by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying and recording, or in any information storage or retrieval system, without permission in writing from the publishers. Every effort has been made to ensure that the advice and information in this book is t...

  6. Impact of lipid-based drug delivery systems on the transport and uptake of insulin across Caco-2 Cell monolayers

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2016-01-01

    Self-(nano)-emulsifying drug delivery systems (SNEDDSs) used to deliver peptides and proteins across biological barriers, such as the small intestinal membrane, represents an increasingly interesting field in nanomedicine. Hence, the present study was designed to evaluate the impact of SNEDDS...

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

    Science.gov (United States)

    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.

  8. Hydrogen storage and delivery system development: Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Handrock, J.L. [Sandia National Labs., Livermore, CA (United States)

    1996-10-01

    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. This project is part of the Field Work Proposal entitled Hydrogen Utilization in Internal Combustion Engines (ICE). The goal of the Hydrogen Storage and Delivery System Development Project is to expand the state-of-the-art of hydrogen storage and delivery system design and development. At the foundation of this activity is the development of both analytical and experimental evaluation platforms. These tools provide the basis for an integrated approach for coupling hydrogen storage and delivery technology to the operating characteristics of potential hydrogen energy use applications. Results of the analytical model development portion of this project will be discussed. Analytical models have been developed for internal combustion engine (ICE) hybrid and fuel cell driven vehicles. The dependence of hydride storage system weight and energy use efficiency on engine brake efficiency and exhaust temperature for ICE hybrid vehicle applications is examined. Results show that while storage system weight decreases with increasing engine brake efficiency energy use efficiency remains relatively unchanged. The development, capability, and use of a recently developed fuel cell vehicle storage system model will also be discussed. As an example of model use, power distribution and control for a simulated driving cycle is presented. Model calibration results of fuel cell fluid inlet and exit temperatures at various fuel cell idle speeds, assumed fuel cell heat capacities, and ambient temperatures are presented. The model predicts general increases in temperature with fuel cell power and differences between inlet and exit temperatures, but under predicts absolute temperature values, especially at higher power levels.

  9. Software Build and Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Robey, Robert W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-10

    This presentation deals with the hierarchy of software build and delivery systems. One of the goals is to maximize the success rate of new users and developers when first trying your software. First impressions are important. Early successes are important. This also reduces critical documentation costs. This is a presentation focused on computer science and goes into detail about code documentation.

  10. A gene delivery system with a human artificial chromosome vector based on migration of mesenchymal stem cells towards human glioblastoma HTB14 cells.

    Science.gov (United States)

    Kinoshita, Yusuke; Kamitani, Hideki; Mamun, Mahabub Hasan; Wasita, Brian; Kazuki, Yasuhiro; Hiratsuka, Masaharu; Oshimura, Mitsuo; Watanabe, Takashi

    2010-05-01

    Mesenchymal stem cells (MSCs) have been expected to become useful gene delivery vehicles against human malignant gliomas when coupled with an appropriate vector system, because they migrate towards the lesion. Human artificial chromosomes (HACs) are non-integrating vectors with several advantages for gene therapy, namely, no limitations on the size and number of genes that can be inserted. We investigated the migration of human immortalized MSCs bearing a HAC vector containing the herpes simplex virus thymidine kinase gene (HAC-tk-hiMSCs) towards malignant gliomas in vivo. Red fluorescence protein-labeled human glioblastoma HTB14 cells were implanted into a subcortical region in nude mice. Four days later, green fluorescence protein-labeled HAC-tk-hiMSCs were injected into a contralateral subcortical region (the HTB14/HAC-tk-hiMSC injection model). Tropism to the glioma mass and the route of migration were visualized by fluorescence microscopy and immunohistochemical staining. HAC-tk-hiMSCs began to migrate toward the HTB14 glioma area via the corpus callosum on day 4, and gathered around the HTB14 glioma mass on day 7. To test whether the delivered gene could effectively treat glioblastoma in vivo, HTB14/HAC-tk-hiMSC injected mice were treated with ganciclovir (GCV) or PBS. The HTB14 glioma mass was significantly reduced by GCV treatment in mice injected with HAC-tk-hiMSCs. It was confirmed that gene delivery by our HAC-hiMSC system was effective after migration of MSCs to the glioma mass in vivo. Therefore, MSCs containing HACs carrying an anticancer gene or genes may provide a new tool for the treatment of malignant gliomas and possibly of other tumor types.

  11. MINI-SLAR delivery system

    International Nuclear Information System (INIS)

    Alstein, D.

    1996-01-01

    In the Spring of 1993, a need to complete Spacer Location and Repositioning (SLAR) on the Bruce 'A', Unit 1 Reactor was identified. An alternate SLAR delivery system was required due to conversion constraints that prevented the existing Bruce SLAR System from being used in Unit 1. A Portable SLAR Delivery System called MINI-SLAR Delivery System was developed, designed and fabricated in a 14 month period, then used to successfully SLAR 109 channels. The system is a portable remotely operated Nuclear Class 1 registered fitting that is independent of the Fuelling Machine, allowing the station to continue normal Fuelling and Maintenance activities. It is designed to a Level 'D' faulted condition of HPECI Pressure thus minimizing PHT Heat Sink configuration requirements and minimizing outage set-up times. The system is based on a modular design allowing for easy fabrication, assembly and repair. It consists of a Snout Assembly, a Closure Plug Assembly, Shield Plug Assembly, SLAR Ram assembly, Work Table Assembly and Control Panel. Controls are through a Programmable Logic Controller with software tested and certified to a Software Quality Assurance of Level Ill. (author). 2 refs., 2 figs

  12. MINI-SLAR delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Alstein, D [Ontario Hydro, Tiverton, ON (Canada). Bruce Nuclear Generating Station-A; Dalton, K [Spectrum Engineering, Peterborough, ON (Canada)

    1997-12-31

    In the Spring of 1993, a need to complete Spacer Location and Repositioning (SLAR) on the Bruce `A`, Unit 1 Reactor was identified. An alternate SLAR delivery system was required due to conversion constraints that prevented the existing Bruce SLAR System from being used in Unit 1. A Portable SLAR Delivery System called MINI-SLAR Delivery System was developed, designed and fabricated in a 14 month period, then used to successfully SLAR 109 channels. The system is a portable remotely operated Nuclear Class 1 registered fitting that is independent of the Fuelling Machine, allowing the station to continue normal Fuelling and Maintenance activities. It is designed to a Level `D` faulted condition of HPECI Pressure thus minimizing PHT Heat Sink configuration requirements and minimizing outage set-up times. The system is based on a modular design allowing for easy fabrication, assembly and repair. It consists of a Snout Assembly, a Closure Plug Assembly, Shield Plug Assembly, SLAR Ram assembly, Work Table Assembly and Control Panel. Controls are through a Programmable Logic Controller with software tested and certified to a Software Quality Assurance of Level Ill. (author). 2 refs., 2 figs.

  13. Sterile Product Packaging and Delivery Systems.

    Science.gov (United States)

    Akers, Michael J

    2015-01-01

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

  14. Electronic Nicotine Delivery Systems Key Facts Infographic

    Data.gov (United States)

    U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

  15. Preparing and evaluating delivery systems for proteins

    DEFF Research Database (Denmark)

    Jorgensen, L; Moeller, E H; van de Weert, M

    2006-01-01

    From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping...... and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge...... for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions....

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

    Science.gov (United States)

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

    2018-01-01

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

  17. Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release kinetics in a 3D microparticle-hydrogel drug delivery system.

    Science.gov (United States)

    Pinezich, Meghan R; Russell, Lauren N; Murphy, Nicholas P; Lampe, Kyle J

    2018-04-16

    Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol-based hydrogel. The goal of this DDS was to better understand the relationship between PDGF-AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF-AA under seven different delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCs in vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF-AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

  18. Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

    Science.gov (United States)

    Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

    2016-09-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

  19. Design of magnetic gene complexes as effective and serum resistant gene delivery systems for mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Tian-Yuan; Wu, Jia-He; Xu, Qian-Hao; Wang, Xia-Rong; Lu, Jingxiong; Hu, Ying; Jo, Jun-Ichiro; Yamamoto, Masaya; Ling, Daishun; Tabata, Yasuhiko; Gao, Jian-Qing

    2017-03-30

    Gene engineered mesenchymal stem cells (MSCs) have been proposed as promising tools for their various applications in biomedicine. Nevertheless, the lack of an effective and safe way to genetically modify these stem cells is still a major obstacle in the current studies. Herein, we designed novel magnetic complexes by assembling cationized pullulan derivatives with magnetic iron oxide nanoparticles for delivering target genes to MSCs. Results showed that this complexes achieved effective gene expression with the assistance of external magnetic field, and resisted the adverse effect induced by serum proteins on the gene delivery. Moreover, neither significant cytotoxicity nor the interference on the osteogenic differentiation to MSCs were observed after magnetofection. Further studies revealed that this effective and serum resistant gene transfection was partly due to the accelerated and enhanced intracellular uptake process driven by external magnetic field. To conclude, the current study presented a novel option for genetic modification of MSCs in an effective, relatively safe and serum compatible way. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Colloidal drug delivery system: amplify the ocular delivery.

    Science.gov (United States)

    Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

    2016-01-01

    The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

  1. DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

    Directory of Open Access Journals (Sweden)

    Dolores L. Guzmán-Herrador

    2017-08-01

    Full Text Available We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

  2. Integrated delivery systems. Evolving oligopolies.

    Science.gov (United States)

    Malone, T A

    1998-01-01

    The proliferation of Integrated Delivery Systems (IDSs) in regional health care markets has resulted in the movement of these markets from a monopolistic competitive model of behavior to an oligopoly. An oligopoly is synonymous with competition among the few, as a small number of firms supply a dominant share of an industry's total output. The basic characteristics of a market with competition among the few are: (1) A mutual interdependence among the actions and behaviors of competing firms; (2) competition tends to rely on the differentiation of products; (3) significant barriers to entering the market exist; (4) the demand curve for services may be kinked; and (5) firms can benefit from economies of scale. An understanding of these characteristics is essential to the survival of IDSs as regional managed care markets mature.

  3. Collagen macromolecular drug delivery systems

    International Nuclear Information System (INIS)

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t 1/2 and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and 14 C-inulin release rates were evaluated subcutaneously in rats

  4. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Directory of Open Access Journals (Sweden)

    Luping Du

    2018-01-01

    Full Text Available Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide (PLGA nanoparticles (NPs with Ulex europaeus agglutinin 1 (UEA-1 and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5] or subunit vaccine ORF5-encoded glycoprotein (GP5 from exposure to the gastrointestinal (GI tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05. Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system.

  5. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Science.gov (United States)

    Du, Luping; Yu, Zhengyu; Pang, Fengjiao; Xu, Xiangwei; Mao, Aihua; Yuan, Wanzhe; He, Kongwang; Li, Bin

    2018-01-01

    Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells) within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Ulex europaeus agglutinin 1 (UEA-1) and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5)] or subunit vaccine ORF5-encoded glycoprotein (GP5) from exposure to the gastrointestinal (GI) tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05). Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system. PMID:29423381

  6. Levodopa delivery systems: advancements in delivery of the gold standard.

    Science.gov (United States)

    Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

    2010-02-01

    Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

  7. A Systems Approach to Nitrogen Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States)

    2017-10-23

    A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

  8. A Systems Approach to Nitrogen Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

    2017-10-17

    A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

  9. A study on nanodiamond-based drug delivery system

    International Nuclear Information System (INIS)

    Li Jing; Zhang Xiaoyong; Zhu Ying; Li Wenxin; Huang Qing

    2010-01-01

    A multifunctional drug delivery system based on nanodiamonds (NDs) has been developed. FITC, HCPT and TF were absorbed on NDs successively to form the multifunctional complex. The NDs and ND complex samples were characterized by TEM, FR-IR and UV-V. The results indicated that this drug delivery system is a high loading system. Efficacy of the drug delivery system on Hela cell was evaluated with MTT assays and fluorescence microscopy. The results show that multifunction of the NDs complex include fluorescence, targeting and high efficacy. (authors)

  10. Biomimetics in drug delivery systems: A critical review.

    Science.gov (United States)

    Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

    2017-05-10

    Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Effective mRNA Inhibition in PANC-1 Cells in Vitro Mediated via an mPEG-SeSe-PEI Delivery System.

    Science.gov (United States)

    Zhang, Yuefeng; Yang, Bin; Liu, Yajie; Qin, Wenjie; Li, Chao; Wang, Lantian; Zheng, Wen; Wu, Yulian

    2016-05-01

    RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG-SeSe-PEI, was developed and its efficacy evaluated. We prepared three mPEG-SeSe-PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG11.6-SeSe-PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG11.6-SeSe-PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG11.6-SeSe-PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).

  12. Cell and biomolecule delivery for regenerative medicine

    Science.gov (United States)

    Smith, Ian O; Ma, Peter X

    2010-01-01

    Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell–material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine. PMID:27877317

  13. Silk Electrogel Based Gastroretentive Drug Delivery System

    Science.gov (United States)

    Wang, Qianrui

    Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

  14. Fiber coupled optical spark delivery system

    Science.gov (United States)

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

    A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

  15. Oral Delivery of Protein Drugs Bioencapsulated in Plant Cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Daniell, Henry

    2016-08-01

    Plants cells are now approved by the FDA for cost-effective production of protein drugs (PDs) in large-scale current Good Manufacturing Practice (cGMP) hydroponic growth facilities. In lyophilized plant cells, PDs are stable at ambient temperature for several years, maintaining their folding and efficacy. Upon oral delivery, PDs bioencapsulated in plant cells are protected in the stomach from acids and enzymes but are subsequently released into the gut lumen by microbes that digest the plant cell wall. The large mucosal area of the human intestine offers an ideal system for oral drug delivery. When tags (receptor-binding proteins or cell-penetrating peptides) are fused to PDs, they efficiently cross the intestinal epithelium and are delivered to the circulatory or immune system. Unique tags to deliver PDs to human immune or nonimmune cells have been developed recently. After crossing the epithelium, ubiquitous proteases cleave off tags at engineered sites. PDs are also delivered to the brain or retina by crossing the blood-brain or retinal barriers. This review highlights recent advances in PD delivery to treat Alzheimer's disease, diabetes, hypertension, Gaucher's or ocular diseases, as well as the development of affordable drugs by eliminating prohibitively expensive purification, cold chain and sterile delivery.

  16. Liver cell-targeted delivery of therapeutic molecules.

    Science.gov (United States)

    Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

    2016-01-01

    The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

  17. Organoclays for drug delivery Systems

    OpenAIRE

    Canovas Creus, Alba

    2008-01-01

    Modified clays can be used as carriers of drugs due to their suitable properties and structure in order to achieve improvements in drug delivery. The study of this thesis starts with an introduction to mineral clays and its classification, properties and characterization, then deepens into modified clays (properties, comparison with mineral clays, applications and procedure of modification). Another chapter is focused in drug delivery: definition, its difficulties nowadays and the different w...

  18. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  19. Nanostructured delivery system for zinc phthalocyanine: preparation, characterization, and phototoxicity study against human lung adenocarcinoma A549 cells

    Directory of Open Access Journals (Sweden)

    Mariana da Volta Soares

    2011-01-01

    Full Text Available Mariana da Volta Soares1, Mainara Rangel Oliveira1, Elisabete Pereira dos Santos1, Lycia de Brito Gitirana2, Gleyce Moreno Barbosa3, Carla Holandino Quaresma3, Eduardo Ricci-Júnior11Department of Medicines, Laboratório de Desenvolvimento Galênico (LADEG, Faculty of Pharmacy, 2Laboratory of Animal and Comparative Histology, Glycobiology Research Program, Institute of Biomedical Science, 3Department of Medicines, Laboratório Multidisciplinar de Ciências Farmacêuticas, Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ, Rio de Janeiro, BrazilAbstract: In this study, zinc phthalocyanine (ZnPc was loaded onto poly-ε-caprolactone (PCL nanoparticles (NPs using a solvent emulsification–evaporation method. The process yield and encapsulation efficiency were 74.2% ± 1.2% and 67.1% ± 0.9%, respectively. The NPs had a mean diameter of 187.4 ± 2.1 nm, narrow distribution size with a polydispersity index of 0.096 ± 0.004, zeta potential of -4.85 ± 0.21 mV, and spherical shape. ZnPc has sustained release, following Higuchi’s kinetics. The photobiological activity of the ZnPc-loaded NPs was evaluated on human lung adenocarcinoma A549 cells. Cells were incubated with free ZnPc or ZnPc-loaded NPs for 4 h and then washed with phosphate-buffered saline. Culture medium was added to the wells containing the cells. Finally, the cells were exposed to red light (660 nm with a light dose of 100 J/cm2. The cellular viability was determined after 24 h of incubation. ZnPc-loaded NPs and free photosensitizer eliminated about 95.9% ± 1.8% and 28.7% ± 2.2% of A549 cells, respectively. The phototoxicity was time dependent up to 4 h and concentration dependent at 0–5 µg ZnPc. The cells viability decreased with the increase of the light dose in the range of 10–100 J/cm2. Intense lysis was observed in the cells incubated with the ZnPc-loaded NPs and irradiated with red light. ZnPc-loaded PCL NPs are the release systems that promise photodynamic

  20. The enhanced inhibitory effect of different antitumor agents in self-microemulsifying drug delivery systems on human cervical cancer HeLa cells.

    Science.gov (United States)

    Ujhelyi, Zoltán; Kalantari, Azin; Vecsernyés, Miklós; Róka, Eszter; Fenyvesi, Ferenc; Póka, Róbert; Kozma, Bence; Bácskay, Ildikó

    2015-07-21

    The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations.

  1. Engineering the system of healthcare delivery

    National Research Council Canada - National Science Library

    Rouse, William B; Cortese, Denis A

    2010-01-01

    "As the United States continues to debate reform of its healthcare system, this book argues that providing health insurance for all without improving the delivery system will not improve the current...

  2. Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.

    Science.gov (United States)

    Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

    2017-11-23

    Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

  3. New Delivery Systems and Propellants

    Directory of Open Access Journals (Sweden)

    Myrna Dolovich

    1999-01-01

    Full Text Available The removal of chlorofluorocarbon (CFC propellants from industrial and household products has been agreed to by over 165 countires of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada – Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.

  4. Nonviral Delivery Systems For Cancer Gene Therapy: Strategies And Challenges.

    Science.gov (United States)

    Shim, Gayong; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Kwon, Taekhyun; Oh, Yu-Kyoung

    2018-01-19

    Gene therapy has been receiving widespread attention due to its unique advantage in regulating the expression of specific target genes. In the field of cancer gene therapy, modulation of gene expression has been shown to decrease oncogenic factors in cancer cells or increase immune responses against cancer. Due to the macromolecular size and highly negative physicochemical features of plasmid DNA, efficient delivery systems are an essential ingredient for successful gene therapy. To date, a variety of nanostructures and materials have been studied as nonviral gene delivery systems. In this review, we will cover nonviral delivery strategies for cancer gene therapy, with a focus on target cancer genes and delivery materials. Moreover, we will address current challenges and perspectives for nonviral delivery-based cancer gene therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. The Research Progress of Targeted Drug Delivery Systems

    Science.gov (United States)

    Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

    2017-06-01

    Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

  6. Distance Synchronous Information Systems Course Delivery

    Science.gov (United States)

    Peslak, Alan R.; Lewis, Griffith R.; Aebli, Fred

    2014-01-01

    Teaching computer information systems via distance education is a challenge for both student and faculty. Much research work has been performed on methods of teaching via distance education. Today we are faced with a variety of options for course delivery. Asynchronous delivery via online or lesson instruction still remains most common. But…

  7. A Novel Drug Delivery System for Preventing the Extension of the Telomeric Ends of DNA and Preventing the Unlimited Proliferation of Cancer Cells

    International Nuclear Information System (INIS)

    Laster, Brenda; Issacson, Carol; Msamra, Maha; Perez, Ekterina; Kost, Jospeh

    2014-01-01

    Telomerase is an enzyme present in the majority of malignant tumors. It is well-documented that radiotherapy and chemotherapy activate the enzyme telomerase that immortalizes cancer cells . Telomerase prevents the shortening of the telomeric ends of DNA that is required for cell lethality; therefore, inhibiting its activation would be a useful approach to cancer treatment. However, inhibiting telomerase activation (TA) is no easy task. Despite the plethora of new drugs synthesized as potential clinical candidates for telomerase inhibition, their success or failure in the medical clinic will probably be more a function of their mode of administration once they have demonstrated TI in the research laboratory. A major physiological barrier to TI is the absolute requirement for the inhibitor to remain continuously present in the tumor throughout the long term treatment period. This is due to both the reactivation of telomerase that occurs upon the removal of the inhibitor, and the re-lengthening of the telomeres in the absence of the inhibitor. Because the systemic i.v. administration of drugs is associated with their rapid clearance from the body, the effectiveness of the inhibitor drug would be dramatically reduced due to telomerase re-activation. Under normal conditions, when telomerase is inactive, the telomeres shorten with each cell division until such time as the cell reaches its normal life expectancy. The unrestricted proliferation of cancer cells, after treatments that activate telomerase, poses a risk for local recurrence, invasion, metastases, or even second primaries and present an issue that must be addressed. Therefore, critical for clinical success is the identification of an agent whose mechanism of action has been proven to inhibit TA and whose toxicity is negligible. Equally important is the development of a drug delivery system that assures the continuous long-term presence of the drug in the tumor. The latter criterion is required to compensate for

  8. Future of Automated Insulin Delivery Systems.

    Science.gov (United States)

    Castle, Jessica R; DeVries, J Hans; Kovatchev, Boris

    2017-06-01

    Advances in continuous glucose monitoring (CGM) have brought on a paradigm shift in the management of type 1 diabetes. These advances have enabled the automation of insulin delivery, where an algorithm determines the insulin delivery rate in response to the CGM values. There are multiple automated insulin delivery (AID) systems in development. A system that automates basal insulin delivery has already received Food and Drug Administration approval, and more systems are likely to follow. As the field of AID matures, future systems may incorporate additional hormones and/or multiple inputs, such as activity level. All AID systems are impacted by CGM accuracy and future CGM devices must be shown to be sufficiently accurate to be safely incorporated into AID. In this article, we summarize recent achievements in AID development, with a special emphasis on CGM sensor performance, and discuss the future of AID systems from the point of view of their input-output characteristics, form factor, and adaptability.

  9. Macromolecular systems for vaccine delivery.

    Science.gov (United States)

    MuŽíková, G; Laga, R

    2016-10-20

    Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

  10. Macromolecular systems for vaccine delivery

    Czech Academy of Sciences Publication Activity Database

    Mužíková, Gabriela; Laga, Richard

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S203-S216 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : vaccine delivery * cellular and humoral immunity * polymer immunostimulants Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S203.pdf

  11. Cyclodextrins in delivery systems: Applications

    Directory of Open Access Journals (Sweden)

    Gaurav Tiwari

    2010-01-01

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

  12. Nanoparticulate systems for nucleic acid delivery

    NARCIS (Netherlands)

    Varkouhi, A.K.

    2011-01-01

    Development of carrier systems with controllable physicochemical and delivery properties has opened up the possibility of nanomedicines containing nucleic acids. In the last decades, much effort has been dedicated to two exciting approaches in biomedicine, namely gene and RNA interference

  13. A Sample Delivery System for Planetary Missions

    Data.gov (United States)

    National Aeronautics and Space Administration — The project will develop, test and characterize the performance of a prototype /sample delivery system (SDS) implemented as an end effector on a robotic arm capable...

  14. Microemulsion Drug Delivery Systems for Radiopharmacy Studies

    Directory of Open Access Journals (Sweden)

    Emre Ozgenc

    2016-11-01

    Full Text Available Microemulsions have been used increasingly for last year’s because of ideal properties like favorable drug delivery, ease of preparation and physical stability. They have been improved the solubility and efficacy of the drug and reduce the side effects. Use of radiolabeled microemulsions plays an alternative role in drug delivery systems by investigating the formation, stability and application of microemulsions in radiopharmacy. Gama scintigraphic method is well recognized for developing and detecting the biodistribution of newly developed drugs or formulation. This review will focus on how radionuclides are able to play role with characterization studies of microemulsion drug delivery systems.

  15. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    Science.gov (United States)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  16. A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM

    OpenAIRE

    Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel

    2012-01-01

    Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...

  17. Using DNA nanotechnology to produce a drug delivery system

    International Nuclear Information System (INIS)

    La, Thi Huyen; Nguyen, Thi Thu Thuy; Pham, Van Phuc; Nguyen, Thi Minh Huyen; Le, Quang Huan

    2013-01-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. (paper)

  18. Using DNA nanotechnology to produce a drug delivery system

    Science.gov (United States)

    Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

    2013-03-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

  19. T cells enhance gold nanoparticle delivery to tumors in vivo

    Science.gov (United States)

    Kennedy, Laura C.; Bear, Adham S.; Young, Joseph K.; Lewinski, Nastassja A.; Kim, Jean; Foster, Aaron E.; Drezek, Rebekah A.

    2011-12-01

    Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

  20. Sustained subconjunctival protein delivery using a thermosetting gel delivery system.

    Science.gov (United States)

    Rieke, Erin R; Amaral, Juan; Becerra, S Patricia; Lutz, Robert J

    2010-02-01

    An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37 degrees C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye.

  1. STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS

    OpenAIRE

    Gannu Praveen Kumar

    2012-01-01

    The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS...

  2. Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells

    Directory of Open Access Journals (Sweden)

    Sun X

    2012-06-01

    Full Text Available Xun Sun, Simu Chen, Jianfeng Han, Zhirong ZhangKey Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of ChinaBackground: To establish a potential gene-delivery system with the ability to deliver plasmid DNA to dendritic cells (DCs more efficiently and specifically, we designed and synthesized a low-molecular-weight polyethyleneimine and triethyleneglycol polymer (PEI–TEG and a series of its mannosylated derivatives.Methods: PEI–TEG was synthesized from PEI2000 and PEI600 with TEG as the cross-linker. PEI–TEG was then linked to mannose via a phenylisothiocyanate bridge to obtain man-PEI–TEG conjugates. The DNA conveyance abilities of PEI–TEG, man-PEI–TEG, as well as control PEI25k were evaluated by measuring their zeta potential, particle size, and DNA-binding abilities. The in vitro cytotoxicity, cell uptake, and transfection efficiency of these PEI/DNA complexes were examined on the DC2.4 cell line. Finally, a maturation experiment evaluated the effect of costimulatory molecules CD40, CD80, and CD86 on murine bone marrow-derived DCs (BMDCs using flow cytometry.Results: PEI–TEG and man-PEI–TEG were successfully synthesized and were shown to retain the excellent properties of PEI25k for condensing DNA. Compared with PEI–TEG as well as PEI25k, the man-PEI–TEG had less cytotoxicity and performed better in both cellular uptake and transfection assays in vitro. The results of the maturation experiment showed that all the PEI/DNA complexes induced an adequate upregulation of surface markers for DC maturation.Conclusion: These results demonstrated that man-PEI–TEG can be employed as a DC-targeting gene-delivery system.Keywords: dendritic cells, DCs, mannose, polyethyleneimine, PEI, gene delivery

  3. Smart Drug Delivery Systems in Cancer Therapy.

    Science.gov (United States)

    Unsoy, Gozde; Gunduz, Ufuk

    2018-02-08

    Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Servir: an automated document delivery system

    International Nuclear Information System (INIS)

    Lima, E.C.; Azevedo Coutinho, O.C. de

    1986-01-01

    SERVIR, an automated document delivery system developed by CIN/CNEN, is described. Parametric procedures for reading bibliographic data bases and requesting documents from libraries through computer are specified. Statistical procedures, accounting system and the on-line fulfillment of requests are presented. (Author) [pt

  5. Heparin-immobilized hydroxyapatite nanoparticles as a lactoferrin delivery system for improving osteogenic differentiation of adipose-derived stem cells

    International Nuclear Information System (INIS)

    Kim, Sung Eun; Yun, Young-Pil; Kim, Hak-Jun; Lee, Deok-Won; Shim, Kyu-Sik; Jeon, Daniel I; Rhee, Jin-Kyu; Park, Kyeongsoon

    2016-01-01

    The aim of this study is to fabricate lactoferrin (LF)-carrying hydroxyapatite nanoparticles (HAp NPs) to enhance osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). HAp NPs were modified with heparin-dopamine (Hep-DOPA) (Hep-HAp) and further immobilized with LF (LF/Hep-HAp). Heparin immobilization on HAp NPs prevented aggregation of HAp NPs in aqueous solution and prolonged the release of LF from LF/Hep-HAp NPs. In vitro studies of rADSCs have demonstrated that LF-Hep/HAp NPs significantly increase alkaline phosphatase (ALP) activity, calcium deposition, and both mRNA expression of osteocalcin (OCN) and osteopontin (OPN) in comparison with HAp and Hep-HAp NPs. These results suggest that LF/Hep-HAp NPs can effectively induce osteogenic differentiation of rADSCs. (paper)

  6. Renewable energy delivery systems and methods

    Science.gov (United States)

    Walker, Howard Andrew

    2013-12-10

    A system, method and/or apparatus for the delivery of energy at a site, at least a portion of the energy being delivered by at least one or more of a plurality of renewable energy technologies, the system and method including calculating the load required by the site for the period; calculating the amount of renewable energy for the period, including obtaining a capacity and a percentage of the period for the renewable energy to be delivered; comparing the total load to the renewable energy available; and, implementing one or both of additional and alternative renewable energy sources for delivery of energy to the site.

  7. A nonviral DNA delivery system based on surface modified silica-nanoparticles can efficiently transfect cells in vitro.

    Science.gov (United States)

    Kneuer, C; Sameti, M; Bakowsky, U; Schiestel, T; Schirra, H; Schmidt, H; Lehr, C M

    2000-01-01

    Diverse polycationic polymers have been used as nonviral transfection agents. Here we report the ability of colloidal silica particles with covalently attached cationic surface modifications to transfect plasmid DNA in vitro and make an attempt to describe the structure of the resulting transfection complexes. In analogy to the terms lipoplex and polyplex, we propose to describe the nanoparticle-DNA complexes by the term "nanoplex". Three batches, Si10E, Si100E, and Si26H, sized between 10 and 100 nm and with zeta potentials ranging from +7 to +31 mV at pH 7.4 were evaluated. The galactosidase expression plasmid DNA pCMVbeta was immobilized on the particle surface and efficiently transfected Cos-1 cells. The transfection activity was accompanied by very low cytotoxicity, with LD(50) values in the milligrams per milliliter range. The most active batch, Si26H, was produced by modification of commercially available silica particles with N-(6-aminohexyl)-3-aminopropyltrimethoxysilane, yielding spherical nanoparticles with a mean diameter of 26 nm and a zeta potential of +31 mV at pH 7.4. Complexes of Si26H and pCMVbeta plasmid DNA formed at w/w ratios of 10 were most effective in promoting transfection of Cos-1 cells in the absence of serum. At this ratio, >90% of the DNA was associated with the particles, yielding nanoplexes with a net negative surface charge. When the transfection medium was supplemented with 10% serum, maximum gene expression was observed at a w/w ratio of 30, at which the resulting particle-DNA complexes possessed a positive surface charge. Transfection was strongly increased in the presence of 100 microM chloroquine in the incubation medium and reached approximately 30% of the efficiency of a 60 kDa polyethylenimine. In contrast to polyethylenimine, no toxicity was observed at the concentrations required. Atomic force microscopy of Si26H-DNA complexes revealed a spaghetti-meatball-like structure. The surface of complexes prepared at a w/w ratio of

  8. Prospective Preliminary In Vitro Investigation of a Magnetic Iron Oxide Nanoparticle Conjugated with Ligand CD80 and VEGF Antibody As a Targeted Drug Delivery System for the Induction of Cell Death in Rodent Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Anne Marie Kay Kovach

    2016-10-01

    Full Text Available Target drug deliveries using nanotechnology are a novel consideration in the treatment of cancer. We present herein an in vitro mouse model for the preliminary investigation of the efficacy of an iron oxide nanoparticle complex conjugated to vascular endothelial growth factor (VEGF antibody and ligand cluster of differentiation 80 (CD80 for the purpose of eventual translational applications in the treatment of human osteosarcoma (OSA. The 35 nm diameter iron oxide magnetic nanoparticles are functionalized with an n-hydroxysuccinimide biocompatible coating and are conjugated on the surface to proteins VEGF antibody and ligand CD80. Combined, these proteins have the ability to target OSA cells and induce apoptosis. The proposed system was tested on a cancerous rodent osteoblast cell line (ATCCTMNPO CRL-2836 at four different concentrations (0.1, 1.0, 10.0, and 100.0 μg/mL of ligand CD80 alone, VEGF antibody alone, and a combination thereof (CD80+VEGF. Systems were implemented every 24 h over different sequential treatment timelines: 24, 48, and 72 h, to find the optimal protein concentration required for a reduction in cell proliferation. Results demonstrated that a combination of ligand CD80 and VEGF antibody was consistently most effective at reducing aberrant osteoblastic proliferation for both the 24- and 72-h timelines. At 48 h, however, an increase in cell proliferation was documented for the 0.1 and 1 μg/mL groups. For the 24- and 72-h tests, concentrations of 1.0 μg/mL of CD80+VEGF and 0.1 μg/mL of VEGF antibody were most effective. Concentrations of 10.0 and 100.0 μg/mL of CD80+VEGF reduced cell proliferation, but not as remarkably as the 1.0 μg/mL concentration. In addition, cell proliferation data showed that multiple treatments (72-h test induced cell death in the osteoblasts better than a single treatment. Future targeted drug delivery system research includes trials in OSA cell lines from greater phylum

  9. Ion-Responsive Drug Delivery Systems.

    Science.gov (United States)

    Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

    2018-02-08

    Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Some Recent Advances in Transdermal Drug Delivery Systems ...

    African Journals Online (AJOL)

    Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

  11. Waste Feed Delivery Transfer System Analysis

    Energy Technology Data Exchange (ETDEWEB)

    JULYK, L.J.

    2000-05-05

    This document provides a documented basis for the required design pressure rating and pump pressure capacity of the Hanford Site waste-transfer system in support of the waste feed delivery to the privatization contractor for vitrification. The scope of the analysis includes the 200 East Area double-shell tank waste transfer pipeline system and the associated transfer system pumps for a11 Phase 1B and Phase 2 waste transfers from AN, AP, AW, AY, and A2 Tank Farms.

  12. Waste Feed Delivery Transfer System Analysis

    International Nuclear Information System (INIS)

    JULYK, L.J.

    2000-01-01

    This document provides a documented basis for the required design pressure rating and pump pressure capacity of the Hanford Site waste-transfer system in support of the waste feed delivery to the privatization contractor for vitrification. The scope of the analysis includes the 200 East Area double-shell tank waste transfer pipeline system and the associated transfer system pumps for a11 Phase 1B and Phase 2 waste transfers from AN, AP, AW, AY, and A2 Tank Farms

  13. Delivery Systems for Biopharmaceuticals. Part I: Nanoparticles and Microparticles.

    Science.gov (United States)

    Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

    2015-01-01

    Pharmaceutical biotechnology has been showing therapeutic success never achieved with conventional drug molecules. Therefore, biopharmaceutical products are currently well-established in clinic and the development of new ones is expected. These products comprise mainly therapeutic proteins, although nucleic acids and cells are also included. However, according to their sensitive molecular structures, the efficient delivery of biopharmaceuticals is challenging. Several delivery systems (e.g. microparticles and nanoparticles) composed of different materials (e.g. polymers and lipids) have been explored and demonstrated excellent outcomes, such as: high cellular transfection efficiency for nucleic acids, cell targeting, increased proteins and peptides bioavailability, improved immune response in vaccination, and viability maintenance of microencapsulated cells. Nonetheless, important issues need to be addressed before they reach clinics. For example, more in vivo studies in animals, accessing the toxicity potential and predicting in vivo failure of these delivery systems are required. This is the Part I of two review articles, which presents the state of the art of delivery systems for biopharmaceuticals. Part I deals with microparticles and polymeric and lipid nanoparticles.

  14. Targeted multidrug delivery system to overcome chemoresistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Tang Y

    2017-01-01

    Full Text Available Yuan Tang,1 Fariborz Soroush,1 Zhaohui Tong,2 Mohammad F Kiani,1 Bin Wang1,3 1Department of Mechanical Engineering, Temple University, Philadelphia, PA, 2Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL, 3Department of Biomedical Engineering, Widener University, Chester, PA, USA Abstract: Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy. In this study, a novel combinational targeted drug delivery system was developed by encapsulating antiangiogenesis drug bevacizumab into liposomes and encapsulating chemotherapy drug doxorubicin (DOX into immunoliposomes where the human epidermal growth factor receptor 2 (HER2 antibody was used as a targeting ligand. This novel combinational system was tested in vitro using a HER2 positive and multidrug resistant breast cancer cell line (BT-474/MDR, and in vivo using a xenograft mouse tumor model. In vitro cell culture experiments show that immunoliposome delivery led to a high cell nucleus accumulation of DOX, whereas free DOX was observed mostly near the cell membrane and in cytoplasm due to the action of P-gp. Combining liposomal bevacizumab with immunoliposomal DOX achieved the best tumor growth inhibition and the lowest toxicity. Tumor size decreased steadily within a 60-day observation period indicating a potential synergistic effect between DOX and bevacizumab through the targeted delivery. Our findings clearly indicate that tumor growth was significantly

  15. Immunological Risk of Injectable Drug Delivery Systems

    NARCIS (Netherlands)

    Jiskoot, W.; van Schie, R.M.F.; Carstens, M.G.; Schellekens, H.

    2009-01-01

    Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These

  16. Distance Learning Delivery Systems: Instructional Options.

    Science.gov (United States)

    Steele, Ray L.

    1993-01-01

    Discusses the availability of satellite and cable programing to provide distance education opportunities in school districts. Various delivery systems are described, including telephones with speakers, personal computers, and satellite dishes; and a sidebar provides a directory of distance learning opportunities, including telecommunications…

  17. Auditing Information System : Delivery Product Service

    Directory of Open Access Journals (Sweden)

    Purwoko Purwoko

    2011-05-01

    Full Text Available Purpose of the research is to ensure the securities of information system asset and to ensure if informa-tion system support the operational and data collected was valid. Research method that used in this research were library studies and field studies. Field studies such an observation, questioner, and inter-view. the expected result are founding the weakness of security management control, operational man-agement control, input control, and output control of risk happened in the company. Conclusion of this research are the system on the company work good and there’s no potential risk happened and make an impact to the delivery process of information system.Index Terms - Auditing Information system, Delivery product process.

  18. Regional Delivery of Chimeric Antigen Receptor (CAR) T-Cells for Cancer Therapy.

    Science.gov (United States)

    Sridhar, Praveen; Petrocca, Fabio

    2017-07-18

    Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. We reviewed completed clinical trials for the treatment of glioblastoma and metastatic colorectal cancer and examined the data in these studies for safety, efficacy, and potential advantages that regional delivery may confer over systemic delivery. Our appraisal of the available literature revealed that regional delivery of CAR-T cells in both glioblastoma and hepatic colorectal metastases was generally well tolerated and efficacious in select instances. We propose that the regional delivery of CAR-T cells is an area of potential growth in the solid tumor immunotherapy, and look towards future clinical trials in head and neck cancer, mesothelioma, and peritoneal carcinomatosis as the use of this technique expands.

  19. Regional Delivery of Chimeric Antigen Receptor (CAR T-Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Praveen Sridhar

    2017-07-01

    Full Text Available Chimeric Antigen Receptor (CAR T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. We reviewed completed clinical trials for the treatment of glioblastoma and metastatic colorectal cancer and examined the data in these studies for safety, efficacy, and potential advantages that regional delivery may confer over systemic delivery. Our appraisal of the available literature revealed that regional delivery of CAR-T cells in both glioblastoma and hepatic colorectal metastases was generally well tolerated and efficacious in select instances. We propose that the regional delivery of CAR-T cells is an area of potential growth in the solid tumor immunotherapy, and look towards future clinical trials in head and neck cancer, mesothelioma, and peritoneal carcinomatosis as the use of this technique expands.

  20. Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery.

    Science.gov (United States)

    Tan, Kei X; Danquah, Michael K; Sidhu, Amandeep; Yon, Lau Sie; Ongkudon, Clarence M

    2018-02-08

    The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with

  1. Chitosan microspheres in novel drug delivery systems.

    Science.gov (United States)

    Mitra, Analava; Dey, Baishakhi

    2011-07-01

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

  2. Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jiandi Wan

    2012-04-01

    Full Text Available Encapsulation of cells in hydrogel particles has been demonstrated as an effective approach to deliver therapeutic agents. The properties of hydrogel particles, such as the chemical composition, size, porosity, and number of cells per particle, affect cellular functions and consequently play important roles for the cell-based drug delivery. Microfluidics has shown unparalleled advantages for the synthesis of polymer particles and been utilized to produce hydrogel particles with a well-defined size, shape and morphology. Most importantly, during the encapsulation process, microfluidics can control the number of cells per particle and the overall encapsulation efficiency. Therefore, microfluidics is becoming the powerful approach for cell microencapsulation and construction of cell-based drug delivery systems. In this article, I summarize and discuss microfluidic approaches that have been developed recently for the synthesis of hydrogel particles and encapsulation of cells. I will start by classifying different types of hydrogel material, including natural biopolymers and synthetic polymers that are used for cell encapsulation, and then focus on the current status and challenges of microfluidic-based approaches. Finally, applications of cell-containing hydrogel particles for cell-based drug delivery, particularly for cancer therapy, are discussed.

  3. A wireless actuating drug delivery system

    International Nuclear Information System (INIS)

    Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan

    2015-01-01

    A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s −1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator. (paper)

  4. Gene Delivery into Plant Cells for Recombinant Protein Production

    Directory of Open Access Journals (Sweden)

    Qiang Chen

    2015-01-01

    Full Text Available Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene delivery into plant cells for large-scale manufacturing of recombinant proteins. General gene delivery methodologies in plants are first summarized, followed by extensive discussion on the application and scalability of each agroinfiltration method. New development of a spray-based agroinfiltration and its application on field-grown plants is highlighted. The discussion of agroinfiltration vectors focuses on their applications for producing complex and heteromultimeric proteins and is updated with the development of bridge vectors. Progress on agroinfiltration in Nicotiana and non-Nicotiana plant hosts is subsequently showcased in context of their applications for producing high-value human biologics and low-cost and high-volume industrial enzymes. These new advancements in agroinfiltration greatly enhance the robustness and scalability of transgene delivery in plants, facilitating the adoption of plant transient expression systems for manufacturing recombinant proteins with a broad range of applications.

  5. Enzymatically triggered multifunctional delivery system based on hyaluronic acid micelles

    KAUST Repository

    Deng, Lin

    2012-01-01

    Tumor targetability and stimuli responsivity of drug delivery systems (DDS) are key factors in cancer therapy. Implementation of multifunctional DDS can afford targetability and responsivity at the same time. Herein, cholesterol molecules (Ch) were coupled to hyaluronic acid (HA) backbones to afford amphiphilic conjugates that can self-assemble into stable micelles. Doxorubicin (DOX), an anticancer drug, and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), magnetic resonance imaging (MRI) contrast agents, were encapsulated by Ch-HA micelles and were selectively released in the presence of hyaluronidase (Hyals) enzyme. Cytotoxicity and cell uptake studies were done using three cancer cell lines (HeLa, HepG2 and MCF7) and one normal cell line (WI38). Higher Ch-HA micelles uptake was seen in cancer cells versus normal cells. Consequently, DOX release was elevated in cancer cells causing higher cytotoxicity and enhanced cell death. © 2012 The Royal Society of Chemistry.

  6. [Potential of cell penetrating peptides for cell drug delivery].

    Science.gov (United States)

    Poillot, Cathy; De Waard, Michel

    2011-05-01

    The interest of the scientific community for cell penetrating peptides (CPP) has been growing exponentially for these last years, and the list of novel CPP is increasing. These peptides are powerful tools for the delivery of cargoes to their site of action. Indeed, several drugs that cannot translocate through the cell plasma membrane have been successfully delivered into cells when grafted to a CPP. Various cargoes have been linked to CPP, such as oligonucleotides, pharmacologically active drugs, contrast agents for imaging, or nanoparticles as platforms for multigrafting purposes… This review illustrates the fabulous potential of CPP and the diversity of their use, but their most interesting application appears their future clinical use for the treatment of various pathological conditions. © 2011 médecine/sciences - Inserm / SRMS.

  7. Micelles As Delivery System for Cancer Treatment.

    Science.gov (United States)

    Keskin, Dilek; Tezcaner, Aysen

    2017-01-01

    Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Nanoparticulate delivery systems for antiviral drugs.

    Science.gov (United States)

    Lembo, David; Cavalli, Roberta

    2010-01-01

    Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.

  9. Drug delivery system and radiation therapy

    International Nuclear Information System (INIS)

    Shibata, Tokushi

    2005-01-01

    This paper describes the review of radiation therapy, neutron capture therapy (NCT) and drug delivery system for the latter. In cancer radiation therapy, there are problems of body movement like breathing, needless irradiation of normal tissues, difficulty to decide the correct irradiation position and tumor morphology. NCT has advantages to overcome these, and since boron has a big cross section for thermal neutron, NPT uses the reaction 10 B(n, α) 7 Li in the target cancer which previously incorporated the boron-containing drug. During the period 1966-1996, 246 patients were treated with this in Japan and the treatment has been continued thereafter. The tasks for NCT are developments of drug delivery system efficient to deliver the drug into the tumor and of convenient neutron source like the accelerator. (S.I.)

  10. Chitosan magnetic nanoparticles for drug delivery systems.

    Science.gov (United States)

    Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

    2017-06-01

    The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

  11. Recent Advances in Ocular Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Shinobu Fujii

    2011-01-01

    Full Text Available Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient’s and doctor’s convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

  12. A Comprehensive Review on: Transdermal drug delivery systems.

    OpenAIRE

    Kharat, Rekha; Bathe, Ritesh Suresh

    2016-01-01

    Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

  13. A mucoadhesive in situ gel delivery system for paclitaxel.

    Science.gov (United States)

    Jauhari, Saurabh; Dash, Alekha K

    2006-06-02

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

  14. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

    Science.gov (United States)

    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-01

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  15. Regional Multiteam Systems in Cancer Care Delivery

    Science.gov (United States)

    Monson, John R.T.; Rizvi, Irfan; Savastano, Ann; Green, James S.A.; Sevdalis, Nick

    2016-01-01

    Teamwork is essential for addressing many of the challenges that arise in the coordination and delivery of cancer care, especially for the problems that are presented by patients who cross geographic boundaries and enter and exit multiple health care systems at various times during their cancer care journeys. The problem of coordinating the care of patients with cancer is further complicated by the growing number of treatment options and modalities, incompatibilities among the vast variety of technology platforms that have recently been adopted by the health care industry, and competing and misaligned incentives for providers and systems. Here we examine the issue of regional care coordination in cancer through the prism of a real patient journey. This article will synthesize and elaborate on existing knowledge about coordination approaches for complex systems, in particular, in general and cancer care multidisciplinary teams; define elements of coordination derived from organizational psychology and human factors research that are applicable to team-based cancer care delivery; and suggest approaches for improving multidisciplinary team coordination in regional cancer care delivery and avenues for future research. The phenomenon of the mobile, multisystem patient represents a growing challenge in cancer care. Paradoxically, development of high-quality, high-volume centers of excellence and the ease of virtual communication and data sharing by using electronic medical records have introduced significant barriers to effective team-based cancer care. These challenges urgently require solutions. PMID:27650833

  16. Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

    Directory of Open Access Journals (Sweden)

    Christian Bucher

    2013-01-01

    Full Text Available Intervertebral disc (IVD cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5 by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

  17. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative

  18. Resistive-wall Wake Effect in the Beam Delivery System

    International Nuclear Information System (INIS)

    Delayen, J.R.; Jefferson Lab; Wu, Juhao; Raubenheimer, T.O.; SLAC; Wang, Jiunn-Ming; BNL, NSLS

    2005-01-01

    General formulae for resistive-wall induced beam dilution are presented and then applied to the final beam delivery system of linear colliders. Criteria for the design of final beam delivery systems are discussed

  19. Establishment of protein delivery systems targeting podocytes.

    Directory of Open Access Journals (Sweden)

    Wen Chih Chiang

    2010-07-01

    Full Text Available Podocytes are uniquely structured cells that are critical to the kidney filtration barrier. Their anatomic location on the outer side of the glomerular capillaries expose podocytes to large quantities of both plasma and urinary components and thus are reachable for drug delivery. Recent years have made clear that interference with podocyte-specific disease pathways can modulate glomerular function and influence severity and progression of glomerular disease.Here, we describe studies that show efficient transport of proteins into the mammalian cells mouse 3T3 fibroblasts and podocytes, utilizing an approach termed profection. We are using synthetic lipid structures that allow the safe packing of proteins or antibodies resulting in the subsequent delivery of protein into the cell. The uptake of lipid coated protein is facilitated by the intrinsic characteristic of cells such as podocytes to engulf particles that are physiologically retained in the extracellular matrix. Profection of the restriction enzyme MunI in 3T3 mouse fibroblasts caused an increase in DNA degradation. Moreover, purified proteins such as beta-galactosidase and the large GTPase dynamin could be profected into podocytes using two different profection reagents with the success rate of 95-100%. The delivered beta-galactosidase enzyme was properly folded and able to cleave its substrate X-gal in podocytes. Diseased podocytes are also potential recipients of protein cargo as we also delivered fluorophore labeled IgG into puromycin treated podocytes. We are currently optimizing our protocol for in vivo profection.Protein transfer is developing as an exciting tool to study and target highly differentiated cells such as podocytes.

  20. Spray-on transdermal drug delivery systems.

    Science.gov (United States)

    Ibrahim, Sarah A

    2015-02-01

    Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

  1. Nature engineered diatom biosilica as drug delivery systems.

    Science.gov (United States)

    Uthappa, U T; Brahmkhatri, Varsha; Sriram, G; Jung, Ho-Young; Yu, Jingxian; Kurkuri, Nikita; Aminabhavi, Tejraj M; Altalhi, Tariq; Neelgund, Gururaj M; Kurkuri, Mahaveer D

    2018-05-14

    Diatoms, unicellular photosynthetic algae covered with siliceous cell wall, are also called frustule. These are the most potential naturally available materials for the development of cost-effective drug delivery systems because of their excellent biocompatibility, high surface area, low cost and ease of surface modification. Mesoporous silica materials such as MCM-41 and SBA-15 have been extensively used in drug delivery area. Their synthesis is challenging, time consuming, requires toxic chemicals and are energy intensive, making the entire process expensive and non-viable. Therefore, it is necessary to explore alternative materials. Surprisingly, nature has provided some exciting materials called diatoms; biosilica is one such a material that can be potentially used as a drug delivery vehicle. The present review focuses on different types of diatom species used in drug delivery with respect to their structural properties, morphology, purification process and surface functionalization. In this review, recent advances along with their limitations as well as the future scope to develop them as potential drug delivery vehicles are discussed. Copyright © 2018. Published by Elsevier B.V.

  2. Au nanoinjectors for electrotriggered gene delivery into the cell nucleus.

    Science.gov (United States)

    Kang, Mijeong; Kim, Bongsoo

    2015-01-01

    Intracellular delivery of exogenous materials is an essential technique required for many fundamental biological researches and medical treatments. As our understanding of cell structure and function has been improved and diverse therapeutic agents with a subcellular site of action have been continuously developed, there is a demand to enhance the performance of delivering devices. Ideal intracellular delivery devices should convey various kinds of exogenous materials without deteriorating cell viability regardless of cell type and, furthermore, precisely control the location and the timing of delivery as well as the amount of delivered materials for advanced researches.In this chapter the development of a new intracellular delivery device, a nanoinjector made of a Au (gold) nanowire (a Au nanoinjector) is described in which delivery is triggered by external application of an electric pulse. As a model study, a gene was delivered directly into the nucleus of a neuroblastoma cell, and successful delivery without cell damage was confirmed by the expression of the delivered gene. The insertion of a Au nanoinjector directly into a cell can be generally applied to any kind of cell, and a high degree of surface modification of Au allows attachment of diverse materials such as proteins, small molecules, or nanoparticles as well as genes on Au nanoinjectors. This expands their applicability, and it is expected that they will provide important information on the effects of delivered exogenous materials and consequently contribute to the development of related therapeutic or clinical technologies.

  3. Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

    Science.gov (United States)

    2012-05-16

    This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

  4. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    Directory of Open Access Journals (Sweden)

    Shyamal Kumar Kundu

    2014-01-01

    Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

  5. Autologous bone marrow mononuclear cell delivery to dilated ...

    African Journals Online (AJOL)

    Autologous bone marrow mononuclear cell delivery to dilated cardiomyopathy patients: A clinical trial. PLN Kaparthi, G Namita, LK Chelluri, VSP Rao, PK Shah, A Vasantha, SK Ratnakar, K Ravindhranath ...

  6. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  7. Microemulsions based transdermal drug delivery systems.

    Science.gov (United States)

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

  8. Integrated delivery systems: the cure for fragmentation.

    Science.gov (United States)

    Enthoven, Alain C

    2009-12-01

    Our healthcare system is fragmented, with a misalignment of incentives, or lack of coordination, that spawns inefficient allocation of resources. Fragmentation adversely impacts quality, cost, and outcomes. Eliminating waste from unnecessary, unsafe care is crucial for improving quality and reducing costs--and making the system financially sustainable. Many believe this can be achieved through greater integration of healthcare delivery, more specifically via integrated delivery systems (IDSs). An IDS is an organized, coordinated, and collaborative network that links various healthcare providers to provide a coordinated, vertical continuum of services to a particular patient population or community. It is also accountable, both clinically and fiscally, for the clinical outcomes and health status of the population or community served, and has systems in place to manage and improve them. The marketplace already contains numerous styles and degrees of integration, ranging from Kaiser Permanente-style full integration, to more loosely organized individual practice associations, to public-private partnerships. Evidence suggests that IDSs can improve healthcare quality, improve outcomes, and reduce costs--especially for patients with complex needs--if properly implemented and coordinated. No single approach or public policy will fix the fragmented healthcare system, but IDSs represent an important step in the right direction.

  9. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  10. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  11. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.

    Science.gov (United States)

    Kessler, P D; Podsakoff, G M; Chen, X; McQuiston, S A; Colosi, P C; Matelis, L A; Kurtzman, G J; Byrne, B J

    1996-11-26

    Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the beta-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies.

  12. Injectable shear-thinning nanoengineered hydrogels for stem cell delivery

    DEFF Research Database (Denmark)

    Thakur, Ashish; Jaiswal, Manish K.; Peak, Charles W.

    2016-01-01

    -thinning characteristics, and enhanced mechanical stiffness, elastomeric properties, and physiological stability. The shear-thinning characteristics of nanocomposite hydrogels are investigated for human mesenchymal stem cell (hMSC) delivery. The hMSCs showed high cell viability after injection and encapsulated cells......Injectable hydrogels are investigated for cell encapsulation and delivery as they can shield cells from high shear forces. One of the approaches to obtain injectable hydrogels is to reinforce polymeric networks with high aspect ratio nanoparticles such as two-dimensional (2D) nanomaterials. 2D...... showed a circular morphology. The proposed shear-thinning nanoengineered hydrogels can be used for cell delivery for cartilage tissue regeneration and 3D bioprinting....

  13. Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

    Science.gov (United States)

    Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-07-30

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

  14. Mesenchymal stem cell recruitment by stromal derived factor-1-delivery systems based on chitosan/poly(γ-glutamic acid) polyelectrolyte complexes.

    Science.gov (United States)

    Gonçalves, Raquel M; Antunes, Joana C; Barbosa, Mário A

    2012-04-10

    Human mesenchymal stem cells (hMSCs) have an enormous potential for tissue engineering and cell-based therapies. With a potential of differentiation into multiple lineages and immune-suppression, these cells play a key role in tissue remodelling and regeneration. Here a method of hMSC recruitment is described, based on the incorporation of a chemokine in Chitosan (Ch)/Poly(γ-glutamic acid) (γ-PGA) complexes. Ch is a non-toxic, cationic polysaccharide widely investigated. γ-PGA is a hydrophilic, non-toxic, biodegradable and negatively charged poly-amino acid. Ch and γ-PGA, being oppositely charged, can be combined through electrostatic interactions. These biocompatible structures can be used as carriers for active substances and can be easily modulated in order to control the delivery of drugs, proteins, DNA, etc. Using the layer-by-layer method, Ch and γ-PGA were assembled into polyelectrolyte multilayers films (PEMs) with thickness of 120 nm. The chemokine stromal-derived factor-1 (SDF-1) was incorporated in these complexes and was continuously released during 120 h. The method of SDF-1 incorporation is of crucial importance for polymers assembly into PEMs and for the release kinetics of this chemokine. The Ch/γ-PGA PEMs with SDF-1 were able to recruit hMSCs, increasing the cell migration up to 6 fold to a maximum of 16.2 ± 4.9 cells/mm2. The controlled release of SDF-1 would be of great therapeutic value in the process of hMSC homing to injured tissues. This is the first study suggesting Ch/γ-PGA PEMs as SDF-1 reservoirs to recruit hMSCs, describing an efficient method of chemokine incorporation that allows a sustained released up to 5 days and that can be easily scaled-up.

  15. Mesenchymal stem cell recruitment by stromal derived factor-1-delivery systems based on chitosan/poly(γ-glutamic acid polyelectrolyte complexes

    Directory of Open Access Journals (Sweden)

    RM Gonçalves

    2012-04-01

    Full Text Available Human mesenchymal stem cells (hMSCs have an enormous potential for tissue engineering and cell-based therapies. With a potential of differentiation into multiple lineages and immune-suppression, these cells play a key role in tissue remodelling and regeneration. Here a method of hMSC recruitment is described, based on the incorporation of a chemokine in Chitosan (Ch/Poly(γ-glutamic acid (γ-PGA complexes. Ch is a non-toxic, cationic polysaccharide widely investigated. γ-PGA is a hydrophilic, non-toxic, biodegradable and negatively charged poly-amino acid. Ch and γ-PGA, being oppositely charged, can be combined through electrostatic interactions. These biocompatible structures can be used as carriers for active substances and can be easily modulated in order to control the delivery of drugs, proteins, DNA, etc. Using the layer-by-layer method, Ch and γ-PGA were assembled into polyelectrolyte multilayers films (PEMs with thickness of 120 nm. The chemokine stromal-derived factor-1 (SDF-1 was incorporated in these complexes and was continuously released during 120 h. The method of SDF-1 incorporation is of crucial importance for polymers assembly into PEMs and for the release kinetics of this chemokine. The Ch/γ-PGA PEMs with SDF-1 were able to recruit hMSCs, increasing the cell migration up to 6 fold to a maximum of 16.2 ± 4.9 cells/mm2. The controlled release of SDF-1 would be of great therapeutic value in the process of hMSC homing to injured tissues. This is the first study suggesting Ch/γ-PGA PEMs as SDF-1 reservoirs to recruit hMSCs, describing an efficient method of chemokine incorporation that allows a sustained released up to 5 days and that can be easily scaled-up.

  16. Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis.

    Science.gov (United States)

    Diniz, Ivana M A; Chen, Chider; Ansari, Sahar; Zadeh, Homayoun H; Moshaverinia, Maryam; Chee, Daniel; Marques, Márcia M; Shi, Songtao; Moshaverinia, Alireza

    2016-02-01

    Peri-implantitis is one of the most common inflammatory complications in dental implantology. Similar to periodontitis, in peri-implantitis, destructive inflammatory changes take place in the tissues surrounding a dental implant. Bacterial flora at the failing implant sites resemble the pathogens in periodontal disease and consist of Gram-negative anaerobic bacteria including Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a promising stem cell delivery vehicle with antimicrobial properties. Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel microspheres. Stem cell viability, proliferation, and osteo-differentiation capacity were analyzed. Our results showed that SL exhibited antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml showing the greatest antimicrobial properties while still maintaining cell viability. At this concentration, SL-containing alginate hydrogel was able to inhibit Aa growth on the surface of Ti discs and significantly reduce the bacterial load in Aa suspensions. Silver ions were effectively released from the SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were confirmed by the intense mineral matrix deposition and high expression of osteogenesis-related genes. Taken together, our findings confirm that GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise for bone tissue engineering with antimicrobial properties against Aa bacteria in vitro. © 2015 by the American College of Prosthodontists.

  17. Cyclosporine Amicellar delivery system for dry eyes.

    Science.gov (United States)

    Kang, Han; Cha, Kwang-Ho; Cho, Wonkyung; Park, Junsung; Park, Hee Jun; Sun, Bo Kyung; Hyun, Sang-Min; Hwang, Sung-Joo

    2016-01-01

    The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy. CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining. MS-CsA had a smaller particle size (average diameter 14-18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups (Pdry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells. The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes.

  18. Nanoemulsion: A new concept of delivery system

    Directory of Open Access Journals (Sweden)

    Nitin Sharma

    2010-01-01

    Full Text Available Nanoemulsion has been identified as a promising delivery system for various drugs including biopharmaceuticals. Nanoemulsion is a heterogeneous system composed of one immiscible liquid dispersed as droplets within another liquid. The droplets size of nano emulsion is between 20 to 500 nm. Diameter and surface properties of droplets of nanoemulsion plays an important role in the biological behavior of the formulation. Small droplet sizes lead to transparent emulsions so that product appearance is not altered by the addition of an oil phase. In this paper various aspects of nanoemulsion have been discussed including advantages, disadvantages and methods of preparation. Furthermore new approaches of stability of formulation, effect of types and concentration of surfactant, process variables and method are also discussed to improve the stability of nanoemulsion formulation

  19. Fluid Delivery System For Capillary Electrophoretic Applications.

    Science.gov (United States)

    Li, Qingbo; Liu, Changsheng; Kane, Thomas E.; Kernan, John R.; Sonnenschein, Bernard; Sharer, Michael V.

    2002-04-23

    An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths. An off-line capillary reconditioner thoroughly cleans a capillary cartridge to enable simultaneous execution of electrophoresis with another capillary cartridge. The streamlined nature of the off-line capillary reconditioner offers the advantage of increased system throughput with a minimal increase in system cost.

  20. Texosome-based drug delivery system for cancer therapy: from past to present

    International Nuclear Information System (INIS)

    Mahmoodzadeh Hosseini, Hamideh; Halabian, Raheleh; Amin, Mohsen; Imani Fooladi, Abbas Ali

    2015-01-01

    Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Malfunction of the immune system, particularly in the tumor microenvironment, causes tumor growth and enhances tumor progression. Thus, cancer immunotherapy can be an appropriate approach to provoke the systemic immune system to combat tumor expansion. Texosomes, which are endogenous nanovesicles released by all tumor cells, contribute to cell-cell communication and modify the phenotypic features of recipient cells due to the texosomes’ ability to transport biological components. For this reason, texosome-based delivery system can be a valuable strategy for therapeutic purposes. To improve the pharmaceutical behavior of this system and to facilitate its use in medical applications, biotechnology approaches and mimetic techniques have been utilized. In this review, we present the development history of texosome-based delivery systems and discuss the advantages and disadvantages of each system

  1. Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies.

    Science.gov (United States)

    Giordano, Carmen; Albani, Diego; Gloria, Antonio; Tunesi, Marta; Batelli, Sara; Russo, Teresa; Forloni, Gianluigi; Ambrosio, Luigi; Cigada, Alberto

    2009-12-01

    This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimer's and Parkinson's diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of severe neurodegenerative disorders.

  2. Electronic nicotine delivery systems: a research agenda.

    Science.gov (United States)

    Etter, Jean-François; Bullen, Chris; Flouris, Andreas D; Laugesen, Murray; Eissenberg, Thomas

    2011-05-01

    Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives.

  3. Cyclosporine Amicellar delivery system for dry eyes

    Science.gov (United States)

    Kang, Han; Cha, Kwang-Ho; Cho, Wonkyung; Park, Junsung; Park, Hee Jun; Sun, Bo Kyung; Hyun, Sang-Min; Hwang, Sung-Joo

    2016-01-01

    Background The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy. Materials and methods CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining. Results MS-CsA had a smaller particle size (average diameter 14–18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups (P<0.05) in comparison to those of the Restasis-treated group. The number of goblet cells for rabbit conjunctivas after the administration of MS-CsA was 94.83±8.38, a significantly higher result than the 65.17±11.51 seen with Restasis. The conjunctival epithelial morphology of dry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells. Conclusion The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes. PMID:27382280

  4. Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

    Science.gov (United States)

    2015-09-01

    Systems in Systemic , Dermal, Transdermal , and Ocular Drug Delivery . Crit. Rev. Ther. Drug 2008, 25, 545–584. 14. Choy, Y. B.; Park, J.-H.; McCarey, B...AWARD NUMBER: W81XWH-13-1-0146 TITLE: Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries PRINCIPAL INVESTIGATOR: Dr...Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries” 5b. GRANT NUMBER W81XWH-13-1-0146 5c. PROGRAM ELEMENT NUMBER 6

  5. Cell number and transfection volume dependent peptide nucleic acid antisense activity by cationic delivery methods

    DEFF Research Database (Denmark)

    Llovera Nadal, Laia; Berthold, Peter; Nielsen, Peter E

    2012-01-01

    have now quantitatively compared the cellular activity (in the pLuc705 HeLa cell splice correction system) of PNA antisense oligomers using lipoplex delivery of cholesterol- and bisphosphonate-PNA conjugates, polyplex delivery via a PNA-polyethyleneimine conjugate and CPP delivery via a PNA......Efficient intracellular delivery is essential for high activity of nucleic acids based therapeutics, including antisense agents. Several strategies have been developed and practically all rely on auxiliary transfection reagents such as cationic lipids, cationic polymers and cell penetrating...... peptides as complexing agents and carriers of the nucleic acids. However, uptake mechanisms remain rather poorly understood, and protocols always require optimization of transfection parameters. Considering that cationic transfection complexes bind to and thus may up-concentrate on the cell surface, we...

  6. Polymers for Pharmaceutical Packaging and Delivery Systems

    DEFF Research Database (Denmark)

    Fristrup, Charlotte Juel

    materials of interest for pharmaceutical packaging and delivery systems. Confocal fluorescence microscopy studies and stability studies with insulin aspart (AspB28 insulin) were conducted to evaluate the impact of modified PP compared to unmodified PP. In contrast to PEEK, PP did not contain any functional....... In order to decrease the amount of catalyst residual in the modified materials, activator regenerated by electron transfer (ARGET) SI-ATRP was applied in the second experimental round. Two poly(ethylene glycol)methyl ether methacrylate (MPEGMA) monomers with 4 and 23 ethylene oxide units in the side chain......Selection of polymer materials which will be exposed to protein drugs in either containers or medical devices is often very challenging due to the demands on the polymers. Suitable polymer materials should comply with requirements like compatibility with proteins, sterilisability, good barrier...

  7. An effective strategy of magnetic stem cell delivery for spinal cord injury therapy

    Science.gov (United States)

    Tukmachev, Dmitry; Lunov, Oleg; Zablotskii, Vitalii; Dejneka, Alexandr; Babic, Michal; Syková, Eva; Kubinová, Šárka

    2015-02-01

    Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal channel showed a good correlation with the calculated distribution of magnetic forces exerted onto the transplanted cells. The results suggest that focused targeting and fast delivery of stem cells can be achieved using the proposed non-invasive magnetic system. With future implementation the proposed targeting and delivery strategy bears advantages for the treatment of disease requiring fast stem cell transplantation.Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal

  8. Efficient gene delivery using chitosan-polyethylenimine hybrid systems

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Hu-Lin; Kim, Tae-Hee; Kim, You-Kyoung; Park, In-Young; Cho, Chong-Su [Department of Agricultural Bioechnology, Seoul National University, Seoul 151-921 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of)], E-mail: chocs@plaza.snu.ac.kr

    2008-06-01

    Chitosan and chitosan derivatives have been investigated as non-viral vectors because they have several advantages, such as biocompatibility, biodegradability, low cytotoxicity and low immunogenicity. However, low transfection efficiency and low cell specificity must be solved for their use in clinical trials. In this paper, chitosan-polyethylenimine (PEI) hybrid systems such as chitosan/PEI blend and chitosan-graft-PEI are described for efficient gene delivery because the PEI has high transfection efficiency owing to a proton sponge effect and chitosan has biocompatibility. Also, hepatocyte specificity of the galactosylated chitosan is explained after combination with PEI.

  9. Nanoparticulated magnetic drug delivery systems: Preparation and magnetic characterization

    Energy Technology Data Exchange (ETDEWEB)

    Morais, P C, E-mail: pcmor@unb.b [Universidade de BrasIlia, Instituto de Fisica, Nucleo de Fisica Aplicada, Brasilia DF 70910-900 (Brazil)

    2010-03-01

    This paper describes how magnetic resonance can be successfully used as a tool to help customize and quantify nanosized magnetic particles while labeling cells and administered in animals for targeting different biological sites. Customization of magnetic nanoparticles is addressed here in terms of production of complex magnetic drug delivery systems whereas quantification of magnetic nanoparticle in different biological compartments emerges as a key experimental information to assess time-dependent magnetic nanoparticle biodistribution profiles. Examples of using magnetic resonance in unfolding information regarding the pharmacokinetics of intravenously-injected surface-functionalized magnetic nanoparticles in animals are included in the paper.

  10. Efficient gene delivery using chitosan-polyethylenimine hybrid systems

    International Nuclear Information System (INIS)

    Jiang, Hu-Lin; Kim, Tae-Hee; Kim, You-Kyoung; Park, In-Young; Cho, Chong-Su; Cho, Myung-Haing

    2008-01-01

    Chitosan and chitosan derivatives have been investigated as non-viral vectors because they have several advantages, such as biocompatibility, biodegradability, low cytotoxicity and low immunogenicity. However, low transfection efficiency and low cell specificity must be solved for their use in clinical trials. In this paper, chitosan-polyethylenimine (PEI) hybrid systems such as chitosan/PEI blend and chitosan-graft-PEI are described for efficient gene delivery because the PEI has high transfection efficiency owing to a proton sponge effect and chitosan has biocompatibility. Also, hepatocyte specificity of the galactosylated chitosan is explained after combination with PEI

  11. Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

    Directory of Open Access Journals (Sweden)

    Longfa Kou

    2018-01-01

    Full Text Available Targeted nano-drug delivery systems conjugated with specific ligands to target selective cell-surface receptors or transporters could enhance the efficacy of drug delivery and therapy. Transporters are expressed differentially on the cell-surface of different cell types, and also specific transporters are expressed at higher than normal levels in selective cell types under pathological conditions. They also play a key role in intestinal absorption, delivery via non-oral routes (e.g., pulmonary route and nasal route, and transfer across biological barriers (e.g., blood–brain barrier and blood–retinal barrier. As such, the cell-surface transporters represent ideal targets for nano-drug delivery systems to facilitate drug delivery to selective cell types under normal or pathological conditions and also to avoid off-target adverse side effects of the drugs. There is increasing evidence in recent years supporting the utility of cell-surface transporters in the field of nano-drug delivery to increase oral bioavailability, to improve transfer across the blood–brain barrier, and to enhance delivery of therapeutics in a cell-type selective manner in disease states. Here we provide a comprehensive review of recent advancements in this interesting and important area. We also highlight certain key aspects that need to be taken into account for optimal development of transporter-assisted nano-drug delivery systems.

  12. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    Science.gov (United States)

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  13. Bacterial derived proteoliposome as ideal delivery system and cellular adjuvant.

    Science.gov (United States)

    Rodríguez, Tamara; Pérez, Oliver a; Ugrinovic, Sanja; Bracho, Gustavo; Mastroeni, Pietro

    2006-04-12

    We explored the potential of a proteoliposome (PL) from the outer membrane of N. meningitidis B, as an immunopotentiator and as a vector for antigen delivery to dendritic cells (DC). DC were incubated with PL resulting in up-regulation of MHC-II, CD40, CD80, and CD86 expression and production of TNFalpha and IL12(p70). Ovoalbumin (OVA) was incorporated within PL (PL-OVA). PL-OVA presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas. PL exerts an immunomodulatory effect on DC and is a general system to deliver antigens for presentation to CD4+ and CD8+ T-cells possibly implicated in the induction CD8+ cytotoxic T lymphocytes (CTLs) responses.

  14. An overview of Ball Aerospace cryogen storage and delivery systems

    International Nuclear Information System (INIS)

    Marquardt, J; Keller, J; Mills, G; Schmidt, J

    2015-01-01

    Starting on the Gemini program in the 1960s, Beech Aircraft (now Ball Aerospace) has been designing and manufacturing dewars for a variety of cryogens including liquid hydrogen and oxygen. These dewars flew on the Apollo, Skylab and Space Shuttle spacecraft providing fuel cell reactants resulting in over 150 manned spaceflights. Since Space Shuttle, Ball has also built the liquid hydrogen fuel tanks for the Boeing Phantom Eye unmanned aerial vehicle. Returning back to its fuel cell days, Ball has designed, built and tested a volume-constrained liquid hydrogen and oxygen tank system for reactant delivery to fuel cells on unmanned undersea vehicles (UUVs). Herein past history of Ball technology is described. Testing has been completed on the UUV specific design, which will be described. (paper)

  15. Applications of polymeric nanocapsules in field of drug delivery systems.

    Science.gov (United States)

    Rong, Xinyu; Xie, Yinghua; Hao, Xiaomei; Chen, Tao; Wang, Yingming; Liu, Yuanyuan

    2011-09-01

    Drug-loaded polymeric nanocapsules have exhibited potential applications in the field of drug delivery systems in recent years. This article entails the biodegradable polymers generally used for preparing nanocapsules, which include both natural polymers and synthetic polymers. Furthermore, the article presents a general review of the different preparation methods: nanoprecipitation method, emulsion-diffusion method, double emulsification method, emulsion-coacervation method, layer-by-layer assembly method. In addition, the analysis methods of nanocapsule characteristics, such as mean size, morphology, surface characteristics, shell thickness, encapsulation efficiency, active substance release, dispersion stability, are mentioned. Also, the applications of nanocapsules as carriers for use in drug delivery systems are reviewed, which primarily involve targeting drug delivery, controlled/sustained release drug delivery systems, transdermal drug delivery systems and improving stability and bioavailability of drugs. Nanocapsules, prepared with different biodegradable polymers, have received more and more attention and have been regarded as one of the most promising drug delivery systems.

  16. Polymer hydrogels as optimized delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Batista, Jorge G.S.; Varca, Gustavo H.C.; Ferraz, Caroline C.; Garrido, Gabriela P.; Diniz, Bruna M.; Carvalho, Vinicius S.; Lugao, Ademar B., E-mail: jorgegabriel@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Hydrogels are formed by polymers capable of absorbing large quantities of water. They consist of one or more three-dimensionally structured polymer networks formed by macromolecular chains linked by covalent bonds-crosslinks - and physical interactions. The application of hydrogels, has been widely studied. Biodegradable synthetic or natural polymers such as chitosan, starch and poly-lactic-co-glycolic acid, have properties that allow the development of biodegradable systems for drug and nutraceutics delivery. This study aimed to develop polymeric hydrogels based on polyvinyl alcohol, polyacrylamide and polyvinylpyrrolidone using ionizing radiation in order to develop hydrogels for improved loading and release of compounds. Polymer solutions were solubilized in water and poured into thermoformed packages. After sealing, the material was subjected to γ-irradiation at 25kGy. The samples were assayed by means of mechanical properties, gel fraction and swelling degree. Nanostructure characterization was performed using Flory's equation to determine crosslinking density. The systems developed showed swelling degree and adequate mechanical resistance. The nanostructure evaluation showed different results for each system demonstrating the need of choosing the polymer based on the specific properties of each material. (author)

  17. Polymer hydrogels as optimized delivery systems

    International Nuclear Information System (INIS)

    Batista, Jorge G.S.; Varca, Gustavo H.C.; Ferraz, Caroline C.; Garrido, Gabriela P.; Diniz, Bruna M.; Carvalho, Vinicius S.; Lugao, Ademar B.

    2013-01-01

    Hydrogels are formed by polymers capable of absorbing large quantities of water. They consist of one or more three-dimensionally structured polymer networks formed by macromolecular chains linked by covalent bonds-crosslinks - and physical interactions. The application of hydrogels, has been widely studied. Biodegradable synthetic or natural polymers such as chitosan, starch and poly-lactic-co-glycolic acid, have properties that allow the development of biodegradable systems for drug and nutraceutics delivery. This study aimed to develop polymeric hydrogels based on polyvinyl alcohol, polyacrylamide and polyvinylpyrrolidone using ionizing radiation in order to develop hydrogels for improved loading and release of compounds. Polymer solutions were solubilized in water and poured into thermoformed packages. After sealing, the material was subjected to γ-irradiation at 25kGy. The samples were assayed by means of mechanical properties, gel fraction and swelling degree. Nanostructure characterization was performed using Flory's equation to determine crosslinking density. The systems developed showed swelling degree and adequate mechanical resistance. The nanostructure evaluation showed different results for each system demonstrating the need of choosing the polymer based on the specific properties of each material. (author)

  18. Pancreatic Cancer Cell Exosome-Mediated Macrophage Reprogramming and the Role of MicroRNAs 155 and 125b2 Transfection using Nanoparticle Delivery Systems

    Science.gov (United States)

    Su, Mei-Ju; Aldawsari, Hibah; Amiji, Mansoor

    2016-01-01

    Exosomes are nano-sized endosome-derived small intraluminal vesicles, which are important facilitators of intercellular communication by transporting contents, such as protein, mRNA, and microRNAs, between neighboring cells, such as in the tumor microenvironment. The purpose of this study was to understand the mechanisms of exosomes-mediated cellular communication between human pancreatic cancer (Panc-1) cells and macrophages (J771.A1) using a Transwell co-culture system. Following characterization of exosome-mediated cellular communication and pro-tumoral baseline M2 macrophage polarization, the Panc-1 cells were transfected with microRNA-155 (miR-155) and microRNA-125b-2 (miR-125b2) expressing plasmid DNA using hyaluronic acid-poly(ethylene imine)/hyaluronic acid-poly(ethylene glycol) (HA-PEI/HA-PEG) self-assembling nanoparticle-based non-viral vectors. Our results show that upon successful transfection of Panc-1 cells, the exosome content was altered leading to differential communication and reprogramming of the J774.A1 cells to an M1 phenotype. Based on these results, genetic therapies targeted towards selective manipulation of tumor cell-derived exosome content may be very promising for cancer therapy. PMID:27443190

  19. Poking cells for efficient vector-free intracellular delivery

    Science.gov (United States)

    Wang, Ying; Yang, Yang; Yan, Li; Kwok, So Ying; Li, Wei; Wang, Zhigang; Zhu, Xiaoyue; Zhu, Guangyu; Zhang, Wenjun; Chen, Xianfeng; Shi, Peng

    2014-07-01

    Techniques for introducing foreign molecules and materials into living cells are of great value in cell biology research. A major barrier for intracellular delivery is to cross the cell membrane. Here we demonstrate a novel platform utilizing diamond nanoneedle arrays to facilitate efficient vector-free cytosolic delivery. Using our technique, cellular membrane is deformed by an array of nanoneedles with a force on the order of a few nanonewtons. We show that this technique is applicable to deliver a broad range of molecules and materials into different types of cells, including primary neurons in adherent culture. Especially, for delivering plasmid DNAs into neurons, our technique produces at least eightfold improvement (~45% versus ~1-5%) in transfection efficiency with a dramatically shorter experimental protocol, when compared with the commonly used lipofection approach. It is anticipated that our technique will greatly benefit basic research in cell biology and also a wide variety of clinical applications.

  20. Efficient systemic DNA delivery to the tumor by self-assembled nanoparticle

    Science.gov (United States)

    Tang, Hailin; Xie, Xinhua; Guo, Jiaoli; Wei, Weidong; Wu, Minqing; Liu, Peng; Kong, Yanan; Yang, Lu; Hung, Mien-Chie; Xie, Xiaoming

    2014-01-01

    There are few delivery agents that could deliver gene with high efficiency and low toxicity, especially for animal experiments. Therefore, creating vectors with good delivery efficiency and safety profile is a meaningful work. We have developed a self-assembled gene delivery system (XM001), which can more efficiently deliver DNA to multiple cell lines and breast tumor, as compared to commercial delivery agents. In addition, systemically administrated XM001-BikDD (BikDD is a mutant form of proapoptotic gene Bik) significantly inhibited the growth of human breast cancer cells and prolonged the life span in implanted nude mice. This study demonstrates that XM001 is an efficient and widespread transfection agent, which could be a promising tumor delivery vector for cancer targeted therapy.

  1. Description and Documentation of the Dental School Dental Delivery System.

    Science.gov (United States)

    Chase, Rosen and Wallace, Inc., Alexandria, VA.

    A study was undertaken to describe and document the dental school dental delivery system using an integrated systems approach. In late 1976 and early 1977, a team of systems analysts and dental consultants visited three dental schools to observe the delivery of dental services and patient flow and to interview administrative staff and faculty.…

  2. An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway

    International Nuclear Information System (INIS)

    Zhu, Haiyan; Wang, Lan; Ruan, Yuanyuan; Zhou, Lei; Zhang, Dongmei; Min, Zhihui; Xie, Jianhui; Yu, Min; Gu, Jianxin

    2011-01-01

    Research highlights: → Hsp60 transported to cell surface through the classical secretory pathway was modified with N-glycosylation. → HSAPB-N18 could efficiently deliver Hsp60 to the cell surface via the unconventional secretory pathway. → Cell surface Hsp60 delivered by HASPB-N18 has a proper conformation. → HASPB-N18 is an efficient delivery signal for other DAMP molecules such as Hsp70 and HMGB1. -- Abstract: Damage-associated molecular patterns (DAMPs) are signals released from dying cells evoking the immune system response in several inflammatory disorders. In normal situations, many of DAMPs are nuclear or cytosolic proteins with defined intracellular function, but they could be found on the cell surface following tissue injury. The biological function of the translocated DAMPs is still not well known and an efficient delivery of these molecules on the cell surface is required to clarify their biological effects. In this study, we demonstrated that an unclassical secretory signal peptide, N-terminal 18 amino acids of HASPB (HASPB-N18), could efficiently deliver Hsp60, Hsp70, and HMGB1 on the cell surface. Furthermore, the delivery of these molecules on the cell surface by HASPB-N18 is not limited to a special cell line because several cell lines could use this delivery signal to deliver these molecules on the cell surface. Moreover, we demonstrated that Hsp60 on the cell surface delivered by HASPB-N18 could be recognized by a soluble form of LOX-1, which implies that DAMPs on the cell surface delivered by HASPB-N18 have a proper conformation during transport. Therefore, delivery of DAMPs by HASPB-N18 is a reliable model to further understand the biological significance of DAMPs on the cell surface.

  3. Nano-scale gene delivery systems; current technology, obstacles, and future directions.

    Science.gov (United States)

    Garcia-Guerra, Antonio; Dunwell, Thomas L; Trigueros, Sonia

    2018-01-07

    Within the different applications of nanomedicine currently being developed, nano-gene delivery is appearing as an exciting new technique with the possibility to overcome recognised hurdles and fulfill several biological and medical needs. The central component of all delivery systems is the requirement for the delivery of genetic material into cells, and for them to eventually reside in the nucleus where their desired function will be exposed. However, genetic material does not passively enter cells; thus, a delivery system is necessary. The emerging field of nano-gene delivery exploits the use of new materials and the properties that arise at the nanometre-scale to produce delivery vectors that can effectively deliver genetic material into a variety of different types of cells. The novel physicochemical properties of the new delivery vectors can be used to address the current challenges existing in nucleic acid delivery in vitro and in vivo. While there is a growing interest in nanostructure-based gene delivery, the field is still in its infancy, and there is yet much to discover about nanostructures and their physicochemical properties in a biological context. We carry out an organized and focused search of bibliographic databases. Our results suggest that despite new breakthroughs in nanostructure synthesis and advanced characterization techniques, we still face many barriers in producing highly efficient and non-toxic delivery systems. In this review, we overview the types of systems currently used for clinical and biomedical research applications along with their advantages and disadvantages, as well as discussing barriers that arise from nano-scale interactions with biological material. In conclusion, we hope that by bringing the far reaching multidisciplinary nature of nano-gene delivery to light, new targeted nanotechnology-bases strategies are developed to overcome the major challenges covered in this review. Copyright© Bentham Science Publishers; For

  4. Future of Automated Insulin Delivery Systems

    NARCIS (Netherlands)

    Castle, Jessica R.; DeVries, J. Hans; Kovatchev, Boris

    2017-01-01

    Advances in continuous glucose monitoring (CGM) have brought on a paradigm shift in the management of type 1 diabetes. These advances have enabled the automation of insulin delivery, where an algorithm determines the insulin delivery rate in response to the CGM values. There are multiple automated

  5. Current trends in microsponge drug delivery system.

    Science.gov (United States)

    Gangadharappa, H V; Gupta, N Vishal; Prasad M, Sarat Chandra; Shivakumar, H G

    2013-08-01

    Microsponge is a microscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microsponge having particle size of 10-25 microns in diameter, have wide range of entrapment of various ingredients in a single microsponges system and release them at desired rates. Conventional topical preparations have various disadvantages due to irritancy, odour, greasiness and patient compliance. In many topical dosage forms fail to reach the systemic circulation in sufficient amounts in few cases. These problems overcome by the usage of formulation as microsponge in the areas of research. Drug release in microsponge is done by the external stimuli like pH, temperature and rubbing. It has several advantageous over the other topical preparations in being non-allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are used in the sun screens, creams, ointments, over-the-counter skin care preparations, recently nanosponge were reported in literature used in delivery of drug by the use of cyclodextrins to enhance the solubility of poorly water soluble drugs, which are meant for topical application.

  6. Archaeosomes: an excellent carrier for drug and cell delivery.

    Science.gov (United States)

    Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-09-01

    Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

  7. Injectable In-Situ Gelling Controlled Release Drug Delivery System

    OpenAIRE

    Kulwant Singh; S. L. HariKumar

    2012-01-01

    The administration of poorly bioavailable drug through parenteral route is regarded the most efficient for drug delivery. Parenteral delivery provides rapid onset even for the drug with narrow therapeutic window, but to maintain the systemic drug level repeated installation are required which cause the patient discomfort. This can be overcome by designing the drug into a system, which control the drug release even through parenteral delivery, which improve patient compliance as well as pharma...

  8. Low cost delivery of proteins bioencapsulated in plant cells to human non-immune or immune modulatory cells.

    Science.gov (United States)

    Xiao, Yuhong; Kwon, Kwang-Chul; Hoffman, Brad E; Kamesh, Aditya; Jones, Noah T; Herzog, Roland W; Daniell, Henry

    2016-02-01

    Targeted oral delivery of GFP fused with a GM1 receptor binding protein (CTB) or human cell penetrating peptide (PTD) or dendritic cell peptide (DCpep) was investigated. Presence of GFP(+) intact plant cells between villi of ileum confirm their protection in the digestive system from acids/enzymes. Efficient delivery of GFP to gut-epithelial cells by PTD or CTB and to M cells by all these fusion tags confirm uptake of GFP in the small intestine. PTD fusion delivered GFP more efficiently to most tissues or organs than the other two tags. GFP was efficiently delivered to the liver by all fusion tags, likely through the gut-liver axis. In confocal imaging studies of human cell lines using purified GFP fused with different tags, GFP signal of DCpep-GFP was only detected within dendritic cells. PTD-GFP was only detected within kidney or pancreatic cells but not in immune modulatory cells (macrophages, dendritic, T, B, or mast cells). In contrast, CTB-GFP was detected in all tested cell types, confirming ubiquitous presence of GM1 receptors. Such low-cost oral delivery of protein drugs to sera, immune system or non-immune cells should dramatically lower their cost by elimination of prohibitively expensive fermentation, protein purification cold storage/transportation and increase patient compliance. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

    Science.gov (United States)

    Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

    2012-01-01

    The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

  10. Self-Assembling Multifunctional Peptide Dimers for Gene Delivery Systems

    Directory of Open Access Journals (Sweden)

    Kitae Ryu

    2015-01-01

    Full Text Available Self-assembling multifunctional peptide was designed for gene delivery systems. The multifunctional peptide (MP consists of cellular penetrating peptide moiety (R8, matrix metalloproteinase-2 (MMP-2 specific sequence (GPLGV, pH-responsive moiety (H5, and hydrophobic moiety (palmitic acid (CR8GPLGVH5-Pal. MP was oxidized to form multifunctional peptide dimer (MPD by DMSO oxidation of thiols in terminal cysteine residues. MPD could condense pDNA successfully at a weight ratio of 5. MPD itself could self-assemble into submicron micelle particles via hydrophobic interaction, of which critical micelle concentration is about 0.01 mM. MPD showed concentration-dependent but low cytotoxicity in comparison with PEI25k. MPD polyplexes showed low transfection efficiency in HEK293 cells expressing low level of MMP-2 but high transfection efficiency in A549 and C2C12 cells expressing high level of MMP-2, meaning the enhanced transfection efficiency probably due to MMP-induced structural change of polyplexes. Bafilomycin A1-treated transfection results suggest that the transfection of MPD is mediated via endosomal escape by endosome buffering ability. These results show the potential of MPD for MMP-2 targeted gene delivery systems due to its multifunctionality.

  11. Key factors regulating the mass delivery of macromolecules to model cell membranes

    DEFF Research Database (Denmark)

    Campbell, Richard A.; Watkins, Erik B.; Jagalski, Vivien

    2014-01-01

    We show that both gravity and electrostatics are key factors regulating interactions between model cell membranes and self-assembled liquid crystalline aggregates of dendrimers and phospholipids. The system is a proxy for the trafficking of reservoirs of therapeutic drugs to cell membranes for slow...... of the aggregates to activate endocytosis pathways on specific cell types is discussed in the context of targeted drug delivery applications....

  12. In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides.

    Science.gov (United States)

    Bolhassani, Azam; Jafarzade, Behnaz Sadat; Mardani, Golnaz

    2017-01-01

    The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full-length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose-dependent approach. A major disadvantage of PTD-fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non-covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP-based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. How can innovative project delivery systems improve the overall efficiency of GDOT in transportation project delivery?

    Science.gov (United States)

    2013-04-01

    The USDOT and Federal Highway Administration (FHWA) recommend the smart use of innovative project : delivery systems, such as design-build, to improve efficiency and effectiveness of developing transportation : projects. Although design-build provide...

  14. Cell-penetrating peptides for drug delivery across membrane barriers

    DEFF Research Database (Denmark)

    Foged, Camilla; Nielsen, Hanne Moerck

    2008-01-01

    During the last decade, cell-penetrating peptides have been investigated for their ability to overcome the plasma membrane barrier of mammalian cells for the intracellular or transcellular delivery of cargoes as diverse as low molecular weight drugs, imaging agents, oligonucleotides, peptides......, proteins and colloidal carriers such as liposomes and polymeric nanoparticles. Their ability to cross biological membranes in a non-disruptive way without apparent toxicity is highly desired for increasing drug bioavailability. This review provides an overview of the application of cell......-penetrating peptides as transmembrane drug delivery agents, according to the recent literature, and discusses critical issues and future challenges in relation to fully understanding the fundamental principles of the cell-penetrating peptide-mediated membrane translocation of cargoes and the exploitation...

  15. Marine Origin Polysaccharides in Drug Delivery Systems.

    Science.gov (United States)

    Cardoso, Matias J; Costa, Rui R; Mano, João F

    2016-02-05

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  16. Marine Origin Polysaccharides in Drug Delivery Systems

    Science.gov (United States)

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  17. Marine Origin Polysaccharides in Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Matias J. Cardoso

    2016-02-01

    Full Text Available Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  18. Insulin delivery systems combined with microneedle technology.

    Science.gov (United States)

    Jin, Xuan; Zhu, Dan Dan; Chen, Bo Zhi; Ashfaq, Mohammad; Guo, Xin Dong

    2018-03-29

    Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and

  19. Guidelines for Psychological Practice in Health Care Delivery Systems

    Science.gov (United States)

    American Psychologist, 2013

    2013-01-01

    Psychologists practice in an increasingly diverse range of health care delivery systems. The following guidelines are intended to assist psychologists, other health care providers, administrators in health care delivery systems, and the public to conceptualize the roles and responsibilities of psychologists in these diverse contexts. These…

  20. Buccal Transmucosal Delivery System of Enalapril for Improved ...

    African Journals Online (AJOL)

    Purpose: To prepare and characterize buccal transmucosal delivery system of enalapril maleate for overcoming its low bioavailability, and hence provide improved therapeutic efficacy and patient compliance. Methods: Transmucosal drug delivery systems of enalapril maleate were formulated as buccal films by solvent ...

  1. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...

  2. Grizzli mobile systems and LPG delivery management; Grizzli mobile systems

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2000-07-01

    Complete text of publication follows: Grizzli Mobile Systems (and its sister companies) specialists in data communications and system solutions, offer their complete management solution for LPG deliveries, right through from remote reading of the gas level in the tank, through route management, management of the delivery itself and finally on-site invoicing and payment. The system permits a supplier to really differentiate itself from its competitors in terms of customer service and control of its operations. Domestic gas tanks are often difficult to access; visual reading of the gauge is not always easy and often leads to the customer re-ordering in panic mode. The supplier has also to react in panic mode to the customer. Grizzli Mobile Systems has developed a radio module that is fitted to the gas tank that calls, at regular set intervals with the tank level to a Call Rider gateway plug. The Call Rider is a small box plugged into the regular telephone socket (also supplying multiple operator telephony and other home automation services). As soon as the gas level reaches a predetermined minimum level, this radio information is relayed via the Internet to the LPG supplier. The supplier can then arrange (in non-panic mode) to deliver gas to the customer, via conventional means or by use of an interactive radio display (attached to a refrigerator or similar by magnets) that communicates with the Call Rider by radio. Once a delivery date has been set, a Grizzli Mobile Systems' dispatch system, installed at the supplier's headquarters creates and transfers routes via GSM communications to its fleet of delivery vehicles. A main-frame mapping software provides real-time follow-up and status checks of the vehicles using the GPS functionality and imports data back from the vehicles and updates databases. The driver is also assisted in localizing delivery sites. Inside the cabin of the vehicle the driver has available a Fujitsu PenCentra pen computer, a Microsoft

  3. Gene delivery systems by the combination of lipid bubbles and ultrasound.

    Science.gov (United States)

    Negishi, Yoichi; Endo-Takahashi, Yoko; Maruyama, Kazuo

    2016-11-28

    Gene therapy is promising for the treatment of many diseases including cancers and genetic diseases. From the viewpoint of safety, ultrasound (US)-mediated gene delivery with nano/ microbubbles was recently developed as a novel non-viral vector system. US-mediated gene delivery using nano/microbubbles are able to produce transient changes in the permeability of the cell membrane after US-induced cavitation while reducing cellular damage and enables the tissue-specific or the site-specific intracellular delivery of gene both in vitro and in vivo. We have recently developed novel lipid nanobubbles (Lipid Bubbles). These nanobubbles can also be used to enhance the efficacy of the US-mediated genes (plasmid DNA, siRNA, and miRNA etc.) delivery. In this review, we describe US-mediated delivery systems combined with nano/microbubbles and discuss their feasibility as non-viral vector systems.

  4. Potential applications for halloysite nanotubes based drug delivery systems

    Science.gov (United States)

    Sun, Lin

    Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery. In this study, a drug delivery system was built based on halloysite via three different fabrication methods: physical adsorption, vacuum loading and layer-by-layer coating. Methotrexate was used as the model drug. Factors that may affect performance in both drug loading and release were tested. Results showed that methotrexate could be incorporated within the HNTs system and released in a sustained manner. Layer-by-layer coating showed a better potential than the other two methods in both MTX loading and release. Besides, lower pH could greatly improve MTX loading and release while the increased number of polyelectrolytes bilayers had a limited impact. Osteosarcoma is the most common primary bone malignancy in children and adolescents. Postoperative recurrence and metastasis has become one of the leading causes for patient death after surgical remove of the tumor mass. A strategy could be a sustained release of chemotherapeutics directly at the primary tumor sites where recurrence would mostly occur. Then, this HNTs based system was tested with osteosarcoma cells in vitro to show the potential of delivering chemotherapeutics in the treatment of osteosarcoma. Methotrexate was incorporated within HNTs with a layer-bylayer coating technique, and drug coated HNTs were filled into nylon-6 which is a common material for surgical sutures in industry. Results showed that (1) methotrexate

  5. Study of interactions between cells and microbubbles in high speed centrifugation field for biomolecule delivery.

    Science.gov (United States)

    He, Chuan; Chen, Jie

    2014-01-01

    Biomolecule delivery has a very wide range of applications in biology and medicine. In this study, a microbubble based delivery method was developed. In a high centrifugation field, cells deform and collide with microbubbles to induce intracellular pathways on cell membranes. As a result, biomaterials can then easily enter cells. Experimental results show that this delivery method can achieve high delivery efficiency. Simulation results showed that cells with more deformed structure experienced higher strain on cell membranes than cells with less deformed structure. The models can help explain how centrifugation affects cell membrane permeability. By controlling cell morphology and its mechanical properties, high biomolecule delivery efficiency can be achieved.

  6. The LITA Drill and Sample Delivery System

    Science.gov (United States)

    Paulsen, G.; Yoon, S.; Zacny, K.; Wettergreeng, D.; Cabrol, N. A.

    2013-12-01

    The Life in the Atacama (LITA) project has a goal of demonstrating autonomous roving, sample acquisition, delivery and analysis operations in Atacama, Chile. To enable the sample handling requirement, Honeybee Robotics developed a rover-deployed, rotary-percussive, autonomous drill, called the LITA Drill, capable of penetrating to ~80 cm in various formations, capturing and delivering subsurface samples to a 20 cup carousel. The carousel has a built-in capability to press the samples within each cup, and position target cups underneath instruments for analysis. The drill and sample delivery system had to have mass and power requirements consistent with a flight system. The drill weighs 12 kg and uses less than 100 watt of power to penetrate ~80 cm. The LITA Drill auger has been designed with two distinct stages. The lower part has deep and gently sloping flutes for retaining powdered sample, while the upper section has shallow and steep flutes for preventing borehole collapse and for efficient movement of cuttings and fall back material out of the hole. The drill uses the so called 'bite-sampling' approach that is samples are taken in short, 5-10 cm bites. To take the first bite, the drill is lowered onto the ground and upon drilling of the first bite it is then retracted into an auger tube. The auger with the auger tube are then lifted off the ground and positioned next to the carousel. To deposit the sample, the auger is rotated and retracted above the auger tube. The cuttings retained on the flutes are either gravity fed or are brushed off by a passive side brush into the cup. After the sample from the first bite has been deposited, the drill is lowered back into the same hole to take the next bite. This process is repeated until a target depth is reached. The bite sampling is analogous to peck drilling in the machining process where a bit is periodically retracted to clear chips. If there is some fall back into the hole once the auger has cleared the hole, this

  7. Intracellular Delivery of Nanomaterials via an Inertial Microfluidic Cell Hydroporator.

    Science.gov (United States)

    Deng, Yanxiang; Kizer, Megan; Rada, Miran; Sage, Jessica; Wang, Xing; Cheon, Dong-Joo; Chung, Aram J

    2018-04-11

    The introduction of nanomaterials into cells is an indispensable process for studies ranging from basic biology to clinical applications. To deliver foreign nanomaterials into living cells, traditionally endocytosis, viral and lipid nanocarriers or electroporation are mainly employed; however, they critically suffer from toxicity, inconsistent delivery, and low throughput and are time-consuming and labor-intensive processes. Here, we present a novel inertial microfluidic cell hydroporator capable of delivering a wide range of nanomaterials to various cell types in a single-step without the aid of carriers or external apparatus. The platform inertially focuses cells into the channel center and guides cells to collide at a T-junction. Controlled compression and shear forces generate transient membrane discontinuities that facilitate passive diffusion of external nanomaterials into the cell cytoplasm while maintaining high cell viability. This hydroporation method shows superior delivery efficiency, is high-throughput, and has high controllability; moreover, its extremely simple and low-cost operation provides a powerful and practical strategy in the applications of cellular imaging, biomanufacturing, cell-based therapies, regenerative medicine, and disease diagnosis.

  8. Nanostructured delivery systems with improved leishmanicidal activity: a critical review.

    Science.gov (United States)

    Bruni, Natascia; Stella, Barbara; Giraudo, Leonardo; Della Pepa, Carlo; Gastaldi, Daniela; Dosio, Franco

    2017-01-01

    Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania , which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

  9. Liposomal Conjugates for Drug Delivery to the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Frieder Helm

    2015-04-01

    Full Text Available Treatments of central nervous system (CNS diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes.

  10. Delivery of Probiotics in the Space Food System

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

  11. Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

    Science.gov (United States)

    Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

    2012-01-01

    Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

  12. Controlled drug delivery systems towards new frontiers in patient care

    CERN Document Server

    Rossi, Filippo; Masi, Maurizio

    2016-01-01

    This book offers a state-of-the-art overview of controlled drug delivery systems, covering the most important innovative applications. The principles of controlled drug release and the mechanisms involved in controlled release are clearly explained. The various existing polymeric drug delivery systems are reviewed, and new frontiers in material design are examined in detail, covering a wide range of polymer modification techniques. The concluding chapter is a case study focusing on use of a drug-eluting stent. The book is designed to provide the reader with a complete understanding of the mechanisms and design of controlled drug delivery systems, and to this end includes numerous step-by-step tutorials. It illustrates how chemical engineers can advance medical care by designing polymeric delivery systems that achieve either temporal or spatial control of drug delivery and thus ensure more effective therapy that eliminates the potential for both under-and overdosing.

  13. Biomaterial-based drug delivery systems for the controlled release of neurotrophic factors

    International Nuclear Information System (INIS)

    Mohtaram, Nima Khadem; Montgomery, Amy; Willerth, Stephanie M

    2013-01-01

    This review highlights recent work on the use of biomaterial-based drug delivery systems to control the release of neurotrophic factors as a potential strategy for the treatment of neurological disorders. Examples of neurotrophic factors include the nerve growth factor, the glial cell line-derived neurotrophic factor, the brain-derived neurotrophic factor and neurotrophin-3. In particular, this review focuses on two methods of drug delivery: affinity-based and reservoir-based systems. We review the advantages and challenges associated with both types of drug delivery system and how these systems can be applied to neurological diseases and disorders. While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels and combinations of these systems. Finally, conclusions are drawn about the current state of such drug delivery systems as applied to neural tissue engineering along with some thoughts on the future direction of the field. (topical review)

  14. Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes.

    Science.gov (United States)

    Heine, Shannon J; Diaz-McNair, Jovita; Andar, Abhay U; Drachenberg, Cinthia B; van de Verg, Lillian; Walker, Richard; Picking, Wendy L; Pasetti, Marcela F

    2014-02-15

    Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.

  15. Thiolated polymers as mucoadhesive drug delivery systems.

    Science.gov (United States)

    Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

    2017-03-30

    Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Reduction of treatment delivery variances with a computer-controlled treatment delivery system

    International Nuclear Information System (INIS)

    Fraass, B.A.; Lash, K.L.; Matrone, G.M.; Lichter, A.S.

    1997-01-01

    Purpose: To analyze treatment delivery variances for 3-D conformal therapy performed at various levels of treatment delivery automation, ranging from manual field setup to virtually complete computer-controlled treatment delivery using a computer-controlled conformal radiotherapy system. Materials and Methods: All external beam treatments performed in our department during six months of 1996 were analyzed to study treatment delivery variances versus treatment complexity. Treatments for 505 patients (40,641 individual treatment ports) on four treatment machines were studied. All treatment variances noted by treatment therapists or quality assurance reviews (39 in all) were analyzed. Machines 'M1' (CLinac (6(100))) and 'M2' (CLinac 1800) were operated in a standard manual setup mode, with no record and verify system (R/V). Machines 'M3' (CLinac 2100CD/MLC) and ''M4'' (MM50 racetrack microtron system with MLC) treated patients under the control of a computer-controlled conformal radiotherapy system (CCRS) which 1) downloads the treatment delivery plan from the planning system, 2) performs some (or all) of the machine set-up and treatment delivery for each field, 3) monitors treatment delivery, 4) records all treatment parameters, and 5) notes exceptions to the electronically-prescribed plan. Complete external computer control is not available on M3, so it uses as many CCRS features as possible, while M4 operates completely under CCRS control and performs semi-automated and automated multi-segment intensity modulated treatments. Analysis of treatment complexity was based on numbers of fields, individual segments (ports), non-axial and non-coplanar plans, multi-segment intensity modulation, and pseudo-isocentric treatments (and other plans with computer-controlled table motions). Treatment delivery time was obtained from the computerized scheduling system (for manual treatments) or from CCRS system logs. Treatment therapists rotate among the machines, so this analysis

  17. Methods and metrics challenges of delivery-system research

    Directory of Open Access Journals (Sweden)

    Alexander Jeffrey A

    2012-03-01

    Full Text Available Abstract Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned. This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1 modeling intervention context; (2 measuring readiness for change; (3 assessing intervention fidelity and sustainability; (4 assessing complex, multicomponent interventions; and (5 incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ, US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on

  18. Microcontainers - an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo

    In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose...... of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion...... medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate...

  19. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    Directory of Open Access Journals (Sweden)

    Balkundi S

    2011-12-01

    Full Text Available Shantanu Balkundi1, Ari S Nowacek1, Ram S Veerubhotla1, Han Chen2, Andrea Martinez-Skinner1, Upal Roy1, R Lee Mosley1,3, Georgette Kanmogne1, Xinming Liu1,3,4, Alexander V Kabanov3,4, Tatiana Bronich3,4, JoEllyn McMillan1, Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; 2Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; 3Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.Keywords: human immunodeficiency virus type one, nanotoxicology, monocyte-derived macrophage, nanoformulated antiretroviral therapy, manufacturing techniques

  20. LOGISTIC SYSTEM OF LOAD DELIVERY AND QUALITY OF ITS OPERATION

    Directory of Open Access Journals (Sweden)

    O. G. Drozdovskaya

    2006-01-01

    Full Text Available The paper considers an opportunity for obtaining a competitive advantage by a transport and dispatch service company in the market of transport services while establishing a logistic system of load delivery. A model of delivery system, an universal scheme of system designing for every specific case are presented and also indices for evaluation of its operational quality are proposed in the paper.

  1. Mechanical valve assembly for xenon 133 gas delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Round, W.H. (Royal Brisbane Hospital, Herston (Australia))

    Some gas delivery systems used in pulmonary ventilation scanning are unable to satisfactorily supply /sup 133/Xe gas to bed-ridden patients. A mechanical gas valve assembly to control the flow of gas in such systems was constructed. A commercially produced /sup 133/Xe gas delivery system when fitted with the new assembly was able to ventilate almost all patients whereas previously this could be achieved with approximately only 50% of patients.

  2. Commissioning of cryogen delivery system for superconducting cyclotron magnet

    International Nuclear Information System (INIS)

    Pal, G.; Nandi, C.; Bhattacharyya, T.K.; Chaudhuri, J.; Bhandari, R.K.

    2005-01-01

    A K-500 superconducting cyclotron is being constructed at VECC Kolkata. The cryogen delivery system distributes liquid helium and liquid nitrogen to the superconducting cyclotron. Liquid helium is required to cool the cyclotron magnet and cryopanels. Liquid nitrogen is used to reduce the capacity of the helium liquefier. This paper describes the system, the current status and the commissioning experiences of cryogen delivery system for cyclotron magnet. (author)

  3. Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

    Science.gov (United States)

    Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

    2009-01-01

    We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

  4. An Improved Method for Magnetic Nanocarrier Drug Delivery across the Cell Membrane

    Directory of Open Access Journals (Sweden)

    Behzad Mehrafrooz

    2018-01-01

    Full Text Available One of the crucial issues in the pharmacological field is developing new drug delivery systems. The main concern is to develop new methods for improving the drug delivery efficiencies such as low disruptions, precise control of the target of delivery and drug sustainability. Nowadays, there are many various methods for drug delivery systems. Carbon-based nanocarriers are a new efficient tool for translocating drug into the defined area or cells inside the body. These nanocarriers can be functionalized with proteins, peptides and used to transport their freight to cells or defined areas. Since functionalized carbon-based nanocarriers show low toxicity and high biocompatibility, they are used in many nanobiotechnology fields. In this study, different shapes of nanocarrier are investigated, and the suitable magnetic field, which is applied using MRI for the delivery of the nanocarrier, is proposed. In this research, based on the force required to cross the membrane and MD simulations, the optimal magnetic field profile is designed. This optimal magnetic force field is derived from the mathematical model of the system and magnetic particle dynamics inside the nanocarrier. The results of this paper illustrate the effects of the nanocarrier’s shapes on the percentage of success in crossing the membrane and the optimal required magnetic field.

  5. Otic drug delivery systems: formulation principles and recent developments.

    Science.gov (United States)

    Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

    2018-04-25

    Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

  6. Construction of Injectable Double-Network Hydrogels for Cell Delivery.

    Science.gov (United States)

    Yan, Yan; Li, Mengnan; Yang, Di; Wang, Qian; Liang, Fuxin; Qu, Xiaozhong; Qiu, Dong; Yang, Zhenzhong

    2017-07-10

    Herein we present a unique method of using dynamic cross-links, which are dynamic covalent bonding and ionic interaction, for the construction of injectable double-network (DN) hydrogels, with the objective of cell delivery for cartilage repair. Glycol chitosan and dibenzaldhyde capped poly(ethylene oxide) formed the first network, while calcium alginate formed the second one, and in the resultant DN hydrogel, either of the networks could be selectively removed. The moduli of the DN hydrogel were significantly improved compared to that of the parent single-network hydrogels and were tunable by changing the chemical components. In situ 3D cell encapsulation could be easily performed by mixing cell suspension to the polymer solutions and transferred through a syringe needle before sol-gel transition. Cell proliferation and mediated differentiation of mouse chondrogenic cells were achieved in the DN hydrogel extracellular matrix.

  7. Biological studies of matrix metalloproteinase sensitive drug delivery systems

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann

    due to severe side effects as a result of drug distribution to healthy tissues. To enhance ecacy of treatment and improve life quality of patients, tumor specific drug delivery strategies, such as liposome encapsulated drugs, which accumulate in tumor tissue, has gained increased attention. Several....... The system exploits the increased MMP-2 activity present in tumor tissue as a site-specific trigger of liposomal activation and controlled drug release after accumulation due to the enhanced permeability and retention effect. Enzymatic activity of MMP-2 results in shedding of a novel PEG coating, consisting...... of a negatively charged lipopeptide-PEG conjugates containing a MMP-2 cleavable peptide, which leads to cationic liposomes with enhanced ability to interact with negatively charged cell membranes. Activation of the liposomal formulation developed here resulted in enhanced association of liposomes with cancer...

  8. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    Science.gov (United States)

    Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

    2015-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.

  9. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    Science.gov (United States)

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  10. Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle

    Science.gov (United States)

    Chen, Yao; Xu, Mengjiao; Guo, Yi; Tu, Keyao; Wu, Weimin; Wang, Jianjun; Tong, Xiaowen; Wu, Wenjuan; Qi, Lifeng; Shi, Donglu

    2017-01-01

    Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

  11. Hollow-duct radiation delivery system investigation

    Directory of Open Access Journals (Sweden)

    Kramer D.

    2013-05-01

    Full Text Available Investigation of hollow-duct structure for high-power laser-diode-array radiation delivery into the end-pumped large-aperture gain media is reported. A ray tracing method has been used to evaluate the performance of the structure designed for maximum transmission efficiency and output beam profile homogeneity. Variable hollow-duct lengths as well as emanating angles of laser-diode-array have been taken into account.

  12. A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device

    Science.gov (United States)

    Hatakeyama, Hiroto; Akita, Hidetaka; Kogure, Kentaro; Harashima, Hideyoshi

    In this review we introduce a new concept for developing a nonviral gene delivery system which we call "Programmed Packaging." Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications. PEG/peptide/DOPE ternary conjugate (PPD)-MEND, a new in vivo gene delivery system for the targeting of tumor cells that dissociates surface-modified PEG in tumor tissue by matrix metalloproteinase (MMP) and exerts significant transfection activities, was developed. In parallel with the development of MEND, a quantitative gene delivery system, Confocal Image-assisted 3-dimensionally integrated quantification (CIDIQ), also was developed. This method identified the rate-limiting step of the nonviral gene delivery system by comparing it with adenoviral-mediated gene delivery. The results of this analysis provide a new direction for the development of rational nonviral gene delivery systems.

  13. Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

    Science.gov (United States)

    Carpenter, Cody Westcott

    Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

  14. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D; Herzog, Roland; Daniell, Henry

    2013-06-15

    Among 12billion injections administered annually, unsafe delivery leads to >20million infections and >100million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1 diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Police and Community-partnered Delivery System to Address ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... Delivery System to Address Violence Against Women in the Punjab (India) ... Education, Scheduled Castes and Other Back Classes, and Land Rural Development. ... IWRA/IDRC webinar on climate change and adaptive water management.

  16. A remotely operated drug delivery system with dose control

    KAUST Repository

    Yi, Ying; Kosel, Jü rgen

    2017-01-01

    include an effective actuation stimulus and a controllable dose release mechanism. This work focuses on remotely powering an implantable drug delivery system and providing a high degree of control over the released dose. This is accomplished by integration

  17. Components of Maternal Healthcare Delivery System Contributing to ...

    African Journals Online (AJOL)

    Components of Maternal Healthcare Delivery System Contributing to Maternal Deaths ... transcripts were analyzed using a directed approach to content analysis. Excerpts were categorized according to three main components of the maternal ...

  18. Buccal Transmucosal Delivery System of Enalapril for Improved ...

    African Journals Online (AJOL)

    Methods: Transmucosal drug delivery systems of enalapril maleate were ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals. (DOAJ) ... investigated for various drugs including protein.

  19. A mucoadhesive in situ gel delivery system for paclitaxel

    OpenAIRE

    Jauhari, Saurabh; Dash, Alekha K.

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at d...

  20. Valveless piezoelectric micropump for fuel delivery in direct methanol fuel cell (DMFC) devices

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Tao; Wang, Qing-Ming [Department of Mechanical Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, PA 15261 (United States)

    2005-01-10

    Fuel cells are being considered as an important technology that can be used for various power applications. For portable electronic devices such as laptops, digital cameras, cell phone, etc., the direct methanol fuel cell (DMFC) is a very promising candidate as a power source. Compared with conventional batteries, DMFC can provide a higher power density with a long-lasting life and recharging which is almost instant. However, many issues related to the design, fabrication and operation of miniaturized DMFC power systems still remain unsolved. Fuel delivery is one of the key issues that will determine the performance of the DMFC. To maintain a desired performance, an efficient fuel delivery system is required to provide an adequate amount of fuel for consumption and remove carbon dioxide generated from fuel cell devices at the same time. In this paper, a novel fuel delivery system combined with a miniaturized DMFC is presented. The core component of this system is a piezoelectric valveless micropump that can convert the reciprocating movement of a diaphragm activated by a piezoelectric actuator into a pumping effect. Nozzle/diffuser elements are used to direct the flow from inlet to outlet. As for DMFC devices, the micropump system needs to meet some specific requirements: low energy consumption but a sufficient fuel flow rate. Based on theoretical analysis, the effect of piezoelectric materials properties, driving voltage, driving frequency, nozzle/diffuser dimension, and other factors on the performance of the whole fuel cell system will be discussed. As a result, a viable design of a micropump system for fuel delivery can be achieved and some simulation results will be presented as well. (author)

  1. Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

    OpenAIRE

    Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

    1988-01-01

    A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time interva...

  2. Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.

    Science.gov (United States)

    Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-01-10

    Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Gold nanoparticles delivery in mammalian live cells: a critical review

    Directory of Open Access Journals (Sweden)

    Raphaël Lévy

    2010-02-01

    Full Text Available Functional nanomaterials have recently attracted strong interest from the biology community, not only as potential drug delivery vehicles or diagnostic tools, but also as optical nanomaterials. This is illustrated by the explosion of publications in the field with more than 2,000 publications in the last 2 years (4,000 papers since 2000; from ISI Web of Knowledge, ‘nanoparticle and cell’ hit. Such a publication boom in this novel interdisciplinary field has resulted in papers of unequal standard, partly because it is challenging to assemble the required expertise in chemistry, physics, and biology in a single team. As an extreme example, several papers published in physical chemistry journals claim intracellular delivery of nanoparticles, but show pictures of cells that are, to the expert biologist, evidently dead (and therefore permeable. To attain proper cellular applications using nanomaterials, it is critical not only to achieve efficient delivery in healthy cells, but also to control the intracellular availability and the fate of the nanomaterial. This is still an open challenge that will only be met by innovative delivery methods combined with rigorous and quantitative characterization of the uptake and the fate of the nanoparticles. This review mainly focuses on gold nanoparticles and discusses the various approaches to nanoparticle delivery, including surface chemical modifications and several methods used to facilitate cellular uptake and endosomal escape. We will also review the main detection methods and how their optimum use can inform about intracellular localization, efficiency of delivery, and integrity of the surface capping. Raphaël Lévy is a BBSRC David Phillips Research Fellow at the University of Liverpool. He graduated in Physics at the University Louis Pasteur in Strasbourg (France. In 2002, after a Master in Soft Condensed Matter Physics, he obtained a PhD in Physics at the University Louis Pasteur. He then moved to

  4. Model for determining and optimizing delivery performance in industrial systems

    Directory of Open Access Journals (Sweden)

    Fechete Flavia

    2017-01-01

    Full Text Available Performance means achieving organizational objectives regardless of their nature and variety, and even overcoming them. Improving performance is one of the major goals of any company. Achieving the global performance means not only obtaining the economic performance, it is a must to take into account other functions like: function of quality, delivery, costs and even the employees satisfaction. This paper aims to improve the delivery performance of an industrial system due to their very low results. The delivery performance took into account all categories of performance indicators, such as on time delivery, backlog efficiency or transport efficiency. The research was focused on optimizing the delivery performance of the industrial system, using linear programming. Modeling the delivery function using linear programming led to obtaining precise quantities to be produced and delivered each month by the industrial system in order to minimize their transport cost, satisfying their customers orders and to control their stock. The optimization led to a substantial improvement in all four performance indicators that concern deliveries.

  5. Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems.

    Science.gov (United States)

    Shinkar, Dattatraya Manohar; Dhake, Avinash Sridhar; Setty, Chitral Mallikarjuna

    2012-01-01

    Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.

  6. Application of drug delivery system to boron neutron capture therapy for cancer.

    Science.gov (United States)

    Yanagië, Hironobu; Ogata, Aya; Sugiyama, Hirotaka; Eriguchi, Masazumi; Takamoto, Shinichi; Takahashi, Hiroyuki

    2008-04-01

    Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons ((10)B + (1)n --> (7)Li + (4)He (alpha) + 2.31 MeV (93.7 %)/2.79 MeV (6.3 %)). The resulting lithium ions and alphaparticles are high linear energy transfer (LET) particles which give a high biological effect. Their short range in tissue (5 - 9 mum) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma. Sodium mercaptoundecahydro-dodecaborate (Na(2)(10)B(12)H(11)SH: BSH) and borono-phenylalanine ((10)BPA) are currently being used in clinical treatments. These low molecule compounds are easily cleared from cancer cells and blood, so high accumulation and selective delivery of boron compounds into tumor tissues and cancer cells are most important to achieve effective BNCT and to avoid damage to adjacent healthy cells. In order to achieve the selective delivery of boron atoms to cancer cells, a drug delivery system (DDS) is an attractive intelligent technology for targeting and controlled release of drugs. We performed literature searches related to boron delivery systems in vitro and in vivo. We describe several DDS technologies for boron delivery to cancer tissues and cancer cells from the past to current status. We are convinced that it will be possible to use liposomes, monoclonal antibodies and WOW emulsions as boron delivery systems for BNCT clinically in accordance with the preparation of good commercial product (GCP) grade materials.

  7. Drug Delivery Systems: A New Frontier in Nano-technology

    Directory of Open Access Journals (Sweden)

    Chamindri Witharana

    2017-09-01

    Full Text Available Nano-technology is a recent advancement in science, defined as “Science, engineering, and technology conducted at the Nano scale” (National nanotechnology initiatives in USA. Applications of Nano-technology cover a vast range from basic material science, personal care applications, agriculture, and medicine. Nano-technology is used in field of medicine for treatment, diagnostic, monitoring, genetic engineering, and drug delivery. There are two main types of Nano Particles (NPs used in drug delivery; organic NPs and inorganic NPs. In drug delivery, the drug-Nano- Particle (NP conjugate should be able to deliver drugs to the target site without degradation in gastrointestinal track and without reducing drug activity. Further, it should attack to target cells without causing any adverse effects. The ultimate goal of NP drug delivery is to improve proper treatment, effectiveness, less side effects with safety and patient adherence as well as reduction in the cost.

  8. Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery.

    Science.gov (United States)

    Parodi, Alessandro; Molinaro, Roberto; Sushnitha, Manuela; Evangelopoulos, Michael; Martinez, Jonathan O; Arrighetti, Noemi; Corbo, Claudia; Tasciotti, Ennio

    2017-12-01

    The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles' surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles. Copyright © 2017. Published by Elsevier Ltd.

  9. Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.

    Science.gov (United States)

    Li, Ling; Hu, Shuo; Chen, Xiaoyuan

    2018-07-01

    In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed. Published by Elsevier Ltd.

  10. Recent trends in challenges and opportunities of Transdermal drug delivery system

    OpenAIRE

    P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

    2012-01-01

    Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

  11. MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies, and Immune Modulation

    Directory of Open Access Journals (Sweden)

    Thomas J. Kean

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are currently being widely investigated both in the lab and in clinical trials for multiple disease states. The differentiation, trophic, and immunomodulatory characteristics of MSCs contribute to their therapeutic effects. Another often overlooked factor related to efficacy is the degree of engraftment. When reported, engraftment is generally low and transient in nature. MSC delivery methods should be tailored to the lesion being treated, which may be local or systemic, and customized to the mechanism of action of the MSCs, which can also be local or systemic. Engraftment efficiency is enhanced by using intra-arterial delivery instead of intravenous delivery, thus avoiding the “first-pass” accumulation of MSCs in the lung. Several methodologies to target MSCs to specific organs are being developed. These cell targeting methodologies focus on the modification of cell surface molecules through chemical, genetic, and coating techniques to promote selective adherence to particular organs or tissues. Future improvements in targeting and delivery methodologies to improve engraftment are expected to improve therapeutic results, extend the duration of efficacy, and reduce the effective (MSC therapeutic dose.

  12. Svelte Integrated Delivery System Performance Examined Through Diagnostic Catheter Delivery : The SPEED Registry

    NARCIS (Netherlands)

    Khattab, Ahmed A.; Nijhoff, Freek; Schofer, Joachim; Berland, Jacques; Meier, Bernhard; Nietlispach, Fabian; Agostoni, Pierfrancesco; Brucks, Steffen; Stella, Pieter

    2015-01-01

    Aims: The multi-center SPEED registry evaluated the procedural success and in-hospital clinical outcomes of direct stenting with the Svelte 'all-in-one' coronary stent Integrated Delivery System (IDS) through diagnostic catheters to identify the clinical indications for which this approach is

  13. Intracellular Protein Delivery System Using a Target-Specific Repebody and Translocation Domain of Bacterial Exotoxin.

    Science.gov (United States)

    Kim, Hee-Yeon; Kang, Jung Ae; Ryou, Jeong-Hyun; Lee, Gyeong Hee; Choi, Dae Seong; Lee, Dong Eun; Kim, Hak-Sung

    2017-11-17

    With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.

  14. Encapsulation systems for the delivery of hydrophilic nutraceuticals: Food application.

    Science.gov (United States)

    Aditya, N P; Espinosa, Yadira Gonzalez; Norton, Ian T

    2017-07-01

    Increased health risk associated with the sedentary life style is forcing the food manufacturers to look for food products with specific or general health benefits e.g. beverages enriched with nutraceuticals like catechin, curcumin rutin. Compounds like polyphenols, flavonoids, vitamins are the good choice of bioactive compounds that can be used to fortify the food products to enhance their functionality. However due to low stability and bioavailability of these bioactives (both hydrophobic and hydrophilic) within the heterogeneous food microstructure and in the Gastro Intestinal Tract (GIT), it becomes extremely difficult to pass on the real health benefits to the consumers. Recent developments in the application of nano-delivery systems for food product development is proving to be a game changer which has raised the expectations of the researchers, food manufacturers and consumers regarding possibility of enhancing the functionality of bioactives within the fortified food products. In this direction, nano/micro delivery systems using lipids, surfactants and other materials (carbohydrates, polymers, complexes, protein) have been fabricated to stabilize and enhance the biological activity of the bioactive compounds. In the present review, current status of the various delivery systems that are used for the delivery of hydrophilic bioactives and future prospects for using other delivery systems that have been not completely explored for the delivery of hydrophilic bioactives e.g. niosomes; bilosomes, cubosomes are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The origins and evolution of "controlled" drug delivery systems.

    Science.gov (United States)

    Hoffman, Allan S

    2008-12-18

    This paper describes the earliest days when the "controlled drug delivery" (CDD) field began, the pioneers who launched this exciting and important field, and the key people who came after them. It traces the evolution of the field from its origins in the 1960s to (a) the 1970s and 1980s, when numerous macroscopic "controlled" drug delivery (DD) devices and implants were designed for delivery as mucosal inserts (e.g., in the eye or vagina), as implants (e.g., sub-cutaneous or intra-muscular), as ingestible capsules (e.g., in the G-I tract), as topical patches (e.g., on the skin), and were approved for clinical use, to (b) the 1980s and 1990s when microscopic degradable polymer depot DD systems (DDS) were commercialized, and to (c) the currently very active and exciting nanoscopic era of targeted nano-carriers, in a sense bringing to life Ehrlich's imagined concept of the "Magic Bullet". The nanoscopic era began with systems proposed in the 1970s, that were first used in the clinic in the 1980s, and which came of age in the 1990s, and which are presently evolving into many exciting and clinically successful products in the 2000s. Most of these have succeeded because of the emergence of three key technologies: (1) PEGylation, (2) active targeting to specific cells by ligands conjugated to the DDS, or passive targeting to solid tumors via the EPR effect. The author has been personally involved in the origins and evolution of this field for the past 38 years (see below), and this review includes information that was provided to him by many researchers in this field about the history of various developments. Thus, this paper is based on his own personal involvements in the CDD field, along with many historical anecdotes provided by the key pioneers and researchers in the field. Because of the huge literature of scientific papers on CDD systems, this article attempts to limit examples to those that have been approved for clinical use, or are currently in clinical trials

  16. Elastin-Like Recombinamers As Smart Drug Delivery Systems.

    Science.gov (United States)

    Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

    2018-02-19

    Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Oral delivery of peptides and proteins using lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-01-01

    INTRODUCTION: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism...... by which intestinal absorption of peptides and proteins is promoted. AREAS COVERED: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two...... and proteins. EXPERT OPINION: Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve...

  18. Hydrocolloid-based nutraceutical delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Janaswamy, Srinivas; Youngren, Susanne R. (Purdue)

    2012-07-11

    Nutraceuticals are important due to their inherent health benefits. However, utilization and consumption are limited by their poor water solubility and instability at normal processing and storage conditions. Herein, we propose an elegant and novel approach for the delivery of nutraceuticals in their active form using hydrocolloid matrices that are inexpensive and non-toxic with generally recognized as safe (GRAS) status. Iota-carrageenan and curcumin have been chosen as models of hydrocolloid and nutraceutical compounds, respectively. The iota-carrageenan network maintains a stable organization after encapsulating curcumin molecules, protects them from melting and then releases them in a sustained manner. These findings lay a strong foundation for developing value-added functional and medicinal foods.

  19. Adamantane in Drug Delivery Systems and Surface Recognition

    OpenAIRE

    Adela Štimac; Marina Šekutor; Kata Mlinarić-Majerski; Leo Frkanec; Ruža Frkanec

    2017-01-01

    The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based struc...

  20. Waste feed delivery program systems engineering implementation plan

    International Nuclear Information System (INIS)

    O'Toole, S.M.; Hendel, B.J.

    1998-01-01

    This document defines the systems engineering processes and products planned by the Waste Feed Delivery Program to develop the necessary and sufficient systems to provide waste feed to the Privatization Contractor for Phase 1. It defines roles and responsibilities for the performance of the systems engineering processes and generation of products

  1. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    International Nuclear Information System (INIS)

    Hong, Sung-Ha; Jenkins, A Toby A; Szili, Endre J; Short, Robert D

    2014-01-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine. (fast track communication)

  2. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    Science.gov (United States)

    Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

    2014-09-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

  3. Inulin based glutathione-responsive delivery system for colon cancer treatment.

    Science.gov (United States)

    Wang, Dongdong; Sun, Feifei; Lu, Chunbo; Chen, Peng; Wang, Zhaojie; Qiu, Yuanhao; Mu, Haibo; Miao, Zehong; Duan, Jinyou

    2018-05-01

    Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA in the system was highly responsive to glutathione, which is commonly abundant in cancer cells. In addition, this drug delivery system was proliferative to Bifidobacterium longum, the common inhabitant of human intestine. Thus, this strategy might be useful to improve colon cancer therapy efficacy of anticancer drugs and meanwhile promote the growth of beneficial commensal flora in the gut. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  5. Polysaccharides-based polyelectrolyte nanoparticles as protein drugs delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Shu Shujun; Sun Lei; Zhang Xinge, E-mail: zhangxinge@nankai.edu.cn [Nankai University, Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry (China); Wu Zhongming [Tianjin Medical University, Metabolic Diseases Hospital (China); Wang Zhen; Li Chaoxing, E-mail: lcx@nankai.edu.cn [Nankai University, Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry (China)

    2011-09-15

    Polysaccharides-based nanoparticles were prepared by synthesized quaternized chitosan and dextran sulfate through simple ionic-gelation self-assembled method. Introduction of quaternized groups was intended to increase water solubility of chitosan and make the nanoparticles have broader pH sensitive range which can remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity. The load of BSA was affected by molecular parameter, i.e., degree of substitution, and average molecular weight of quaternized chitosan, as well as concentration of BSA. Fast release occurred in phosphate buffer solution (pH 7.4) while the release was slow in hydrochloric acid (pH 1.4). The drug release mechanism is Fickian diffusion through release kinetics analysis. Cell uptake demonstrated nanoparicles can internalize into Caco-2 cells, which suggested that nanoparticles had good biocompatibility. No significant conformation change was noted for the released BSA in comparison with native BSA using circular dichroism spectroscopy. This kind of novel composite nanoparticles may be a promising delivery system for oral protein and peptide drugs.

  6. A novel approach for nucleic acid delivery into cancer cells.

    Science.gov (United States)

    Vainauska, Dace; Kozireva, Svetlana; Karpovs, Andrejs; Čistjakovs, Maksims; Bariševs, Mihails

    2012-01-01

    Liposomal magnetofection is based on the use of superparamagnetic particles and cationic lipids and shows better transfection efficiency than other common nonviral gene delivery methods; however, the distribution of aggregate complexes over the cell surface may be ununiform. The use of a dynamic gradient magnetic field could overcome this limitation. A newly developed device for magnetofection under a dynamic magnetic field was used to compare the transfection efficiency of prostate carcinoma cell line PC3 with that obtained by lipofection and magnetofection. Reporter plasmid pcDNA3.1LacZ DNA was used in combination with Lipofectamine2000 reagent and superparamagnetic nanoparticles CombiMag. The effects of incubation time under a dynamic magnetic field and a rotation frequency of magnets on transfection efficiency for PC3 cell line were determined. Alternatively, lipofection and liposomal magnetofection were carried out. Transfection efficiency of delivery methods was estimated by β-galactosidase staining; cell viability, by acridine orange/ethidium bromide staining. Liposomal magnetofection under a dynamic gradient magnetic field demonstrated the highest transfection efficiency: it was greater by almost 21% and 42% in comparison with liposomal magnetofection and lipofection, respectively. The optimal incubation time under dynamic magnetic field and the optimal magnet rotation frequency were 5 minutes and 5 rpm, respectively. Liposomal magnetofection under a dynamic gradient magnetic field was less cytotoxic (7%) than that under a permanent magnetic field (17%) and lipofection (11%). Our new approach, based on the use of a dynamic gradient magnetic field, enhanced the transfection efficiency and had a less cytotoxic effect on prostate cancer cells in comparison with the standard magnetofection and lipofection.

  7. Lignin nanotubes as vehicles for gene delivery into human cells.

    Science.gov (United States)

    Ten, Elena; Ling, Chen; Wang, Yuan; Srivastava, Arun; Dempere, Luisa Amelia; Vermerris, Wilfred

    2014-01-13

    Lignin nanotubes (LNTs) synthesized from the aromatic plant cell wall polymer lignin in a sacrificial alumina membrane template have as useful features their flexibility, ease of functionalization due to the availability of many functional groups, label-free detection by autofluorescence, and customizable optical properties. In this report we show that the physicochemical properties of LNTs can be varied over a wide range to match requirements for specific applications by using lignin with different subunit composition, a function of plant species and genotype, and by choosing the lignin isolation method (thioglycolic acid, phosphoric acid, sulfuric acid (Klason), sodium hydroxide lignin), which influences the size and reactivity of the lignin fragments. Cytotoxicity studies with human HeLa cells showed that concentrations of up to 90 mg/mL are tolerated, which is a 10-fold higher concentration than observed for single- or multiwalled carbon nanotubes (CNTs). Confocal microscopy imaging revealed that all LNT formulations enter HeLa cells without auxiliary agents and that LNTs made from NaOH-lignin penetrate the cell nucleus. We further show that DNA can adsorb to LNTs. Consequently, exposure of HeLa cells to LNTs coated with DNA encoding the green fluorescent protein (GFP) leads to transfection and expression of GFP. The highest transfection efficiency was obtained with LNTs made from NaOH-lignin due to a combination of high DNA binding capacity and DNA delivery directly into the nucleus. These combined features of LNTs make LNTs attractive as smart delivery vehicles of DNA without the cytotoxicity associated with CNTs or the immunogenicity of viral vectors.

  8. Extracellular delivery induced by ultrasound and microbubbles in cells

    Science.gov (United States)

    Hussein, Farah; Antonescu, Costin; Karshafian, Raffi

    2017-03-01

    Ultrasound and microbubble treatment (USMB) can enhance the intracellular uptake of molecules, which otherwise would be excluded from the cell, through USMB-mediated transient membrane disruption and through enhanced endocytosis. However, the effect of USMB on the outward movement of molecules from cells is not well understood. This study investigates the effects of USMB on the release of molecules from various cellular compartments including cytoplasm, lysosomes, and recycling endosomes. In vitro ARPE-19 (RPE henceforth) cells were loaded with Alexa fluor-labeled transferrin as a marker for recycling endosomes, LAMP-1 antibody was used to detect the fusion of lysosomes with the plasma membrane, GFP-transfected RPE cells were used to examine the release of GFP from the cytoplasm, and 7-AAD was used to assess cell viability. Subsequently, cells were exposed to USMB (106 cells/mL, 300 kPa peak negative pressure, 1 min treatment duration, and 20 µL/mL Definity microbubbles). Following USMB, the release of the fluorescent markers was examined at 1.5, 11.5, and 21.5 minutes from the start of USMB. The mean fluorescent intensity (MFI) of untreated and USMB treated samples were measured using flow cytometry. USMB increased the extracellular delivery of GFP molecules from the cytoplasm; the MFI in USMB treated GFP-transfected RPE cells decreased by 17% in viable cells and this MFI decreased by 70% in non-viable cells. This could be due to diffusion of GFP through the membrane disruptions induced by USMB. Additionally, the MFI of viable cells stained with LAMP-1 antibody increased by 50% and this increase was 15 folds in the non-viable cells indicating lysosome exocytosis as a mechanism for membrane repair. Furthermore, the MFI of cells loaded with fluorescent transferrin decreased by 22% after USMB treatment in viable cells, indicating a significant increase in transferrin recycling to the cell membrane. However, the increased recycling was not statistically significant

  9. Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle.

    Science.gov (United States)

    Wendel, Sebastian O; Menon, Sailesh; Alshetaiwi, Hamad; Shrestha, Tej B; Chlebanowski, Lauren; Hsu, Wei-Wen; Bossmann, Stefan H; Narayanan, Sanjeev; Troyer, Deryl L

    2015-01-01

    The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2•106 to 1•105.

  10. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

    Science.gov (United States)

    Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

    2016-01-01

    Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

  11. H2T liquid hydrogen delivery system

    International Nuclear Information System (INIS)

    Roy, S.

    2002-01-01

    This Power Point presentation provides a preliminary evaluation of the cost of delivering liquid hydrogen produced in Quebec to hydrogen fuelled cars in Germany. The presentation describes the chain of events regarding liquid hydrogen delivery, beginning with the production of hydrogen from an initial source of hydro power. Water passes through an electrolyzer where hydrogen is liquefied and then placed into a container which is transported to market via truck, rail or tanker. Once transported, the hydrogen fuel is made available for consumers at refueling stations. The paper lists the costs related to transportation with reference to safety rules, pure transportation costs, leasing fees for the containers, and permission of customs duties for the import of hydrogen and export of empty containers between Quebec and Germany. A graph depicting a typical refueling station in Germany and the refueling events per hour was presented. For safety reasons, refueling is performed by a refueling robot. A blueprint of safety and protection distances at a refueling station was also presented. tabs., figs

  12. Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

    Science.gov (United States)

    Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

    2016-01-01

    Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

  13. Flexible power delivery system and its intelligent functions

    International Nuclear Information System (INIS)

    Glamochanin, Vlastimir; Andonov, Dragan

    1996-01-01

    This paper presents some of the features and capabilities of the novel energy distribution system called FRIENDS. The main FRIENDS objective is distribution system reliability, with flexible system structure reconfiguration, inclusion of dispersed energy generation systems. Altogether, it represents a new concept of reliable and economic electric power delivery to end users. The FRIENDS project is a challenge for future research and development, including new technology and devices for the implementation of such an integrated system. (author)

  14. Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

    Science.gov (United States)

    Nahire, Rahul Rajaram

    Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image

  15. Temperature-sensitive microemulsion gel: an effective topical delivery system for simultaneous delivery of vitamins C and E.

    Science.gov (United States)

    Rozman, Branka; Zvonar, Alenka; Falson, Francoise; Gasperlin, Mirjana

    2009-01-01

    Microemulsions (ME)--nanostructured systems composed of water, oil, and surfactants--have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-like ME with temperature-sensitive rheological properties was formed. The temperature-driven changes in its microstructure were confirmed by rotational rheometry, viscosity measurements, and droplet size determination. The release studies have shown that the vitamins' release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). According to effectiveness in skin delivery of both vitamins, o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer, indicating that no simple correlation between vitamins release and skin absorption could be found. The cytotoxicity studies revealed good cell viability after exposure to ME and confirmed all tested microemulsions as nonirritant.

  16. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein

    Science.gov (United States)

    Kessler, Paul D.; Podsakoff, Gregory M.; Chen, Xiaojuan; McQuiston, Susan A.; Colosi, Peter C.; Matelis, Laura A.; Kurtzman, Gary J.; Byrne, Barry J.

    1996-01-01

    Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the β-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies. PMID:8943064

  17. Acridine Orange Conjugated Polymersomes for Simultaneous Nuclear Delivery of Gemcitabine and Doxorubicin to Pancreatic Cancer Cells.

    Science.gov (United States)

    Anajafi, Tayebeh; Scott, Michael D; You, Seungyong; Yang, Xiaoyu; Choi, Yongki; Qian, Steven Y; Mallik, Sanku

    2016-03-16

    Considering the systemic toxicity of chemotherapeutic agents, there is an urgent need to develop new targeted drug delivery systems. Herein, we have developed a new nuclear targeted, redox sensitive, drug delivery vehicle to simultaneously deliver the anticancer drugs gemcitabine and doxorubicin to the nuclei of pancreatic cancer cells. We prepared polymeric bilayer vesicles (polymersomes), and actively encapsulated the drug combination by the pH gradient method. A redox-sensitive polymer (PEG-S-S-PLA) was incorporated to sensitize the formulation to reducing agent concentration. Acridine orange (AO) was conjugated to the surface of the polymersomes imparting nuclear localizing property. The polymersomes' toxicity and efficacy were compared with those of a free drug combination using monolayer and three-dimensional spheroid cultures of pancreatic cancer cells. We observed that the redox sensitive, nuclear-targeted polymersomes released more than 60% of their encapsulated contents in response to 50 mM glutathione. The nanoparticles are nontoxic; however, the drug encapsulated vesicles have significant toxicity. The prepared formulation can increase the drug's therapeutic index by delivering the drugs directly to the cells' nuclei, one of the key organelles in the cells. This study is likely to initiate research in targeted nuclear delivery using other drug formulations in other types of cancers.

  18. PLGA-carbon nanotube conjugates for intercellular delivery of caspase-3 into osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Qingsu Cheng

    Full Text Available 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.

  19. Drug delivery systems and materials for wound healing applications.

    Science.gov (United States)

    Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

    2018-04-05

    Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Recent trends in drug delivery system using protein nanoparticles.

    Science.gov (United States)

    Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

    2014-09-01

    Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.

  1. Carrier-Based Drug Delivery System for Treatment of Acne

    Science.gov (United States)

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  2. Engaging Faculty in Telecommunications-Based Instructional Delivery Systems.

    Science.gov (United States)

    Swalec, John J.

    In the design and development of telecommunications-based instructional delivery systems, attention to faculty involvement and training is often overlooked until the system is operational. The Waubonsee Telecommunications Instructional Consortium (TIC), in Illinois, is one network that benefited from early faculty input. Even before the first…

  3. An experimental platform for systemic drug delivery to the retina.

    LENUS (Irish Health Repository)

    Campbell, Matthew

    2009-10-20

    Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-\\/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

  4. Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

    Science.gov (United States)

    Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

    1988-01-01

    A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time intervals from 0.5 to 96 hours in cornea, sclera, and conjunctiva and at six time intervals from 0.5 to 12 hours in aqueous. Two peak concentrations were noted at approximately one and eight hours, with measurable levels present at 96 hours. This study demonstrates the ability of this liposomal delivery system to prolong levels of 5-fluorouracial in normal pigmented rabbits. PMID:3179257

  5. A clinical perspective on mucoadhesive buccal drug delivery systems

    Science.gov (United States)

    Gilhotra, Ritu M; Ikram, Mohd; Srivastava, Sunny; Gilhotra, Neeraj

    2014-01-01

    Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems. PMID:24683406

  6. Safety design integrated in the building delivery system

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten

    2013-01-01

    . The purpose of this article is to demonstrate how safety and health can be integrated in the design phases integrated in the management delivery systems within construction, The method for the research was to go through the building delivery system step by step and create a normative description of what, when......In construction, it is important to view safety and health as an integrated part of the way that “designers” are working. The designers cowers architects, constructors, engineers and others who carry out their consulting services in the design phase of a construction project. The philosophy...... and how to fully integrate safety in each part of the process. The result is a concept and guideline including control forms for how to integrate safety design in the Building Delivery System plus what to do and when. The concept has been tested in an educational context. The practical value...

  7. Safety design integrated in the Building Delivery System

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten

    2012-01-01

    phases of the building delivery system by using the principle of the lean construction modelling. The method for the research was to go through the lean construction building delivery system step by step and create a normative description of what to do, when to do and how to do to fully integration...... of safety in each process. The group of participants who created the description had a high experience in a combination of research, safety and health in general and especial in construction and knowledge of the lean construction processes both from the clients perspective as well as from the designers...... and the consultants. The result is a concept and guideline including control schemes for how to integrate safety design in the lean construction building delivery system including what to do and when. The concept has been tested in an educational context and found useful by the designers. The practical value...

  8. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa

    2011-12-01

    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  9. Chemo-enzymatic Synthesis of Propionyl-ester-linked Taxol-monosaccharide Conjugate and its Drug Delivery System Using Hybrid-Bio-nanocapsules Targeting Brain Glioma Cells

    Directory of Open Access Journals (Sweden)

    Hiroki Hamada

    2013-01-01

    Full Text Available Taxol is recognized as one of the most potent anticancer agents used in the treatment of breast and ovarian cancers, which are common cancers in women. To overcome its shortcomings, that is, its low water-solubility that reduces drug loading capacity of DDS carriers when incorporating taxol, chemo-enzymatic synthesis of ester-linked taxol-glucose conjugate, i.e., 7-propionyltaxol 2′- O -α-D-glucoside, as a water soluble taxol prodrug was achieved by using a-glucosidase as a glucosylation catalyst. The water-solubility of 7-propionyltaxol 2′- O -α-D-glucoside (25 mM was 63 fold higher than that of taxol (0.4 mM. The pre-S1 peptide which displays on the surface of bio-nanocapsules, which are nanoparticles composed of the hepatitis B virus surface antigen, was replaced with the antibody affinity motif of protein A. Conjugation of such bio-nanocapsules with anti-human epidermal growth factor receptor antibody gave hybrid bio-nanocapsules. The hybrid bio-nanocapsules were effective for delivering 7-propionyltaxol 2′- O -α-D-glucoside to human brain glioma cells. 7-Propionyltaxol 2′- O -α-D-glucoside was effectively hydrolyzed to give taxol in 95% by human glioma cells. The drug loading capacity of hybrid bio-nanocapsules incorporating 7-propionyltaxol 2′- O -α-D-glucoside was 120 times higher than that incorporating taxol itself.

  10. Oral delivery of peptides and proteins using lipid-based drug delivery systems.

    Science.gov (United States)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-10-01

    In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.

  11. Buccoadhesive drug delivery systems--extensive review on recent patents.

    Science.gov (United States)

    Pathan, Shadab A; Iqbal, Zeenat; Sahani, Jasjeet K; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.

  12. Efficiency performance of China's health care delivery system.

    Science.gov (United States)

    Zhang, Luyu; Cheng, Gang; Song, Suhang; Yuan, Beibei; Zhu, Weiming; He, Li; Ma, Xiaochen; Meng, Qingyue

    2017-07-01

    Improving efficiency performance of the health care delivery system has been on the agenda for the health system reform that China initiated in 2009. This study examines the changes in efficiency performance and determinants of efficiency after the reform to provide evidence to assess the progress of the reform from the perspective of efficiency. Descriptive analysis, Data Envelopment Analysis, the Malmquist Index, and multilevel regressions are used with data from multiple sources, including the World Bank, the China Health Statistical Yearbook, and routine reports. The results indicate that over the last decade, health outcomes compared with health investment were relatively higher in China than in most other countries worldwide, and the trend was stable. The overall efficiency and total factor productivity increased after the reform, indicating that the reform was likely to have had a positive impact on the efficiency performance of the health care delivery system. However, the health care delivery structure showed low system efficiency, mainly attributed to the weakened primary health care system. Strengthening the primary health care system is central to enhancing the future performance of China's health care delivery system. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review

    Science.gov (United States)

    Dubald, Marion; Bourgeois, Sandrine; Andrieu, Véronique; Fessi, Hatem

    2018-01-01

    The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites. PMID:29342879

  14. Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review

    Directory of Open Access Journals (Sweden)

    Marion Dubald

    2018-01-01

    Full Text Available The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.

  15. NOVEL APROACHES ON BUCCAL MUCOADHESIVE DRUG DELIVERY SYSTEM

    OpenAIRE

    Dibyalochan Mohanty* , C. Gurulatha, Dr.Vasudha Bakshi, B. Mavya

    2018-01-01

    Among novel drug delivery system ,Buccal mucoadhesive systems have attracted great attention in recent years due to their ability to adhere and remain on the oral mucosa and to release their drug content gradually ,bioadhesion refers to any bond formed between two biological surface or a bond between a biological and a systemic surface. Buccal mucosa is preferred for both systemic and local drug action. The mucosa has a rich blood supply and it relatively permeable. Buccal mucoadhesive films ...

  16. A real-time virtual delivery system for photon radiotherapy delivery monitoring

    Directory of Open Access Journals (Sweden)

    Feng Shi

    2014-03-01

    Full Text Available Purpose: Treatment delivery monitoring is important for radiotherapy, which enables catching dosimetric error at the earliest possible opportunity. This project develops a virtual delivery system to monitor the dose delivery process of photon radiotherapy in real-time using GPU-based Monte Carlo (MC method.Methods: The simulation process consists of 3 parallel CPU threads. A thread T1 is responsible for communication with a linac, which acquires a set of linac status parameters, e.g. gantry angles, MLC configurations, and beam MUs every 20 ms. Since linac vendors currently do not offer interface to acquire data in real time, we mimic this process by fetching information from a linac dynalog file at the set frequency. Instantaneous beam fluence map (FM is calculated based. A FM buffer is also created in T1 and the instantaneous FM is accumulated to it. This process continues, until a ready signal is received from thread T2 on which an in-house developed MC dose engine executes on GPU. At that moment, the accumulated FM is transferred to T2 for dose calculations, and the FM buffer in T1 is cleared. Once the dose calculation finishes, the resulting 3D dose distribution is directed to thread T3, which displays it in three orthogonal planes in color wash overlaid on the CT image. This process continues to monitor the 3D dose distribution in real-time.Results: An IMRT and a VMAT cases used in our patient-specific QA are studied. Maximum dose differences between our system and treatment planning system are 0.98% and 1.58% for the IMRT and VMAT cases, respectively. The update frequency is >10Hz and the relative uncertainty level is 2%.Conclusion: By embedding a GPU-based MC code in a novel data/work flow, it is possible to achieve real-time MC dose calculations to monitor delivery process.------------------------------Cite this article as: Shi F, Gu X, Graves YJ, Jiang S, Jia X. A real-time virtual delivery system for photon radiotherapy delivery

  17. Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

    Science.gov (United States)

    Goswami, Tarun; Audett, Jay

    2015-01-01

    Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

  18. Adamantane in Drug Delivery Systems and Surface Recognition.

    Science.gov (United States)

    Štimac, Adela; Šekutor, Marina; Mlinarić-Majerski, Kata; Frkanec, Leo; Frkanec, Ruža

    2017-02-16

    The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application.

  19. Adamantane in Drug Delivery Systems and Surface Recognition

    Directory of Open Access Journals (Sweden)

    Adela Štimac

    2017-02-01

    Full Text Available The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application.

  20. Nanocomposites chitosan/montmorillonite for drug delivery system

    International Nuclear Information System (INIS)

    Braga, Carla R. Costa; Barbosa, Rossemberg C.; Lima, Rosemary S. Cunha; Fook, Marcus V. Lia; Silva, Suedina M. Lima

    2009-01-01

    In drugs delivery system the incorporation of an inorganic nanophase in polymer matrix, i.e. production of an inorganic-organic nanocomposite is an attractive alternative to obtain a constant release rate for a prolonged time. This study was performed to obtain films of nanocomposites Chitosan/montmorillonite intercalation by the technique of solution in the proportions of 1:1, 5:1 and 10:1. The nanocomposites were characterized by infrared spectroscopy, X-ray diffraction and thermogravimetric analysis. The results indicated that the feasibility of obtaining films of nanocomposites exfoliate. Among the suggested applications for films developed in this study includes them use for drugs delivery system. (author)

  1. Process development work plan for waste feed delivery system

    International Nuclear Information System (INIS)

    Papp, I.G.

    1998-01-01

    This work plan defines the process used to develop project definition for Waste Feed Delivery (WFD). Project definition provides the direction for development of definitive design media required for the ultimate implementation of operational processing hardware and software. Outlines for the major deliverables are attached as appendices. The implementation of hardware and software will accommodate requirements for safe retrieval and delivery of waste currently stored in Hanford's underground storage tanks. Operations and maintenance ensure the availability of systems, structures, and components for current and future planned operations within the boundary of the Tank Waste Remediation System (TWRS) authorization basis

  2. An improved delivery system for bladder irrigation.

    Science.gov (United States)

    Moslemi, Mohammad K; Rajaei, Mojtaba

    2010-10-05

    Occasionally, urologists may see patients requiring temporary bladder irrigation at hospitals without stocks of specialist irrigation apparatus. One option is to transfer the patient to a urology ward, but often there are outstanding medical issues that require continued specialist input. Here, we describe an improved system for delivering temporary bladder irrigation by utilizing readily available components and the novel modification of a sphygmomanometer blub. This option is good for bladder irrigation in patients with moderate or severe gross hematuria due to various causes. In this prospective study from March 2007 to April 2009, we used our new system in eligible cases. In this system, an irrigant bag with 1 L of normal saline was suspended 80 cm above the indwelled 3-way Foley catheter, and its drainage tube was inserted into the irrigant port of the catheter. To increase the flow rate of the irrigant system, we inserted a traditional sphygmomanometer bulb at the top of the irrigant bag. This closed system was used for continuous bladder irrigation (CBI) in patients who underwent open prostatectomy, transurethral resection of the prostate (TURP), or transurethral resection of the bladder (TURB). This high-pressure system is also used for irrigation during cystourethroscopy, internal urethrotomy, and transurethral lithotripsy. Our 831 eligible cases were divided into two groups: group 1 were endourologic cases and group 2 were open prostatectomy, TURP, and TURB cases. The maximum and average flow rates were evaluated. The efficacy of our new system was compared prospectively with the previous traditional system used in 545 cases. In group 1, we had clear vision at the time of endourologic procedures. The success rate of this system was 99.5%. In group 2, the incidence of clot retention decreased two fold in comparison to traditional gravity-dependent bladder flow system. These changes were statistically significant (P = 0.001). We did not observe any adverse

  3. Chitosan and Glyceryl Monooleate Nanostructures Containing Gemcitabine: Potential Delivery System for Pancreatic Cancer Treatment

    OpenAIRE

    Trickler, William J.; Khurana, Jatin; Nagvekar, Ankita A.; Dash, Alekha K.

    2010-01-01

    The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytot...

  4. FORMULATION AND EVALUATION OF FLOATING DRUG DELIVERY SYSTEM OF AMOXYCILLIN TRIHYDRATE

    OpenAIRE

    Marella Radhakrishna; K.G.Parthiban; Nelluri Ramarao; Nagapuri Santhoshi Deepika; Perumulla Abhishek

    2012-01-01

    The present study was designed to formulate and evaluate balanced Floating Drug Delivery Systems as controlled release modules, which prolongs the release rate of the drugs. Amoxycillin is an anti- bacterial acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell walls of both Gram-positive and Gram-negative bacteria. Helicobacter pylori exists in the gastric mucous layer or ...

  5. Mercury sorbent delivery system for flue gas

    Science.gov (United States)

    Klunder,; Edgar, B [Bethel Park, PA

    2009-02-24

    The invention presents a device for the removal of elemental mercury from flue gas streams utilizing a layer of activated carbon particles contained within the filter fabric of a filter bag for use in a flue gas scrubbing system.

  6. Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

    Science.gov (United States)

    Zhu, Yu

    Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

  7. Cell-based delivery of oncolytic viruses: a new strategic alliance for a biological strike against cancer.

    Science.gov (United States)

    Power, Anthony T; Bell, John C

    2007-04-01

    Recent years have seen tremendous advances in the development of exquisitely targeted replicating virotherapeutics that can safely destroy malignant cells. Despite this promise, clinical advancement of this powerful and unique approach has been hindered by vulnerability to host defenses and inefficient systemic delivery. However, it now appears that delivery of oncolytic viruses within carrier cells may offer one solution to this critical problem. In this review, we compare the advantages and limitations of the numerous cell lineages that have been investigated as delivery platforms for viral therapeutics, and discuss examples showing how combined cell-virus biotherapeutics can be used to achieve synergistic gains in antitumor activity. Finally, we highlight avenues for future preclinical research that might be taken in order to refine cell-virus biotherapeutics in preparation for human trials.

  8. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

    Science.gov (United States)

    Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

    2005-05-01

    Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

  9. Self-emulsifying drug delivery systems: Design of a novel vaginal delivery system for curcumin.

    Science.gov (United States)

    Köllner, S; Nardin, I; Markt, R; Griesser, J; Prüfert, F; Bernkop-Schnürch, A

    2017-06-01

    The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization. The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS. Additionally to mucus binding studies, permeation studies in the mucus were performed. Furthermore, spreading potential of the novel developed formulations was compared with a commercial available o/w cream (non-ionic hydrophilic cream) on vaginal mucosa. SEDDS displayed a mean droplet size between 38 and 141nm and a zeta potential of -0.3 to -1.6mV. The collagen swelling test indicated no significant irritation potential of both formulations over 24h. An immediate interaction of unformulated curcumin with the mucus was determined, whereas both SEDDS facilitated drug permeation through the mucus layer. Formulation B showed a 2.2-fold improved transport ratio of curcumin compared to SEDD formulation A. In comparison to the vaginal cream, SEDD formulation A and B were able to spread over the vaginal mucosa and cover the tissue to a 17.8- and 14.8-fold higher extent, respectively. According to these results, SEDDS seems to be a promising tool for vaginal application. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  11. RaPToRS Sample Delivery System

    Science.gov (United States)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  12. Application of mathematical modeling in sustained release delivery systems.

    Science.gov (United States)

    Grassi, Mario; Grassi, Gabriele

    2014-08-01

    This review, presenting as starting point the concept of the mathematical modeling, is aimed at the physical and mathematical description of the most important mechanisms regulating drug delivery from matrix systems. The precise knowledge of the delivery mechanisms allows us to set up powerful mathematical models which, in turn, are essential for the design and optimization of appropriate drug delivery systems. The fundamental mechanisms for drug delivery from matrices are represented by drug diffusion, matrix swelling, matrix erosion, drug dissolution with possible recrystallization (e.g., as in the case of amorphous and nanocrystalline drugs), initial drug distribution inside the matrix, matrix geometry, matrix size distribution (in the case of spherical matrices of different diameter) and osmotic pressure. Depending on matrix characteristics, the above-reported variables may play a different role in drug delivery; thus the mathematical model needs to be built solely on the most relevant mechanisms of the particular matrix considered. Despite the somewhat diffident behavior of the industrial world, in the light of the most recent findings, we believe that mathematical modeling may have a tremendous potential impact in the pharmaceutical field. We do believe that mathematical modeling will be more and more important in the future especially in the light of the rapid advent of personalized medicine, a novel therapeutic approach intended to treat each single patient instead of the 'average' patient.

  13. Review of Innovative Sediment Delivery Systems

    Science.gov (United States)

    2013-04-01

    Alternative conveyor belt systems appear to be available from the growing hydraulic fracturing ( fracking , shale gas recovery) industry, which use...tons of aggregate material (with diameters up to 2 in.) per hour. This equates to roughly 150 cu yd per hr, de- pending on sand density. As fracking

  14. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  15. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    Directory of Open Access Journals (Sweden)

    Reshmy Rajan

    2011-01-01

    Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.

  16. Optical separation and controllable delivery of cells from particle and cell mixture

    Directory of Open Access Journals (Sweden)

    Li Yuchao

    2015-11-01

    Full Text Available Cell separation and delivery have recently gained significant attention in biological and biochemical studies. In thiswork, an optical method for separation and controllable delivery of cells by using an abruptly tapered fiber probe is reported. By launching a laser beam at the wavelength of 980 nm into the fiber, a mixture of cells with sizes of ~5 and ~3 μm and poly(methyl methacrylate particles with size of 5 μm are separated into three chains along the direction of propagation of light. The cell and particle chains are delivered in three dimensions over 600 μm distance. Experimental results are interpreted by numerical simulations. Optical forces and forward migration velocities of different particles and cells are calculated and discussed.

  17. Direct current power delivery system and method

    Science.gov (United States)

    Zhang, Di; Garces, Luis Jose; Dai, Jian; Lai, Rixin

    2016-09-06

    A power transmission system includes a first unit for carrying out the steps of receiving high voltage direct current (HVDC) power from an HVDC power line, generating an alternating current (AC) component indicative of a status of the first unit, and adding the AC component to the HVDC power line. Further, the power transmission system includes a second unit for carrying out the steps of generating a direct current (DC) voltage to transfer the HVDC power on the HVDC power line, wherein the HVDC power line is coupled between the first unit and the second unit, detecting a presence or an absence of the added AC component in the HVDC power line, and determining the status of the first unit based on the added AC component.

  18. Buccal Drug Delivery System: A Review

    OpenAIRE

    Parth S. Patel; Ashish M. Parmar; Nilang S. Doshi; Hardik V. Patel; Raxit R. Patel; Chetan Nayee

    2013-01-01

    Bioadhesion can be defined as a phenomenon of interfacial molecular attractive forces in the midst of the surfaces of the biological substrate and the natural or synthetic polymers, which allows the polymer to adhere to the biological surface for an extended period of time. Bioadhesive polymeric systems have been used since extent in the development of products for various biomedical applications which include denture adhesives and surgical glue.Considerable attention has been focused in rece...

  19. Initial observations of cell-mediated drug delivery to the deep lung.

    Science.gov (United States)

    Kumar, Arun; Glaum, Mark; El-Badri, Nagwa; Mohapatra, Shyam; Haller, Edward; Park, Seungjoo; Patrick, Leslie; Nattkemper, Leigh; Vo, Dawn; Cameron, Don F

    2011-01-01

    Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (∼90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.

  20. Pricing strategies for capitated delivery systems

    Science.gov (United States)

    Gruenberg, Leonard; Wallack, Stanley S.; Tompkins, Christopher P.

    1986-01-01

    This article discusses alternative methods for establishing a fairer pricing mechanism for Medicare recipients who enroll in health maintenance organizations and other competitive medical plans. The current method, based upon the adjusted average per capita cost, is inadequate because it fails to adjust premium levels for differences in health status; it establishes undesirable incentives that may lead to underservice, and it is tied to costs in the fee-for-service system. Alternative methods would incorporate health status, have Medicare share the risk with HMO's, and base payment on HMO experience. PMID:10311925

  1. Fluorescent graphene quantum dots as traceable, pH-sensitive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Qiu J

    2015-10-01

    Full Text Available Jichuan Qiu,1 Ruibin Zhang,2 Jianhua Li,1 Yuanhua Sang,1 Wei Tang,3 Pilar Rivera Gil,4 Hong Liu1,51Center of Bio and Micro/Nano Functional Materials, State Key Laboratory of Crystal Materials, Shandong University, 2Blood Purification Center, Jinan Central Hospital, 3Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, People’s Republic of China; 4Institute of Chemistry, Rovira i Virgili University, Tarragona, Spain; 5Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaAbstract: Graphene quantum dots (GQDs were rationally fabricated as a traceable drug delivery system for the targeted, pH-sensitive delivery of a chemotherapeutic drug into cancer cells. The GQDs served as fluorescent carriers for a well-known anticancer drug, doxorubicin (Dox. The whole system has the capacity for simultaneous tracking of the carrier and of drug release. Dox release is triggered upon acidification of the intracellular vesicles, where the carriers are located after their uptake by cancer cells. Further functionalization of the loaded carriers with targeting moieties such as arginine-glycine-aspartic acid (RGD peptides enhanced their uptake by cancer cells. DU-145 and PC-3 human prostate cancer cell lines were used to evaluate the anticancer ability of Dox-loaded RGD-modified GQDs (Dox-RGD-GQDs. The results demonstrated the feasibility of using GQDs as traceable drug delivery systems with the ability for the pH-triggered delivery of drugs into target cells.Keywords: graphene quantum dots, drug delivery, pH-sensitive, controlled release, traceable

  2. Printing technologies in fabrication of drug delivery systems.

    Science.gov (United States)

    Kolakovic, Ruzica; Viitala, Tapani; Ihalainen, Petri; Genina, Natalja; Peltonen, Jouko; Sandler, Niklas

    2013-12-01

    There has been increased activity in the field recently regarding the development and research on various printing techniques in fabrication of dosage forms and drug delivery systems. These technologies may offer benefits and flexibility in manufacturing, potentially paving the way for personalized dosing and tailor-made dosage forms. In this review, the most recent observations and advancements in fabrication of drug delivery systems by utilizing printing technologies are summarized. A general overview of 2D printing techniques is presented including a review of the most recent literature where printing techniques are used in fabrication of drug delivery systems. The future perspectives and possible impacts on formulation strategies, flexible dosing and personalized medication of using printing techniques for fabrication of drug delivery systems are discussed. It is evident that there is an urgent need to meet the challenges of rapidly growing trend of personalization of medicines through development of flexible drug-manufacturing approaches. In this context, various printing technologies, such as inkjet and flexography, can play an important role. Challenges on different levels exist and include: i) technological development of printers and production lines; ii) printable formulations and carrier substrates; iii) quality control and characterization; and iv) regulatory perspectives.

  3. Student Attitudes toward Information Systems Graduate Program Design and Delivery

    Science.gov (United States)

    Thouin, Mark F.; Hefley, William E.; Raghunathan, Srinivasan

    2018-01-01

    This study examines student preferences regarding graduate management information systems (MIS) education. One hundred and eighty four graduate students responded to a survey exploring student attitudes towards degree program content, delivery format, and peer group interaction. Study results indicate that students prefer a program with an even…

  4. Development of a Gastroretentive Drug Delivery System based on ...

    African Journals Online (AJOL)

    Erah

    Purpose: The aim of this work was to synthesize superporous hydrogels of rosiglitazone using chitosan and to study its swelling behaviour for application as a gastroretentive drug delivery system. Methods: Chitosan superporous hydrogels were synthesized using glyoxal as a crosslinking agent by gas blowing method.

  5. Safe Active Scanning for Energy Delivery Systems Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Helms, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Salazar, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Scheibel, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Engels, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reiger, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-09-30

    The Department of Energy’s Cybersecurity for Energy Delivery Systems Program has funded Safe(r) Active Scanning for Energy Delivery Systems, led by Lawrence Livermore National Laboratory, to investigate and analyze the impacts of active scanning in the operational environment of energy delivery systems. In collaboration with Pacific Northwest National Laboratory and Idaho National Laboratory, active scans across three testbeds including 38 devices were performed. This report gives a summary of the initial literature survey performed on the SASEDS project as well as industry partner interview summaries and main findings from Phase 1 of the project. Additionally, the report goes into the details of scanning techniques, methodologies for testing, testbed descriptions, and scanning results, with appendices to elaborate on the specific scans that were performed. As a result of testing, a single device out of 38 exhibited problems when actively scanned, and a reboot was required to fix it. This single failure indicates that active scanning is not likely to have a detrimental effect on the safety and resilience of energy delivery systems. We provide a path forward for future research that could enable wide adoption of active scanning and lead utilities to incorporate active scanning as part of their default network security plans to discover and rectify rogue devices, adversaries, and services that may be on the network. This increased network visibility will allow operational technology cybersecurity practitioners to improve their situational awareness of networks and their vulnerabilities.

  6. Targeted nanodrug delivery systems for the treatment of Tuberculosis

    CSIR Research Space (South Africa)

    Lemmer, Yolandy

    2010-06-01

    Full Text Available patient treatment compliance and drug resistance pose a great challenge to TB treatment programs worldwide. To improve the current inadequate therapeutic management of TB, a polymeric anti-TB nanodrug delivery system for anti-TB drugs was developed...

  7. Online Instruction: An Alternative Delivery System for Higher Education

    Science.gov (United States)

    Wronkovich, Michael

    2003-01-01

    In an increasingly technological society, delivery systems for professional development and higher education have greatly expanded. Video conferencing and web-based alternatives provide opportunities to extend the college campus far beyond the boundaries traditionally considered feasible. Adult learners have found the convenience of web-based…

  8. Printing technologies in fabrication of drug delivery systems

    DEFF Research Database (Denmark)

    Kolakovic, Ruzica; Viitala, Tapani; Ihalainen, Petri

    2013-01-01

    INTRODUCTION: There has been increased activity in the field recently regarding the development and research on various printing techniques in fabrication of dosage forms and drug delivery systems. These technologies may offer benefits and flexibility in manufacturing, potentially paving the way...... for personalized dosing and tailor-made dosage forms.\

  9. Bioinspired silica as drug delivery systems and their biocompatibility

    DEFF Research Database (Denmark)

    Steven, Christopher R.; Busby, Grahame A.; Mather, Craig

    2014-01-01

    Silica nanoparticles have been shown to have great potential as drug delivery systems (DDS), however, their fabrication often involves harsh chemicals and energy intensive laborious methods. This work details the employment of a bioinspired "green" method for the controlled synthesis of silica, use...

  10. Quality of experience management in mobile content delivery systems

    NARCIS (Netherlands)

    Agboma, F.; Liotta, A.

    2012-01-01

    This study contributes towards the relatively new but growing discipline of QoE management in content delivery systems. The study focuses on the development of a QoE-based management framework for the construction of QoE models for different types of multimedia contents delivered onto three typical

  11. Polarimeters and energy spectrometers for the ILC beam delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Boogert, S. [London Univ. (United Kingdom). Royal Holloway; Hildreth, M. [Univ. of Notre Dame (United States); Kaefer, K. [DESY, Hamburg (Germany); DESY, Zeuthen (DE)] (and others)

    2009-02-15

    This article gives an overview of current plans and issues for polarimeters and energy spectrometers in the Beam Delivery System of the ILC. It is meant to serve as a useful reference for the Detector Letter of Intent documents currently being prepared. (orig.)

  12. Magnetic microspheres as magical novel drug delivery system: A review

    Directory of Open Access Journals (Sweden)

    Satinder Kakar

    2013-01-01

    Full Text Available Magnetic microspheres hold great promise for reaching the goal of controlled and site specific drug delivery. Magnetic microspheres as an alternative to traditional radiation methods which uses highly penetrating radiations that is absorbed throughout the body. Its use is limited by toxicity and side effects. Now days, several targeted treatment systems including magnetic field, electric field, ultrasound, temperature, UV light and mechanical force are being used in many disease treatments (e.g. cancer, nerve damage, heart and artery, anti-diabetic, eye and other medical treatments. Among them, the magnetic targeted drug delivery system is one of the most attractive and promising strategy for delivering the drug to the specified site. Magnetically controlled drug targeting is one of the various possible ways of drug targeting. This technology is based on binding establish anticancer drug with ferrofluid that concentrate the drug in the area of interest (tumor site by means of magnetic fields. There has been keen interest in the development of a magnetically target drug delivery system. These drug delivery systems aim to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the activity entity to the site of action. Magnetic microspheres were developed to overcome two major problems encountered in drug targeting namely: RES clearance and target site specificity.

  13. Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine.

    Science.gov (United States)

    Wu, Xiuwen; Ren, Jianan; Li, Jieshou

    2012-05-01

    The use of tissue-engineering techniques such as stem-cell therapy to renew injured tissues is a promising strategy in regenerative medicine. As a cell-delivery vehicle, fibrin glues (FG) facilitate cell attachment, growth and differentiation and, ultimately, tissue formation and organization by its three-dimensional structure. Numerous studies have provided evidence that stromal cells derived from bone marrow (bone marrow stromal cells; BMSC) and adipose tissue (adipose-derived stromal cells; ADSC) contain a population of adult multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells that can differentiate into several lineages. By combining MSC with FG, the implantation could take advantage of the mutual benefits. Researchers and physicians have pinned their hopes on stem cells for developing novel approaches in regenerative medicine. This review focuses on the therapeutic potential of MSC with FG in bone defect reconstruction, cartilage and tendon injury repair, ligament, heart and nerve regeneration, and, furthermore, wound healing.

  14. Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Inge L. Huibregtse

    2012-01-01

    Full Text Available Interleukin-10 (IL-10 plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.  lactisIL-10 on DC function in vitro. Monocyte-derived DC incubated with L.  lactisIL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L.  lactisIL-10-derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L.  lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases.

  15. Film forming systems for topical and transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Kashmira Kathe

    2017-11-01

    Full Text Available Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions along with their evaluation parameters have also been reviewed.

  16. Drug delivery systems with modified release for systemic and biophase bioavailability.

    Science.gov (United States)

    Leucuta, Sorin E

    2012-11-01

    This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

  17. A high-density lipoprotein-mediated drug delivery system.

    Science.gov (United States)

    Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

    2016-11-15

    High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A commentary on transdermal drug delivery systems in clinical trials.

    Science.gov (United States)

    Watkinson, Adam C

    2013-09-01

    The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

  19. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    Science.gov (United States)

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  20. Dendrimer advances for the central nervous system delivery of therapeutics.

    Science.gov (United States)

    Xu, Leyuan; Zhang, Hao; Wu, Yue

    2014-01-15

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

  1. Application of nanohydrogels in drug delivery systems: recent patents review.

    Science.gov (United States)

    Dalwadi, Chintan; Patel, Gayatri

    2015-01-01

    Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.

  2. Significant role of cationic polymers in drug delivery systems.

    Science.gov (United States)

    Farshbaf, Masoud; Davaran, Soodabeh; Zarebkohan, Amir; Annabi, Nasim; Akbarzadeh, Abolfazl; Salehi, Roya

    2017-11-06

    Cationic polymers are characterized as the macromolecules that possess positive charges, which can be either inherently in the polymer side chains and/or its backbone. Based on their origins, cationic polymers are divided in two category including natural and synthetic, in which the possessed positive charges are as result of primary, secondary or tertiary amine functional groups that could be protonated in particular situations. Cationic polymers have been employed commonly as drug delivery agents due to their superior encapsulation efficacy, enhanced bioavailability, low toxicity and improved release profile. In this paper, we focus on the most prominent examples of cationic polymers which have been revealed to be applicable in drug delivery systems and we also discuss their general synthesis and surface modification methods as well as their controlled release profile in drug delivery.

  3. Evaluation of Roadmap to Achieve Energy Delivery Systems Cybersecurity

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Adrian R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-10-01

    The Department of Energy/Office of Electricity Delivery and Energy Reliability (DOE/OE) Cybersecurity for Energy Delivery Systems (CEDS) program is currently evaluating the Roadmap to Achieve Energy Delivery Systems Cybersecurity document that sets a vision and outlines a set of milestones. The milestones are divided into five strategic focus areas that include: 1. Build a Culture of Security; 2. Assess and Monitor Risk; 3. Develop and Implement New Protective Measures to Reduce Risk; 4. Manage Incidents; and 5. Sustain Security Improvements. The most current version of the roadmap was last updated in September of 2016. Sandia National Laboratories (SNL) has been tasked with revisiting the roadmap to update the current state of energy delivery systems cybersecurity protections. SNL is currently working with previous and current partners to provide feedback on which of the roadmap milestones have been met and to identify any preexisting or new gaps that are not addressed by the roadmap. The specific focus areas SNL was asked to evaluate are: 1. Develop and Implement New Protective Measures to Reduce Risk and 2. Sustain Security Improvements. SNL has formed an Industry Advisory Board (IAB) to assist in answering these questions. The IAB consists of previous partners on past CEDS funded efforts as well as new collaborators that have unique insights into the current state of cybersecurity within energy delivery systems. The IAB includes asset owners, utilities and vendors of control systems. SNL will continue to maintain regular communications with the IAB to provide various perspectives on potential future updates to further improve the breadth of cybersecurity coverage of the roadmap.

  4. DNA-templated antibody conjugation for targeted drug delivery to cancer cells

    DEFF Research Database (Denmark)

    Liu, Tianqiang

    2016-01-01

    -templated organic synthesis due to the wide existence of the 3-histidine cluster in most wild-type proteins. In this thesis, three projects that relate to targeted drug delivery to cancer cells based on the DTPC method is described. The first project was a delivery system which uses transferrin as the targeting....... The study shows that DNA is a highly useful tool for the assembly of proteins with potential therapeutic applications. The DNA-templated protein conjugation shows a promising application in constructing antibody-toxin conjugates or antibody-drug conjugates. In addition, DNA strands used for antibody...... either antibody engineering or special expression systems and are both time and labor consuming. To avoid the drawbacks caused by conventional chemical modification and recombinant methodologies, an ideal site specific conjugation technique would use natural amino acid residues to the protein by a new...

  5. Integrated delivery systems: mergers and acquisitions.

    Science.gov (United States)

    Pinkerton, S

    1999-01-01

    Mergers and acquisitions are usually the way an IDS is built. The CNO and/or CNOs/DONs have an integral role in the resolution of the M/A process. During this time of significant change, during which there may even be chaos, the CNOs work to maintain stability so there is as little impact as possible on patient outcomes, a core responsibility of the CNOs. The CNOs should focus on identifying and working with the highly skilled individuals in the organization to get to the recovery stage of the M/A process, at which time a high-performing organization is achieved. To build this new organization or IDS, the old organizations of the M/A must be changed (Moss Kanter, 1994). The successful CNOs will manage the trade-offs and will become experts in collaboration. The CNO's goals are to maximize the quality of patient care, the professional satisfaction of the nurse, and the goals of achieving cost effectiveness for the system (Clifford, 1998), and keeping this focus through the M/A process will yield success.

  6. Nanoparticle-based drug delivery systems: promising approaches against infections

    Energy Technology Data Exchange (ETDEWEB)

    Ranghar, Shweta; Sirohi, Parul [Department of Applied Mechanics, Motilal Nehru National Institute of Technology, Allahabad (India); Verma, Pritam; Agarwal, Vishnu [Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad (India)

    2014-03-15

    Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

  7. Nanoparticle-based drug delivery systems: promising approaches against infections

    International Nuclear Information System (INIS)

    Ranghar, Shweta; Sirohi, Parul; Verma, Pritam; Agarwal, Vishnu

    2014-01-01

    Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

  8. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Alka Lohani

    2014-01-01

    Full Text Available Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs.

  9. [Research progress on a nanodrug delivery system for prevention and control of dental caries and periodontal diseases].

    Science.gov (United States)

    Yaling, Jiang; Mingye, Feng; Lei, Cheng

    2017-02-01

    Dental caries and periodontal diseases are common chronic infectious diseases that cause serious damage to oral health. Bacteria is the primary factor leading to such conditions. As a dental plaque control method, chemotherapeutic agents face serious challenges in dental care because of the specific physiological and anatomical characteristics of the oral cavity. Nanodrug delivery system is a series of new drug delivery systems at nanoscale, and it can target cells, promote sustainedrelease effects, and enhance biodegradation. This review focuses on research progress on nanodrug delivery systems for prevention and control of dental caries and periodontal diseases.

  10. Cell-based delivery of glucagon-like peptide-1 using encapsulated mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wallrapp, Christine; Thoenes, Eric; Thürmer, Frank

    2013-01-01

    Glucagon-like peptide-1 (GLP-1) CellBeads are cell-based implants for the sustained local delivery of bioactive factors. They consist of GLP-1 secreting mesenchymal stem cells encapsulated in a spherically shaped immuno-isolating alginate matrix. A highly standardized and reproducible encapsulation...... and quality control is performed in compliance with good manufacturing practice and fulfils all regulatory requirements for human clinical use. GLP-1 CellBeads combine the neuro- and cardioprotective properties of both GLP-1 and mesenchymal stem cells. First promising results were obtained from preclinical...... method is described for the manufacturing of homogeneous CellBeads. Viability and sustained secretion was shown for the recombinant GLP-1 and the cell endogenous bioactive factors like vascular endothelial growth factor, neurotrophin 3 (NT-3) and glial cell line-derived neurotrophic factor. Manufacturing...

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

    Science.gov (United States)

    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.

  12. Immunocompatibility and biocompatibility of cell delivery systems

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka

    2000-01-01

    Roč. 42, č. 1 (2000), s. 65-80 ISSN 0169-409X R&D Projects: GA MZd NC5050; GA MPO PZ-Z2/24/97; GA AV ČR KSK2039602 Institutional research plan: CEZ:A53/98:Z5-020-9ii Subject RIV: EC - Immunology Impact factor: 2.406, year: 2000

  13. Use of radiopharmaceuticals in the development of drug delivery systems

    International Nuclear Information System (INIS)

    Frier, M.

    1997-01-01

    Full text. Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the Gl tract, the depth of penetration of a nebulized solution into the lung, or the residence time of a drug on the cornea. By using the gamma camera to image the in vivo distribution of pharmaceutical formulations radio labelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Example will be shown of studies which examine the rate of transit of orally-administered formulations through the GI tract, as well as describing the development of devices for specific targeting of drugs to the colon. Data will also demonstrate the effectiveness of devices such as spacers in pulmonary drug delivery, in both normal volunteers, and in asthmatic subjects. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers

  14. Dose error analysis for a scanned proton beam delivery system

    International Nuclear Information System (INIS)

    Coutrakon, G; Wang, N; Miller, D W; Yang, Y

    2010-01-01

    All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 x 10 x 8 cm 3 target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy.

  15. Excimer laser beam delivery systems for medical applications

    Science.gov (United States)

    Kubo, Uichi; Hashishin, Yuichi; Okada, Kazuyuki; Tanaka, Hiroyuki

    1993-05-01

    We have been doing the basic experiments of UV laser beams and biotissue interaction with both KrF and XeCl lasers. However, the conventional optical fiber can not be available for power UV beams. So we have been investigating about UV power beam delivery systems. These experiments carry on with the same elements doped quartz fibers and the hollow tube. The doped elements are OH ion, chlorine and fluorine. In our latest work, we have tried ArF excimer laser and biotissue interactions, and the beam delivery experiments. From our experimental results, we found that the ArF laser beam has high incision ability for hard biotissue. For example, in the case of the cow's bone incision, the incision depth by ArF laser was ca.15 times of KrF laser. Therefore, ArF laser would be expected to harden biotissue therapy as non-thermal method. However, its beam delivery is difficult to work in this time. We will develop ArF laser beam delivery systems.

  16. An emerging platform for drug delivery: aerogel based systems.

    Science.gov (United States)

    Ulker, Zeynep; Erkey, Can

    2014-03-10

    Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Nursing Services Delivery Theory: an open system approach.

    Science.gov (United States)

    Meyer, Raquel M; O'Brien-Pallas, Linda L

    2010-12-01

    This paper is a discussion of the derivation of the Nursing Services Delivery Theory from the application of open system theory to large-scale organizations. The underlying mechanisms by which staffing indicators influence outcomes remain under-theorized and unmeasured, resulting in a 'black box' that masks the nature and organization of nursing work. Theory linking nursing work, staffing, work environments, and outcomes in different settings is urgently needed to inform management decisions about the allocation of nurse staffing resources in organizations. A search of CINAHL and Business Source Premier for the years 1980-2008 was conducted using the following terms: theory, models, organization, organizational structure, management, administration, nursing units, and nursing. Seminal works were included. The healthcare organization is conceptualized as an open system characterized by energy transformation, a dynamic steady state, negative entropy, event cycles, negative feedback, differentiation, integration and coordination, and equifinality. The Nursing Services Delivery Theory proposes that input, throughput, and output factors interact dynamically to influence the global work demands placed on nursing work groups at the point of care in production subsystems. THE Nursing Services Delivery Theory can be applied to varied settings, cultures, and countries and supports the study of multi-level phenomena and cross-level effects. The Nursing Services Delivery Theory gives a relational structure for reconciling disparate streams of research related to nursing work, staffing, and work environments. The theory can guide future research and the management of nursing services in large-scale healthcare organizations. © 2010 Blackwell Publishing Ltd.

  18. Nursing Services Delivery Theory: an open system approach

    Science.gov (United States)

    Meyer, Raquel M; O’Brien-Pallas, Linda L

    2010-01-01

    meyer r.m. & o’brien-pallas l.l. (2010)Nursing services delivery theory: an open system approach. Journal of Advanced Nursing66(12), 2828–2838. Aim This paper is a discussion of the derivation of the Nursing Services Delivery Theory from the application of open system theory to large-scale organizations. Background The underlying mechanisms by which staffing indicators influence outcomes remain under-theorized and unmeasured, resulting in a ‘black box’ that masks the nature and organization of nursing work. Theory linking nursing work, staffing, work environments, and outcomes in different settings is urgently needed to inform management decisions about the allocation of nurse staffing resources in organizations. Data sources A search of CINAHL and Business Source Premier for the years 1980–2008 was conducted using the following terms: theory, models, organization, organizational structure, management, administration, nursing units, and nursing. Seminal works were included. Discussion The healthcare organization is conceptualized as an open system characterized by energy transformation, a dynamic steady state, negative entropy, event cycles, negative feedback, differentiation, integration and coordination, and equifinality. The Nursing Services Delivery Theory proposes that input, throughput, and output factors interact dynamically to influence the global work demands placed on nursing work groups at the point of care in production subsystems. Implications for nursing The Nursing Services Delivery Theory can be applied to varied settings, cultures, and countries and supports the study of multi-level phenomena and cross-level effects. Conclusion The Nursing Services Delivery Theory gives a relational structure for reconciling disparate streams of research related to nursing work, staffing, and work environments. The theory can guide future research and the management of nursing services in large-scale healthcare organizations. PMID:20831573

  19. Monolithic Controlled Delivery Systems: Part I. Basic Characteristics and Mechanisms

    Directory of Open Access Journals (Sweden)

    Rumiana Blagoeva

    2006-04-01

    Full Text Available The article considers contemporary systems for controlled delivery of active agents, such as drugs, agricultural chemicals, pollutants and additives in the environment. A useful classification of the available controlled release systems (CRS is proposed according to the type of control (passive, active or self-preprogrammed and according to the main controlling mechanism (diffusion, swelling, dissolution or erosion. Special attention is given to some of the most used CRS - polymer monoliths. The structural and physical-chemical characteristics of CRS as well as the basic approaches to their production are examined. The basic mechanisms of controlled agent release are reviewed in detail and factors influencing the release kinetics are classified according to their importance. The present study can be helpful for understanding and applying the available mathematical models and for developing more comprehensive ones intended for design of new controlled delivery systems.

  20. Chitosan-based delivery systems for diclofenac delivery: preparation and characterization

    International Nuclear Information System (INIS)

    Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil

    2009-01-01

    The preparation and characterization of novel materials for drug delivery has rapidly gained importance in development of innovative medicine. The paper concerns the uses of chitosan as an excipient in oral formulations and as a drug delivery vehicle for burnt painful injuries. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare liquid release systems as hydrogels and solid release systems as sponges is presented. In this paper the preparation of CTS hydrogels and sponges carrying diclofenac (DCF), as anti-inflammatory drug is reported. The immobilization of DCF in CTS is done by mixing the CTS hydrogel with the anti-inflammatory drug solutions. The concentration of anti-inflammatory drug in the CTS hydrogel generating the sponges was of 57 mg/l, 72 mg/l and 114 mg/l. The CTS sponges with anti-inflammatory drugs were prepared by freeze-drying at -610 0 C and 0,09 atm. The characterization of the hydrogels and sponges was done by infrared spectra (FTIR) and ultraviolet-visible spectroscopy (UV-VIS). The results indicated the formation of CTS-DCF intermediates. The DCF molecules are forming temporary chelates in CTS hydrogels and sponges and they are compatible with skin or some of biological fluids with satisfactory results.

  1. Chitosan-based delivery systems for diclofenac delivery: preparation and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil, E-mail: simina.dreve@itim-cj.r [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath, 400293 Cluj-Napoca (Romania)

    2009-08-01

    The preparation and characterization of novel materials for drug delivery has rapidly gained importance in development of innovative medicine. The paper concerns the uses of chitosan as an excipient in oral formulations and as a drug delivery vehicle for burnt painful injuries. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare liquid release systems as hydrogels and solid release systems as sponges is presented. In this paper the preparation of CTS hydrogels and sponges carrying diclofenac (DCF), as anti-inflammatory drug is reported. The immobilization of DCF in CTS is done by mixing the CTS hydrogel with the anti-inflammatory drug solutions. The concentration of anti-inflammatory drug in the CTS hydrogel generating the sponges was of 57 mg/l, 72 mg/l and 114 mg/l. The CTS sponges with anti-inflammatory drugs were prepared by freeze-drying at -610{sup 0}C and 0,09 atm. The characterization of the hydrogels and sponges was done by infrared spectra (FTIR) and ultraviolet-visible spectroscopy (UV-VIS). The results indicated the formation of CTS-DCF intermediates. The DCF molecules are forming temporary chelates in CTS hydrogels and sponges and they are compatible with skin or some of biological fluids with satisfactory results.

  2. Chitosan and glyceryl monooleate nanostructures containing gemcitabine: potential delivery system for pancreatic cancer treatment.

    Science.gov (United States)

    Trickler, William J; Khurana, Jatin; Nagvekar, Ankita A; Dash, Alekha K

    2010-03-01

    The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2 and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 +/- 28.6 nm, and 385.2 +/- 16.1 nm, respectively with a surface charge of +21.94 +/- 4.37 and +21.23 +/- 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone. The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic compounds to potentially provide an effective treatment option in human pancreatic cancer.

  3. Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

    Science.gov (United States)

    Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

    2017-09-10

    New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    Science.gov (United States)

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

  5. Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

    Science.gov (United States)

    Ruskowitz, Emily R.; Deforest, Cole A.

    2018-02-01

    Biological signalling is regulated through a complex and tightly choreographed interplay between cells and their extracellular matrix. The spatiotemporal control of these interactions is essential for tissue function, and disruptions to this dialogue often result in aberrant cell fate and disease. When disturbances are well understood, correct biological function can be restored through the precise introduction of therapeutics. Moreover, model systems with modifiable physiochemical properties are needed to probe the effects of therapeutic molecules and to investigate cell-matrix interactions. Photoresponsive biomaterials benefit from spatiotemporal tunability, which allows for site-specific therapeutic delivery in vivo and 4D modulation of synthetic cell culture platforms to mimic the dynamic heterogeneity of the human body in vitro. In this Review, we discuss how light can be exploited to modify different biomaterials in the context of photomediated drug delivery and phototunable cell culture platforms. We survey various photochemistries for their applicability in vitro and in vivo and for the biochemical and biophysical modification of materials. Finally, we highlight emerging tools and provide an outlook for the field of photoresponsive biomaterials.

  6. Nebuliser systems for drug delivery in cystic fibrosis.

    Science.gov (United States)

    Daniels, Tracey; Mills, Nicola; Whitaker, Paul

    2013-04-30

    Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing

  7. Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

    International Nuclear Information System (INIS)

    Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar; Singh, Satyawan

    2013-01-01

    Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

  8. Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

    Directory of Open Access Journals (Sweden)

    Swatantra Kumar Singh Kushwaha

    2013-12-01

    Full Text Available Carbon nanotubes (CNTs were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field.

  9. Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

    Energy Technology Data Exchange (ETDEWEB)

    Kushwaha, Swatantra Kumar Singh; Ghoshal, SauravI; Rai, Awani Kumar, E-mail: swatantrakushwaha@yahoo.co.in [Pranveer Singh Institute of Technology, Kanpur (India); Singh, Satyawan [Saroj Institute of Technology and Management, Lucknow (India)

    2013-10-15

    Carbon nanotubes (CNTs) were discovered in 1991 and shown to have certain unique physicochemical properties, attracting considerable interest in their application in various fields including drug delivery. The unique properties of CNTs such as ease of cellular uptake, high drug loading, thermal ablation, among others, render them useful for cancer therapy. Cancer is one of the most challenging diseases of modern times because its therapy involves distinguishing normal healthy cells from affected cells. Here, CNTs play a major role because phenomena such as EPR, allow CNTs to distinguish normal cells from affected ones, the Holy Grail in cancer therapy. Considerable work has been done on CNTs as drug delivery systems over the last two decades. However, concerns over certain issues such as biocompatibility and toxicity have been raised and warrant extensive research in this field. (author)

  10. Gamma- scintigraphy in the evaluation of drug delivery systems

    International Nuclear Information System (INIS)

    Shahhosseini, S.; Beiki, D.; Eftekhari, M.

    2003-01-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical delivery systems, particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate radionuclide such as technetium-99m or indium-111 into the formulation or by addition of a non- radioactive isotope such as samarium-152 followed by neutron activation of the final product. Drug delivery systems can be tested in vitro using various techniques like dissolution rate. Since in vitro testing methods are not predictive of in vivo results, such systems should be evaluated in vivo using animal models, especially oral dosage forms. Altered gastrointestinal transit due to individual variation, physiologic factors, or the presence of food may influence bioavailability. Distribution or drug release may be premature or delayed in vivo. Similarly, altered deposition or clearance from other routes of administration such as nasal, ocular, or inhalation may explain drug absorption anomalies. Therefore, there is a growing tendency for new drug delivery systems to be tested, whenever possible, in human subjects in a so called phase 1 clinical evaluation. Gamma- scintigraphy combined with knowledge of physiological and dosage from design can help to identify some of these variables. the resulting insight can be used to accelerate the formulation development process and to ensure success in early clinical trials

  11. Quantitative dosimetric verification of an IMRT planning and delivery system

    International Nuclear Information System (INIS)

    Low, D.A.; Mutic, S.; Dempsey, J.F.; Gerber, R.L.; Bosch, W.R.; Perez, C.A.; Purdy, J.A.

    1998-01-01

    Background and purpose: The accuracy of dose calculation and delivery of a commercial serial tomotherapy treatment planning and delivery system (Peacock, NOMOS Corporation) was experimentally determined. Materials and methods: External beam fluence distributions were optimized and delivered to test treatment plan target volumes, including three with cylindrical targets with diameters ranging from 2.0 to 6.2 cm and lengths of 0.9 through 4.8 cm, one using three cylindrical targets and two using C-shaped targets surrounding a critical structure, each with different dose distribution optimization criteria. Computer overlays of film-measured and calculated planar dose distributions were used to assess the dose calculation and delivery spatial accuracy. A 0.125 cm 3 ionization chamber was used to conduct absolute point dosimetry verification. Thermoluminescent dosimetry chips, a small-volume ionization chamber and radiochromic film were used as independent checks of the ion chamber measurements. Results: Spatial localization accuracy was found to be better than ±2.0 mm in the transverse axes (with one exception of 3.0 mm) and ±1.5 mm in the longitudinal axis. Dosimetric verification using single slice delivery versions of the plans showed that the relative dose distribution was accurate to ±2% within and outside the target volumes (in high dose and low dose gradient regions) with a mean and standard deviation for all points of -0.05% and 1.1%, respectively. The absolute dose per monitor unit was found to vary by ±3.5% of the mean value due to the lack of consideration for leakage radiation and the limited scattered radiation integration in the dose calculation algorithm. To deliver the prescribed dose, adjustment of the monitor units by the measured ratio would be required. Conclusions: The treatment planning and delivery system offered suitably accurate spatial registration and dose delivery of serial tomotherapy generated dose distributions. The quantitative dose

  12. A novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy.

    LENUS (Irish Health Repository)

    van Pijkeren, Jan Peter

    2012-01-31

    Bacteria-mediated transfer of plasmid DNA to mammalian cells (bactofection) has been shown to have significant potential as an approach to express heterologous proteins in various cell types. This is achieved through entry of the entire bacterium into cells, followed by release of plasmid DNA. In a murine model, we show that Listeria monocytogenes can invade and spread in tumors, and establish the use of Listeria to deliver genes to tumors in vivo. A novel approach to vector lysis and release of plasmid DNA through antibiotic administration was developed. Ampicillin administration facilitated both plasmid transfer and safety control of vector. To further improve on the gene delivery system, we selected a Listeria monocytogenes derivative that is more sensitive to ampicillin, and less pathogenic than the wild-type strain. Incorporation of a eukaryotic-transcribed lysin cassette in the plasmid further increased bacterial lysis. Successful gene delivery of firefly luciferase to growing tumors in murine models and to patient breast tumor samples ex vivo was achieved. The model described encompasses a three-phase treatment regimen, involving (1) intratumoral administration of vector followed by a period of vector spread, (2) systemic ampicillin administration to induce vector lysis and plasmid transfer, and (3) systemic administration of combined moxifloxacin and ampicillin to eliminate systemic vector. For the first time, our results reveal the potential of Listeria monocytogenes for in vivo gene delivery.

  13. Design of Drug Delivery Systems Containing Artemisinin and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Blessing Atim Aderibigbe

    2017-02-01

    Full Text Available Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials. In order to enhance their therapeutic efficacy, they are incorporated onto different drug delivery systems, thus yielding improved biological outcomes. This review article is focused on the currently synthesized derivatives of artemisinin and different delivery systems used for the incorporation of artemisinin and its derivatives.

  14. Feasibility Study: Ductless Hydronic Distribution Systems with Fan Coil Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.; Dakin, B.; Backman, C.

    2012-07-01

    The primary objectives of this study are to estimate potential energy savings relative to conventional ducted air distribution, and to identify equipment requirements, costs, and barriers with a focus on ductless hydronic delivery systems that utilize water-to-air terminal units in each zone. Results indicate that annual heating and cooling energy use can be reduced by up to 27% assuming replacement of the conventional 13 SEER heat pump and coil with a similarly rated air-to-water heat pump.

  15. Zeolites: promising candidates for drug delivery systems (DDSs)

    OpenAIRE

    Vilaça, Natália; Amorim, Ricardo; Baltazar, Fátima; Fonseca, António Manuel; Neves, Isabel C.

    2012-01-01

    [Excerpt] The aim of controlled drug delivery systems (DDSs) is to administer the necessary amount of drug safely and effectively to specific sites in the human body and to regulate the temporal drug profile for maximum therapeutic benefits.[1] Zeolites are crystalline aluminosilicates solids with very regular microporous structures and they have been recently considered for medical use due to their biological properties and stability in biological environments.[1,2] The large variety in ...

  16. Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres.

    Science.gov (United States)

    Keohane, Kieran; Rosa, Mónica; Coulter, Ivan S; Griffin, Brendan T

    2016-01-01

    Investigate the potential of coated minispheres (SmPill®) to enhance localized Ciclosporin A (CsA) delivery to the colon. CsA self-emulsifying drug delivery systems (SEDDS) were encapsulated into SmPill® minispheres. Varying degrees of coating thickness (low, medium and high) were applied using ethylcellulose and pectin (E:P) polymers. In vitro CsA release was evaluated in simulated gastric and intestinal media. Bioavailability of CsA in vivo following oral administration to pigs of SmPill® minispheres was compared to Neoral® po and Sandimmun® iv in a pig model. CsA concentrations in blood and intestinal tissue were determined by HPLC-UV. In vitro CsA release from coated minispheres decreased with increasing coating thickness. A linear relationship was observed between in vitro CsA release and in vivo bioavailability (r(2) = 0.98). CsA concentrations in the proximal, transverse and distal colon were significantly higher following administration of SmPill®, compared to Neoral® po and Sandimmun® iv (p < 0.05). Analysis of transverse colon tissue subsections also revealed significantly higher CsA concentrations in the mucosa and submucosa using SmPill® minispheres (p < 0.05). Modulating E:P coating thickness controls release of CsA from SmPill® minispheres. Coated minispheres limited CsA release in the small intestine and enhanced delivery and uptake in the colon. These findings demonstrate clinical advantages of an oral coated minisphere-enabled CsA formulation in the treatment of inflammatory conditions of the large intestine.

  17. Protamine-based nanoparticles as new antigen delivery systems.

    Science.gov (United States)

    González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Novel delivery systems with nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Cvijić Sandra

    2016-01-01

    Full Text Available Chronic use of oral nonsteroidal anti-inflammatory drugs (NSAIDs is associated with increased risk of serious gastrointestinal side effects. Therefore, recent trends in the development of NSAIDs aim to reduce the incidence of side effects, and improve patient compliance. One of the strategies to improve efficacy and safety of oral NSAIDs is the development of combination products that contain gastroprotective agents. Several products containing NSAID in combination with proton pump inhibitors (ketoprofen/omeprazole, naproxen/esomeprazole, H2-receptor antagonists (ibuprofen/famotidine, and prostaglandin analogues (diclofenac/misoprostol are currently available on the market. Another approach refer to the special formulation design to allow dose reduction while preserving drug therapeutic efficacy. An example is SoluMatrix® technology, a manufacturing process that produce submicron-sized drug particles with enhanced dissolution and absorption properties. Patented SoluMatrix® technology has been successfully employed to develop low-dose diclofenac, meloxicam, indomethacin and naproxen products. Topical NSAID formulations enable drug delivery to target tissues, while reducing systemic exposure and concomitant side effects associated with oral NSAIDs. Dermal/transdermal NSAID delivery systems are subject of intensive investigation. So far, several 'advanced' drug delivery systems with diclofenac, ibuprofen and ketoprofen have been designed.

  19. Food Delivery System with the Utilization of Vehicle Using Geographical Information System (GIS) and A Star Algorithm

    Science.gov (United States)

    Siregar, B.; Gunawan, D.; Andayani, U.; Sari Lubis, Elita; Fahmi, F.

    2017-01-01

    Food delivery system is one kind of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery system is the way to determine the shortest path and food delivery vehicle movement tracking. Therefore, to make sure that the digitation process of food delivery system can be applied efficiently, it is needed to add shortest path determination facility and food delivery vehicle tracking. This research uses A Star (A*) algorithm for determining shortest path and location-based system (LBS) programming for moving food delivery vehicle object tracking. According to this research, it is generated the integrated system that can be used by food delivery driver, customer, and administrator in terms of simplifying the food delivery system. Through the application of shortest path and the tracking of moving vehicle, thus the application of food delivery system in the scope of geographical information system (GIS) can be executed.

  20. Comet Assay: A Method to Evaluate Genotoxicity of Nano-Drug Delivery System

    Science.gov (United States)

    Vandghanooni, Somayeh; Eskandani, Morteza

    2011-01-01

    Introduction Drug delivery systems could induce cellular toxicity as side effect of nanomaterials. The mechanism of toxicity usually involves DNA damage. The comet assay or single cell gel electrophoresis (SCGE) is a sensitive method for detecting strand damages in the DNA of a cell with applications in genotoxicity testing and molecular epidemiology as well as fundamental research in DNA damage and repair. Methods In the current study, we reviewed recent drug delivery researches related to SCGE. Results We found that one preference for choosing the assay is that comet images may result from apoptosis-mediated nuclear fragmentation. This method has been widely used over the last decade in several different areas. Overall cells, such as cultured cells are embedded in agarose on a microscope slide, lysed with detergent, and treated with high salt. Nucleoids are supercoiled DNA form. When the slide is faced to alkaline electrophoresis any breakages present in the DNA cause the supercoiling to relax locally and loops of DNA extend toward the anode as a ‘‘comet tail’’. Conclusion This article provides a relatively comprehensive review upon potentiality of the comet assay for assessment of DNA damage and accordingly it can be used as an informative platform in genotoxicity studies of drug delivery systems. PMID:23678412

  1. Cell-type-specific gene delivery into neuronal cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Parveen, Zahida; Mukhtar, Muhammad; Rafi, Mohammed; Wenger, David A.; Siddiqui, Khwaja M.; Siler, Catherine A.; Dietzschold, Bernhard; Pomerantz, Roger J.; Schnell, Matthias J.; Dornburg, Ralph

    2003-01-01

    The avian retroviruses reticuloendotheliosis virus strain A (REV-A) and spleen necrosis virus (SNV) are not naturally infectious in human cells. However, REV-A-derived viral vectors efficiently infect human cells when they are pseudotyped with envelope proteins displaying targeting ligands specific for human cell-surface receptors. Here we report that vectors containing the gag region of REV-A and pol of SNV can be pseudotyped with the envelope protein of vesicular stomatitis virus (VSV) and the glycoproteins of different rabies virus (RV) strains. Vectors pseudotyped with the envelope protein of the highly neurotropic RV strain CVS-N2c facilitated cell type-specific gene delivery into mouse and human neurons, but did not infect other human cell types. Moreover, when such vector particles were injected into the brain of newborn mice, only neuronal cells were infected in vivo. Cell-type-specific gene delivery into neurons may present quite specific gene therapy approaches for many degenerative diseases of the brain

  2. Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery

    Science.gov (United States)

    Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; ur Rehman, Asim; ud Din, Fakhar

    2017-08-01

    Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

  3. Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery.

    Science.gov (United States)

    Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; Ur Rehman, Asim; Ud Din, Fakhar

    2017-08-17

    Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

  4. Nanoparticle-Based Delivery System for Biomedical Applications of RNAi

    DEFF Research Database (Denmark)

    Yang, Chuanxu

    RNA interference (RNAi) is a post-transcriptional gene silencing process triggered by double-strand RNA, including synthetic short interfering RNA (siRNA) and endogenous microRNA (miRNA). RNAi has attracted great attention for developing a new class of therapeutics, due to its capability to speci......RNA/miRNA and transport them to the action site in the target cells. This thesis describes the development of various nanocarriers for siRNA/miRNA delivery and investigate their potential biomedical applications including: anti-inflammation, tissue engineering and cancer...

  5. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

    Directory of Open Access Journals (Sweden)

    Li X

    2015-12-01

    Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent

  6. A Review of Gene Delivery and Stem Cell Based Therapies for Regenerating Inner Ear Hair Cells

    Directory of Open Access Journals (Sweden)

    Michael S. Detamore

    2011-09-01

    Full Text Available Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  7. A review of gene delivery and stem cell based therapies for regenerating inner ear hair cells.

    Science.gov (United States)

    Devarajan, Keerthana; Staecker, Hinrich; Detamore, Michael S

    2011-09-13

    Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  8. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2005-01-01

    Full Text Available The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, FungisomeTM drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India

  9. Cell membrane-inspired polymeric micelles as carriers for drug delivery.

    Science.gov (United States)

    Liu, Gongyan; Luo, Quanqing; Gao, Haiqi; Chen, Yuan; Wei, Xing; Dai, Hong; Zhang, Zongcai; Ji, Jian

    2015-03-01

    In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.

  10. Optimization of conditions for gene delivery system based on PEI

    Directory of Open Access Journals (Sweden)

    Roya Cheraghi

    2017-01-01

    Full Text Available Objective(s: PEI based nanoparticle (NP due to dual capabilities of proton sponge and DNA binding is known as powerful tool for nucleic acid delivery to cells. However, serious cytotoxicity and complicated conditions, which govern NPs properties and its interactions with cells practically, hindered achievement to high transfection efficiency. Here, we have tried to optimize the properties of PEI/ firefly luciferase plasmid complexes and cellular condition to improve transfection efficiency. Materials and Methods: For this purpose, firefly luciferase, as a robust gene reporter, was complexed with PEI to prepare NPs with different size and charge. The physicochemical properties of nanoparticles were evaluated using agarose gel retardation and dynamic light scattering.  MCF7 and BT474 cells at different confluency were also transfected with prepared nanoparticles at various concentrations for short and long times. Results: The branched PEI can instantaneously bind to DNA and form cationic NPs. The results demonstrated the production of nanoparticles with size about 100-500 nm dependent on N/P ratio. Moreover, increase of nanoparticles concentration on the cell surface drastically improved the transfection rate, so at a concentration of 30 ng/ìl, the highest transfection efficiency was achieved. On the other side, at confluency between 40-60%, the maximum efficiency was obtained. The result demonstrated that N/P ratio of 12 could establish an optimized ratio between transfection efficiency and cytotoxicity of PEI/plasmid nanoparticles. The increase of NPs N/P ratio led to significant cytotoxicity. Conclusion: Obtained results verified the optimum conditions for PEI based gene delivery in different cell lines.

  11. Ex vivo investigation of magnetically targeted drug delivery system

    International Nuclear Information System (INIS)

    Yoshida, Y.; Fukui, S.; Fujimoto, S.; Mishima, F.; Takeda, S.; Izumi, Y.; Ohtani, S.; Fujitani, Y.; Nishijima, S.

    2007-01-01

    In conventional systemic drug delivery the drug is administered by intravenous injection; it then travels to the heart from where it is pumped to all regions of the body. When the drug is aimed at a small target region, this method is extremely inefficient and leads to require much larger doses than those being necessary. In order to overcome this problem a number of targeted drug delivery methods are developed. One of these, magnetically targeted drug delivery system (MT-DDS) will be a promising way, which involves binding a drug to small biocompatible magnetic particles, injecting these into the blood stream and using a high gradient magnetic field to pull them out of suspension in the target region. In the present paper, we describe an ex vivo experimental work. It is also reported that navigation and accumulation test of the magnetic particles in the Y-shaped glass tube was performed in order to examine the threshold of the magnetic force for accumulation. It is found that accumulation of the magnetic particles was succeeded in the blood vessel when a permanent magnet was placed at the vicinity of the blood vessel. This result indicates the feasibility of the magnetically drug targeting in the blood vessel

  12. An implantable thermoresponsive drug delivery system based on Peltier device.

    Science.gov (United States)

    Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury

    2013-04-15

    Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drug delivery system. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drug delivery system to form a new drug delivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Cellulose Nanocrystal Membranes as Excipients for Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Ananda M. Barbosa

    2016-12-01

    Full Text Available In this work, cellulose nanocrystals (CNCs were obtained from flax fibers by an acid hydrolysis assisted by sonochemistry in order to reduce reaction times. The cavitation inducted during hydrolysis resulted in CNC with uniform shapes, and thus further pretreatments into the cellulose are not required. The obtained CNC exhibited a homogeneous morphology and high crystallinity, as well as typical values for surface charge. Additionally, CNC membranes were developed from CNC solution to evaluation as a drug delivery system by the incorporation of a model drug. The drug delivery studies were carried out using chlorhexidine (CHX as a drug and the antimicrobial efficiency of the CNC membrane loaded with CHX was examined against Gram-positive bacteria Staphylococcus aureus (S. Aureus. The release of CHX from the CNC membranes is determined by UV-Vis. The obtaining methodology of the membranes proved to be simple, and these early studies showed a potential use in antibiotic drug delivery systems due to the release kinetics and the satisfactory antimicrobial activity.

  14. An Effective Delivery System of Sitagliptin Using Optimized Mucoadhesive Nanoparticles

    Directory of Open Access Journals (Sweden)

    Afzal Haq Asif

    2018-05-01

    Full Text Available Sitagliptin (MK-0431, is a potent oral hypoglycemic drug that is used for treating type 2 diabetes mellitus. However, the short half-life of sitagliptin requires patients to take a high dose of 50 mg twice per day, and the fraction of sitagliptin reversibly bound to plasma proteins is as low as 38%. In addition, it was reported that approximately 79% of sitagliptin is excreted unchanged in the urine for elimination without metabolism. Thus, a better delivery system is needed to improve the benefits of sitagliptin in patients. The drug content and percentage yield were found to be 73 ± 2% and 92 ± 2%, respectively. The optimized sitagliptin nanoparticle sizes were between 350–950 nm, and the surfaces were smooth and nearly spherical in shape. In addition, the optimized sitagliptin nanoparticles have an indicated excellent bioadhesion property of (6.1 ± 0.5 h. The swelling of the nanoparticles is 168 ± 15%. The pattern of sitagliptin release from the mucoadhesive nanoparticles follows the Korsmeyer-Peppas model. More importantly, the extended sitagliptin retention time, of up to 12 h in the gastrointestinal tract, suggests that the optimized mucoadhesive nanoparticle formulation is more efficient, and has a greater potential to be used for oral delivery compared to the conventional sitagliptin administration in the drug solution. This is the first developed delivery system using the optimized mucoadhesive nanoparticles to enhance the effectiveness of sitagliptin.

  15. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells.

    Directory of Open Access Journals (Sweden)

    Sanne Hindriksen

    Full Text Available The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC. We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B.

  16. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells.

    Science.gov (United States)

    Hindriksen, Sanne; Bramer, Arne J; Truong, My Anh; Vromans, Martijn J M; Post, Jasmin B; Verlaan-Klink, Ingrid; Snippert, Hugo J; Lens, Susanne M A; Hadders, Michael A

    2017-01-01

    The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC). We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B.

  17. Electronic Nicotine Delivery Systems (ENDS): What Nurses Need to Know.

    Science.gov (United States)

    Essenmacher, Carol; Naegle, Madeline; Baird, Carolyn; Vest, Bridgette; Spielmann, Rene; Smith-East, Marie; Powers, Leigh

    Efforts to decrease adverse effects of tobacco use are affected by emergence of new nicotine delivery products. Advertising, product promotion, and social media promote use of these products, yet a lack of evidence regarding safety leaves nurses unprepared to counsel patients. To critically evaluate current research, reviews of literature, expert opinion, and stakeholder policy proposals on use and safety of electronic nicotine delivery systems (ENDS). A targeted examination of literature generated by key stakeholders and subject matter experts was conducted using key words, modified by risk factors, and limited to the past 8 years. Current knowledge gaps in research literature and practice implications of the literature are discussed. The safety of ENDS is questionable and unclear. There are clear health risks of nicotine exposure to developing brains. Potential health risks of ENDS secondhand emissions exposure exist. Using ENDS to facilitate total tobacco cessation is not proven.

  18. Sustained Delivery of Chondroitinase ABC from Hydrogel System

    Directory of Open Access Journals (Sweden)

    Filippo Rossi

    2012-03-01

    Full Text Available In the injured spinal cord, chondroitin sulfate proteoglycans (CSPGs are the principal responsible of axon growth inhibition and they contribute to regenerative failure, promoting glial scar formation. Chondroitinase ABC (chABC is known for being able to digest proteoglycans, thus degrading glial scar and favoring axonal regrowth. However, its classic administration is invasive, infection-prone and clinically problematic. An agarose-carbomer (AC1 hydrogel, already used in SCI repair strategies, was here investigated as a delivery system capable of an effective chABC administration: the material ability to include chABC within its pores and the possibility to be injected into the target tissue were firstly proved. Subsequently, release kinetic and the maintenance of enzymatic activity were positively assessed: AC1 hydrogel was thus confirmed to be a feasible tool for chABC delivery and a promising device for spinal cord injury topic repair strategies.

  19. Towards an Innovative Web-Based Lab Delivery System for a Management Information Systems Course

    Science.gov (United States)

    Breimer, Eric; Cotler, Jami; Yoder, Robert

    2011-01-01

    While online systems are an essential component of distance learning, they can also play a critical role in improving the delivery of activities in a traditional laboratory setting. The quality and effectiveness of online course delivery is often compared to equivalent face-to-face alternatives. In our approach, we have harnessed what we feel to…

  20. [Recent technical advances in portable oxygen delivery systems].

    Science.gov (United States)

    Machida, K; Kawabe, Y; Mori, M; Haga, T

    1992-08-01

    According to a Japanese national survey (June 30, 1990), the number of patients receiving home oxygen therapy (HOT) has been greater than 18,000 since March 1985, when HOT was first covered by health insurance. The oxygen concentrator, especially the molecular sieve type, is the most common method of delivery (more than 90%). In April 1988, the portable oxygen cylinder was acknowledged by health insurance, and the liquid oxygen supply system in April 1990. Three types of portable oxygen delivery systems are available; oxygen cyclinder, liquid oxygen system, and oxygen concentrator (membrane type), of which the oxygen cylinder is most commonly used. In our hospital, portable oxygen supply systems were used in 80% of 168 HOT cases in 1990, and the use of 400 L aluminum oxygen cylinders at a flow rate of 1-2 L/min has been most popular. There is an strong desire from patients for lighter portable oxygen supply system of longer duration. In 19 patients with chronic respiratory failure, we evaluated a newly designed demand oxygen delivery system (DODS), which weighs 2.4 kg including the DOD device (TER-20 Teijin), 1.1 L oxygen cylinder made of ultressor, nasal cannula, and carrier. Arterial blood gases at rest (room air) were PaO2 61.9 +/- 6.3 torr, PaCO2 63.8 +/- 9.4 torr and pH 7.40 +/- 0.04. A crossover trial was performed under three conditions; breathing room air with no weight, and pulse oxygen flow and continuous oxygen flow each carrying 2.4 kg of weight. Both 6 minute walking (E1) and walking on a slow speed treadmill (E2) were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

    Directory of Open Access Journals (Sweden)

    Eiji Yuba

    2017-11-01

    Full Text Available (1 Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2 Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3 Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4 Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

  2. Tumor cell survival dependence on helical tomotherapy, continuous arc and segmented dose delivery

    International Nuclear Information System (INIS)

    Yang Wensha; Wang Li; Larner, James; Read, Paul; Benedict, Stan; Sheng Ke

    2009-01-01

    The temporal pattern of radiation delivery has been shown to influence the tumor cell survival fractions for the same radiation dose. To study the effect more specifically for state of the art rotational radiation delivery modalities, 2 Gy of radiation dose was delivered to H460 lung carcinoma, PC3 prostate cancer cells and MCF-7 breast tumor cells by helical tomotherapy (HT), seven-field LINAC (7F), and continuous dose delivery (CDD) over 2 min that simulates volumetric rotational arc therapy. Cell survival was measured by the clonogenic assay. The number of viable H460 cell colonies was 23.2 ± 14.4% and 27.7 ± 15.6% lower when irradiated by CDD compared with HT and 7F, respectively, and the corresponding values were 36.8 ± 18.9% and 35.3 ± 18.9% lower for MCF7 cells (p < 0.01). The survival of PC3 was also lower when irradiated by CDD than by HT or 7F but the difference was not as significant (p = 0.06 and 0.04, respectively). The higher survival fraction from HT delivery was unexpected because 90% of the 2 Gy was delivered in less than 1 min at a significantly higher dose rate than the other two delivery techniques. The results suggest that continuous dose delivery at a constant dose rate results in superior in vitro tumor cell killing compared with prolonged, segmented or variable dose rate delivery.

  3. Healthcare delivery systems: designing quality into health information systems.

    Science.gov (United States)

    Joyce, Phil; Green, Rosamund; Winch, Graham

    2007-01-01

    To ensure that quality is 'engineered in' a holistic, integrated and quality approach is required, and Total Quality Management (TQM) principles are the obvious foundations for this. This paper describes a novel approach to viewing the operations of a healthcare provider where electronic means could be used to distribute information (including electronic fund settlements), building around the Full Service Provider core. Specifically, an approach called the "triple pair flow" model is used to provide a view of healthcare delivery that is integrated, yet detailed, and that combines the strategic enterprise view with a business process view.

  4. Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells.

    Science.gov (United States)

    Gardell, Jennifer L; Parker, David C

    2017-01-01

    Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

  5. Metal organic frameworks as a drug delivery system for flurbiprofen.

    Science.gov (United States)

    Al Haydar, Muder; Abid, Hussein Rasool; Sunderland, Bruce; Wang, Shaobin

    2017-01-01

    Metal organic frameworks (MOFs) have attracted more attention in the last decade because of a suitable pore size, large surface area, and high pore volume. Developing biocompatible MOFs such as the MIL family as a drug delivery system is possible. Flurbiprofen (FBP), a nonsteroidal anti-inflammatory agent, is practically insoluble in aqueous solution, and, therefore, needs suitable drug delivery systems. Different biocompatible MOFs such as Ca-MOF and Fe-MILs (53, 100, and 101) were synthesized and employed for FBP delivery. A sample of 50 mg of each MOF was mixed and stirred for 24 h with 10 mL of 5 mg FBP in acetonitrile (40%) in a sealed container. The supernatant of the mixture after centrifuging was analyzed by high-performance liquid chromatography to determine the loaded quantity of FBP on the MOF. The overnight-dried solid material after centrifuging the mixture was analyzed for loading percent using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, nuclear magnetic resonance, and FBP release profile. The loading values of FBP were achieved at 10.0%±1%, 20%±0.8%, 37%±2.3%, and 46%±3.1% on Ca-MOF, Fe-MIL-53, Fe-MIL-101, and Fe-MIL-100, respectively. The FBP release profiles were investigated in a phosphate buffer solution at pH 7.4. The total release of the FBP after 2 days was obtained at 72.9, 75.2, 78.3, and 90.3% for Ca-MOF, Fe-MIL-100, Fe-MIL-53, and Fe-MIL-101, respectively. The MOFs are shown to be a promising drug delivery option for FBP with a significant loading percent and relatively prolonged drug release.

  6. A clinician-driven home care delivery system.

    Science.gov (United States)

    August, D A; Faubion, W C; Ryan, M L; Haggerty, R H; Wesley, J R

    1993-12-01

    The financial, entrepreneurial, administrative, and legal forces acting within the home care arena make it difficult for clinicians to develop and operate home care initiatives within an academic setting. HomeMed is a clinician-initiated and -directed home care delivery system wholly owned by the University of Michigan. The advantages of a clinician-directed system include: Assurance that clinical and patient-based factors are the primary determinants of strategic and procedural decisions; Responsiveness of the system to clinician needs; Maintenance of an important role for the referring physician in home care; Economical clinical research by facilitation of protocol therapy in ambulatory and home settings; Reduction of lengths of hospital stays through clinician initiatives; Incorporation of outcome analysis and other research programs into the mission of the system; Clinician commitment to success of the system; and Clinician input on revenue use. Potential disadvantages of a clinician-based system include: Entrepreneurial, financial, and legal naivete; Disconnection from institutional administrative and data management resources; and Inadequate clinician interest and commitment. The University of Michigan HomeMed experience demonstrates a model of clinician-initiated and -directed home care delivery that has been innovative, profitable, and clinically excellent, has engendered broad physician, nurse, pharmacist, and social worker enthusiasm, and has supported individual investigator clinical protocols as well as broad outcomes research initiatives. It is concluded that a clinician-initiated and -directed home care program is feasible and effective, and in some settings may be optimal.

  7. Halloysite clay nanotubes for resveratrol delivery to cancer cells.

    Science.gov (United States)

    Vergaro, Viviana; Lvov, Yuri M; Leporatti, Stefano

    2012-09-01

    Halloysite is natural aluminosilicate clay with hollow tubular structure which allows loading with low soluble drugs using their saturated solutions in organic solvents. Resveratrol, a polyphenol known for having antioxidant and antineoplastic properties, is loaded inside these clay nanotubes lumens. Release time of 48 h is demonstrated. Spectroscopic and ζ-potential measurements are used to study the drug loading/release and for monitoring the nanotube layer-by-layer (LbL) coating with polyelectrolytes for further release control. Resveratrol-loaded clay nanotubes are added to breast cell cultures for toxicity tests. Halloysite functionalization with LbL polyelectrolyte multilayers remarkably decrease nanotube self-toxicity. MTT measurements performed with a neoplastic cell lines model system (MCF-7) as function of the resveratrol-loaded nanotubes concentration and incubation time indicate that drug-loaded halloysite strongly increase of cytotoxicity leading to cell apoptosis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis.

    Science.gov (United States)

    Eseonu, Onyedikachi I; De Bari, Cosimo

    2015-02-01

    Mesenchymal stem cells (MSCs) are multipotent cells with the capacity to undergo chondrogenic differentiation. Systemically administered MSCs have been shown to preferentially accumulate at sites of tissue damage and inflammation, thus MSC-based therapy holds great promise for the treatment of inflammatory diseases such as RA. Modulation of MSC homing may allow targeted delivery of systemically administered MSCs to damaged articular cartilage, where they can suppress immune-mediated cartilage destruction and contribute to cartilage repair via a combination of chondrogenic differentiation and paracrine stimulation of intrinsic residual repair. To harness the potential of MSC homing, a thorough understanding of the mechanism is key. This review discusses current knowledge of the mechanism of MSC homing to injured/inflamed tissue and its implications for targeted MSC-based therapy in arthritis. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Recombinant human parvovirus B19 vectors: erythroid cell-specific delivery and expression of transduced genes.

    Science.gov (United States)

    Ponnazhagan, S; Weigel, K A; Raikwar, S P; Mukherjee, P; Yoder, M C; Srivastava, A

    1998-06-01

    A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562-566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111-1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited and

  10. Recombinant Human Parvovirus B19 Vectors: Erythroid Cell-Specific Delivery and Expression of Transduced Genes

    Science.gov (United States)

    Ponnazhagan, Selvarangan; Weigel, Kirsten A.; Raikwar, Sudhanshu P.; Mukherjee, Pinku; Yoder, Mervin C.; Srivastava, Arun

    1998-01-01

    A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562–566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111–1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited

  11. A remotely operated drug delivery system with dose control

    KAUST Repository

    Yi, Ying

    2017-05-08

    “On demand” implantable drug delivery systems can provide optimized treatments, due to their ability to provide targeted, flexible and precise dose release. However, two important issues that need to be carefully considered in a mature device include an effective actuation stimulus and a controllable dose release mechanism. This work focuses on remotely powering an implantable drug delivery system and providing a high degree of control over the released dose. This is accomplished by integration of a resonance-based wireless power transfer system, a constant voltage control circuit and an electrolytic pump. Upon the activation of the wireless power transfer system, the electrolytic actuator is remotely powered by a constant voltage regardless of movements of the device within an effective range of translation and rotation. This in turn contributes to a predictable dose release rate and greater flexibility in the positioning of external powering source. We have conducted proof-of-concept drug delivery studies using the liquid drug in reservoir approach and the solid drug in reservoir approach, respectively. Our experimental results demonstrate that the range of flow rate is mainly determined by the voltage controlled with a Zener diode and the resistance of the implantable device. The latter can be adjusted by connecting different resistors, providing control over the flow rate to meet different clinical needs. The flow rate can be maintained at a constant level within the effective movement range. When using a solid drug substitute with a low solubility, solvent blue 38, the dose release can be kept at 2.36μg/cycle within the effective movement range by using an input voltage of 10Vpp and a load of 1.5 kΩ, which indicates the feasibility and controllability of our system without any complicated closed-loop sensor.

  12. Mesoporous silica for drug delivery: Interactions with model fluorescent lipid vesicles and live cells.

    Science.gov (United States)

    Bardhan, Munmun; Majumdar, Anupa; Jana, Sayantan; Ghosh, Tapas; Pal, Uttam; Swarnakar, Snehasikta; Senapati, Dulal

    2018-01-01

    Formulated mesoporous silica nanoparticle (MSN) systems offer the best possible drug delivery system through the release of drug molecules from the accessible pores. In the present investigation, steady state and time resolved fluorescence techniques along with the fluorescence imaging were applied to investigate the interactions of dye loaded MSN with fluorescent unilamellar vesicles and live cells. Here 1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC) was used to prepare Small Unilamellar Vesicles (SUVs) as the model membrane with fluorescent 1,6-diphenyl-1,3,5-hexatriene (DPH) molecule incorporated inside the lipid bilayer. The interaction of DPH incorporated DMPC membrane with Fluorescein loaded MSN lead to the release of Fluorescein (Fl) dye from the interior pores of MSN systems. The extent of release of Fl and spatial distribution of the DPH molecule has been explored by monitoring steady-state fluorescence intensity and fluorescence lifetime at physiological condition. To investigate the fate of drug molecule released from MSN, fluorescence anisotropy has been used. The drug delivery efficiency of the MSN as a carrier for doxorubicin (DOX), a fluorescent chemotherapeutic drug, has also been investigated at physiological conditions. The study gives a definite confirmation for high uptake and steady release of DOX in primary oral mucosal non-keratinized squamous cells in comparison to naked DOX treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers.

    Science.gov (United States)

    Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

    2015-01-01

    Biopharmaceuticals are a generation of drugs that include peptides, proteins, nucleic acids and cell products. According to their particular molecular characteristics (e.g. high molecular size, susceptibility to enzymatic activity), these products present some limitations for administration and usually parenteral routes are the only option. To avoid these limitations, different colloidal carriers (e.g. liposomes, micelles, microemulsions and dendrimers) have been proposed to improve biopharmaceuticals delivery. Liposomes are promising drug delivery systems, despite some limitations have been reported (e.g. in vivo failure, poor long-term stability and low transfection efficiency), and only a limited number of formulations have reached the market. Micelles and microemulsions require more studies to exclude some of the observed drawbacks and guarantee their potential for use in clinic. According to their peculiar structures, dendrimers have been showing good results for nucleic acids delivery and a great development of these systems during next years is expected. This is the Part II of two review articles, which provides the state of the art of biopharmaceuticals delivery systems. Part II deals with liposomes, micelles, microemulsions and dendrimers.

  14. Preparation, characterization and drug delivery study of a novel nanobiopolymeric multidrug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Dadkhah Tehrani, Abbas, E-mail: A_dadkhahtehrani@yahoo.com; Parsamanesh, Masoumeh

    2017-04-01

    New nanocarrier for codelivery of curcumin and doxorubicin as the anticancer drugs was synthesized using biocompatible and biodegradable materials. Firstly, an inclusion complex of amylose (Am) and curcumin (CUR) was formed through entrapment of curcumin into the amylose helices. Then the surface of amylose-curcumin (Am-CUR) complex was modified by polycaprolactone (PCL) via esterification reaction between hydroxyl functional groups of amylose and carbonyl groups of PCL. Finally, poly citric acid (PCA) reacted with terminal hydroxyl groups of PCL by esterification reaction. Then, doxorubicin (DOX) reacted with the surface carboxylic acid functional groups of Am-CUR-PCL-PCA through noncovalent interactions to form Am-CUR-PCL-PCA-DOX as a multidrug delivery system. These new synthesized nanomaterials were characterized by spectroscopic measurement methods such as IR spectroscopy, UV–vis spectroscopy, NMR spectroscopy, and scanning electron microscopy. FE-SEM analyses and DLS measurements showed that the hydrodynamic dimensions of Am-Cur-PCL-PCA were about 50 nm. Due to the presence of ester bonds, the synthesized nanomaterials are pH sensitive. Furthermore, the resulting copolymer was completely water soluble because of the hydrophilic nature of poly citric acid part of copolymer and therefore successfully can be utilized in biomedical applications. - Highlights: • A drug delivery system based on amylose-graft-PCL-PCA developed for codelivery of curcumin and DOX. • The IR and NMR spectra confirmed successful preparation of the copolymer. • The drugs release were more favorable at acidic pH for both drugs. • DLS measurements showed that the hydrodynamic dimensions of Am-Cur-PCL-PCA was about 50 nm.

  15. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  16. Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.

    Science.gov (United States)

    Arai, Takao; Benny, Ofra; Joki, Tatsuhiro; Menon, Lata G; Machluf, Marcelle; Abe, Toshiaki; Carroll, Rona S; Black, Peter M

    2010-04-01

    The purpose of our study was to evaluate the application of thermoreversible gelation polymer (TGP) as a local drug delivery system for malignant glioma. Polymeric microspheres or liposomes loaded with doxorubicin (sphere-dox or lipo-dox) were combined with TGP to provide continuous drug delivery of doxorubicin (dox) for kinetic release studies and cell viability assays on glioma cell lines in vitro. For in vivo studies, TGP loaded with dox alone (TGP-dox) was combined with sphere-dox or lipo-dox. Their antitumor effects on subcutaneous human glioma xenografts were evaluated in nude mice. In vitro, TGP combined with sphere-dox or lipo-dox released dox for up to 30 days. In vivo, TGP-dox combined with sphere-dox or lipo-dox inhibited subcutaneous glioma tumor growth until day 32 and day 38, respectively. TGP in combination with microspheres or liposomes successfully prolonged the release of dox and its antitumor effects.

  17. Delivery Systems for Birch-Bark Triterpenoids and Their Derivatives in Anticancer Research.

    Science.gov (United States)

    Mierina, Inese; Vilskersts, Reinis; Turks, Maris

    2018-05-29

    Birch-bark triterpenoids and their semi-synthetic derivatives possess a wide range of biological activities including cytotoxic effects on various tumour cell lines. However, due to the low solubility and bioavailability, their medicinal applications are rather limited. The use of various nanotechnology-based drug delivery systems is rapidly developing approach to the solubilisation of insufficiently bioavailable pharmaceuticals. Herein, the drug delivery systems deemed to be applicable for birch-bark triterpenoid structures are reviewed. The aforementioned disadvantages of birch-bark triterpenoids and their semi-synthetic derivatives can be overcome through their incorporation into organic nanoparticles, which include various dendrimeric systems, as well as embedding the active compounds into polymer matrices or complexation with carbohydrate nanoparticles without covalent bonding. Some of the known triterpenoid delivery systems consist of nanoparticles featuring inorganic cores covered with carbohydrates or other polymers. Methods for delivering the title compounds through encapsulation and emulsification into lipophilic media are also suitable. Besides, the birch-bark triterpenoids can form self-assembling systems with increased bio-availability. Even more, the self-assembling systems are used as carriers for delivering other chemotherapeutic agents. Another advantage besides increased bioavailability and anticancer activity is the reduced overall systemic toxicity in most of the cases, when triterpenoids are delivered with any of the carriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Magnetic Nanoparticles of Chitosan for Targeted Delivery System of Plasmids to the Lungs

    International Nuclear Information System (INIS)

    Baez, C.A.A.; Cruz, I.E.L.; Padilla, M.C.R.; Gonzalez, J.M.A.

    2014-01-01

    One of the major problems of gene therapy is the efficient, specific, and targeted delivery as well as the safety of the materials used in such systems. The specific targeted delivery of genes to the lung offers the possibility to treat a variety of specific diseases. We developed chitosan nanoparticles with the plasmid pCEM-Luc, which contains a promoter activated by magnetic field. Nanoparticles of 200-250 nm obtained by ionic gelation with a 99% retention rate were transfected in B16F10 cells and in vivo in the lungs of Balb/c mice by intratracheal administration. We observed that an external magnetic field increased the expression of the luciferase reporter gene in B16F10 cells transfected with magnetic nanoparticles and in homogenized lungs of mice which determined differences in levels of expression between different regions of the lungs (apical or distal and left or right). The highest levels of luciferase activity were observed in the apical left region. The magnetic nanoparticles prove an efficient delivery system to in vitro transfection of cells and lung tissue.

  19. Cell-based delivery of glucagon-like peptide-1 using encapsulated mesenchymal stem cells.

    Science.gov (United States)

    Wallrapp, Christine; Thoenes, Eric; Thürmer, Frank; Jork, Anette; Kassem, Moustapha; Geigle, Peter

    2013-01-01

    Glucagon-like peptide-1 (GLP-1) CellBeads are cell-based implants for the sustained local delivery of bioactive factors. They consist of GLP-1 secreting mesenchymal stem cells encapsulated in a spherically shaped immuno-isolating alginate matrix. A highly standardized and reproducible encapsulation method is described for the manufacturing of homogeneous CellBeads. Viability and sustained secretion was shown for the recombinant GLP-1 and the cell endogenous bioactive factors like vascular endothelial growth factor, neurotrophin 3 (NT-3) and glial cell line-derived neurotrophic factor. Manufacturing and quality control is performed in compliance with good manufacturing practice and fulfils all regulatory requirements for human clinical use. GLP-1 CellBeads combine the neuro- and cardioprotective properties of both GLP-1 and mesenchymal stem cells. First promising results were obtained from preclinical studies and an ongoing safety trial in humans but further studies have to prove the overall potential of CellBead technology in cell-based regenerative medicine.

  20. Thiomers: potential excipients for non-invasive peptide delivery systems.

    Science.gov (United States)

    Bernkop-Schnürch, Andreas; Krauland, Alexander H; Leitner, Verena M; Palmberger, Thomas

    2004-09-01

    In recent years thiolated polymers or so-called thiomers have appeared as a promising alternative in the arena of non-invasive peptide delivery. Thiomers are generated by the immobilisation of thiol-bearing ligands to mucoadhesive polymeric excipients. By formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of these polymers are improved up to 130-fold. Due to formation of inter- and intramolecular disulfide bonds within the thiomer itself, dosage forms such as tablets or microparticles display strong cohesive properties resulting in comparatively higher stability, prolonged disintegration times and a more controlled release of the embedded peptide drug. The permeation of peptide drugs through mucosa can be improved by the use of thiolated polymers. Additionally some thiomers exhibit improved inhibitory properties towards peptidases. The efficacy of thiomers in non-invasive peptide delivery could be demonstrated by various in vivo studies. Tablets comprising a thiomer and pegylated insulin, for instance, resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Furthermore, a pharmacological efficacy of 1.3% was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Human growth hormone in a thiomer-gel was applied nasally to rats and led to a bioavailability of 2.75%. In all these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. According to these results drug carrier systems based on thiomers seem to be a promising tool for non-invasive peptide drug delivery.

  1. New Delivery Systems for Local Anaesthetics—Part 2

    Directory of Open Access Journals (Sweden)

    Edward A. Shipton

    2012-01-01

    Full Text Available Part 2 of this paper deals with the techniques for drug delivery of topical and injectable local anaesthetics. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous are explored. To enhance transdermal local anaesthetic permeation, additional methods to the use of an eutectic mixture of local anaesthetics and the use of controlled heat can be used. These methods include iontophoresis, electroporation, sonophoresis, and magnetophoresis. The potential clinical uses of topical local anaesthetics are elucidated. Iontophoresis, the active transportation of a drug into the skin using a constant low-voltage direct current is discussed. It is desirable to prolong local anaesthetic blockade by extending its sensory component only. The optimal release and safety of the encapsulated local anaesthetic agents still need to be determined. The use of different delivery systems should provide the clinician with both an extended range and choice in the degree of prolongation of action of each agent.

  2. Packaged Au-PPy valves for drug delivery systems

    Science.gov (United States)

    Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc

    2006-03-01

    The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

  3. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  4. Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

    Science.gov (United States)

    Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

    2018-05-17

    Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable

  5. Effective plasmid DNA and small interfering RNA delivery to diseased human brain microvascular endothelial cells.

    Science.gov (United States)

    Slanina, H; Schmutzler, M; Christodoulides, M; Kim, K S; Schubert-Unkmeir, A

    2012-01-01

    Expression of exogenous DNA or small interfering RNA (siRNA) in vitro is significantly affected by the particular delivery system utilized. In this study, we evaluated the transfection efficiency of plasmid DNA and siRNA into human brain microvascular endothelial cells (HBMEC) and meningioma cells, which constitute the blood-cerebrospinal fluid barrier, a target of meningitis-causing pathogens. Chemical transfection methods and various lipofection reagents including Lipofectamin™, FuGene™, or jetPRIME®, as well as physical transfection methods and electroporation techniques were applied. To monitor the transfection efficiencies, HBMEC and meningioma cells were transfected with the reporter plasmid pTagGFP2-actin vector, and efficiency of transfection was estimated by fluorescence microscopy and flow cytometry. We established protocols based on electroporation using Cell Line Nucleofector® Kit V with the Amaxa® Nucleofector® II system from Lonza and the Neon® Transfection system from Invitrogen resulting in up to 41 and 82% green fluorescent protein-positive HBMEC, respectively. Optimal transfection solutions, pulse programs and length were evaluated. We furthermore demonstrated that lipofection is an efficient method to transfect meningioma cells with a transfection efficiency of about 81%. Finally, we applied the successful electroporation protocols to deliver synthetic siRNA to HBMEC and analyzed the role of the actin-binding protein cortactin in Neisseria meningitidis pathogenesis. Copyright © 2012 S. Karger AG, Basel.

  6. A Promising Combo Gene Delivery System Developed from (3-Aminopropyl)triethoxysilane-Modified Iron Oxide Nanoparticles and Cationic Polymers

    Science.gov (United States)

    Zhang, Zubin; Song, Lina; Dong, Jinlai; Guo, Dawei; Du, Xiaolin; Cao, Biyin; Zhang, Yu; Gu, Ning; Mao, Xinliang

    2013-05-01

    (3-Aminopropyl)triethoxysilane-modified iron oxide nanoparticles (APTES-IONPs) have been evaluated for various biomedical applications, including medical imaging and drug delivery. Cationic polymers (CPs) such as Lipofectamine and TurboFect are widely used for research in gene delivery, but their toxicity and low in vivo efficiency limited their further application. In the present study, we synthesized water-soluble APTES-IONPs and developed a combo gene delivery system based on APTES-IONPs and CPs. This system significantly increased gene-binding capacity, protected genes from degradation, and improved gene transfection efficiency for DNA and siRNA in both adherent and suspension cells. Because of its great biocompatibility, high gene-carrying ability, and very low cytotoxicity, this combo gene delivery system will be expected for a wide application, and it might provide a new method for gene therapy.

  7. A Promising Combo Gene Delivery System Developed from (3-Aminopropyl)triethoxysilane-Modified Iron Oxide Nanoparticles and Cationic Polymers

    International Nuclear Information System (INIS)

    Zhang Zubin; Song Lina; Dong Jinlai; Guo Dawei; Du Xiaolin; Cao Biyin; Zhang Yu; Gu Ning; Mao Xinliang

    2013-01-01

    (3-Aminopropyl)triethoxysilane-modified iron oxide nanoparticles (APTES-IONPs) have been evaluated for various biomedical applications, including medical imaging and drug delivery. Cationic polymers (CPs) such as Lipofectamine and TurboFect are widely used for research in gene delivery, but their toxicity and low in vivo efficiency limited their further application. In the present study, we synthesized water-soluble APTES-IONPs and developed a combo gene delivery system based on APTES-IONPs and CPs. This system significantly increased gene-binding capacity, protected genes from degradation, and improved gene transfection efficiency for DNA and siRNA in both adherent and suspension cells. Because of its great biocompatibility, high gene-carrying ability, and very low cytotoxicity, this combo gene delivery system will be expected for a wide application, and it might provide a new method for gene therapy.

  8. Empty Turnip yellow mosaic virus capsids as delivery vehicles to mammalian cells.

    Science.gov (United States)

    Kim, Doyeong; Lee, Younghee; Dreher, Theo W; Cho, Tae-Ju

    2018-05-03

    Turnip yellow mosaic virus (TYMV) was able to enter animal cells when the spherical plant virus was conjugated with Tat, a cell penetrating peptide (CPP). Tat was chemically attached to the surface lysine residues of TYMV using hydrazone chemistry. Baby hamster kidney (BHK) cells were incubated with either unmodified or Tat-conjugated TYMV and examined by flow cytometry and confocal microscopic analyses. Tat conjugation was shown to be more efficient than Lipofectamine in allowing TYMV to enter the mammalian cells. Tat-assisted-transfection was also associated with less loss of cell viability than lipofection. Among the CPPs tested (Tat, R8, Pep-1 and Pen), it was observed that R8 and Pen were also effective while Pep-1 was not. We also examined if the internal space of TYMV can be used to load fluorescein dye as a model cargo. When TYMV is treated by freezing and thawing, the virus is known to convert into a structure with a 6-8 nm hole and release viral RNA. When the resultant pot-like particles were reacted with fluorescein-5-maleimide using interior sulfhydryl groups as conjugation sites, about 145 fluorescein molecules were added per particle. The fluorescein-loaded TYMV particles were conjugated with Tat and introduced into BHK cells, again with higher transfection efficiency compared to lipofection. Our studies demonstrate the potential of modified TYMV as an efficient system for therapeutic cargo delivery to mammalian cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    International Nuclear Information System (INIS)

    Hwang, Tae Heon; Kim, Jin Bum; Yang, Da Som; Ryu, WonHyoung; Park, Yong-il

    2013-01-01

    Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro. (paper)

  10. A framework for the organization and delivery of systemic treatment.

    Science.gov (United States)

    Vandenberg, T; Coakley, N; Nayler, J; Degrasse, C; Green, E; Mackay, J A; McLennan, C; Smith, A; Wilcock, L; Trudeau, M E

    2009-01-01

    Increasing systemic treatment and shortages of oncology professionals in Canada require innovative approaches to the safe and effective delivery of intravenous (IV) cancer treatment. We conducted a systematic review of the clinical and scientific literature, and an environmental scan of models in Canada, the United Kingdom, Australia, and New Zealand. We then developed a framework for the organization and delivery of IV systemic treatment. The systematic review covered the medline, embase, cinahl, and HealthStar databases. The environmental scan retrieved published and unpublished sources, coupled with a free key word search using the Google search engine. The Systemic Treatment Working Group reviewed the evidence and developed a draft framework using evidence-based analysis, existing recommendations from various jurisdictions, and expert opinion based on experience and consensus. The draft was assessed by Ontario stakeholders and reviewed and approved by Cancer Care Ontario. The poor quantity and quality of the evidence necessitated a consensus-derived model. That model comprises four levels of care determined by a regional systemic treatment program and three integrated structures (integrated cancer programs, affiliate institutions, and satellite institutions), each with a defined scope of practice and a specific organizational framework. New models of care are urgently required beyond large centres, particularly in geographically remote or rural areas. Despite limited applicable evidence, the development and successful implementation of this framework is intended to create sustainable, accessible, quality care and to measurably improve patient outcomes.

  11. Efficient siRNA delivery system using carboxilated single-wall carbon nanotubes in cancer treatment.

    Science.gov (United States)

    Neagoe, Ioana Berindan; Braicu, Cornelia; Matea, Cristian; Bele, Constantin; Florin, Graur; Gabriel, Katona; Veronica, Chedea; Irimie, Alexandru

    2012-08-01

    Several functionalized carbon nanotubes have been designed and tested for the purpose of nucleic acid delivery. In this study, the capacity of SWNTC-COOH for siRNA deliverey were investigated delivery in parallel with an efficient commercial system. Hep2G cells were reverse-transfected with 50 nM siRNA (p53 siRNA, TNF-alphasiRNA, VEGFsiRNA) using the siPORT NeoFX (Ambion) transfection agent in paralel with SWNTC-COOH, functionalised with siRNA. The highest level of gene inhibition was observed in the cases treated with p53 siRNA gene; in the case of transfection with siPort, the NeoFX value was 33.8%, while in the case of SWNTC-COOH as delivery system for p53 siRNA was 37.5%. The gene silencing capacity for VEGF was 53.7%, respectively for TNF-alpha 56.7% for siPORT NeoFX delivery systems versus 47.7% (VEGF) and 46.5% (TNF-alpha) for SWNTC-COOH delivery system. SWNTC-COOH we have been showed to have to be an efficient carrier system. The results from the inhibition of gene expresion for both transfection systems were confirmed at protein level. Overall, the lowest mRNA expression was confirmed at protein level, especially in the case of p53 siRNA and TNF-alpha siRNA transfection. Less efficient reduction protein expressions were observed in the case of VEGF siRNA, for both transfection systems at 24 h; only at 48 h, there was a statistically significant reduction of VEGF protein expression. SWCNT-COOH determined an efficient delivery of siRNA. SWNTC-COOH, combined with suitable tumor markers like p53 siRNA, TNFalpha siRNA or VEGF siRNA can be used for the efficient delivery of siRNA.

  12. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system.

    Science.gov (United States)

    Kibria, Golam; Hatakeyama, Hiroto; Harashima, Hideyoshi

    2014-01-01

    Multidrug resistance (MDR), the principal mechanism by which many cancers develop resistance to chemotherapy, is one of the major obstacles to the successful clinical treatment of various types of cancer. Several key regulators are responsible for mediating MDR, a process that renders chemotherapeutic drugs ineffective in the internal organelles of target cells. A nanoparticulate drug delivery system (DDS) is a potentially promising tool for circumventing such MDR, which can be achieved by targeting tumor cells themselves or tumor endothelial cells that support the survival of MDR cancer cells. The present article discusses key factors that are responsible for MDR in cancer cells, with a specific focus on the application of DDS to overcome MDR via the use of chemotherapy or macromolecules.

  13. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  14. Utilization of solid lipid nanoparticles for enhanced delivery of curcumin in cocultures of HT29-MTX and Caco-2 cells.

    Science.gov (United States)

    Guri, Anilda; Gülseren, Ibrahim; Corredig, Milena

    2013-09-01

    Solid lipid nanoparticles (SLN) have shown potential for encapsulation, protection and delivery of lipophilic functional components. In this study, we have investigated the capabilities of SLN to deliver a hydrophobic polyphenol compound, curcumin, in a coculture system of absorptive Caco-2 and mucus secreting HT29-MTX cells. The cells were grown on transport filters to mimic the human intestinal epithelium. Because of the hydrophobic nature of curcumin, its delivery to the basolateral compartment is expected to take place via a paracellular route. The changes in curcumin concentration in various compartments (i.e., apical, basolateral, mucus, and cell lysates) were evaluated using fluorescence spectroscopy. Two SLN systems were prepared with different emulsifying agents. The encapsulation of curcumin in SLN caused enhanced delivery compared to unencapsulated curcumin. In addition, SLN showed enhanced delivery compared to emulsion droplets containing liquid soy oil. The SLN were retained on the apical mucosal layer to a greater extent than emulsion droplets. The presence of SLN did not affect the integrity of the cellular junctions, as indicated by the TEER values, and the route of transport of the solid particles was simple diffusion, with permeability rates of about 7 × 10(-6) cm s(-1). Approximately 1% of total curcumin was delivered to the basolateral compartment, suggesting that most of the curcumin was absorbed and metabolized by the cell.

  15. Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus.

    Directory of Open Access Journals (Sweden)

    Rebekah L Scheuerle

    Full Text Available Zinc delivery from a nipple shield delivery system (NSDS, a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32-51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch's correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia.

  16. Reliability review of the remote tool delivery system locomotor

    Energy Technology Data Exchange (ETDEWEB)

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  17. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    Directory of Open Access Journals (Sweden)

    Wildemeersch D

    2017-01-01

    currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant® when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in reducing side effects. Keywords: LNG-IUS, frameless, efficacy, safety, acceptability

  18. Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells.

    Science.gov (United States)

    Imani, Rana; Shao, Wei; Taherkhani, Samira; Emami, Shahriar Hojjati; Prakash, Satya; Faghihi, Shahab

    2016-11-01

    The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA loaded nano-carrier is used for internalization to MCF-7 cells and its gene silencing ability is compared with AllStars Hs Cell Death siRNA as a model gene. The nano-carrier remains stable in biological solution, exhibits excellent cytocompatibility, retards the siRNA migration and protects it against enzyme degradation. The buffering capacity analysis shows that incorporation of the peptide in nano-carrier structure would increase the resistance to endo/lysosomal like acidic condition (pH 6-4) The functionalized nano-carrier which is loaded with siRNA in an optimal N:P ratio presents superior internalization efficiency (82±5.1% compared to HiPerFect(®)), endosomal escape quality and capable of inducing cell death in MCF-7 cancer cells (51±3.1% compared to non-treated cells). The success of siRNA-based therapy is largely dependent on the safe and efficient delivery system, therefore; the dual functionalized rGO introduced here could have a great potential to be used as a carrier for siRNA delivery with relevancy in therapeutics and clinical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

    Science.gov (United States)

    Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang

    2016-02-01

    The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.

  20. Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

    Science.gov (United States)

    Penumarthi, Alekhya; Parashar, Deepti; Abraham, Amanda N.; Dekiwadia, Chaitali; Macreadie, Ian; Shukla, Ravi; Smooker, Peter M.

    2017-06-01

    There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA-SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

  1. Chewing gum and lozenges as delivery systems for noscapine

    DEFF Research Database (Denmark)

    Norgaard Jensen, L.; Christrup, Lona Louring; Menger, N.

    1991-01-01

    Chewing gum and lozenges were evaluated as delivery systems for noscapine with the aim of developing improved antitussive preparations. The formulations studied were prepared with both the water-soluble hydrochloride salt of noscapine and with the poorly soluble embonate salt and noscapine free...... base. The release characteristics of the preparations were evaluated both in vitro and in vivo, and their taste properties examined. Only the formulations containing noscapine base were without any appreciable taste. Chewing gum containing this compound showed, however, a low level of drug release both...

  2. A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine

    Directory of Open Access Journals (Sweden)

    Chen CY

    2017-06-01

    Full Text Available Chuanyu Chen, Peijun You Department of Anesthesiology, Shandong Jining No 1 People’s Hospital, Jining, Shandong, People’s Republic of China Purpose: Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC systems for the delivery of local anesthetic drug, ropivacaine (RVC. Methods: In this study, transcriptional transactivator peptide (TAT-decorated RVC-loaded NCs (TAT-RVC/NCs were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. Results: The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. Conclusion: These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia. Keywords: local anesthetic system, ropivacaine, transcriptional transactivator peptide, nanocarriers, skin delivery

  3. Targeted delivery of immunotoxin by antibody to ganglioside GD3: a novel drug delivery route for tumor cells.

    Directory of Open Access Journals (Sweden)

    Vanina Torres Demichelis

    Full Text Available Gangliosides are sialic acid-containing glycolipids expressed on plasma membranes from nearly all vertebrate cells. The expression of ganglioside GD3, which plays essential roles in normal brain development, decreases in adults but is up regulated in neuroectodermal and epithelial derived cancers. R24 antibody, directed against ganglioside GD3, is a validated tumor target which is specifically endocytosed and accumulated in endosomes. Here, we exploit the internalization feature of the R24 antibody for the selective delivery of saporin, a ribosome-inactivating protein, to GD3-expressing cells [human (SK-Mel-28 and mouse (B16 melanoma cells and Chinese hamster ovary (CHO-K1 cells]. This immunotoxin showed a specific cytotoxicity on tumor cells grew on 2D monolayers, which was further evident by the lack of any effect on GD3-negative cells. To estimate the potential antitumor activity of R24-saporin complex, we also evaluated the effect of the immunotoxin on the clonogenic growth of SK-Mel-28 and CHO-K1(GD3+ cells cultured in attachment-free conditions. A drastic growth inhibition (>80-90% of the cell colonies was reached after 3 days of immunotoxin treatment. By the contrary, colonies continue to growth at the same concentration of the immuntoxin, but in the absence of R24 antibody, or in the absence of both immunotoxin and R24, undoubtedly indicating the specificity of the effect observed. Thus, the ganglioside GD3 emerge as a novel and attractive class of cell surface molecule for targeted delivery of cytotoxic agents and, therefore, provides a rationale for future therapeutic intervention in cancer.

  4. Food emulsions as delivery systems for flavor compounds: A review.

    Science.gov (United States)

    Mao, Like; Roos, Yrjö H; Biliaderis, Costas G; Miao, Song

    2017-10-13

    Food flavor is an important attribute of quality food, and it largely determines consumer food preference. Many food products exist as emulsions or experience emulsification during processing, and therefore, a good understanding of flavor release from emulsions is essential to design food with desirable flavor characteristics. Emulsions are biphasic systems, where flavor compounds are partitioning into different phases, and the releases can be modulated through different ways. Emulsion ingredients, such as oils, emulsifiers, thickening agents, can interact with flavor compounds, thus modifying the thermodynamic behavior of flavor compounds. Emulsion structures, including droplet size and size distribution, viscosity, interface thickness, etc., can influence flavor component partition and their diffusion in the emulsions, resulting in different release kinetics. When emulsions are consumed in the mouth, both emulsion ingredients and structures undergo significant changes, resulting in different flavor perception. Special design of emulsion structures in the water phase, oil phase, and interface provides emulsions with great potential as delivery systems to control flavor release in wider applications. This review provides an overview of the current understanding of flavor release from emulsions, and how emulsions can behave as delivery systems for flavor compounds to better design novel food products with enhanced sensorial and nutritional attributes.

  5. Polymer based drug delivery systems for mycobacterial infections.

    Science.gov (United States)

    Pandey, Rajesh; Khuller, G K

    2004-07-01

    In the last decade, polymer based technologies have found wide biomedical applications. Polymers, whether synthetic (e.g. polylactide-co-glycolide or PLG) or natural (e.g. alginate, chitosan etc.), have the property of encapsulating a diverse range of molecules of biological interest and bear distinct therapeutic advantages such as controlled release of drugs, protection against the premature degradation of drugs and reduction in drug toxicity. These are important considerations in the long-duration treatment of chronic infectious diseases such as tuberculosis in which patient non-compliance is the major obstacle to successful chemotherapy. Antitubercular drugs, singly or in combination, have been encapsulated in polymers to provide controlled drug release and the system also offers the flexibility of selecting various routes of administration such as oral, subcutaneous and aerosol. The present review highlights the approaches towards the preparation of polymeric antitubercular drug delivery systems, emphasizing how the route of administration may influence drug bioavailability as well as the chemotherapeutic efficacy. In addition, the pros and cons of the various delivery systems are also discussed.

  6. The Oral Health Care Delivery System in 2040: Executive Summary.

    Science.gov (United States)

    Bailit, Howard L

    2017-09-01

    This executive summary for Section 4 of the "Advancing Dental Education in the 21 st Century" project examines the projected oral health care delivery system in 2040 and the likely impact of system changes on dental education. Dental care is at an early stage of major changes with the decline in solo practice and increase in large group practices. These groups are not consolidated at the state level, but further consolidation is expected as they try to increase their negotiating leverage with dental insurers. At this time, there is limited integration of medical and dental care in terms of financing, regulation, education, and delivery. This pattern may change as health maintenance organizations and integrated medical systems begin to offer dental care to their members. By 2040, it is expected that many dentists will be employed in large group practices and working with allied dental staff with expanded duties and other health professionals, and more dental graduates will seek formal postdoctoral training to obtain better positions in group practices.

  7. Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Piyush Mehta

    2016-01-01

    Full Text Available Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases.

  8. Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

    Science.gov (United States)

    Wang, Xueting; Wang, Ning; Li, Ning; Zhen, Yuanyuan; Wang, Ting

    2016-01-01

    ABSTRACT To overcome drawbacks of current injection vaccines, such as causing needle phobia, needing health professionals for inoculation, and generating dangerous sharps wastes, researchers have designed novel vaccines that are combined with various microneedle arrays (MAs), in particular, with the multifunctional particle-constructed MAs (MPMAs). MPMAs prove able to enhance vaccine stability through incorporating vaccine ingredients in the carrier, and can be painlessly inoculated by minimally trained workers or by self-administration, leaving behind no metal needle pollution while eliciting robust systemic and mucosal immunity to antigens, thanks to delivering vaccines to cutaneous or mucosal compartments enriched in professional antigen-presenting cells (APCs). Especially, MPMAs can be easily integrated with functional molecules fulfilling targeting vaccine delivery or controlling immune response toward a Th1 or Th2 pathway to generate desired immunity against pathogens. Herein, we introduce the latest research and development of various MPMAs which are a novel but promising vaccine adjuvant delivery system (VADS). PMID:27159879

  9. Knock-down of ELMO1 in Paediatric Rhabdomyosarcoma Cells by Nanoparticle Mediated siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Xinyue Huang

    2016-03-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue sarcoma that is found in children and has a poor outcome for those with metastatic disease. Two histological groups have been distinguished - embryonal (ERMS and alveolar (ARMS forms. The ARMS subtype has higher rates of metastasis, as well as higher levels of ELMO1, which is thought to be involved in cell migration. Therefore, the knock-down of ELMO1 by targeted siRNA could provide a mechanism to prevent the metastatic behaviour of ARMS cells. However, challenges still lie in the delivery of nucleotides to a tumour site. Herein, we have described the use of a variety of mesoporous silica nanoparticles as a delivery system for siRNA that is specific for ELMO1 and shown the effective reduction in cell invasive behaviour in these cells.

  10. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells

    NARCIS (Netherlands)

    Hindriksen, Sanne; Bramer, Arne J; Truong, My Anh; Vromans, Martijn J M; Post, Jasmin B; Verlaan-Klink, Ingrid; Snippert, Hugo J; Lens, Susanne M A; Hadders, Michael A

    2017-01-01

    The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited

  11. Waste Feed Delivery System Phase 1 Preliminary RAM Analysis

    International Nuclear Information System (INIS)

    DYKES, A.A.

    2000-01-01

    This report presents the updated results of the preliminary reliability, availability, and maintainability (RAM) analysis of selected waste feed delivery (WFD) operations to be performed by the Tank Farm Contractor (TFC) during Phase I activities in support of the Waste Treatment and Immobilization Plant (WTP). For planning purposes, waste feed tanks are being divided into five classes in accordance with the type of waste in each tank and the activities required to retrieve, qualify, and transfer waste feed. This report reflects the baseline design and operating concept, as of the beginning of Fiscal Year 2000, for the delivery of feed from three of these classes, represented by source tanks 241-AN-102, 241-AZ-101 and 241-AN-105. The preliminary RAM analysis quantifies the potential schedule delay associated with operations and maintenance (OBM) field activities needed to accomplish these operations. The RAM analysis is preliminary because the system design, process definition, and activity planning are in a state of evolution. The results are being used to support the continuing development of an O and M Concept tailored to the unique requirements of the WFD Program, which is being documented in various volumes of the Waste Feed Delivery Technical Basis (Carlson. 1999, Rasmussen 1999, and Orme 2000). The waste feed provided to the WTP must: (1) meet limits for chemical and radioactive constituents based on pre-established compositional envelopes (i.e., feed quality); (2) be in acceptable quantities within a prescribed sequence to meet feed quantities; and (3) meet schedule requirements (i.e., feed timing). In the absence of new criteria related to acceptable schedule performance due to the termination of the TWRS Privatization Contract, the original criteria from the Tank Waste Remediation System (77443s) Privatization Contract (DOE 1998) will continue to be used for this analysis

  12. Computer control of the TFTR tritium storage and delivery system

    International Nuclear Information System (INIS)

    Youssef, N.; Phillips, H.; Yemin, L.; Dong, J.; Pierce, C.

    1980-01-01

    The Tritium Storage and Delivery System (TSDS) will deliver to the torus the required tritium gas in precisely controlled injection profiles. This system will utilize advanced Central Instrumentation, Control and Data Acquisition (CICADA) computer-control techniques, in normal and malfunction-recovery modes of operation. The control scheme of the TSDS is built of three main control scenarios. An operating mode defines the permissives, sequence and path of a process during each scenario. The computerized control of the TSDS has four distinct advantages: (1) versatile control with fast response times both for tritium gas generation and for gas injection into the torus; (2) ease of selecting the proper operating modes of a control scenario, (3) ease of operation without disturbing the multiple levels of containment, and (4) simple fast trouble shooting of system malfunction utilizing programmed procedures and on-line diagnosis. The TSDS has both remote nd local control capability

  13. [Formulation aspects and ex-vivo examination of buccal drug delivery systems].

    Science.gov (United States)

    Szabó, Barnabás; Hetényi, Gergely; Majoros, Klaudia; Miszori, Veronika; Kállai, Nikolett; Zelkó, Romána

    2011-01-01

    Application of buccal dosage forms has several advantages. Buccal route can be used for systemic delivery because the mucosa has a rich blood supply and it is relatively permeable. This route of drug delivery is of special advantages, including the bypass of first pass effect and the avoidance of presystemic elimination within the GIT. Buccal delivery systems enable the systemic delivery of peptides and proteins. In our previous study the physiological background of this application and the excipients of the possible formulations were reviewed. In the present work the formulation and ex vivo examination aspects of buccal drug delivery systems are summarized.

  14. Application of pulsed-magnetic field enhances non-viral gene delivery in primary cells from different origins

    Energy Technology Data Exchange (ETDEWEB)

    Kamau Chapman, Sarah W. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057 Zurich (Switzerland); Hassa, Paul O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057 Zurich (Switzerland); European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg (Germany); Koch-Schneidemann, Sabine; Rechenberg, Brigitte von [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Hofmann-Amtenbrink, Margarethe [MatSearch, Chemin Jean Pavillard 14, 1009 Pully (Switzerland); Steitz, Benedikt; Petri-Fink, Alke; Hofmann, Heinrich [Laboratory of Powder Technology, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland); Hottiger, Michael O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057 Zurich (Switzerland)], E-mail: hottiger@vetbio.uzh.ch

    2008-04-15

    Primary cell lines are more difficult to transfect when compared to immortalized/transformed cell lines, and hence new techniques are required to enhance the transfection efficiency in these cells. We isolated and established primary cultures of synoviocytes, chondrocytes, osteoblasts, melanocytes, macrophages, lung fibroblasts, and embryonic fibroblasts. These cells differed in several properties, and hence were a good representative sample of cells that would be targeted for expression and delivery of therapeutic genes in vivo. The efficiency of gene delivery in all these cells was enhanced using polyethylenimine-coated polyMAG magnetic nanoparticles, and the rates (17-84.2%) surpassed those previously achieved using other methods, especially in cells that are difficult to transfect. The application of permanent and pulsating magnetic fields significantly enhanced the transfection efficiencies in synoviocytes, chondrocytes, osteoblasts, melanocytes and lung fibroblasts, within 5 min of exposure to these magnetic fields. This is an added advantage for future in vivo applications, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occurs.

  15. Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration.

    Science.gov (United States)

    Tarafder, Solaiman; Koch, Alia; Jun, Yena; Chou, Conrad; Awadallah, Mary R; Lee, Chang H

    2016-04-25

    Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF's bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing cartridges during a single printing process. Spatially controlled delivery of GFs, with a prolonged release, guided formation of multi-tissue interfaces from bone marrow derived mesenchymal stem/progenitor cells (MSCs). To investigate efficacy of the micro-precise delivery system embedded in 3D printed scaffold, temporomandibular joint (TMJ) disc scaffolds were fabricated with micro-precise spatiotemporal delivery of CTGF and TGFβ3, mimicking native-like multiphase fibrocartilage. In vitro, TMJ disc scaffolds spatially embedded with CTGF/TGFβ3-μS resulted in formation of multiphase fibrocartilaginous tissues from MSCs. In vivo, TMJ disc perforation was performed in rabbits, followed by implantation of CTGF/TGFβ3-μS-embedded scaffolds. After 4 wks, CTGF/TGFβ3-μS embedded scaffolds significantly improved healing of the perforated TMJ disc as compared to the degenerated TMJ disc in the control group with scaffold embedded with empty μS. In addition, CTGF/TGFβ3-μS embedded scaffolds significantly prevented arthritic changes on TMJ condyles. In conclusion, our micro-precise spatiotemporal delivery system embedded in 3D printing may serve as an efficient tool to regenerate complex and inhomogeneous tissues.

  16. Photodynamic efficacy of hypericin targeted by two delivery techniques to hepatocellular carcinoma cells.

    Science.gov (United States)

    Fadel, Maha; Kassab, Kawser; Youssef, Tareq

    2010-09-01

    The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry (DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2 cells were analyzed by means of spectrofluorometry and fluorescence microscopy. Spectroscopic measurements demonstrated that Hyp binds to anti-HSA in its monomeric form. The photocytotoxic effect of Hyp depended clearly on the form of Hyp administered, either in free form, loaded into liposomes or conjugated with anti-HSA. While liposomes loaded with Hyp (Lip-Hyp) did not induce significant phototoxicity, both free Hyp or anti-HSA-Hyp inflicted substantial cell mortality, after photoirradiation. The intracellular uptake of Lip-Hyp by HepG2 cells was estimated to be 20% less compared to free Hyp or anti-HSA-Hyp. In spite of the equal uptake of both free Hyp and anti-HSA-Hyp, HepG2 cells demonstrated a relatively higher mortality with anti-HSA-Hyp compared to free Hyp.

  17. Communication Between Devices in the Viola Document Delivery System

    Directory of Open Access Journals (Sweden)

    Theodor Tolstoy

    2015-01-01

    Full Text Available Viola is a newly developed document delivery system that handles incoming and outgoing requests for printed books, articles, sharing electronic resources, and other document delivery services on the local level in a library organisation. An important part of Viola is the stack fetching Android application that enables librarians to collect books in the open and closed stacks in an efficient manner using a smartphone and a Bluetooth connected portable printer. The aim of this article is to show how information is transferred between systems and devices in Viola. The article presents code examples from Viola that use current .NET technologies. The examples span from the creation of high-level REST-based JSON APIs to byte array communication with a Bluetooth connected printer and the reading of RFID tags. Please note that code examples in this article are for illustration purposes only. Null checking and other exception handling has been removed for clarity. Code that is separated in Viola for testability and other reasons has been brought together to make it more readable.

  18. Development of antimigraine transdermal delivery systems of pizotifen malate.

    Science.gov (United States)

    Serna-Jiménez, C E; del Rio-Sancho, S; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; López-Castellano, A; Merino, V

    2015-08-15

    The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Nanoemulsifying drug delivery system to improve the bioavailability of piroxicam.

    Science.gov (United States)

    Motawea, Amira; Borg, Thanaa; Tarshoby, Manal; Abd El-Gawad, Abd El-Gawad H

    2017-05-01

    The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy. The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets. The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (Feldene ® ) (commercial dosage form (CD)). The relative bioavailability of S-sSNEDDS (F12) relative to PP or CD was about 151.01 and 98.96%, respectively. The obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.

  20. Updates on smart polymeric carrier systems for protein delivery.

    Science.gov (United States)

    El-Sherbiny, Ibrahim; Khalil, Islam; Ali, Isra; Yacoub, Magdi

    2017-10-01

    Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.

  1. Gastroretentive drug delivery systems for therapeutic management of peptic ulcer.

    Science.gov (United States)

    Garg, Tarun; Kumar, Animesh; Rath, Goutam; Goyal, Amit K

    2014-01-01

    A peptic ulcer, stomach ulcer, or gastric ulcer, also known as peptic ulcer disease (PUD), is a very common chronic disorder of the stomach which is mainly caused by damage or impairment of the stomach lining. Various factors such as pepsin, gastric acid, H. pylori, NSAIDs, prostaglandins, mucus, bicarbonate, and blood flow to mucosa play an important role in causing peptic ulcers. In this review article, our main focus is on some important gastroretentive drug delivery systems (GRDDS) (floating, bioadhesive, high density, swellable, raft forming, superporous hydrogel, and magnetic systems) which will be helpful in gastroretention of different dosage forms for treatment of peptic ulcer. GRDDS provides a mean for controlled release of compounds that are absorbed by active transport in the upper intestine. It also enables controlled delivery for paracellularly absorbed drugs without a decrease in bioavailability. The above approaches are specific for targeting and leading to a marked improvement in the quality of life for a large number of patients. In the future, it is expected that they will become of growing significance, finally leading to improved efficiencies of various types of pharmacotherapies.

  2. Metal organic frameworks as a drug delivery system for flurbiprofen

    Directory of Open Access Journals (Sweden)

    AL Haydar M

    2017-09-01

    Full Text Available Muder AL Haydar,1,2 Hussein Rasool Abid,3,4 Bruce Sunderland,2 Shaobin Wang5,6 1Pharmaceutics Department, College of the Pharmacy, University of Kerbala, Kerbala, Iraq; 2Pharmaceutics Department, School of Pharmacy, Faculty of Health Sciences, Curtin University, Perth, WA, Australia; 3Department of Chemical Engineering, Curtin University, Perth, WA, Australia; 4College of Applied Medical Sciences, University of Kerbala, Kerbala, Iraq; 5School of Pharmacy, Faculty of Health Sciences, Curtin University, Perth, WA, Australia; 6Department of Chemical Engineering, School of Chemical and Petroleum Engineering, Faculty of Science and Engineering, Curtin University, Perth, WA, Australia Background: Metal organic frameworks (MOFs have attracted more attention in the last decade because of a suitable pore size, large surface area, and high pore volume. Developing biocompatible MOFs such as the MIL family as a drug delivery system is possible. Purpose: Flurbiprofen (FBP, a nonsteroidal anti-inflammatory agent, is practically insoluble in aqueous solution, and, therefore, needs suitable drug delivery systems. Different biocompatible MOFs such as Ca-MOF and Fe-MILs (53, 100, and 101 were synthesized and employed for FBP delivery. Patients and methods: A sample of 50 mg of each MOF was mixed and stirred for 24 h with 10 mL of 5 mg FBP in acetonitrile (40% in a sealed container. The supernatant of the mixture after centrifuging was analyzed by high-performance liquid chromatography to determine the loaded quantity of FBP on the MOF. The overnight-dried solid material after centrifuging the mixture was analyzed for loading percent using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, nuclear magnetic resonance, and FBP release profile. Results: The loading values of FBP were achieved at 10.0%±1%, 20%±0.8%, 37%±2.3%, and 46%±3.1% on Ca-MOF, Fe-MIL-53, Fe-MIL-101, and Fe-MIL-100, respectively. The FBP release

  3. Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue

    Directory of Open Access Journals (Sweden)

    Zhang X

    2017-08-01

    Full Text Available Xuemei Zhang,1–3 Xuejuan Li,1,4 Hongchen Hua,1 Aiping Wang,1 Wanhui Liu,1–3 Youxin Li,1–3 Fenghua Fu,1–3 Yanan Shi,5 Kaoxiang Sun1 1School of Pharmacy, Yantai University, Yantai, Shandong Province, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, People’s Republic of China; 3Luye Pharmaceutical Co., Ltd., Shandong Province, People’s Republic of China; 4National Engineering and Technology Research Center of Chirality Pharmaceutical, Lunan Pharmaceutical Group Co., Ltd., Shandong Province, People’s Republic of China; 5School of Pharmacy, Binzhou Medical University, Shandong Province, People’s Republic of China Abstract: Glioma has one of the highest mortality rates among primary brain tumors. The clinical treatment for glioma is very difficult due to its infiltration and specific growth locations. To achieve improved drug delivery to a brain tumor, we report the preparation and in vitro and in vivo evaluation of curcumin nanoparticles (Cur-NPs. The cyclic hexapeptide c(RGDf(N-meVK-C (cHP has increased affinity for cells that overexpress integrins and was designed to target Cur-NPs to tumors. Functional polyethyleneglycol-modified poly(D,L-lactide-co-glycolide (PEG-PLGA conjugated to cHP was synthesized, and targeted Cur-NPs were prepared using a self-assembly nanoprecipitation process. The physicochemical properties and the in vitro cytotoxicity, accuracy, and penetration capabilities of Cur-NPs targeting cells with high levels of integrin expression were investigated. The in vivo targeting and penetration capabilities of the NPs were also evaluated against glioma in rats using in vivo imaging equipment. The results showed that the in vitro cytotoxicity of the targeted cHP-modified curcumin nanoparticles (cHP/Cur-NPs was higher than that of either free curcumin or non-targeted Cur-NPs due to the superior ability of the cHP/Cur-NPs to target tumor cells

  4. Ultrasound and photoacoustic imaging to monitor ocular stem cell delivery and tissue regeneration (Conference Presentation)

    Science.gov (United States)

    Kubelick, Kelsey; Snider, Eric; Yoon, Heechul; Ethier, C. Ross; Emelianov, Stanislav Y.

    2017-03-01

    Glaucoma is associated with dysfunction of the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising treatment involves delivery of stem cells to the TM to restore tissue function. Currently histology is the gold standard for tracking stem cell delivery and differentiation. To expedite clinical translation, non-invasive longitudinal monitoring in vivo is desired. Our current research explores a technique combining ultrasound (US) and photoacoustic (PA) imaging to track mesenchymal stem cells (MSCs) after intraocular injection. Adipose-derived MSCs were incubated with gold nanospheres to label cells (AuNS-MSCs) for PA imaging. Successful labeling was first verified with in vitro phantom studies. Next, MSC delivery was imaged ex vivo in porcine eyes, while intraocular pressure was hydrostatically clamped to maintain a physiological flow rate through the TM. US/PA imaging was performed before, during, and after AuNS-MSC delivery. Additionally, spectroscopic PA imaging was implemented to isolate PA signals from AuNS-MSCs. In vitro cell imaging showed AuNS-MSCs produce strong PA signals, suggesting that MSCs can be tracked using PA imaging. While the cornea, sclera, iris, and TM region can be visualized with US imaging, pigmented tissues also produce PA signals. Both modalities provide valuable anatomical landmarks for MSC localization. During delivery, PA imaging can visualize AuNS-MSC motion and location, creating a unique opportunity to guide ocular cell delivery. Lastly, distinct spectral signatures of AuNS-MSCs allow unmixing, with potential for quantitative PA imaging. In conclusion, results show proof-of-concept for monitoring MSC ocular delivery, raising opportunities for in vivo image-guided cell delivery.

  5. Application of drug delivery system for boron neutron capture therapy. Basic research toward clinical application

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Takahashi, Hiroyuki

    2010-01-01

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B and thermal neutrons ( 10 B+ 1 n → 7 Li+ 4 He (α) +2.31 MeV (93.7%)/2.79 MeV (6.3%)). The resulting lithium ions and αparticles are high linear energy transfer (LET) particles which give high biological effect. Their short range in tissue (5-9 μm) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma etc, recently. Sodium borocaptate (Na 2 10 B 12 H 11 SH; BSH) and borono-phenylalanine ( 10 BPA) are currently being used in clinical treatments. To achieve the selective delivery of boron atoms to cancer cells, drug delivery system (DDS) becomes an attractive intelligent technology as targeting and controlled release of drugs. We have firstly reported that 10 B atoms delivered by immunoliposomes are cytotoxic to human pancreatic carcinoma cells (AsPC-1) after thermal neutron irradiation in vitro. The intra-tumoural injection of boronated immunoliposomes can increase the retention of 10 B atoms in tumour cells, causing suppression of tumour growth in vivo following thermal neutron irradiation. We prepared polyethylene-glycol binding liposomes (PEG-liposomes) as an effective 10 B carrier to obviate phagocytosis by reticuloendotherial systems. We had prepared 10 BSH entrapped Water-in-Oil-in-Water (WOW) emulsion. The 10 B concentration in VX-2 tumour after intra-arterial injection of 10 BSH entrapped WOW emulsion was superior to the groups of 10 BSH entrapped conventional Lipiodol mix emulsion. 10 Boron entrapped WOW emulsion is one of the most useful for intra-arterial boron delivery carrier on BNCT to hepatocellular carcinoma. (author)

  6. Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

    Directory of Open Access Journals (Sweden)

    Ranganathan R

    2012-02-01

    Full Text Available Ramya Ranganathan1,*, Shruthilaya Madanmohan1,*, Akila Kesavan1, Ganga Baskar1, Yoganathan Ramia Krishnamoorthy2, Roy Santosham3, D Ponraju4, Suresh Kumar Rayala2, Ganesh Venkatraman1 1Department of Human Genetics, Sri Ramachandra University, Porur, 2Department of Biotechnology, Indian Institute of Technology, Madras, 3Department of Radiology and Imaging Sciences, Sri Ramachandra University, Porur, Chennai, 4Safety Engineering Division, Nuclear and Engineering Safety Group, Indira Gandhi Center for Atomic Research, Kalpakkam, India*Authors contributed equally to this workAbstract: The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems.Keywords: patient-friendly, drug-delivery systems, cancer, nanomedicine

  7. Biomimetic chimeric peptide-tethered hydrogels for human mesenchymal stem cell delivery.

    Science.gov (United States)

    Shim, Gayong; Kim, Gunwoo; Choi, Junhyeok; Yi, TacGhee; Cho, Yun Kyoung; Song, Sun Uk; Byun, Youngro; Oh, Yu-Kyoung

    2015-12-01

    Here, we report a chimeric peptide-tethered fibrin hydrogel scaffold for delivery of human mesenchymal stem cells (hMSC). Osteopontin-derived peptide (OP) was used as an hMSC-tethering moiety. OP showed hMSC adhesion properties and enhanced hMSC proliferation. A natural fibrin-binding protein-derived peptide (FBP) was tested for its ability to tether hMSC to the fibrin gel matrix. FBP loading on fibrin gels was 8.2-fold higher than that of a scrambled peptide (scFBP). FBP-loaded fibrin gels were retained at injection sites longer than scFBP-loaded fibrin gels, showing a 15.9-fold higher photon intensity of fluorescent FBP-grafted fibrin gels than fluorescent scFBP-loaded fibrin gels 48 h after injection. On the basis of the fibrin gel-binding properties of FBP and the hMSC-binding and proliferation-supporting properties of OP, we constructed chimeric peptides containing FBP and OP linked with a spacer (FBPsOP). Four days after transplantation, the survival of hMSC in FBPsOP-grafted fibrin gels was 3.9-fold higher than hMSC in fibrin gels alone. Our results suggest the potential of FBPsOP-grafted fibrin gels as a bioactive delivery system for enhanced survival of stem cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. DNA Tetrahedron Delivery Enhances Doxorubicin-Induced Apoptosis of HT-29 Colon Cancer Cells

    Science.gov (United States)

    Zhang, Guiyu; Zhang, Zhiyong; Yang, Junen

    2017-08-01

    As a nano-sized drug carrier with the advantage of modifiability and proper biocompatibility, DNA tetrahedron (DNA tetra) delivery is hopeful to enhance the inhibitory efficiency of nontargeted anticancer drugs. In this investigation, doxorubicin (Dox) was assembled to a folic acid-modified DNA tetra via click chemistry to prepare a targeted antitumor agent. Cellular uptake efficiency was measured via fluorescent imaging. Cytotoxicity, inhibition efficiency, and corresponding mechanism on colon cancer cell line HT-29 were evaluated by MTT assay, cell proliferation curve, western blot, and flow cytometry. No cytotoxicity was induced by DNA tetra, but the cellular uptake ratio increased obviously resulting from the DNA tetra-facilitated penetration through cellular membrane. Accordingly, folic acid-DNA tetra-Dox markedly increased the antitumor efficiency with increased apoptosis levels. In details, 100 μM was the effective concentration and a 6-h incubation period was needed for apoptosis induction. In conclusion, nano-sized DNA tetrahedron was a safe and effective delivery system for Dox and correspondingly enhanced the anticancer efficiency.

  9. In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

    Science.gov (United States)

    Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

    2013-12-28

    Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the

  10. Technical Evaluation Report 5: Classification of DE Delivery Systems

    Directory of Open Access Journals (Sweden)

    Diane Belyk

    2002-01-01

    Full Text Available For their optimal use in distance education (DE, online educational applications need to be integrated within a comprehensive course management system (CMS. Such systems are server-based software that supports the development, delivery, administration, and evaluation of online learning environments. The selection of an appropriate CMS should be considered from the multiple perspectives of the student, the course developer, the course instructor/ tutor, the technical support staff, and the DE institution’s administration. The current evaluation of CMS packages was conducted by a team of individuals with experience and contacts in relation to each of these DE user types. The report compares a series of CMS packages in terms of their range of features, and in relation to their satisfaction of international online education standards.

  11. Spatial service delivery system for smart licensing & enforcement management

    Science.gov (United States)

    Wahap, N. A.; Ismail, N. M.; Nor, N. M.; Ahmad, N.; Omar, M. F.; Termizi, A. A. A.; Zainal, D.; Noordin, N. M.; Mansor, S.

    2016-06-01

    Spatial information has introduced a new sense of urgency for a better understanding of the public needs in term of what, when and where they need services and through which devices, platform or physical locations they need them. The objective of this project is to value- add existing license management process for business premises which comes under the responsibility of Local Authority (PBT). Manipulation of geospatial and tracing technology via mobile platform allows enforcement officers to work in real-time, use a standardized system, improve service delivery, and optimize operation management. This paper will augment the scope and capabilities of proposed concept namely, Smart Licensing/Enforcement Management (SLEm). It will review the current licensing and enforcement practice of selected PBT in comparison to the enhanced method. As a result, the new enhanced system is expected to offer a total solution for licensing/enforcement management whilst increasing efficiency and transparency for smart city management and governance.

  12. Applications of nanoparticle systems in drug delivery technology

    Directory of Open Access Journals (Sweden)

    Syed A.A. Rizvi

    2018-01-01

    Full Text Available The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.

  13. Colloidal formulations for probiotics delivery and Pickering systems

    DEFF Research Database (Denmark)

    Yücel Falco, Cigdem

    countries. One emerging functional food area is the efficient delivery of health-promoting probiotics. Although much progress has already been made in the development and understanding of novel microencapsulation systems, maintaining viability during gastric passage and being effective at the target site...... is still an issue for probiotics. On the other hand, one of the foremost challenges in the production of physically stable foods during the defined shelf life is the identification of new food-grade ingredients. In this context, the replacement of classical emulsifiers with solid particles is one...... of the advancing food research areas, though the number of food-grade solid particles investigated is still insufficient. Edible probiotic strains can potentially be valorised as particles similar to micron-sized fat particles in Pickering systems such as ice cream due to their low calories and their availability...

  14. Managerial competence at senior levels of integrated delivery systems.

    Science.gov (United States)

    Longest, B B

    1998-01-01

    The advent of integrated delivery systems (IDSs) in the healthcare industry has changed much about the work involved in running many healthcare organizations. As a result of these changes, senior healthcare managers in IDSs need different skills and knowledge (competencies) than managers of other healthcare systems. The work of managers is changed by the shift to more organizational integration in the healthcare industry because they become responsible for coordinated continuation of services, accountable for the overall health status of the populations they serve, and involved in more complex organizational structures. The article identifies six distinct managerial competencies--conceptual, technical managerial/clinical, interpersonal/collaborative, political, commercial, and governance--and describes how they relate to an IDS senior manager's successful work performance. The implications of these competencies are considered for practicing senior managers in IDSs, as well as those who aspire to such positions, and those who help educate them.

  15. Microfluidic Devices for Drug Delivery Systems and Drug Screening

    Science.gov (United States)

    Kompella, Uday B.; Damiati, Safa A.

    2018-01-01

    Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

  16. Operating experience with TFTR's Tritium Storage and Delivery System

    International Nuclear Information System (INIS)

    Voorhees, D.R.

    1995-01-01

    The Tritium Storage and Delivery System (TSDS) at TFTR was fabricated at Monsanto Mound Lab in the late 1970's and delivered to PPPL in the early 1980's. Commissioning progressed slowly and was finally completed in 1992 following a series of Preoperational tests and Integrated Systems tests. Those tests included thorough leak testing of glove boxes and process piping, electrical interlocks and controls, instrumentation calibrations, volume determinations and verification of uranium bed capacity. The system accepted tritium in dilute form in May of 1993 and began serious usage of pure tritium in November 1993. As the throughput of high purity tritium increased, shortcomings of the system became evident and extensive repairs were implemented. System leakage and material compatibility were the primary causes of the problems. To date, the system has received, stored and delivered over 500 kCi of tritium and is performing very well. The dedicated quadrupole mass spectrometer and beta scintillator system has been analyzing tritium bearing and pure gas streams for over 3 years with minimal downtime

  17. Polymer-Based Novel Lung Targeted Delivery Systems.

    Science.gov (United States)

    Elmowafy, Enas; Osman, Rihab; Ishak, Rania A H

    2017-01-01

    Due to its unique features, the respiratory tract had received great attention as a promising non-invasive route for drug administration to achieve both local and systemic effects. Efforts spent to tailor systems able to overcome the lung defence mechanisms and biological barriers are followed in this review. Aerodynamic diameter, morphology, lung deposition and drug release profiles are the main criteria describing the selected new smart lung targeted delivery systems. Novel systems such as nanoparticles, nano-embedded-in microparticles (NEM), small microparticles (MP), large porous particles (LPP), PulmospheresTM and polymeric micelles are used to passively target different areas in the respiratory tract. The most common preparation methods are outlined in the article. Special emphasis was given to the characteristics of the polymers used to fabricate the developed systems. Efforts made to prepare systems using chitosan (CS), alginate (alg), hyaluronic acid (HA), gelatin and albumin as examples of natural polymers and poly lactic-co-glycolic acid (PLGA) and poly(Ɛ-caprolactone) (PCL) as synthetic polymers were compiled. The continuous development and work in the area of lung targeting resulted in the development of engineered smart platforms with the capability to carry small drug molecules, proteins and genes to treat a variety of local and systemic diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

    Science.gov (United States)

    Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

    2017-06-01

    A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

  19. Solar cell concentrating system

    International Nuclear Information System (INIS)

    Garg, H.P.; Sharma, V.K.; Agarwal, R.K.

    1986-11-01

    This study reviews fabrication techniques and testing facilities for different solar cells under concentration which have been developed and tested. It is also aimed to examine solar energy concentrators which are prospective candidates for photovoltaic concentrator systems. This may provide an impetus to the scientists working in the area of solar cell technology

  20. Assessment of Advanced Logistics Delivery System (ALDS) Launch Systems Concepts

    National Research Council Canada - National Science Library

    Anderson, Gregory W; Borraccini, Joseph P; Fitzpatrick, Brian K; Lynch, William A; McGinnis, Patrick J

    2004-01-01

    .... A study to analyze the machinery technologies capable of meeting this requirement identified a near term solution based on electric linear motor technology derived from the Electromagnetic Aircraft Launch System (EMALS...

  1. Potential and problems in ultrasound-responsive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Zhao YZ

    2013-04-01

    Full Text Available Ying-Zheng Zhao,1,3 Li-Na Du,2 Cui-Tao Lu,1 Yi-Guang Jin,2 Shu-Ping Ge3 1Wenzhou Medical College, Wenzhou City, Zhejiang Province, 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3St Christopher’s Hospital for Children/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. Keywords: ultrasound, targeted therapy, clinical application

  2. Gamma-sterilization-induced radicals in biodegradable drug delivery systems

    International Nuclear Information System (INIS)

    Maeder, K.; Swartz, H.M.; Domb, A.

    1996-01-01

    Electron paramagnetic resonance (EPR) spectroscopy (1.2 and 9.25 GHz, 25 o C) was used to characterize free radicals in gamma-ray sterilized biodegradable polymers of the type which are in clinical use. Free radicals were detected in all irradiated polymer samples. The temperature of irradiation (25 o vs dry ice temperature) had only a minor influence on the yield of radicals and the shape of the EPR spectra. In contrast, the composition of the polymers and the drugs incorporated in them did strongly influence the amount of radiation-induced free radicals and their reactivity. In general, polymers with high melting points and crystallinity had the highest yields of radicals observable at room temperature. We were able to use the free radicals induced by the usual sterilization procedures to follow the penetration of water and the degradation of the polymers in vitro and in vivo. The ability of in vivo EPR to follow drug delivery noninvasively and continuously in vivo, using the free radicals induced in the usual sterilization process indicates that this approach could be applied immediately for the characterization of these drug delivery systems in experimental animals and in the near future should be able to be used in human subjects. (author)

  3. Design and evaluate alginate nanoparticles as a protein delivery system

    Directory of Open Access Journals (Sweden)

    Saraei, F.

    2013-12-01

    Full Text Available In recent years, encapsulation of drugs and antigens in hydrogels, specifically in calcium alginate particles, is an interesting and practical technique that was developed widespread. It is well known that alginate solution, under proper conditions, can form suitable nanoparticles as a promising carrier system, for vaccine delivery. The aim of this study was to synthesis alginate nanoparticles as protein carrier and to evaluate the influence of various factors on nanoparticles properties. Alginate nanoparticles were prepared by ionic gelation method. Briefly, various concentrations of CaCl2 were added to different concentrations of sodium alginate dropwisly by homogenizing magnetically at 1300 rpm. The effects of homogenization time and (- rate were investigated on nanoparticle feature. Nanoparticles were characterized for their morphology and size distribution. Evaluation of loading capacity and loading efficiency of nanoparticles were performed by using various concentration of BSA. The concentration of 0.3%w/v sodium alginate and 0.1%w/v CaCl2 solution, homogenization time 45 min and homogenization rate 1300 rpm were observed as suitable condition - to prepare optimized nanoparticles. It can be concluded that the properties of nanoparticles are strongly dependent on the physicochemical conditions. The optimum concentrations of alginate and CaCl2and appropriate condition led to forming desirable nanoparticles that can be used as carrier for drug and vaccine delivery.

  4. Delivery Systems for In Vivo use of Nucleic Acid Drugs

    Directory of Open Access Journals (Sweden)

    Resende R.R

    2007-01-01

    Full Text Available The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affi nity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cellular internalization. This review discusses some of the mechanisms of action and the application of therapies based on nucleic acids such as aptamers and RNA interference as well as platforms for cellular uptake and intracellular delivery of therapeutic oligonucleotides and their trade-offs.

  5. Strategic workforce planning for a multihospital, integrated delivery system.

    Science.gov (United States)

    Datz, David; Hallberg, Colleen; Harris, Kathy; Harrison, Lisa; Samples, Patience

    2012-01-01

    Banner Health has long recognized the need to anticipate, beyond the immediate operational realities or even the annual budgeting projection exercises, the necessary workforce needs of the future. Thus, in 2011, Banner implemented a workforce planning model that included structures, processes, and tools for predicting workforce needs, with particular focus on identified critical systemwide practice areas. The model represents the incorporation of labor management tools and processes with more strategic, broad-view, long-term assessment and planning mechanisms. The sequential tying of the workforce planning lifecycle with the organization's strategy and financial planning process supports alignment of goals, objectives, and resource allocation. Collaboration among strategy, finance, human resources, and operations has provided us with the ability to identify critical position groups based on 3-year strategic priorities. By engaging leaders from across the organization, focusing on activities at facility, regional, and system levels, and building in mechanisms for accountability, we are now engaged in continuous evaluations of our delivery models, the competencies and preparations necessary for the staff to effectively function within those delivery models, and developing and implementing action plans designed to ensure adequate numbers of the staff whose competencies will be suited to the work expected of them.

  6. Single-cell manipulation and DNA delivery technology using atomic force microscopy and nanoneedle.

    Science.gov (United States)

    Han, Sung-Woong; Nakamura, Chikashi; Miyake, Jun; Chang, Sang-Mok; Adachi, Taiji

    2014-01-01

    The recent single-cell manipulation technology using atomic force microscopy (AFM) not only allows high-resolution visualization and probing of biomolecules and cells but also provides spatial and temporal access to the interior of living cells via the nanoneedle technology. Here we review the development and application of single-cell manipulations and the DNA delivery technology using a nanoneedle. We briefly describe various DNA delivery methods and discuss their advantages and disadvantages. Fabrication of the nanoneedle, visualization of nanoneedle insertion into living cells, DNA modification on the nanoneedle surface, and the invasiveness of nanoneedle insertion into living cells are described. Different methods of DNA delivery into a living cell, such as lipofection, microinjection, and nanoneedles, are then compared. Finally, single-cell diagnostics using the nanoneedle and the perspectives of the nanoneedle technology are outlined. The nanoneedle-based DNA delivery technology provides new opportunities for efficient and specific introduction of DNA and other biomolecules into precious living cells with a high spatial resolution within a desired time frame. This technology has the potential to be applied for many basic cellular studies and for clinical studies such as single-cell diagnostics.

  7. Near-Infrared Light Activation of Proteins Inside Living Cells Enabled by Carbon Nanotube-Mediated Intracellular Delivery.

    Science.gov (United States)

    Li, He; Fan, Xinqi; Chen, Xing

    2016-02-01

    Light-responsive proteins have been delivered into the cells for controlling intracellular events with high spatial and temporal resolution. However, the choice of wavelength is limited to the UV and visible range; activation of proteins inside the cells using near-infrared (NIR) light, which has better tissue penetration and biocompatibility, remains elusive. Here, we report the development of a single-walled carbon nanotube (SWCNT)-based bifunctional system that enables protein intracellular delivery, followed by NIR activation of the deliver