Nanoparticle Approaches against Bacterial Infections

PubMed Central

Gao, Weiwei; Thamphiwatana, Soracha; Angsantikul, Pavimol; Zhang, Liangfang

2014-01-01

Despite the wide success of antibiotics, the treatment of bacterial infection still faces significant challenges, particularly the emergence of antibiotic resistance. As a result, nanoparticle drug delivery platforms including liposomes, polymeric nanoparticles, dendrimers, and various inorganic nanoparticles have been increasingly exploited to enhance the therapeutic effectiveness of existing antibiotics. This review focuses on areas where nanoparticle approaches hold significant potential to advance the treatment of bacterial infection. These areas include targeted antibiotic delivery, environmentally responsive antibiotic delivery, combinatorial antibiotic delivery, nanoparticle-enabled antibacterial vaccination, and nanoparticle-based bacterial detection. In each area we highlight the innovative antimicrobial nanoparticle platforms and review their progress made against bacterial infections. PMID:25044325

Environmental Assessment Addressing the Expansion of Sortie-Operations at Moody Air Force Base, Georgia

DTIC Science & Technology

2012-08-01

include the tactical delivery of air-to-ground munitions, laser designation of targets from ground and airborne platforms, and threat evasion. These...world events, which include the tactical delivery of air-to-ground munitions, laser designation of targets from ground and airborne platforms, and...Closure CAA Clean Air Act CAU Classic Associate Unit CEQ Council on Environmental Quality CFR Code of Federal Regulations CO carbon monoxide

Design, Synthesis, and Biological Functionality of a Dendrimer-based Modular Drug Delivery Platform

PubMed Central

Mullen, Douglas G.; McNerny, Daniel Q.; Desai, Ankur; Cheng, Xue-min; DiMaggio, Stassi C.; Kotlyar, Alina; Zhong, Yueyang; Qin, Suyang; Kelly, Christopher V.; Thomas, Thommey P.; Majoros, Istvan; Orr, Bradford G.; Baker, James R.; Banaszak Holl, Mark M.

2011-01-01

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction (‘click’ chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate ‘click’ reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by 1H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the over-expressed folic acid receptor. PMID:21425790

Nanochannel Electroporation as a Platform for Living Cell Interrogation in Acute Myeloid Leukemia.

PubMed

Zhao, Xi; Huang, Xiaomeng; Wang, Xinmei; Wu, Yun; Eisfeld, Ann-Kathrin; Schwind, Sebastian; Gallego-Perez, Daniel; Boukany, Pouyan E; Marcucci, Guido I; Lee, Ly James

2015-12-01

A living cell interrogation platform based on nanochannel electroporation is demonstrated with analysis of RNAs in single cells. This minimally invasive process is based on individual cells and allows both multi-target analysis and stimulus-response analysis by sequential deliveries. The unique platform possesses a great potential to the comprehensive and lysis-free nucleic acid analysis on rare or hard-to-transfect cells.

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

NASA Astrophysics Data System (ADS)

Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

2014-08-01

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

NASA Astrophysics Data System (ADS)

Subramaniam, Prasad

Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on the synthesis and use of a biodegradable dendritic polypeptide-based nanocarrier for the delivery of multiple anticancer drugs and siRNA to brain tumor cells. The co-delivery of important anticancer agents using a single platform was shown to increase the efficacy of the drugs manyfold, ensuring the cancer cell-specific delivery and minimizing dose limiting toxicities of the individual drugs. This would be of immense importance when used in vivo.

Rhamnogalacturonan-I Based Microcapsules for Targeted Drug Release

PubMed Central

Kusic, Anja; De Gobba, Cristian; Larsen, Flemming H.; Sassene, Philip; Zhou, Qi; van de Weert, Marco; Mullertz, Anette; Jørgensen, Bodil; Ulvskov, Peter

2016-01-01

Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were loaded with a fluorescent dye (model drug). The capsules showed negligible and very little in vitro release when subjected to media simulating gastric and intestinal fluids, respectively. However, upon exposure to a cocktail of commercial RG-I cleaving enzymes, ~ 9 times higher release was observed, demonstrating that the capsules can be opened by enzymatic degradation. The combined results suggest a potential platform for targeted drug delivery in the terminal gastro-intestinal tract. PMID:27992455

A Versatile Bioorthogonal Copper-free Click Chemistry Platform to Functionalize Cisplatin Prodrugs

PubMed Central

Pathak, Rakesh K.; McNitt, Christopher D.; Popik, Vladimir V.; Dhar, Shanta

2015-01-01

The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities by considering the sensitivity of Pt(IV) centers to reduction, thiols, etc, we used a strain promoted azide alkyne cycloaddition (SPAAC) approach to provide a novel platform where new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nano-delivery vehicle and conjugation to fluorescent reporters were also investigated. PMID:24756923

SMS-Based Learning in Tertiary Education: Achievement and Attitudinal Outcomes

ERIC Educational Resources Information Center

Katz, Yaacov J.

2013-01-01

SMS delivery platforms are being increasingly used at the university level to enhance student achievement as well as traits and attitudes related to the learning process. SMS delivery provides access to learning materials without being limited by space or time and sophisticated technological advances in SMS delivery have led to enhanced learner…

Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

PubMed Central

McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

2014-01-01

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept.

PubMed

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-05-28

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an "intelligent" drug delivery system based on a feedback loop to monitor drug delivery.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept

PubMed Central

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-01-01

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μM was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an “intelligent” drug delivery system based on a feedback loop to monitor drug delivery. PMID:27240377

Strategies to Maximize the Potential of Marine Biomaterials as a Platform for Cell Therapy

PubMed Central

Kim, Hyeongmin; Lee, Jaehwi

2016-01-01

Marine biopolymers have been explored as a promising cell therapy system for efficient cell delivery and tissue engineering. However, the marine biomaterial-based systems themselves have exhibited limited performance in terms of maintenance of cell viability and functions, promotion of cell proliferation and differentiation as well as cell delivery efficiency. Thus, numerous novel strategies have been devised to improve cell therapy outcomes. The strategies include optimization of physical and biochemical properties, provision of stimuli-responsive functions, and design of platforms for efficient cell delivery and tissue engineering. These approaches have demonstrated substantial improvement of therapeutic outcomes in a variety of research settings. In this review, therefore, research progress made with marine biomaterials as a platform for cell therapy is reported along with current research directions to further advance cell therapies as a tool to cure incurable diseases. PMID:26821034

A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer.

PubMed

Levy, Oren; Brennen, W Nathaniel; Han, Edward; Rosen, David Marc; Musabeyezu, Juliet; Safaee, Helia; Ranganath, Sudhir; Ngai, Jessica; Heinelt, Martina; Milton, Yuka; Wang, Hao; Bhagchandani, Sachin H; Joshi, Nitin; Bhowmick, Neil; Denmeade, Samuel R; Isaacs, John T; Karp, Jeffrey M

2016-06-01

Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

High content analysis platform for optimization of lipid mediated CRISPR-Cas9 delivery strategies in human cells.

PubMed

Steyer, Benjamin; Carlson-Stevermer, Jared; Angenent-Mari, Nicolas; Khalil, Andrew; Harkness, Ty; Saha, Krishanu

2016-04-01

Non-viral gene-editing of human cells using the CRISPR-Cas9 system requires optimized delivery of multiple components. Both the Cas9 endonuclease and a single guide RNA, that defines the genomic target, need to be present and co-localized within the nucleus for efficient gene-editing to occur. This work describes a new high-throughput screening platform for the optimization of CRISPR-Cas9 delivery strategies. By exploiting high content image analysis and microcontact printed plates, multi-parametric gene-editing outcome data from hundreds to thousands of isolated cell populations can be screened simultaneously. Employing this platform, we systematically screened four commercially available cationic lipid transfection materials with a range of RNAs encoding the CRISPR-Cas9 system. Analysis of Cas9 expression and editing of a fluorescent mCherry reporter transgene within human embryonic kidney cells was monitored over several days after transfection. Design of experiments analysis enabled rigorous evaluation of delivery materials and RNA concentration conditions. The results of this analysis indicated that the concentration and identity of transfection material have significantly greater effect on gene-editing than ratio or total amount of RNA. Cell subpopulation analysis on microcontact printed plates, further revealed that low cell number and high Cas9 expression, 24h after CRISPR-Cas9 delivery, were strong predictors of gene-editing outcomes. These results suggest design principles for the development of materials and transfection strategies with lipid-based materials. This platform could be applied to rapidly optimize materials for gene-editing in a variety of cell/tissue types in order to advance genomic medicine, regenerative biology and drug discovery. CRISPR-Cas9 is a new gene-editing technology for "genome surgery" that is anticipated to treat genetic diseases. This technology uses multiple components of the Cas9 system to cut out disease-causing mutations in the human genome and precisely suture in therapeutic sequences. Biomaterials based delivery strategies could help transition these technologies to the clinic. The design space for materials based delivery strategies is vast and optimization is essential to ensuring the safety and efficacy of these treatments. Therefore, new methods are required to rapidly and systematically screen gene-editing efficacy in human cells. This work utilizes an innovative platform to generate and screen many formulations of synthetic biomaterials and components of the CRISPR-Cas9 system in parallel. On this platform, we watch genome surgery in action using high content image analysis. These capabilities enabled us to identify formulation parameters for Cas9-material complexes that can optimize gene-editing in a specific human cell type. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Stent-mediated gene and drug delivery for cardiovascular disease and cancer: A brief insight.

PubMed

Krishnagopal, Akshaya; Reddy, Aakash; Sen, Dwaipayan

2017-05-01

This review concisely recapitulates the different existing modes of stent-mediated gene/drug delivery, their considerable advancement in clinical trials and a rationale for other merging new technologies such as nanotechnology and microRNA-based therapeutics, in addition to addressing the limitations in each of these perpetual stent platforms. Over the past decade, stent-mediated gene/drug delivery has materialized as a hopeful alternative for cardiovascular disease and cancer in contrast to routine conventional treatment modalities. Regardless of the phenomenal recent developments achieved by coronary interventions and cancer therapies that employ gene and drug-eluting stents, practical hurdles still remain a challenge. The present review highlights the limitations that each of the existing stent-based gene/drug delivery system encompasses and therefore provides a vision for the future with respect to discovering an ideal stent therapeutic platform that would circumvent all the practical hurdles witnessed with the existing technology. Further study of the improvisation of next-generation drug-eluting stents has helped to overcome the issue of restenosis to some extent. However, current stent formulations fall short of the anticipated clinically meaningful outcomes and there is an explicit need for more randomized trials aiming to further evaluate stent platforms in favour of enhanced safety and clinical value. Gene-eluting stents may hold promise in contributing new ideas for stent-based prevention of in-stent restenosis through genetic interventions by capitalizing on a wide variety of molecular targets. Therefore, the central consideration directs us toward finding an ideal stent therapeutic platform that would tackle all of the gaps in the existing technology. Copyright © 2017 John Wiley & Sons, Ltd.

Metronomic chemotherapy and nanocarrier platforms.

PubMed

Abu Lila, Amr S; Ishida, Tatsuhiro

2017-08-01

The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods -known as "metronomic chemotherapy"- is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic "metronomic" therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TiO2 nanotube platforms for smart drug delivery: a review

PubMed Central

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Chen, Zhong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Al-Deyab, Salem S; Lai, Yue-Kun

2016-01-01

Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided. PMID:27703349

TiO2 nanotube platforms for smart drug delivery: a review.

PubMed

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Chen, Zhong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Al-Deyab, Salem S; Lai, Yue-Kun

Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided.

Graphene-based platforms for cancer therapeutics

PubMed Central

Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

2016-01-01

Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management. PMID:26769305

Graphene-based platforms for cancer therapeutics.

PubMed

Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

2016-01-01

Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management.

Course Evaluation: Reconfigurations for Learning with Learning Management Systems

ERIC Educational Resources Information Center

Park, Ji Yong

2014-01-01

The introduction of online delivery platforms such as learning management systems (LMS) in tertiary education has changed the methods and modes of curriculum delivery and communication. While course evaluation methods have also changed from paper-based in-class-administered methods to largely online-administered methods, the data collection…

Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

PubMed

Milan, Aroha Sanchez; Campmany, Ana Cristina Calpena; Naveros, Beatriz Clares

2017-01-01

Melatonin is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective in a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on melatonin for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. This review focuses on nanocarrier production strategies, dermal melatonin application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted melatonin delivery have also been discussed. In the current review, we have revised relevant articles of the available literature using the major scientific databases. One hundred and thirteen papers were included in the review, the majority of which represent latest researches in nanosized platforms for the dermal delivery of melatonin including liposomes, ethosomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles and cyclodextrins. Furthermore, relevant papers reporting in vitro and in vivo application studies of these nano-based melatonin platforms were also discussed. The use of nanoplatforms for the dermal melatonin delivery as antioxidant agent could improve the efficacy of conventional melatonin administration due to the preservation of the drug from premature oxidation and the enhancement of drug permeation through the skin providing greater exposure times. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microfluidic assembly of a nano-in-micro dual drug delivery platform composed of halloysite nanotubes and a pH-responsive polymer for colon cancer therapy.

PubMed

Li, Wei; Liu, Dongfei; Zhang, Hongbo; Correia, Alexandra; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2017-01-15

Harsh conditions of the gastrointestinal tract hinder the oral delivery of many drugs. Developing oral drug delivery systems based on commercially available materials is becoming more challenging due to the demand for simultaneously delivering physicochemically different drugs for treating complex diseases. A novel architecture, namely nanotube-in-microsphere, was developed as a drug delivery platform by encapsulating halloysite nanotubes (HNTs) in a pH-responsive hydroxypropyl methylcellulose acetate succinate polymer using microfluidics. HNTs were selected as orally acceptable clay mineral and their lumen was enlarged by selective acid etching. Model drugs (atorvastatin and celecoxib) with different physicochemical properties and synergistic effect on colon cancer prevention and inhibition were simultaneously incorporated into the microspheres at a precise ratio, with atorvastatin and celecoxib being loaded in the HNTs and polymer matrix, respectively. The microspheres showed spherical shape, narrow particle size distribution and pH-responsive dissolution behavior. This nanotube/pH-responsive polymer composite protected the loaded drugs from premature release at pH⩽6.5, but allowed their fast release and enhanced the drug permeability, and the inhibition of colon cancer cell proliferation at pH 7.4. Overall, the nano-in-micro drug delivery composite fabricated by microfluidics is a promising and flexible platform for the delivery of multiple drugs for combination therapy. Halloysite nanotubes (HNTs) are attracting increasing attention for drug delivery applications. However, conventional HNTs-based oral drug delivery systems are lack of the capability to precisely control the drug release at a desired site in the gastrointestinal tract. In this study, a nanotube-in-microsphere drug delivery platform is developed by encapsulating HNTs in a pH-responsive polymer using microfluidics. Drugs with different physicochemical properties and synergistic effect on colon cancer therapy were simultaneously incorporated in the microspheres. The prepared microspheres prevented the premature release of the loaded drugs after exposure to the harsh conditions of the gastrointestinal tract, but allowed their simultaneously fast release, and enhanced the drug permeability and the inhibition of colon cancer cell proliferation in response to the colon pH. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Progress in the Field of Constructing Near-Infrared Light-Responsive Drug Delivery Platforms.

PubMed

Zhou, Fang; Wang, Hanjie; Chang, Jin

2016-03-01

Stimuli-responsive materials have taken replace of traditional drug carriers due to their ability to achieve controlled release of their encapsulated contents. A variety of sensitive materials, such as polymers that respond to pH, light, and magnetic fields, are widely used to construct drug carriers, and achieved good results. Specifically, near-infrared light (NIR) responsive materials are of particular interest in drug delivery, as NIR can penetrate body tissue and is minimally absorbed by the body's water and hemoglobin and is less harmful to healthy cells than UV or visible light. Thus, the near-infrared excitation drug delivery systems (NIRDDSs) have some essential advantages just like being efficient to kill tumor cells, accurate to achieve the tumor sites and less damage to human body. Also, in the process of building the carriers, we may achieve a combination of controlled release chemotherapy, photothermal therapy (PTT) or photodynamic therapy (PDT). In addition, besides utilizing as drug delivery platforms, some carriers can achieve multifunctional tumor diagnosis and treatment, such as magnetic resonance imaging, optical imaging, drug carriers and PTT. In this review, based on the mechanism of NIR, we highlight diverse near-infrared light-responsive drug delivery platforms and recent advances in the development of NIRDDSs for cancer therapy primarily.

Multilayer engineered nanoliposomes as a novel tool for oral delivery of lipopeptide-based vaccines against group A Streptococcus.

PubMed

Marasini, Nirmal; Giddam, Ashwini K; Ghaffar, Khairunnisa A; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

2016-05-01

To develop an oral nanovaccine delivery system for lipopeptide-based vaccine candidate against group A Streptococcus. Lipid-core peptide-1-loaded nanoliposomes were prepared as a template and coated with opposite-charged polyelectrolytes to produce particles with size <200 nm. Efficacy of this oral nanovaccine delivery system was evaluated in mice model. Polymer-coated liposomes produced significantly higher antigen-specific mucosal IgA and systemic IgG titers in comparison to vaccine formulated with a strong mucosal adjuvant upon oral immunization in mice. Moreover, high levels of systemic antibody titers were retained even at day 185 postprimary immunization. Efficient oral delivery platform for lipopeptide-based vaccines has been developed.

A RNA nanotechnology platform for a simultaneous two-in-one siRNA delivery and its application in synergistic RNAi therapy

PubMed Central

Jang, Mihue; Han, Hee Dong; Ahn, Hyung Jun

2016-01-01

Incorporating multiple copies of two RNAi molecules into a single nanostructure in a precisely controlled manner can provide an efficient delivery tool to regulate multiple gene pathways in the relation of mutual dependence. Here, we show a RNA nanotechnology platform for a two-in-one RNAi delivery system to contain polymeric two RNAi molecules within the same RNA nanoparticles, without the aid of polyelectrolyte condensation reagents. As our RNA nanoparticles lead to the simultaneous silencing of two targeted mRNAs, of which biological functions are highly interdependent, combination therapy for multi-drug resistance cancer cells, which was studied as a specific application of our two-in-one RNAi delivery system, demonstrates the efficient synergistic effects for cancer therapy. Therefore, this RNA nanoparticles approach has an efficient tool for a simultaneous co-delivery of RNAi molecules in the RNAi-based biomedical applications, and our current studies present an efficient strategy to overcome multi-drug resistance caused by malfunction of genes in chemotherapy. PMID:27562435

A microarray MEMS device for biolistic delivery of vaccine and drug powders.

PubMed

Pirmoradi, Fatemeh Nazly; Pattekar, Ashish V; Linn, Felicia; Recht, Michael I; Volkel, Armin R; Wang, Qian; Anderson, Greg B; Veiseh, Mandana; Kjono, Sandra; Peeters, Eric; Uhland, Scott A; Chow, Eugene M

2015-01-01

We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.

A microarray MEMS device for biolistic delivery of vaccine and drug powders

PubMed Central

Pirmoradi, Fatemeh Nazly; Pattekar, Ashish V; Linn, Felicia; Recht, Michael I; Volkel, Armin R; Wang, Qian; Anderson, Greg B; Veiseh, Mandana; Kjono, Sandra; Peeters, Eric; Uhland, Scott A; Chow, Eugene M

2015-01-01

We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles. PMID:26090875

Functionalization of protein-based nanocages for drug delivery applications.

PubMed

Schoonen, Lise; van Hest, Jan C M

2014-07-07

Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

A Patient-Held Smartcard With a Unique Identifier and an mHealth Platform to Improve the Availability of Prenatal Test Results in Rural Nigeria: Demonstration Study

PubMed Central

Eze, Chuka; Olawepo, John Olajide; Iwelunmor, Juliet; Sarpong, Daniel F; Ogidi, Amaka Grace; Patel, Dina; Oko, John Okpanachi; Onoka, Chima; Ezeanolue, Echezona Edozie

2018-01-01

Background Community-based strategies to test for HIV, hepatitis B virus (HBV), and sickle cell disease (SCD) have expanded opportunities to increase the proportion of pregnant women who are aware of their diagnosis. In order to use this information to implement evidence-based interventions, these results have to be available to skilled health providers at the point of delivery. Most electronic health platforms are dependent on the availability of reliable Internet connectivity and, thus, have limited use in many rural and resource-limited settings. Objective Here we describe our work on the development and deployment of an integrated mHealth platform that is able to capture medical information, including test results, and encrypt it into a patient-held smartcard that can be read at the point of delivery without the need for an Internet connection. Methods We engaged a team of implementation scientists, public health experts, and information technology specialists in a requirement-gathering process to inform the design of a prototype for a platform that uses smartcard technology, database deployment, and mobile phone app development. Key design decisions focused on usability, scalability, and security. Results We successfully designed an integrated mHealth platform and deployed it in 4 health facilities across Benue State, Nigeria. We developed the Vitira Health platform to store test results of HIV, HBV, and SCD in a database, and securely encrypt the results on a Quick Response code embedded on a smartcard. We used a mobile app to read the contents on the smartcard without the need for Internet connectivity. Conclusions Our findings indicate that it is possible to develop a patient-held smartcard and an mHealth platform that contains vital health information that can be read at the point of delivery using a mobile phone-based app without an Internet connection. Trial Registration ClinicalTrials.gov NCT03027258; https://clinicaltrials.gov/ct2/show/NCT03027258 (Archived by WebCite at http://www.webcitation.org/6owR2D0kE) PMID:29335234

Magnetic nanoparticles: Applications in gene delivery and gene therapy.

PubMed

Majidi, Sima; Zeinali Sehrig, Fatemeh; Samiei, Mohammad; Milani, Morteza; Abbasi, Elham; Dadashzadeh, Kianoosh; Akbarzadeh, Abolfazl

2016-06-01

Gene therapy is defined as the direct transfer of genetic material to tissues or cells for the treatment of inherited disorders and acquired diseases. For gene delivery, magnetic nanoparticles (MNPs) are typically combined with a delivery platform to encapsulate the gene, and promote cell uptake. Delivery technologies that have been used with MNPs contain polymeric, viral, as well as non-viral platforms. In this review, we focus on targeted gene delivery using MNPs.

Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.

PubMed

Arnaboldi, Paul M; Sambir, Mariya; D'Arco, Christina; Peters, Lauren A; Seegers, Jos F M L; Mayer, Lloyd; McCormick, Alison A; Dattwyler, Raymond J

2016-11-11

Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery

NASA Astrophysics Data System (ADS)

Hayward, Stephen L.; Francis, David M.; Sis, Matthew J.; Kidambi, Srivatsan

2015-10-01

The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.

The Ad5 [E1-, E2b-]-based vector: a new and versatile gene delivery platform

NASA Astrophysics Data System (ADS)

Jones, Frank R.; Gabitzsch, Elizabeth S.; Balint, Joseph P.

2015-05-01

Based upon advances in gene sequencing and construction, it is now possible to identify specific genes or sequences thereof for gene delivery applications. Recombinant adenovirus serotype-5 (Ad5) viral vectors have been utilized in the settings of gene therapy, vaccination, and immunotherapy but have encountered clinical challenges because they are recognized as foreign entities to the host. This recognition leads to an immunologic clearance of the vector that contains the inserted gene of interest and prevents effective immunization(s). We have reported on a new Ad5-based viral vector technology that can be utilized as an immunization modality to induce immune responses even in the presence of Ad5 vector immunity. We have reported successful immunization and immunotherapy results to infectious diseases and cancers. This improved recombinant viral platform (Ad5 [E1-, E2b-]) can now be utilized in the development of multiple vaccines and immunotherapies.

Degradable Magnetic Composites for Minimally Invasive Interventions: Device Fabrication, Targeted Drug Delivery, and Cytotoxicity Tests.

PubMed

Peters, Christian; Hoop, Marcus; Pané, Salvador; Nelson, Bradley J; Hierold, Christofer

2016-01-20

Superparamagnetic nanoparticles and a functional, degradable polymer matrix based on poly(ethylene glycol) are combined to enable fully degradable magnetic microdevices for minimally invasive biomedical applications. A bioinspired helical microrobot platform mimicking Escherichia coli bacteria is fabricated and actuated using weak rotating magnetic fields. Locomotion based on corkscrew propulsion, targeted drug delivery, and low-degradation-product cytotoxicity are demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FIRE: an open-software suite for real-time 2D/3D image registration for image guided radiotherapy research

NASA Astrophysics Data System (ADS)

Furtado, H.; Gendrin, C.; Spoerk, J.; Steiner, E.; Underwood, T.; Kuenzler, T.; Georg, D.; Birkfellner, W.

2016-03-01

Radiotherapy treatments have changed at a tremendously rapid pace. Dose delivered to the tumor has escalated while organs at risk (OARs) are better spared. The impact of moving tumors during dose delivery has become higher due to very steep dose gradients. Intra-fractional tumor motion has to be managed adequately to reduce errors in dose delivery. For tumors with large motion such as tumors in the lung, tracking is an approach that can reduce position uncertainty. Tumor tracking approaches range from purely image intensity based techniques to motion estimation based on surrogate tracking. Research efforts are often based on custom designed software platforms which take too much time and effort to develop. To address this challenge we have developed an open software platform especially focusing on tumor motion management. FLIRT is a freely available open-source software platform. The core method for tumor tracking is purely intensity based 2D/3D registration. The platform is written in C++ using the Qt framework for the user interface. The performance critical methods are implemented on the graphics processor using the CUDA extension. One registration can be as fast as 90ms (11Hz). This is suitable to track tumors moving due to respiration (~0.3Hz) or heartbeat (~1Hz). Apart from focusing on high performance, the platform is designed to be flexible and easy to use. Current use cases range from tracking feasibility studies, patient positioning and method validation. Such a framework has the potential of enabling the research community to rapidly perform patient studies or try new methods.

Advanced Networks in Dental Rich Online MEDiA (ANDROMEDA)

NASA Astrophysics Data System (ADS)

Elson, Bruce; Reynolds, Patricia; Amini, Ardavan; Burke, Ezra; Chapman, Craig

There is growing demand for dental education and training not only in terms of knowledge but also skills. This demand is driven by continuing professional development requirements in the more developed economies, personnel shortages and skills differences across the European Union (EU) accession states and more generally in the developing world. There is an excellent opportunity for the EU to meet this demand by developing an innovative online flexible learning platform (FLP). Current clinical online systems are restricted to the delivery of general, knowledge-based training with no easy method of personalization or delivery of skill-based training. The PHANTOM project, headed by Kings College London is developing haptic-based virtual reality training systems for clinical dental training. ANDROMEDA seeks to build on this and establish a Flexible Learning Platform that can integrate the haptic and sensor based training with rich media knowledge transfer, whilst using sophisticated technologies such as including service-orientated architecture (SOA), Semantic Web technologies, knowledge-based engineering, business intelligence (BI) and virtual worlds for personalization.

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery.

PubMed

Niedermayer, Stefan; Weiss, Veronika; Herrmann, Annika; Schmidt, Alexandra; Datz, Stefan; Müller, Katharina; Wagner, Ernst; Bein, Thomas; Bräuchle, Christoph

2015-05-07

A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.

Silk-Based Biomaterials for Sustained Drug Delivery

PubMed Central

Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

2014-01-01

Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

Thermal and Power Challenges in High Performance Computing Systems

NASA Astrophysics Data System (ADS)

Natarajan, Venkat; Deshpande, Anand; Solanki, Sudarshan; Chandrasekhar, Arun

2009-05-01

This paper provides an overview of the thermal and power challenges in emerging high performance computing platforms. The advent of new sophisticated applications in highly diverse areas such as health, education, finance, entertainment, etc. is driving the platform and device requirements for future systems. The key ingredients of future platforms are vertically integrated (3D) die-stacked devices which provide the required performance characteristics with the associated form factor advantages. Two of the major challenges to the design of through silicon via (TSV) based 3D stacked technologies are (i) effective thermal management and (ii) efficient power delivery mechanisms. Some of the key challenges that are articulated in this paper include hot-spot superposition and intensification in a 3D stack, design/optimization of thermal through silicon vias (TTSVs), non-uniform power loading of multi-die stacks, efficient on-chip power delivery, minimization of electrical hotspots etc.

A modular platform for targeted RNAi therapeutics.

PubMed

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-03-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs 1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting 4-8 , their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

A modular platform for targeted RNAi therapeutics

NASA Astrophysics Data System (ADS)

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-01-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.

PubMed

Schaffert, David H; Okholm, Anders H; Sørensen, Rasmus S; Nielsen, Jesper S; Tørring, Thomas; Rosen, Christian B; Kodal, Anne Louise B; Mortensen, Michael R; Gothelf, Kurt V; Kjems, Jørgen

2016-05-01

DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protected Graft Copolymer (PGC) in Imaging and Therapy: A Platform for the Delivery of Covalently and Non-Covalently Bound Drugs.

PubMed

Bogdanov, Alexei A; Mazzanti, Mary; Castillo, Gerardo; Bolotin, Elijah

2012-01-01

Initially developed in 1992 as an MR imaging agent, the family of protected graft copolymers (PGC) is based on a conjugate of polylysine backbone to which methoxypoly(ethylene glycol) (MPEG) chains are covalently linked in a random fasion via N-ε-amino groups. While PGC is relatively simple in terms of its chemcial composition and structure, it has proved to be a versatile platform for in vivo drug delivery. The advantages of poly amino acid backbone grafting include multiple available linking sites for drug and adaptor molecules. The grafting of PEG chains to PGC does not compromise biodegradability and does not result in measurable toxicity or immunogenicity. In fact, the biocompatablility of PGC has resulted in its being one of the few 100% synthetic non-proteinaceous macromolecules that has suceeded in passing the initial safety phase of clinical trials. PGC is capable of long circulation times after injection into the blood stream and as such found use early on as a carrier system for delivery of paramagnetic imaging compounds for angiography. Other PGC types were later developed for use in nuclear medicine and optical imaging applications in vivo. Recent developments in PGC-based drug carrier formulations include the use of zinc as a bridge between the PGC carrier and zinc-binding proteins and re-engineering of the PGC carrier as a covalent amphiphile that is capabe of binding to hydrophobic residues of small proteins and peptides. At present, PGC-based formulations have been developed and tested in various disease models for: 1) MR imaging local blood circulation in stroke, cancer and diabetes; 2) MR and nuclear imaging of blood volume and vascular permeability in inflammation; 3) optical imaging of proteolytic activity in cancer and inflammation; 4) delivery of platinum(II) compounds for treating cancer; 5) delivery of small proteins and peptides for treating diabetes, obesity and myocardial infarction. This review summarizes the experience accumulated by various research groups that chose to use PGC as a drug delivery platform.

Nanotechnology applications in thoracic surgery

PubMed Central

Hofferberth, Sophie C.; Grinstaff, Mark W.; Colson, Yolonda L.

2016-01-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of ‘theranostic’ multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. PMID:26843431

A Patient-Held Smartcard With a Unique Identifier and an mHealth Platform to Improve the Availability of Prenatal Test Results in Rural Nigeria: Demonstration Study.

PubMed

Gbadamosi, Semiu Olatunde; Eze, Chuka; Olawepo, John Olajide; Iwelunmor, Juliet; Sarpong, Daniel F; Ogidi, Amaka Grace; Patel, Dina; Oko, John Okpanachi; Onoka, Chima; Ezeanolue, Echezona Edozie

2018-01-15

Community-based strategies to test for HIV, hepatitis B virus (HBV), and sickle cell disease (SCD) have expanded opportunities to increase the proportion of pregnant women who are aware of their diagnosis. In order to use this information to implement evidence-based interventions, these results have to be available to skilled health providers at the point of delivery. Most electronic health platforms are dependent on the availability of reliable Internet connectivity and, thus, have limited use in many rural and resource-limited settings. Here we describe our work on the development and deployment of an integrated mHealth platform that is able to capture medical information, including test results, and encrypt it into a patient-held smartcard that can be read at the point of delivery without the need for an Internet connection. We engaged a team of implementation scientists, public health experts, and information technology specialists in a requirement-gathering process to inform the design of a prototype for a platform that uses smartcard technology, database deployment, and mobile phone app development. Key design decisions focused on usability, scalability, and security. We successfully designed an integrated mHealth platform and deployed it in 4 health facilities across Benue State, Nigeria. We developed the Vitira Health platform to store test results of HIV, HBV, and SCD in a database, and securely encrypt the results on a Quick Response code embedded on a smartcard. We used a mobile app to read the contents on the smartcard without the need for Internet connectivity. Our findings indicate that it is possible to develop a patient-held smartcard and an mHealth platform that contains vital health information that can be read at the point of delivery using a mobile phone-based app without an Internet connection. ClinicalTrials.gov NCT03027258; https://clinicaltrials.gov/ct2/show/NCT03027258 (Archived by WebCite at http://www.webcitation.org/6owR2D0kE). ©Semiu Olatunde Gbadamosi, Chuka Eze, John Olajide Olawepo, Juliet Iwelunmor, Daniel F Sarpong, Amaka Grace Ogidi, Dina Patel, John Okpanachi Oko, Chima Onoka, Echezona Edozie Ezeanolue. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.01.2018.

Targeted and Controlled Anticancer Drug Delivery and Release with Magnetoelectric Nanoparticles

NASA Astrophysics Data System (ADS)

Rodzinski, Alexandra

A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow for discrete manipulation of the drug delivery and drug release mechanisms to allow an unprecedented level of control in cancer targeting. In this study, we demonstrate the physics behind the MEN drug delivery platform, test the MEN drug delivery platform for the first time in a humanized mouse model of cancer, and characterize the biodistribution and clearance of MENs. We found that MENs were able to fully cure the model cancer, which in this case was human ovarian carcinoma treated with paclitaxel. When compared to conventional magnetic nanoparticles and FDA approved organic PLGA nanoparticles, MENs are the highest performing treatment, even in the absence of peripheral active targeting molecules. We also mapped the movement through peripheral organs and established clearance trends of the MENs. The MENs cancer treatment platform has immense potential for future medicine, as it is generalizable, personalizable, and readily traceable in the context of treating essentially any type of cancer.

Addressing the challenges of diagnostics demand and supply: insights from an online global health discussion platform.

PubMed

Engel, Nora; Wachter, Keri; Pai, Madhukar; Gallarda, Jim; Boehme, Catharina; Celentano, Isabelle; Weintraub, Rebecca

2016-01-01

Several barriers challenge development, adoption and scale-up of diagnostics in low and middle income countries. An innovative global health discussion platform allows capturing insights from the global health community on factors driving demand and supply for diagnostics. We conducted a qualitative content analysis of the online discussion 'Advancing Care Delivery: Driving Demand and Supply of Diagnostics' organised by the Global Health Delivery Project (GHD) (http://www.ghdonline.org/) at Harvard University. The discussion, driven by 12 expert panellists, explored what must be done to develop delivery systems, business models, new technologies, interoperability standards, and governance mechanisms to ensure that patients receive the right diagnostic at the right time. The GHD Online (GHDonline) platform reaches over 19 000 members from 185 countries. Participants (N=99) in the diagnostics discussion included academics, non-governmental organisations, manufacturers, policymakers, and physicians. Data was coded and overarching categories analysed using qualitative data analysis software. Participants considered technical characteristics of diagnostics as smaller barriers to effective use of diagnostics compared with operational and health system challenges, such as logistics, poor fit with user needs, cost, workforce, infrastructure, access, weak regulation and political commitment. Suggested solutions included: health system strengthening with patient-centred delivery; strengthened innovation processes; improved knowledge base; harmonised guidelines and evaluation; supply chain innovations; and mechanisms for ensuring quality and capacity. Engaging and connecting different actors involved with diagnostic development and use is paramount for improving diagnostics. While the discussion participants were not representative of all actors involved, the platform enabled a discussion between globally acknowledged experts and physicians working in different countries.

Development of a gastroretentive pulsatile drug delivery platform.

PubMed

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

PubMed

Zhang, Hongbo; Liu, Dongfei; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Herranz-Blanco, Bárbara; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-07-09

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protein based therapeutic delivery agents: Contemporary developments and challenges.

PubMed

Yin, Liming; Yuvienco, Carlo; Montclare, Jin Kim

2017-07-01

As unique biopolymers, proteins can be employed for therapeutic delivery. They bear important features such as bioavailability, biocompatibility, and biodegradability with low toxicity serving as a platform for delivery of various small molecule therapeutics, gene therapies, protein biologics and cells. Depending on size and characteristic of the therapeutic, a variety of natural and engineered proteins or peptides have been developed. This, coupled to recent advances in synthetic and chemical biology, has led to the creation of tailor-made protein materials for delivery. This review highlights strategies employing proteins to facilitate the delivery of therapeutic matter, addressing the challenges for small molecule, gene, protein and cell transport. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyamidoamine dendrimer hydrogel for enhanced delivery of antiglaucoma drugs.

PubMed

Holden, Christopher A; Tyagi, Puneet; Thakur, Ashish; Kadam, Rajendra; Jadhav, Gajanan; Kompella, Uday B; Yang, Hu

2012-07-01

Dendrimer hydrogel (DH), made from ultraviolet-cured polyamidoamine dendrimer G3.0 tethered with three polyethylene glycol (PEG, 12,000 Da)-acrylate chains (8.1% w/v) in pH 7.4 phosphate buffered saline (PBS), was studied for the delivery of brimonidine (0.1% w/v) and timolol maleate (0.5% w/v), two antiglaucoma drugs. DH was found to be mucoadhesive to mucin particles and nontoxic to human corneal epithelial cells. DH increased the PBS solubility of brimonidine by 77.6% and sustained the in vitro release of both drugs over 56-72 hours. As compared to eye drop formulations (PBS-drug solutions), DH brought about substantially higher human corneal epithelial cells uptake and significantly increased bovine corneal transport for both drugs. DH increased timolol maleate uptake in bovine corneal epithelium, stroma, and endothelium by 0.4- to 4.6-fold. This work demonstrated that DH can enhance the delivery of antiglaucoma drugs in multiple aspects and represents a novel platform for ocular drug delivery. Dendrimer hydrogel was studied as agent for simultaneous delivery of two anti-glaucoma drugs, one hydrophobic and one hydrophilic. Superiority over standard PBS-based formulation was clearly demonstrated for both drugs. The work may be a novel platform for ocular drug delivery. Copyright © 2012 Elsevier Inc. All rights reserved.

Hydrogen peroxide mechanosynthesis in siloxane-hydrogel contact lenses.

PubMed

Tavazzi, Silvia; Ferraro, Lorenzo; Cozza, Federica; Pastori, Valentina; Lecchi, Marzia; Farris, Stefano; Borghesi, Alessandro

2014-11-26

Drug-loaded contact lenses are emerging as the preferred treatment method for several ocular diseases, and efforts are being directed to promote extended and controlled delivery. One strategy is based on delivery induced by environmental triggers. One of these triggers can be hydrogen peroxide, since many platforms based on drug-loaded nanoparticles were demonstrated to be hydrogen-peroxide responsive. This is particularly interesting when hydrogen peroxide is the result of a specific pathophysiological condition. Otherwise, an alternative route to induce drug delivery is here proposed, namely the mechano-synthesis. The present work represents the proof-of-concept of the mechanosynthesis of hydrogen peroxide in siloxane-hydrogel contact lenses as a consequence of the cleavage of siloxane bonds at the interface between the polymer and water in aqueous phase. Their spongy morphology makes contact lenses promising systems for mechanical-to-chemical energy conversion, since the amount of hydrogen peroxide is expected to scale with the interfacial area between the polymer and water. The eyelid pressure during wear is sufficient to induce the hydrogen peroxide synthesis with concentrations which are biocompatible and suitable to trigger the drug release through hydrogen-peroxide-responsive platforms. For possible delivery on demand, the integration of piezoelectric polymers in the siloxane-hydrogel contact lenses could be designed, whose mechanical deformation could be induced by an applied wireless-controlled voltage.

Pectin-based oral drug delivery to the colon.

PubMed

Sande, Sverre Arne

2005-05-01

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

NASA Astrophysics Data System (ADS)

Mullen, Douglas Gurnett

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules can be attached and has the potential to dramatically improve platform efficacy. An additional investigation of reproducibility challenges for current dendrimer-based platform designs is also described. The mass transport quality during the partial acetylation reaction of the dendrimer was found to have a major impact on subsequent dendrimer-ligand distributions that cannot be detected by standard analytical techniques. Consequently, this reaction should be eliminated from the platform design. Finally, optimized protocols for purification and characterization of PAMAM dendrimer were detailed.

Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery

PubMed Central

Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji

2013-01-01

Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants. PMID:23818778

Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery.

PubMed

Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji

2013-01-01

Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants.

Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain

PubMed Central

Mastorakos, Panagiotis; Song, Eric; Zhang, Clark; Berry, Sneha; Park, Hee Won; Kim, Young Eun; Park, Jong Sung; Lee, Seulki; Suk, Jung Soo; Hanes, Justin

2016-01-01

Successful gene therapy of neurological disorders is predicated on achieving widespread and uniform transgene expression throughout the affected disease area in the brain. However, conventional gene vectors preferentially travel through low-resistance perivascular spaces and/or are confined to the administration site even with the aid of a pressure-driven flow provided by convection-enhanced delivery. Biodegradable DNA nanoparticles offer a safe gene delivery platform devoid of adverse effects associated with virus-based or synthetic non-biodegradable systems. Using a state-of-the-art biodegradable polymer, poly(β-amino ester), we engineered colloidally stable sub-100 nm DNA nanoparticles coated with a non-adhesive polyethylene glycol corona that are able to avoid the adhesive and steric hindrances imposed by the extracellular matrix. Following convection enhanced delivery, these brain-penetrating nanoparticles were able to homogeneously distribute throughout the rodent striatum and mediate widespread and high-level transgene expression. These nanoparticles provide a biodegradable DNA nanoparticle platform enabling uniform transgene expression patterns in vivo and hold promise for the treatment of neurological diseases. PMID:26680637

Patient Perceptions of Treatment Delivery Platforms for Cognitive Behavioral Therapy for Insomnia.

PubMed

Cheung, Janet M Y; Bartlett, Delwyn J; Armour, Carol L; Laba, Tracey-Lea; Saini, Bandana

2017-03-21

Stepped care has given rise to the proliferation of abbreviated CBT-I programs and delivery formats. This includes interventions delivered by allied health professionals and those delivered electronically through the Internet. This article aims to explore patient perceptions between electronic and face-to-face (FTF) delivery platforms for (abbreviated) CBT-I. Patients with insomnia from specialist sleep or psychology clinics and those from the general community in Sydney, Australia. Semistructured interviews were conducted with patients with insomnia, guided by a schedule of questions and a choice task to explore patient perceptions of the different CBT-I treatment delivery platforms (e.g., perceived advantages and disadvantages or willingness to engage with either platform). Interviews were transcribed verbatim and analyzed using Framework Analysis. Participants also completed a battery of clinical mood and insomnia measures. Fifty-one interviews were conducted with patients with insomnia from specialist sleep or psychology clinics (n = 22) and the general community (n = 29). Synthesis of the qualitative data set revealed three themes pertinent to the patients' perspective toward electronic and FTF CBT-I delivery: Concepts of Efficacy, Concerns About Treatment, and Treatment on My Terms. Participants' choice to engage with either platform was also informed by diverse factors including perceived efficacy of treatment, personal commitments, lifestyle, and beliefs about sleep and insomnia. Clarifying patient treatment priorities and allaying potential concerns about engaging with an electronic treatment platform represent important steps for disseminating eCBT-I into mainstream practice.

Packaging biological cargoes in mesoporous materials: opportunities for drug delivery.

PubMed

Siefker, Justin; Karande, Pankaj; Coppens, Marc-Olivier

2014-11-01

Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants. Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments. The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed.

Albumin-based drug delivery: harnessing nature to cure disease.

PubMed

Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke; Howard, Kenneth A

2016-01-01

The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform.

Real-time intra-fraction-motion tracking using the treatment couch: a feasibility study

NASA Astrophysics Data System (ADS)

D'Souza, Warren D.; Naqvi, Shahid A.; Yu, Cedric X.

2005-09-01

Significant differences between planned and delivered treatments may occur due to respiration-induced tumour motion, leading to underdosing of parts of the tumour and overdosing of parts of the surrounding critical structures. Existing methods proposed to counter tumour motion include breath-holds, gating and MLC-based tracking. Breath-holds and gating techniques increase treatment time considerably, whereas MLC-based tracking is limited to two dimensions. We present an alternative solution in which a robotic couch moves in real time in response to organ motion. To demonstrate proof-of-principle, we constructed a miniature adaptive couch model consisting of two movable platforms that simulate tumour motion and couch motion, respectively. These platforms were connected via an electronic feedback loop so that the bottom platform responded to the motion of the top platform. We tested our model with a seven-field step-and-shoot delivery case in which we performed three film-based experiments: (1) static geometry, (2) phantom-only motion and (3) phantom motion with simulated couch motion. Our measurements demonstrate that the miniature couch was able to compensate for phantom motion to the extent that the dose distributions were practically indistinguishable from those in static geometry. Motivated by this initial success, we investigated a real-time couch compensation system consisting of a stereoscopic infra-red camera system interfaced to a robotic couch known as the Hexapod™, which responds in real time to any change in position detected by the cameras. Optical reflectors placed on a solid water phantom were used as surrogates for motion. We tested the effectiveness of couch-based motion compensation for fixed fields and a dynamic arc delivery cases. Due to hardware limitations, we performed film-based experiments (1), (2) and (3), with the robotic couch at a phantom motion period and dose rate of 16 s and 100 MU min-1, respectively. Analysis of film measurements showed near-equivalent dose distributions (<=2 mm agreement of corresponding isodose lines) for static geometry and motion-synchronized real-time robotic couch tracking-based radiation delivery.

Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics

PubMed Central

Hong, Seong-Chul; Yoo, Seung-Yup; Kim, Hyeongmin; Lee, Jaehwi

2017-01-01

Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives. PMID:28257059

Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons.

PubMed

Westmark, Cara J

2016-01-01

Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition.

Experiences and lessons learned for delivery of micronutrient powders interventions

PubMed Central

Reerink, Ietje; Poonawala, Alia; Nyhus Dhillon, Christina; Aburto, Nancy; Chaudhery, Deepika; Kroeun, Hou; Griffiths, Marcia; Haque, Mohammad Raisul; Bonvecchio, Anabelle; Jefferds, Maria Elena; Rawat, Rahul

2017-01-01

Abstract An effective delivery strategy coupled with relevant social and behaviour change communication (SBCC) have been identified as central to the implementation of micronutrient powders (MNP) interventions, but there has been limited documentation of what works. Under the auspices of “The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance,” three working groups were formed to summarize experiences and lessons across countries regarding MNP interventions for young children. This paper focuses on programmatic experiences related to MNP delivery (models, platforms, and channels), SBCC, and training. Methods included a review of published and grey literature, interviews with key informants, and deliberations throughout the consultation process. We found that most countries distributed MNP free of charge via the health sector, although distribution through other platforms and using subsidized fee for product or mixed payment models have also been used. Community‐based distribution channels have generally shown higher coverage and when part of an infant and young child feeding approach, may provide additional benefit given their complementarity. SBCC for MNP has worked best when focused on meeting the MNP behavioural objectives (appropriate use, intake adherence, and related infant and young child feeding behaviours). Programmers have learned that reincorporating SBCC and training throughout the intervention life cycle has allowed for much needed adaptations. Diverse experiences delivering MNP exist, and although no one‐size‐fits‐all approach emerged, well‐established delivery platforms, community involvement, and SBCC‐centred designs tended to have more success. Much still needs to be learned on MNP delivery, and we propose a set of implementation research questions that require further investigation. PMID:28960878

Nanomaterials for miRNA delivery and non-invasive imaging in cardiovascular regeneration

NASA Astrophysics Data System (ADS)

Gomes, Renata Sofia Mota

The development of noninvasive platforms to assess cell fate after transplantation is of utmost importance in the context of Regenerative Medicine. Magnetic Resonance Imaging (MRI) is a powerful non-invasive imaging platform, heavily relying on the use of contrast agents, mostly nanoparticles (NPs). Gadolinium (Gd) and Superparamagnetic Iron Oxide (SPIO) NPs are contrast agents in clinical use, however these agents may cause liver toxicity, give rise to image artifacts in MRI, and typically have not been used as a drug delivery system. In this work, we developed a novel NP formulation containing fluorine to overcome the previous limitations. The NPs are based on poly(lactic-co-glycolic acid) (PLGA) which is a biocompatible and versatile polymer approved for human use . PLGA NPs containing fluorine were developed to label and track cells overtime and as vectors for microRNA (miR) delivery, which improves cell survival in hypoxic conditions. Herein we show that the fluorine-based NPs are a reliable approach to track non-invasively cells with clinical relevance (endothelial cells and cord-blood derived mononuclear cells) and simultaneously control the intracellular delivery of pro-survival and pro-angiogenic miRs. Also systems for in vitro and in vivo imaging via MRI of fluorine are developed and here explained. Furthermore in vivo studies are performed which show the therapeutic uses of such system. Additionally we also address the optimization of protocols for stem cell culture which may enhance proliferation and promote pluripotency in cardiac stem cells (CSCs) so as we can fully explore the potential of these cells in vivo using out novel theranostic NPs platform. We are the first authors developing and relating these novel developments.

The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

PubMed

Ge, Yanxiu; Ma, Yakun; Li, Lingbing

2016-10-01

Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of small RNA delivery systems for lung cancer therapy.

PubMed

Fujita, Yu; Kuwano, Kazuyoshi; Ochiya, Takahiro

2015-03-06

RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment.

Flexible Wing Base Micro Aerial Vehicles: Micro Air Vehicles (MAVs) for Surveillance and Remote Sensor Delivery

NASA Technical Reports Server (NTRS)

Ifju, Peter

2002-01-01

Micro Air Vehicles (MAVs) will be developed for tracking individuals, locating terrorist threats, and delivering remote sensors, for surveillance and chemical/biological agent detection. The tasks are: (1) Develop robust MAV platform capable of carrying sensor payload. (2) Develop fully autonomous capabilities for delivery of sensors to remote and distant locations. The current capabilities and accomplishments are: (1) Operational electric (inaudible) 6-inch MAVs with novel flexible wing, providing superior aerodynamic efficiency and control. (2) Vision-based flight stability and control (from on-board cameras).

Application of liposomal technologies for delivery of platinum analogs in oncology

PubMed Central

Liu, Demin; He, Chunbai; Wang, Andrew Z; Lin, Wenbin

2013-01-01

Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™), SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research. PMID:24023517

Nanoparticle-based drug delivery to the vagina: a review

PubMed Central

Ensign, Laura M.; Cone, Richard; Hanes, Justin

2014-01-01

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery.

PubMed

Hung, Michelle E; Leonard, Joshua N

2016-01-01

Extracellular vesicles (EVs) mediate intercellular communication through transfer of RNA and protein between cells. Thus, understanding how cargo molecules are loaded and delivered by EVs is of central importance for elucidating the biological roles of EVs and developing EV-based therapeutics. While some motifs modulating the loading of biomolecular cargo into EVs have been elucidated, the general rules governing cargo loading and delivery remain poorly understood. To investigate how general biophysical properties impact loading and delivery of RNA by EVs, we developed a platform for actively loading engineered cargo RNAs into EVs. In our system, the MS2 bacteriophage coat protein was fused to EV-associated proteins, and the cognate MS2 stem loop was engineered into cargo RNAs. Using this Targeted and Modular EV Loading (TAMEL) approach, we identified a configuration that substantially enhanced cargo RNA loading (up to 6-fold) into EVs. When applied to vesicles expressing the vesicular stomatitis virus glycoprotein (VSVG) - gesicles - we observed a 40-fold enrichment in cargo RNA loading. While active loading of mRNA-length (>1.5 kb) cargo molecules was possible, active loading was much more efficient for smaller (~0.5 kb) RNA molecules. We next leveraged the TAMEL platform to elucidate the limiting steps in EV-mediated delivery of mRNA and protein to prostate cancer cells, as a model system. Overall, most cargo was rapidly degraded in recipient cells, despite high EV-loading efficiencies and substantial EV uptake by recipient cells. While gesicles were efficiently internalized via a VSVG-mediated mechanism, most cargo molecules were rapidly degraded. Thus, in this model system, inefficient endosomal fusion or escape likely represents a limiting barrier to EV-mediated transfer. Altogether, the TAMEL platform enabled a comparative analysis elucidating a key opportunity for enhancing EV-mediated delivery to prostate cancer cells, and this technology should be of general utility for investigations and applications of EV-mediated transfer in other systems.

Polymer nanogels: a versatile nanoscopic drug delivery platform

PubMed Central

Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

2012-01-01

In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

Vitamin-C delivery from CoCr alloy surfaces using polymer-free and polymer-based platforms for cardiovascular stent applications.

PubMed

Thiruppathi, Eagappanath; Mani, Gopinath

2014-06-03

Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (l-ascorbic acid, l-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of l-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly(lactic-co-glycolic acid) (PLGA) platform were used for coating l-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of l-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of l-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that l-AA (276 μg/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the l-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that l-AA was incorporated into the bulk of the PLGA film. DSC showed that the l-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that l-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of l-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of l-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.

Nanotechnology applications in thoracic surgery.

PubMed

Hofferberth, Sophie C; Grinstaff, Mark W; Colson, Yolonda L

2016-07-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery.

PubMed

Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi

2016-02-01

Self-assembly of peptides can yield an array of well-defined nanostructures that are highly attractive nanomaterials for many biomedical applications such as drug delivery. Some of the advantages of self-assembled peptide nanostructures over other delivery platforms include their chemical diversity, biocompatibility, high loading capacity for both hydrophobic and hydrophilic drugs, and their ability to target molecular recognition sites. Furthermore, these self-assembled nanostructures could be designed with novel peptide motifs, making them stimuli-responsive and achieving triggered drug delivery at disease sites. The goal of this work is to present a comprehensive review of the most recent studies on self-assembled peptides with a focus on their "smart" activity for formation of targeted and responsive drug-delivery carriers.

Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

PubMed

Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

2016-06-01

Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

SU-G-BRC-10: Feasibility of a Web-Based Monte Carlo Simulation Tool for Dynamic Electron Arc Radiotherapy (DEAR)

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

Rodrigues, A; Wu, Q; Sawkey, D

Purpose: DEAR is a radiation therapy technique utilizing synchronized motion of gantry and couch during delivery to optimize dose distribution homogeneity and penumbra for treatment of superficial disease. Dose calculation for DEAR is not yet supported by commercial TPSs. The purpose of this study is to demonstrate the feasibility of using a web-based Monte Carlo (MC) simulation tool (VirtuaLinac) to calculate dose distributions for a DEAR delivery. Methods: MC simulations were run through VirtuaLinac, which is based on the GEANT4 platform. VirtuaLinac utilizes detailed linac head geometry and material models, validated phase space files, and a voxelized phantom. The inputmore » was expanded to include an XML file for simulation of varying mechanical axes as a function of MU. A DEAR XML plan was generated and used in the MC simulation and delivered on a TrueBeam in Developer Mode. Radiographic film wrapped on a cylindrical phantom (12.5 cm radius) measured dose at a depth of 1.5 cm and compared to the simulation results. Results: A DEAR plan was simulated using an energy of 6 MeV and a 3×10 cm{sup 2} cut-out in a 15×15 cm{sup 2} applicator for a delivery of a 90° arc. The resulting data were found to provide qualitative and quantitative evidence that the simulation platform could be used as the basis for DEAR dose calculations. The resulting unwrapped 2D dose distributions agreed well in the cross-plane direction along the arc, with field sizes of 18.4 and 18.2 cm and penumbrae of 1.9 and 2.0 cm for measurements and simulations, respectively. Conclusion: Preliminary feasibility of a DEAR delivery using a web-based MC simulation platform has been demonstrated. This tool will benefit treatment planning for DEAR as a benchmark for developing other model based algorithms, allowing efficient optimization of trajectories, and quality assurance of plans without the need for extensive measurements.« less

Learner Perspectives of Online Problem-Based Learning and Applications from Cognitive Load Theory

ERIC Educational Resources Information Center

Chen, Ruth

2016-01-01

Problem-based learning (PBL) courses have historically been situated in physical classrooms involving in-person interactions. As online learning is embraced in higher education, programs that use PBL can integrate online platforms to support curriculum delivery and facilitate student engagement. This report describes student perspectives of the…

Synthesis of PLGA-Lipid Hybrid Nanoparticles for siRNA Delivery Using the Emulsion Method PLGA-PEG-Lipid Nanoparticles for siRNA Delivery.

PubMed

Wang, Lei; Griffel, Benjamin; Xu, Xiaoyang

2017-01-01

The effective delivery of small interfering RNA (siRNA) to tumor cells remains a challenge for applications in cancer therapy. The development of polymeric nanoparticles with high siRNA loading efficacy has shown great potential for cancer targets. Double emulsion solvent evaporation technique is a useful tool for encapsulation of hydrophilic molecules (e.g., siRNA). Here we describe a versatile platform for siRNA delivery based on PLGA-PEG-cationic lipid nanoparticles by using the double emulsion method. The resulting nanoparticles show high encapsulation efficiency for siRNA (up to 90%) and demonstrate effective downregulation of the target genes in vitro and vivo.

Evaluation of biocompatibility and administration site reactogenicity of polyanhydride-particle-based platform for vaccine delivery.

PubMed

Huntimer, Lucas; Ramer-Tait, Amanda E; Petersen, Latrisha K; Ross, Kathleen A; Walz, Katherine A; Wang, Chong; Hostetter, Jesse; Narasimhan, Balaji; Wannemuehler, Michael J

2013-02-01

Efficacy, purity, safety, and potency are important attributes of vaccines. Polyanhydride particles represent a novel class of vaccine adjuvants and delivery platforms that have demonstrated the ability to enhance the stability of protein antigens as well as elicit protective immunity against bacterial pathogens. This work aims to elucidate the biocompatibility, inflammatory reactions, and particle effects on mice injected with a 5 mg dose of polyanhydride nanoparticles via common parenteral routes (subcutaneous and intramuscular). Independent of polymer chemistry, nanoparticles more effectively disseminated away from the injection site as compared to microparticles, which exhibited a depot effect. Using fluorescent probes, the in vivo distribution of three formulations of nanoparticles, following subcutaneous administration, indicated migration away from the injection site. Less inflammation was observed at the injection sites of mice-administered nanoparticles as compared to Alum and incomplete Freund's adjuvant. Furthermore, histological evaluation revealed minimal adverse injection site reactions and minimal toxicological effects associated with the administration of nanoparticles at 30 days post-administration. Collectively, these results demonstrate that polyanhydride nanoparticles do not induce inflammation as a cumulative effect of particle persistence or degradation and are, therefore, a viable candidate for a vaccine delivery platform. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A silk-based scaffold platform with tunable architecture for engineering critically-sized tissue constructs.

PubMed

Wray, Lindsay S; Rnjak-Kovacina, Jelena; Mandal, Biman B; Schmidt, Daniel F; Gil, Eun Seok; Kaplan, David L

2012-12-01

In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable biomaterial scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the scaffold bulk. The scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering 'tailored' scaffolds for a range of tissue engineering and regenerative medicine needs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sustainable Development in Surgery: The Health, Poverty, and Equity Impacts of Charitable Surgery in Uganda

PubMed Central

Shrime, Mark G.; Sekidde, Serufusa; Linden, Allison; Cohen, Jessica L.; Weinstein, Milton C.; Salomon, Joshua A.

2016-01-01

Background The recently adopted Sustainable Development Goals call for the end of poverty and the equitable provision of healthcare. These goals are often at odds, however: health seeking can lead to catastrophic spending, an outcome for which cancer patients and the poor in resource-limited settings are at particularly high risk. How various health policies affect the additional aims of financial wellbeing and equity is poorly understood. This paper evaluates the health, financial, and equity impacts of governmental and charitable policies for surgical oncology in a resource-limited setting. Methods Three charitable platforms for surgical oncology delivery in Uganda were compared to six governmental policies aimed at improving healthcare access. An extended cost-effectiveness analysis using an agent-based simulation model examined the numbers of lives saved, catastrophic expenditure averted, impoverishment averted, costs, and the distribution of benefits across the wealth spectrum. Findings Of the nine policies and platforms evaluated, two were able to provide simultaneous health and financial benefits efficiently and equitably: mobile surgical units and governmental policies that simultaneously address surgical scaleup, the cost of surgery, and the cost of transportation. Policies that only remove user fees are dominated, as is the commonly employed short-term “surgical mission trip”. These results are robust to scenario and sensitivity analyses. Interpretation The most common platforms for increasing access to surgical care appear unable to provide health and financial risk protection equitably. On the other hand, mobile surgical units, to date an underutilized delivery platform, are able to deliver surgical oncology in a manner that meets sustainable development goals by improving health, financial solvency, and equity. These platforms compare favorably with policies that holistically address surgical delivery and should be considered as countries strengthen health systems. PMID:28036357

Sustainable Development in Surgery: The Health, Poverty, and Equity Impacts of Charitable Surgery in Uganda.

PubMed

Shrime, Mark G; Sekidde, Serufusa; Linden, Allison; Cohen, Jessica L; Weinstein, Milton C; Salomon, Joshua A

2016-01-01

The recently adopted Sustainable Development Goals call for the end of poverty and the equitable provision of healthcare. These goals are often at odds, however: health seeking can lead to catastrophic spending, an outcome for which cancer patients and the poor in resource-limited settings are at particularly high risk. How various health policies affect the additional aims of financial wellbeing and equity is poorly understood. This paper evaluates the health, financial, and equity impacts of governmental and charitable policies for surgical oncology in a resource-limited setting. Three charitable platforms for surgical oncology delivery in Uganda were compared to six governmental policies aimed at improving healthcare access. An extended cost-effectiveness analysis using an agent-based simulation model examined the numbers of lives saved, catastrophic expenditure averted, impoverishment averted, costs, and the distribution of benefits across the wealth spectrum. Of the nine policies and platforms evaluated, two were able to provide simultaneous health and financial benefits efficiently and equitably: mobile surgical units and governmental policies that simultaneously address surgical scaleup, the cost of surgery, and the cost of transportation. Policies that only remove user fees are dominated, as is the commonly employed short-term "surgical mission trip". These results are robust to scenario and sensitivity analyses. The most common platforms for increasing access to surgical care appear unable to provide health and financial risk protection equitably. On the other hand, mobile surgical units, to date an underutilized delivery platform, are able to deliver surgical oncology in a manner that meets sustainable development goals by improving health, financial solvency, and equity. These platforms compare favorably with policies that holistically address surgical delivery and should be considered as countries strengthen health systems.

Remotely Delivered Exercise-Based Cardiac Rehabilitation: Design and Content Development of a Novel mHealth Platform.

PubMed

Rawstorn, Jonathan C; Gant, Nicholas; Meads, Andrew; Warren, Ian; Maddison, Ralph

2016-06-24

Participation in traditional center-based cardiac rehabilitation exercise programs (exCR) is limited by accessibility barriers. Mobile health (mHealth) technologies can overcome these barriers while preserving critical attributes of center-based exCR monitoring and coaching, but these opportunities have not yet been capitalized on. We aimed to design and develop an evidence- and theory-based mHealth platform for remote delivery of exCR to any geographical location. An iterative process was used to design and develop an evidence- and theory-based mHealth platform (REMOTE-CR) that provides real-time remote exercise monitoring and coaching, behavior change education, and social support. The REMOTE-CR platform comprises a commercially available smartphone and wearable sensor, custom smartphone and Web-based applications (apps), and a custom middleware. The platform allows exCR specialists to monitor patients' exercise and provide individualized coaching in real-time, from almost any location, and provide behavior change education and social support. Intervention content incorporates Social Cognitive Theory, Self-determination Theory, and a taxonomy of behavior change techniques. Exercise components are based on guidelines for clinical exercise prescription. The REMOTE-CR platform extends the capabilities of previous telehealth exCR platforms and narrows the gap between existing center- and home-based exCR services. REMOTE-CR can complement center-based exCR by providing an alternative option for patients whose needs are not being met. Remotely monitored exCR may be more cost-effective than establishing additional center-based programs. The effectiveness and acceptability of REMOTE-CR are now being evaluated in a noninferiority randomized controlled trial.

The potential of polymeric film-forming systems as sustained delivery platforms for topical drugs.

PubMed

Frederiksen, Kit; Guy, Richard H; Petersson, Karsten

2016-01-01

Dosing regimens requiring multiple daily applications frequently result in poor patient compliance, especially in the treatment of chronic skin diseases. Consequently, development of sustained delivery systems for topical drugs permitting less frequent dosing is of continuing interest for dermatological therapy. This potential of polymeric film-forming systems (FFS), created in situ on the skin, as sustained delivery platforms for topical drug delivery is reviewed. Key formulation parameters that determine delivery efficiency are considered focussing on those that permit a drug reservoir to be established in the upper layers of the skin and/or on the skin surface from which release can be sustained over a prolonged period. The advantageous and superior cosmetic attributes of FFS (compared to conventional semi-solid formulations) that offer significantly improved patient compliance are also addressed. The promise of polymeric FFS as convenient and aesthetic platforms for sustained topical drug delivery is clear. Manipulation of the formulation allows the delivery profile to be customized and optimized to take advantage of both a rapid, initial input of drug into the skin (likely due to a transient period of supersaturation) and a slower, controlled release over an extended time from the residual film created thereafter.

Testing Delivery Platforms for New Anticancer tRNA-Based Drugs

DTIC Science & Technology

2011-03-01

measurement of aminoacylated killer tRNA. Killer tRNA aminoacylated with lysine via a ribozyme is sufficiently stable in the culture media to enable...translational efficiency which helps the design of optimal killer tRNAs. - Determined that the flexi- ribozyme can be used to attach non-serine amino acids to...tRNAs using the flexi- ribozyme strategy. REPORTABLE OUTCOME - A dual GFP-mCherry reporter plasmid DNA useful to monitor delivery of tRNA in

Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons

PubMed Central

Westmark, Cara J.

2017-01-01

Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition. PMID:28149839

Nanochemistry of Protein-Based Delivery Agents

PubMed Central

Rajendran, Subin R. C. K.; Udenigwe, Chibuike C.; Yada, Rickey Y.

2016-01-01

The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior. PMID:27489854

Nanochemistry of protein-based delivery agents

NASA Astrophysics Data System (ADS)

Rajendran, Subin; Udenigwe, Chibuike; Yada, Rickey

2016-07-01

The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior.

A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

NASA Astrophysics Data System (ADS)

Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

2014-01-01

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

Copper-free click-chemistry platform to functionalize cisplatin prodrugs.

PubMed

Pathak, Rakesh K; McNitt, Christopher D; Popik, Vladimir V; Dhar, Shanta

2014-06-02

The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of Pt(IV) centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experiences and lessons learned for delivery of micronutrient powders interventions.

PubMed

Reerink, Ietje; Namaste, Sorrel Ml; Poonawala, Alia; Nyhus Dhillon, Christina; Aburto, Nancy; Chaudhery, Deepika; Kroeun, Hou; Griffiths, Marcia; Haque, Mohammad Raisul; Bonvecchio, Anabelle; Jefferds, Maria Elena; Rawat, Rahul

2017-09-01

An effective delivery strategy coupled with relevant social and behaviour change communication (SBCC) have been identified as central to the implementation of micronutrient powders (MNP) interventions, but there has been limited documentation of what works. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," three working groups were formed to summarize experiences and lessons across countries regarding MNP interventions for young children. This paper focuses on programmatic experiences related to MNP delivery (models, platforms, and channels), SBCC, and training. Methods included a review of published and grey literature, interviews with key informants, and deliberations throughout the consultation process. We found that most countries distributed MNP free of charge via the health sector, although distribution through other platforms and using subsidized fee for product or mixed payment models have also been used. Community-based distribution channels have generally shown higher coverage and when part of an infant and young child feeding approach, may provide additional benefit given their complementarity. SBCC for MNP has worked best when focused on meeting the MNP behavioural objectives (appropriate use, intake adherence, and related infant and young child feeding behaviours). Programmers have learned that reincorporating SBCC and training throughout the intervention life cycle has allowed for much needed adaptations. Diverse experiences delivering MNP exist, and although no one-size-fits-all approach emerged, well-established delivery platforms, community involvement, and SBCC-centred designs tended to have more success. Much still needs to be learned on MNP delivery, and we propose a set of implementation research questions that require further investigation. © 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

An injectable particle-hydrogel hybrid system for glucose-regulatory insulin delivery.

PubMed

Zhao, Fuli; Wu, Di; Yao, Dan; Guo, Ruiwei; Wang, Weiwei; Dong, Anjie; Kong, Deling; Zhang, Jianhua

2017-12-01

Long-term and daily subcutaneous injections of insulin for the treatment of insulin-dependent diabetic patients often lead to poor patient compliance and undesired complications. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, their applications are limited by clinically irrelevant glucose-responsive range, slow response rate, low tissue-adhesiveness and poor biodegradability, undesirable leakage at normoglycemic state. Herein, we report a novel implantable insulin hydrogel for glucose-regulated delivery of insulin based on a unique particle-hydrogel hybrid platform featuring fast glucose responsiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, and full biodegradability for safe use. The system was thoroughly characterized both in vitro and in vivo and was demonstrated to hold these unique functions. Using streptozotocin-induced diabetic mice as a model, it was shown that a single subcutaneous injection of the insulin-loaded particle-hydrogel formulation led to quasi-steady-state blood glucose levels within the normal range for about two weeks. In addition, the preparation of the formulation only involved simple mixing and self-assembling processes, and thus it had great scalability and reproducibility for practical use. The highly feasible preparation, excellent performance, inherent biocompatibility and biodegradability make this novel composite hydrogel promising platform for diabetes therapy. Phenylboronic acid (PBA)-based polymeric hydrogels have been widely considered as one of the most promising insulin delivery system to replace the frequent insulin injections. However, these hydrogels, mostly based on a variety of PBA-containing acrylamide monomers, are still far from clinical reality. Building upon a unique particle-hydrogel hybrid platform, herein we report a novel implantable insulin storage and delivery system with multifunctionalities including fast glucose-sensitiveness at physiological pH, shear-thinning behavior for injection, tissue-adhesive function for long-lasting adherence, biodegradable materials for safe use and well-controlled insulin release. These unique functions were demonstrated through research both in vitro and in vivo. In addition, the preparation of the formulation was simple, and thus it had great scalability and reproducibility for practical use. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Using Technology to Improve Treatment Outcomes for Children and Adolescents with Eating Disorders.

PubMed

Darcy, Alison M; Lock, James

2017-01-01

Dissemination and implementation of evidence-based treatments are among the biggest challenges facing clinical psychiatry. Developing scalable evidence-based treatments is a major priority and fraught with challenges. This article describes the development of 3 technology-based innovations. It discusses the use of massive open online courses (MOOCs) and mobile applications. Three projects are presented: (1) the modification of a MOOC methodology for psychotherapy training clinicians in manualized family-based therapy (FBT) for adolescents with anorexia nervosa; (2) a modified MOOC platform for the delivery of FBT; and (3) the development of mobile applications for treatment augmentation and delivery. Copyright © 2016 Elsevier Inc. All rights reserved.

Endosomolytic Nano-Polyplex Platform Technology for Cytosolic Peptide Delivery To Inhibit Pathological Vasoconstriction.

PubMed

Evans, Brian C; Hocking, Kyle M; Kilchrist, Kameron V; Wise, Eric S; Brophy, Colleen M; Duvall, Craig L

2015-06-23

A platform technology has been developed and tested for delivery of intracellular-acting peptides through electrostatically complexed nanoparticles, or nano-polyplexes, formulated from an anionic endosomolytic polymer and cationic therapeutic peptides. This delivery platform has been initially tested and optimized for delivery of two unique vasoactive peptides, a phosphomimetic of heat shock protein 20 and an inhibitor of MAPKAP kinase II, to prevent pathological vasoconstriction (i.e., vasospasm) in human vascular tissue. These peptides inhibit vasoconstriction and promote vasorelaxation by modulating actin dynamics in vascular smooth muscle cells. Formulating these peptides into nano-polyplexes significantly enhances peptide uptake and retention, facilitates cytosolic delivery through a pH-dependent endosomal escape mechanism, and enhances peptide bioactivity in vitro as measured by inhibition of F-actin stress fiber formation. In comparison to treatment with the free peptides, which were endowed with cell-penetrating sequences, the nano-polyplexes significantly increased vasorelaxation, inhibited vasoconstriction, and decreased F-actin formation in the human saphenous vein ex vivo. These results suggest that these formulations have significant potential for treatment of conditions such as cerebral vasospasm following subarachnoid hemorrhage. Furthermore, because many therapeutic peptides include cationic cell-penetrating segments, this simple and modular platform technology may have broad applicability as a cost-effective approach for enhancing the efficacy of cytosolically active peptides.

Ubiquitous Discussion Forum: Introducing Mobile Phones and Voice Discussion into a Web Discussion Forum

ERIC Educational Resources Information Center

Wei, Fu-Hsiang; Chen, Gwo-Dong; Wang, Chin-Yeh; Li, Liang-Yi

2007-01-01

Web-based discussion forums enable users to share knowledge in straightforward and popular platforms. However, discussion forums have several problems, such as the lack of immediate delivery and response, the heavily text-based medium, inability to hear expressions of voice and the heuristically created discussion topics which can impede the…

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

Virus-Mimetic Fusogenic Exosomes for Direct Delivery of Integral Membrane Proteins to Target Cell Membranes.

PubMed

Yang, Yoosoo; Hong, Yeonsun; Nam, Gi-Hoon; Chung, Jin Hwa; Koh, Eunee; Kim, In-San

2017-04-01

An efficient system for direct delivery of integral membrane proteins is successfully developed using a new biocompatible exosome-based platform. Fusogenic exosomes harboring viral fusogen, vascular stomatitis virus (VSV)-G protein, can fuse with and modify plasma membranes in a process called "membrane editing." This can facilitate the transfer of biologically active membrane proteins into the target cell membranes both in vitro and in vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.

PubMed

Wang, Ming; Zuris, John A; Meng, Fantao; Rees, Holly; Sun, Shuo; Deng, Pu; Han, Yong; Gao, Xue; Pouli, Dimitra; Wu, Qi; Georgakoudi, Irene; Liu, David R; Xu, Qiaobing

2016-03-15

A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing. These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%. In addition, we demonstrate that these lipids are effective for functional protein delivery into mouse brain for gene recombination in vivo. Therefore, the integration of this bioreducible lipid platform with protein engineering has the potential to advance the therapeutic relevance of protein-based genome editing.

Improving Small Interfering RNA Delivery In Vivo Through Lipid Conjugation.

PubMed

Osborn, Maire F; Khvorova, Anastasia

2018-05-10

RNA interference (RNAi)-based therapeutics are approaching clinical approval for genetically defined diseases. Current clinical success is a result of significant innovations in the development of chemical architectures that support sustained, multi-month efficacy in vivo following a single administration. Conjugate-mediated delivery has established itself as the most promising platform for safe and targeted small interfering RNA (siRNA) delivery. Lipophilic conjugates represent a major class of modifications that improve siRNA pharmacokinetics and enable efficacy in a broad range of tissues. Here, we review current literature and define key features and limitations of this approach for in vivo modulation of gene expression.

Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics

PubMed Central

Marrache, Sean; Dhar, Shanta

2012-01-01

Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various mitochondria-acting therapeutics by blending a targeted poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)-triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA-b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro screening of a library of charge- and size-varied NPs, and mitochondrial uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG-TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD. The versatility of this platform was demonstrated by studying various mitochondria-acting therapeutics for different applications, including the mitochondria-targeting chemotherapeutics lonidamine and α-tocopheryl succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer’s disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These biomolecules were loaded into blended NPs with high loading efficiencies. Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable improvement in the drug therapeutic index for cancer, Alzheimer’s disease, and obesity compared with the nontargeted construct or the therapeutics in their free form. This work represents the potential of a single, programmable NP platform for the diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction-related diseases. PMID:22991470

Single‐fraction spine SBRT end‐to‐end testing on TomoTherapy, Vero, TrueBeam, and CyberKnife treatment platforms using a novel anthropomorphic phantom

PubMed Central

Kaufman, Isaac; Powell, Rachel; Pandya, Shalini; Somnay, Archana; Bossenberger, Todd; Ramirez, Ezequiel; Reynolds, Robert; Solberg, Timothy; Burmeister, Jay

2015-01-01

Spine SBRT involves the delivery of very high doses of radiation to targets adjacent to the spinal cord and is most commonly delivered in a single fraction. Highly conformal planning and accurate delivery of such plans is imperative for successful treatment without catastrophic adverse effects. End–to‐end testing is an important practice for evaluating the entire treatment process from simulation through treatment delivery. We performed end‐to‐end testing for a set of representative spine targets planned and delivered using four different treatment planning systems (TPSs) and delivery systems to evaluate the various capabilities of each. An anthropomorphic E2E SBRT phantom was simulated and treated on each system to evaluate agreement between measured and calculated doses. The phantom accepts ion chambers in the thoracic region and radiochromic film in the lumbar region. Four representative targets were developed within each region (thoracic and lumbar) to represent different presentations of spinal metastases and planned according to RTOG 0631 constraints. Plans were created using the TomoTherapy TPS for delivery using the Hi·Art system, the iPlan TPS for delivery using the Vero system, the Eclipse TPS for delivery using the TrueBeam system in both flattened and flattening filter free (FFF), and the MultiPlan TPS for delivery using the CyberKnife system. Delivered doses were measured using a 0.007 cm3 ion chamber in the thoracic region and EBT3 GAFCHROMIC film in the lumbar region. Films were scanned and analyzed using an Epson Expression 10000XL flatbed scanner in conjunction with FilmQAPro2013. All treatment platforms met all dose constraints required by RTOG 0631. Ion chamber measurements in the thoracic targets delivered an overall average difference of 1.5%. Specifically, measurements agreed with the TPS to within 2.2%, 3.2%, 1.4%, 3.1%, and 3.0% for all three measureable cases on TomoTherapy, Vero, TrueBeam (FFF), TrueBeam (flattened), and CyberKnife, respectively. Film measurements for the lumbar targets resulted in average global gamma index passing rates of 100% at 3%/3 mm, 96.9% at 2%/2 mm, and 61.8% at 1%/1 mm, with a 10% minimum threshold for all plans on all platforms. Local gamma analysis was also performed with similar results. While gamma passing rates were consistently accurate across all platforms through 2%/2 mm, treatment beam‐on delivery times varied greatly between each platform with TrueBeam FFF being shortest, averaging 4.4 min, TrueBeam using flattened beam at 9.5 min, TomoTherapy at 30.5 min, Vero at 19 min, and CyberKnife at 46.0 min. In spite of the complexity of the representative targets and their proximity to the spinal cord, all treatment platforms were able to create plans meeting all RTOG 0631 dose constraints and produced exceptional agreement between calculated and measured doses. However, there were differences in the plan characteristics and significant differences in the beam‐on delivery time between platforms. Thus, clinical judgment is required for each particular case to determine most appropriate treatment planning/delivery platform. PACS number: 87.53.Ly PMID:25679169

Remotely Delivered Exercise-Based Cardiac Rehabilitation: Design and Content Development of a Novel mHealth Platform

PubMed Central

Gant, Nicholas; Meads, Andrew; Warren, Ian; Maddison, Ralph

2016-01-01

Background Participation in traditional center-based cardiac rehabilitation exercise programs (exCR) is limited by accessibility barriers. Mobile health (mHealth) technologies can overcome these barriers while preserving critical attributes of center-based exCR monitoring and coaching, but these opportunities have not yet been capitalized on. Objective We aimed to design and develop an evidence- and theory-based mHealth platform for remote delivery of exCR to any geographical location. Methods An iterative process was used to design and develop an evidence- and theory-based mHealth platform (REMOTE-CR) that provides real-time remote exercise monitoring and coaching, behavior change education, and social support. Results The REMOTE-CR platform comprises a commercially available smartphone and wearable sensor, custom smartphone and Web-based applications (apps), and a custom middleware. The platform allows exCR specialists to monitor patients’ exercise and provide individualized coaching in real-time, from almost any location, and provide behavior change education and social support. Intervention content incorporates Social Cognitive Theory, Self-determination Theory, and a taxonomy of behavior change techniques. Exercise components are based on guidelines for clinical exercise prescription. Conclusions The REMOTE-CR platform extends the capabilities of previous telehealth exCR platforms and narrows the gap between existing center- and home-based exCR services. REMOTE-CR can complement center-based exCR by providing an alternative option for patients whose needs are not being met. Remotely monitored exCR may be more cost-effective than establishing additional center-based programs. The effectiveness and acceptability of REMOTE-CR are now being evaluated in a noninferiority randomized controlled trial. PMID:27342791

EMERGING MICROTECHNOLOGIES FOR THE DEVELOPMENT OF ORAL DRUG DELIVERY DEVICES

PubMed Central

Chirra, Hariharasudhan D.; Desai, Tejal A.

2012-01-01

The development of oral drug delivery platforms for administering therapeutics in a safe and effective manner across the gastrointestinal epithelium is of much importance. A variety of delivery systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, orally administered drugs suffer from poor localization and therapeutic efficacy due to various physiological conditions such as low pH, and high shear intestinal fluid flow. Novel platforms combining controlled release, improved adhesion, tissue penetration, and selective intestinal targeting may overcome these issues and potentially diminish the toxicity and high frequency of administration associated with conventional oral delivery. Microfabrication along with appropriate surface chemistry, provide a means to fabricate these platforms en masse with flexibility in tailoring the shape, size, reservoir volume, and surface characteristics of microdevices. Moreover, the same technology can be used to include integrated circuit technology and sensors for designing sophisticated autonomous drug delivery devices that promise to significantly improve point of care diagnostic and therapeutic medical applications. This review sheds light on some of the fabrication techniques and addresses a few of the microfabricated devices that can be effectively used for controlled oral drug delivery applications. PMID:22981755

Syngeneic AAV pseudo-particles potentiate gene transduction of AAV vectors

USDA-ARS?s Scientific Manuscript database

Gene delivery vectors based on adeno-associated virus (AAV) have emerged as safe and efficient therapeutic platform for numerous diseases. Excessive empty particles were generated as impurities during AAV vector production, but their effects on clinical outcome of AAV gene therapy are unclear. Here,...

Recent advances in recombinant protein-based malaria vaccines

PubMed Central

Draper, Simon J.; Angov, Evelina; Horii, Toshihiro; Miller, Louis H.; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-01-01

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle–including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. PMID:26458807

The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function.

PubMed

Turturro, Sanja B; Guthrie, Micah J; Appel, Alyssa A; Drapala, Pawel W; Brey, Eric M; Pérez-Luna, Victor H; Mieler, William F; Kang-Mieler, Jennifer J

2011-05-01

There is significant interest in biomaterials that provide sustained release of therapeutic molecules to the retina. Poly(N-isopropylacrylamide) (PNIPAAm)-based materials have received significant attention as injectable drug delivery platforms due to PNIPAAm's thermo-responsive properties at approximately 32 °C. While the drug delivery properties of PNIPAAm materials have been studied extensively, there is a need to evaluate the safety effects of hydrogel injection on retinal function. The purpose of this study was to examine the effect of poly(ethylene glycol) diacrylate (PEG-DA) crosslinked PNIPAAm hydrogel injection on retinal function. Utilizing scanning laser ophthalmoscopy (SLO), optical coherent tomography (OCT), and electroretinography (ERG), retinal function was assessed following hydrogel injection. In region near the hydrogel, there was a significant decrease in arterial and venous diameters (∼4%) and an increase in venous blood velocity (∼8%) 1 week post-injection. Retinal thickness decreased (∼6%) at 1 week and the maximum a- and b-wave amplitudes of ERG decreased (∼15%). All data returned to baseline values after week 1. These data suggest that the injection of PEG-DA crosslinked PNIPAAm hydrogel results in a small transient effect on retinal function without any long-term effects. These results further support the potential of PNIPAAm-based materials as an ocular drug delivery platform. Copyright © 2011 Elsevier Ltd. All rights reserved.

Leveraging socially networked mobile ICT platforms for the last-mile delivery problem.

PubMed

Suh, Kyo; Smith, Timothy; Linhoff, Michelle

2012-09-04

Increasing numbers of people are managing their social networks on mobile information and communication technology (ICT) platforms. This study materializes these social relationships by leveraging spatial and networked information for sharing excess capacity to reduce the environmental impacts associated with "last-mile" package delivery systems from online purchases, particularly in low population density settings. Alternative package pickup location systems (PLS), such as a kiosk on a public transit platform or in a grocery store, have been suggested as effective strategies for reducing package travel miles and greenhouse gas emissions, compared to current door-to-door delivery models (CDS). However, our results suggest that a pickup location delivery system operating in a suburban setting may actually increase travel miles and emissions. Only once a social network is employed to assist in package pickup (SPLS) are significant reductions in the last-mile delivery distance and carbon emissions observed across both urban and suburban settings. Implications for logistics management's decades-long focus on improving efficiencies of dedicated distribution systems through specialization, as well as for public policy targeting carbon emissions of the transport sector are discussed.

A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery.

PubMed

Zhong, Jiaju; Li, Lian; Zhu, Xi; Guan, Shan; Yang, Qingqing; Zhou, Zhou; Zhang, Zhirong; Huang, Yuan

2015-10-01

Tumor cell nucleus-targeted delivery of antitumor agents is of great interest in cancer therapy, since the nucleus is one of the most frequent targets of drug action. Here we report a smart polymeric conjugate platform, which utilizes stimulus-responsive strategies to achieve multistage nuclear drug delivery upon systemic administration. The conjugates composed of a backbone based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer and detachable nucleus transport sub-units that sensitive to lysosomal enzyme. The sub-units possess a biforked structure with one end conjugated with the model drug, H1 peptide, and the other end conjugated with a novel pH-responsive targeting peptide (R8NLS) that combining the strength of cell penetrating peptide and nuclear localization sequence. The conjugates exhibited prolonged circulation time and excellent tumor homing ability. And the activation of R8NLS in acidic tumor microenvironment facilitated tissue penetration and cellular internalization. Once internalized into the cell, the sub-units were unleashed for nuclear transport through nuclear pore complex. The unique features resulted in 50-fold increase of nuclear drug accumulation relative to the original polymer-drug conjugates in vitro, and excellent in vivo nuclear drug delivery efficiency. Our report provides a strategy in systemic nuclear drug delivery by combining the microenvironment-responsive structure and detachable sub-units. Copyright © 2015 Elsevier Ltd. All rights reserved.

A novel self-assembled nanoparticle platform based on pectin-eight-arm polyethylene glycol-drug conjugates for co-delivery of anticancer drugs.

PubMed

Liu, Yanxue; Liu, Kefeng; Li, Xiaomin; Xiao, Shangzhen; Zheng, Dan; Zhu, Pengbo; Li, Chunxiao; Liu, Jing; He, Jing; Lei, Jiandu; Wang, Luying

2018-05-01

The application of non-toxic carriers to increase drug loading, multi-drug delivery, and extremely small size of nano-drugs to construct a tremendous transmission system is the goal for all researchers to be pursued. The proposal of natural pectin nano-platform for delivery of multiple drugs is critical for biomedical research, especially a particle size of below 100nm with high yield. Here we design a new core-shell structure pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle (Pec-8PUH NPs) through a special self-assembly method for stabilizing and dispersing particles, improving water-solubility, and achieving drug controlled release. The obtained Pec-8PUH NPs possessed appropriate size (~91nm), drug-loaded efficiency and encapsulation efficiency through the regulation of eight-arm polyethylene glycol. In addition, Pec-8PUH NPs could enhance cell cytotoxicity, shorten blood retention time (7.3-fold UA, 7.2-fold HCPT) and more effective cellular uptake than free drugs, which exhibited an obvious synergistic effect of UA and HCPT by the co-delivery. 4T1 tumor-bearing mice also showed a higher survival rate than free UA and free HCPT. The result further shows that this novel drug delivery system has a promising potential for anti-cancer combination therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies.

PubMed

Riffault, Mathieu; Six, Jean-Luc; Netter, Patrick; Gillet, Pierre; Grossin, Laurent

2015-12-01

Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint.

Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery.

PubMed

Liu, Dongfei; Zhang, Hongbo; Herranz-Blanco, Bárbara; Mäkilä, Ermei; Lehto, Vesa-Pekka; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-05-28

We report an advanced drug delivery platform for combination chemotherapy by concurrently incorporating two different drugs into microcompoistes with ratiometric control over the loading degree. Atorvastatin and celecoxib were selected as model drugs due to their different physicochemical properties and synergetic effect on colorectal cancer prevention and inhibition. To be effective in colorectal cancer prevention and inhibition, the produced microcomposite contained hypromellose acetate succinate, which is insoluble in acidic conditions but highly dissolving at neutral or alkaline pH conditions. Taking advantage of the large pore volume of porous silicon (PSi), atorvastatin was firstly loaded into the PSi matrix, and then encapsulated into the pH-responsive polymer microparticles containing celecoxib by microfluidics in order to obtain multi-drug loaded polymer/PSi microcomposites. The prepared microcomposites showed monodisperse size distribution, multistage pH-response, precise ratiometric controlled loading degree towards the simultaneously loaded drug molecules, and tailored release kinetics of the loaded cargos. This attractive microcomposite platform protects the payloads from being released at low pH-values, and enhances their release at higher pH-values, which can be further used for colon cancer prevention and treatment. Overall, the pH-responsive polymer/PSi-based microcomposite can be used as a universal platform for the delivery of different drug molecules for combination therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comprehensive screening platform for aerosolizable protein formulations for intranasal and pulmonary drug delivery.

PubMed

Röhm, Martina; Carle, Stefan; Maigler, Frank; Flamm, Johannes; Kramer, Viktoria; Mavoungou, Chrystelle; Schmid, Otmar; Schindowski, Katharina

2017-10-30

Aerosolized administration of biopharmaceuticals to the airways is a promising route for nasal and pulmonary drug delivery, but - in contrast to small molecules - little is known about the effects of aerosolization on safety and efficacy of biopharmaceuticals. Proteins are sensitive against aerosolization-associated shear stress. Tailored formulations can shield proteins and enhance permeation, but formulation development requires extensive screening approaches. Thus, the aim of this study was to develop a cell-based in vitro technology platform that includes screening of protein quality after aerosolization and transepithelial permeation. For efficient screening, a previously published aerosolization-surrogate assay was used in a design of experiments approach to screen suitable formulations for an IgG and its antigen-binding fragment (Fab) as exemplary biopharmaceuticals. Efficient, dose-controlled aerosol-cell delivery was performed with the ALICE-CLOUD system containing RPMI 2650 epithelial cells at the air-liquid interface. We could demonstrate that our technology platform allows for rapid and efficient screening of formulations consisting of different excipients (here: arginine, cyclodextrin, polysorbate, sorbitol, and trehalose) to minimize aerosolization-induced protein aggregation and maximize permeation through an in vitro epithelial cell barrier. Formulations reduced aggregation of native Fab and IgG relative to vehicle up to 50% and enhanced transepithelial permeation rate up to 2.8-fold. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

PubMed

Moreno, Ana M; Fu, Xin; Zhu, Jie; Katrekar, Dhruva; Shih, Yu-Ru V; Marlett, John; Cabotaje, Jessica; Tat, Jasmine; Naughton, John; Lisowski, Leszek; Varghese, Shyni; Zhang, Kang; Mali, Prashant

2018-04-25

Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to develop a modular adeno-associated viral (AAV) vector platform for CRISPR-Cas9 delivery to enable the full spectrum of targeted in situ gene regulation functionalities, demonstrating robust transcriptional repression (up to 80%) and activation (up to 6-fold) of target genes in cell culture and mice. We also applied our platform for targeted in vivo gene-repression-mediated gene therapy for retinitis pigmentosa. Specifically, we engineered targeted repression of Nrl, a master regulator of rod photoreceptor determination, and demonstrated Nrl knockdown mediates in situ reprogramming of rod cells into cone-like cells that are resistant to retinitis pigmentosa-specific mutations, with concomitant prevention of secondary cone loss. Furthermore, we benchmarked our results from Nrl knockdown with those from in vivo Nrl knockout via gene editing. Taken together, our AAV-CRISPR-Cas9 platform for in vivo epigenome engineering enables a robust approach to target disease in a genomically scarless and potentially reversible manner. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Refactored M13 Bacteriophage as a Platform for Tumor Cell Imaging and Drug Delivery

PubMed Central

MOSER, FELIX; ENDY, DREW; BELCHER, ANGELA M.

2014-01-01

M13 bacteriophage is a well-characterized platform for peptide display. The utility of the M13 display platform is derived from the ability to encode phage protein fusions with display peptides at the genomic level. However, the genome of the phage is complicated by overlaps of key genetic elements. These overlaps directly couple the coding sequence of one gene to the coding or regulatory sequence of another, making it difficult to alter one gene without disrupting the other. Specifically, overlap of the end of gene VII and the beginning of gene IX has prevented the functional genomic modification of the N-terminus of p9. By redesigning the M13 genome to physically separate these overlapping genetic elements, a process known as “refactoring,” we enabled independent manipulation of gene VII and gene IX and the construction of the first N-terminal genomic modification of p9 for peptide display. We demonstrate the utility of this refactored genome by developing an M13 bacteriophage-based platform for targeted imaging of and drug delivery to prostate cancer cells in vitro. This successful use of refactoring principles to reengineer a natural biological system strengthens the suggestion that natural genomes can be rationally designed for a number of applications. PMID:23656279

Refactored M13 bacteriophage as a platform for tumor cell imaging and drug delivery.

PubMed

Ghosh, Debadyuti; Kohli, Aditya G; Moser, Felix; Endy, Drew; Belcher, Angela M

2012-12-21

M13 bacteriophage is a well-characterized platform for peptide display. The utility of the M13 display platform is derived from the ability to encode phage protein fusions with display peptides at the genomic level. However, the genome of the phage is complicated by overlaps of key genetic elements. These overlaps directly couple the coding sequence of one gene to the coding or regulatory sequence of another, making it difficult to alter one gene without disrupting the other. Specifically, overlap of the end of gene VII and the beginning of gene IX has prevented the functional genomic modification of the N-terminus of p9. By redesigning the M13 genome to physically separate these overlapping genetic elements, a process known as "refactoring," we enabled independent manipulation of gene VII and gene IX and the construction of the first N-terminal genomic modification of p9 for peptide display. We demonstrate the utility of this refactored genome by developing an M13 bacteriophage-based platform for targeted imaging of and drug delivery to prostate cancer cells in vitro. This successful use of refactoring principles to re-engineer a natural biological system strengthens the suggestion that natural genomes can be rationally designed for a number of applications.

Magnetic microbubble: A biomedical platform co-constructed from magnetics and acoustics

NASA Astrophysics Data System (ADS)

Yang, Fang; Gu, Zhu-Xiao; Jin, Xin; Wang, Hao-Yao; Gu, Ning

2013-10-01

Generation of magnetic micrbubbles and their basic magnetic and acoustic mechanism are reviewed. The ultrasound (US) and magnetic resonance (MR) dual imaging, the controlled therapeutic delivery, as well as theranostic multifunctions are all introduced based on recent research results. Some on-going research is also discussed.

The Usage of an Online Discussion Forum for the Facilitation of Case-Based Learning in an Intermediate Accounting Course: A New Zealand Case

ERIC Educational Resources Information Center

Weil, Sidney; McGuigan, Nicholas; Kern, Thomas

2011-01-01

This paper describes the implementation of an online discussion forum as a means of facilitating case-based learning in an intermediate financial accounting course. The paper commences with a review of case-based learning literature and the use of online discussions as a delivery platform, linking these pedagogical approaches to the emerging needs…

Film coatings for oral pulsatile release.

PubMed

Maroni, Alessandra; Zema, Lucia; Loreti, Giulia; Palugan, Luca; Gazzaniga, Andrea

2013-12-05

Pulsatile delivery is generally intended as a release of the active ingredient that is delayed for a programmable period of time to meet particular chronotherapeutic needs and, in the case of oral administration, also target distal intestinal regions, such as the colon. Most oral pulsatile delivery platforms consist in coated formulations wherein the applied polymer serves as the release-controlling agent. When exposed to aqueous media, the coating initially performs as a protective barrier and, subsequently, undergoes a timely failure based on diverse mechanisms depending on its physico-chemical and formulation characteristics. Indeed, it may be ruptured because of the gradual expansion of the core, swell and/or erode due to the glassy-rubbery polymer transition or become permeable thus allowing the drug molecules to diffuse outwards. Otherwise, when the coating is a semipermeable membrane provided with one or more orifices, the drug is released through the latter as a result of an osmotic water influx. The vast majority of pulsatile delivery systems described so far have been prepared by spray-coating, which offers important versatility and feasibility advantages over other techniques such as press- and dip-coating. In the present article, the design, manufacturing and performance of spray-coated pulsatile delivery platforms is thus reviewed. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthesis and characterization of a multifunctional gold-doxorubicin nanoparticle system for pH triggered intracellular anticancer drug release.

PubMed

Khutale, Ganesh V; Casey, Alan

2017-10-01

A nanoparticle drug carrier system has been developed to alter the cellular uptake and chemotherapeutic performance of an available chemotherapeutic drug. The system comprises of a multifunctional gold nanoparticle based drug delivery system (Au-PEG-PAMAM-DOX) as a novel platform for intracellular delivery of doxorubicin (DOX). Spherical gold nanoparticles were synthesized by a gold chloride reduction, stabilized with thiolated polyethylene glycol (PEG) and then covalently coupled with a polyamidoamine (PAMAM) G4 dendrimer. Further, conjugation of an anti-cancer drug doxorubicin to the dendrimer via amide bond resulted in Au-PEG-PAMAM-DOX drug delivery system. Acellular drug release studies proved that DOX released from Au-PEG-PAMAM-DOX at physiological pH was negligible but it was significantly increased at a weak acidic milieu. The intracellular drug release was monitored with confocal laser scanning microscopy analysis. In vitro viability studies showed an increase in the associated doxorubicin cytotoxicity not attributed to carrier components indicating the efficiency of the doxorubicin was improved, upon conjugation to the nano system. As such it is postulated that the developed pH triggered multifunctional doxorubicin-gold nanoparticle system, could lead to a promising platform for intracellular delivery of variety of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a software for quantitative evaluation radiotherapy target and organ-at-risk segmentation comparison.

PubMed

Kalpathy-Cramer, Jayashree; Awan, Musaddiq; Bedrick, Steven; Rasch, Coen R N; Rosenthal, David I; Fuller, Clifton D

2014-02-01

Modern radiotherapy requires accurate region of interest (ROI) inputs for plan optimization and delivery. Target delineation, however, remains operator-dependent and potentially serves as a major source of treatment delivery error. In order to optimize this critical, yet observer-driven process, a flexible web-based platform for individual and cooperative target delineation analysis and instruction was developed in order to meet the following unmet needs: (1) an open-source/open-access platform for automated/semiautomated quantitative interobserver and intraobserver ROI analysis and comparison, (2) a real-time interface for radiation oncology trainee online self-education in ROI definition, and (3) a source for pilot data to develop and validate quality metrics for institutional and cooperative group quality assurance efforts. The resultant software, Target Contour Testing/Instructional Computer Software (TaCTICS), developed using Ruby on Rails, has since been implemented and proven flexible, feasible, and useful in several distinct analytical and research applications.

Angiogenic therapy for cardiac repair based on protein delivery systems.

PubMed

Formiga, F R; Tamayo, E; Simón-Yarza, T; Pelacho, B; Prósper, F; Blanco-Prieto, M J

2012-05-01

Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents

PubMed Central

Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

2015-01-01

A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation. PMID:26225356

Smart Cancer Cell Targeting Imaging and Drug Delivery System by Systematically Engineering Periodic Mesoporous Organosilica Nanoparticles.

PubMed

Lu, Nan; Tian, Ying; Tian, Wei; Huang, Peng; Liu, Ying; Tang, Yuxia; Wang, Chunyan; Wang, Shouju; Su, Yunyan; Zhang, Yunlei; Pan, Jing; Teng, Zhaogang; Lu, Guangming

2016-02-10

The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we first present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near-infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8% in 10 mM of GSH solution within 24 h, which is more than 2-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6% at pH 5 and 31.7% at pH 7.4 within 24 h. Confocal laser scanning microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a novel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug release, and high tumor cell targeting ability.

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

PubMed Central

Richardson, R. Mark; Kells, Adrian P.; Martin, Alastair J.; Larson, Paul S.; Starr, Philip A.; Piferi, Peter G.; Bates, Geoffrey; Tansey, Lisa; Rosenbluth, Kathryn H.; Bringas, John R.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Background/Aims A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. PMID:21494065

Percutaneous Steerable Robotic Tool Delivery Platform and Metal MEMS Device for Tissue Manipulation and Approximation: Closure of Patent Foramen Ovale in an Animal Model

PubMed Central

Vasilyev, Nikolay V.; Gosline, Andrew H.; Butler, Evan; Lang, Nora; Codd, Patrick J.; Yamauchi, Haruo; Feins, Eric N.; Folk, Chris R.; Cohen, Adam L.; Chen, Richard; Zurakowski, David; del Nido, Pedro J.; Dupont, Pierre E

2013-01-01

Background Beating-heart image-guided intracardiac interventions have been evolving rapidly. To extend the domain of catheter-based and transcardiac interventions into reconstructive surgery, a new robotic tool delivery platform (TDP) and tissue approximation device have been developed. Initial results employing these tools to perform patent foramen ovale (PFO) closure are described. Methods and Results A robotic TDP comprised of superelastic metal tubes provides the capability of delivering and manipulating tools and devices inside the beating heart. A new device technology is also presented that utilizes a metal-based MicroElectroMechanical Systems (MEMS) manufacturing process to produce fully-assembled and fully-functional millimeter-scale tools. As a demonstration of both technologies, a PFO creation and closure was performed in a swine model. In the first group of animals (N=10), a preliminary study was performed. The procedural technique was validated with a transcardiac handheld delivery platform and epicardial echocardiography, video-assisted cardioscopy and fluoroscopy. In the second group (N=9), the procedure was performed percutaneously using the robotic TDP under epicardial echocardiography and fluoroscopy imaging. All PFO’s were completely closed in the first group. In the second group, the PFO was not successfully created in 1 animal, and the defects were completely closed in 6 of the 8 remaining animals. Conclusions In contrast to existing robotic catheter technologies, the robotic TDP utilizes a combination of stiffness and active steerability along its length to provide the positioning accuracy and force application capability necessary for tissue manipulation. In combination with a MEMS tool technology, it can enable reconstructive procedures inside the beating heart. PMID:23899870

Addition of poly (propylene glycol) to multiblock copolymer to optimize siRNA delivery.

PubMed

Dai, Zhi; Arévalo, Maria T; Li, Junwei; Zeng, Mingtao

2014-01-01

Previous studies have examined different strategies for siRNA delivery with varying degrees of success. These include use of viral vectors, cationic liposomes, and polymers. Several copolymers were designed and synthesized based on blocks of poly(ethylene glycol) PEG, poly(propylene glycol) PPG, and poly(l-lysine). These were designated as P1, P2, and P3. We studied the copolymer self-assembly, siRNA binding, particle size, surface potential, architecture of the complexes, and siRNA delivery. Silencing of GFP using copolymer P3 to deliver GFP-specific siRNA to Neuro-2a cells expressing GFP was almost as effective as using Lipofectamine 2000, with minimal cytotoxicity. Thus, we have provided a new copolymer platform for siRNA delivery that we can continue to modify for improved delivery of siRNA in vitro and eventually in vivo.

Polysaccharide-based Noncovalent Assembly for Targeted Delivery of Taxol

NASA Astrophysics Data System (ADS)

Yang, Yang; Zhang, Ying-Ming; Chen, Yong; Chen, Jia-Tong; Liu, Yu

2016-01-01

The construction of synthetic straightforward, biocompatible and biodegradable targeted drug delivery system with fluorescent tracking abilities, high anticancer activities and low side effects is still a challenge in the field of biochemistry and material chemistry. In this work, we constructed targeted paclitaxel (Taxol) delivery nanoparticles composed of permethyl-β-cyclodextrin modified hyaluronic acid (HApCD) and porphyrin modified paclitaxel prodrug (PorTaxol), through host-guest and amphiphilic interactions. The obtained nanoparticles (HATXP) were biocompatible and enzymatic biodegradable due to their hydrophilic hyaluronic acid (HA) shell and hydrophobic Taxol core, and exhibited specific targeting internalization into cancer cells via HA receptor mediated endocytosis effects. The cytotoxicity experiments showed that the HATXP exhibited similar anticancer activities to, but much lower side effects than commercial anticancer drug Taxol. The present work would provide a platform for targeted paclitaxel drug delivery and a general protocol for the design of advanced multifunctional nanoscale biomaterials for targeted drug/gene delivery.

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

PubMed

Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

2016-02-10

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Canonical and non-canonical barriers facing antimiR cancer therapeutics.

PubMed

Cheng, Christopher J; Saltzman, W Mark; Slack, Frank J

2013-01-01

Once considered genetic "oddities", microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms-ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles-are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.

Light-sensitive Lipid-based Nanoparticles for Drug Delivery: Design Principles and Future Considerations for Biological Applications

PubMed Central

Yavlovich, Amichai; Smith, Brandon; Gupta, Kshitij; Blumenthal, Robert; Puri, Anu

2011-01-01

Radiation-based therapies aided by nanoparticles have been developed since decades, and can be primarily categorized into two main platforms. First, delivery of payload of photo-reactive drugs (photosensitizers) using the conventional nanoparticles, and second, design and development of photo-triggerable nanoparticles (primarily liposomes) to attain light-assisted on-demand drug delivery. The main focus of this review is to provide an update of the history, current status and future applications of photo-triggerable lipid-based nanoparticles (light-sensitive liposomes). We will begin with a brief overview on the applications of liposomes for delivery of photosensitizers, including the choice of photosensitizers for photodynamic therapy, as well as the currently available light sources (lasers) used for these applications. The main segment of this review will encompass the details on the strategies to develop photo-triggerable designer liposomes for their drug delivery function. The principles underlying the assembly of photoreactive lipids into nanoparticles (liposomes) and photo-triggering mechanisms will be presented. We will also discuss factors that limit the applications of these liposomes for in vivo triggered drug delivery and emerging concepts that may lead to the biologically viable photo-activation strategies. We will conclude with our view point on the future perspectives of light-sensitive liposomes in the clinic. PMID:20939770

Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells.

PubMed

Taratula, Olena; Dani, Raj Kumar; Schumann, Canan; Xu, Hong; Wang, Andrew; Song, Han; Dhagat, Pallavi; Taratula, Oleh

2013-12-15

A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40°C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach. Copyright © 2013 Elsevier B.V. All rights reserved.

Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins.

PubMed

Ryou, Sang-Mi; Yeom, Ji-Hyun; Kang, Hyo Jung; Won, Miae; Kim, Jin-Sik; Lee, Boeun; Seong, Maeng-Je; Ha, Nam-Chul; Bae, Jeehyeon; Lee, Kangseok

2014-12-28

Although the delivery of biologically functional protein(s) into mammalian cells could be of tremendous value to biomedical research, the development of such technology has been hindered by the lack of a safe and effective delivery method. Here, we present a simple, efficient, and versatile gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system, with nanoblock-like properties, that allows any recombinant protein to be loaded without additional modifications and delivered into mammalian living systems. AuNP-Apt-based protein delivery system was able to deliver various proteins into variety of cell types in vitro without showing cytotoxicity. This AuNP-Apt system was also effective for the local and systemic targeted delivery of proteins in vivo. A local injection of the AuNP-Apt loaded with the apoptosis-inducing BIM protein efficiently inhibited the growth of xenograft tumors in mice. Furthermore, an intravenous injection of AuNP-Apt loaded with both epidermal growth factor (EGF) and BIM resulted in the targeted delivery of BIM into a xenograft tumor derived from EGF receptor-overexpressing cancer cells with no detectable systemic toxicity. Our findings show that this system can serve as an innovative platform for the development of protein-based biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Telemedicine and the sharing economy: the "Uber" for healthcare.

PubMed

Miller, Brian J; Moore, Derek W; Schmidt, Chester W

2016-12-01

Telehealth platforms, which include both competitors and complements to traditional care delivery, will offer many benefits for both consumers and clinicians, and may promote increased specialization and competition in service delivery. Traditional medical services providers face a challenge similar to that faced by traditional taxicabs after Uber entered the marketplace: how to compete with a connection services platform that threatens to disrupt existing, regulated, and licensed service providers.

Hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform: an advanced vehicle for topical delivery of antiglaucoma drugs and a likely solution to improving compliance and adherence in glaucoma management.

PubMed

Yang, Hu; Leffler, Christopher T

2013-03-01

Glaucoma therapy typically begins with topical medications, of which there are 4 major classes in common use in the United States: beta-adrenergic antagonists, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Unfortunately, all 4 classes require at least daily dosing, and 3 of the 4 classes are approved to be administered 2 or 3 times daily. This need for frequent dosing with multiple medications makes compliance difficult. Longer-acting formulations and combinations that require less frequent administration might improve compliance and therefore medication effectiveness. Recently, we developed an ocular drug delivery system, a hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform for delivering glaucoma therapeutics topically. This platform is designed to deliver glaucoma drugs to the eye efficiently and release the drug in a slow fashion. Furthermore, this delivery platform is designed to be compatible with many of the glaucoma drugs that are currently approved for use. In this article, we review this new delivery system with in-depth discussion of its structural features, properties, and preclinical application in glaucoma treatment. In addition, future directions and translational efforts for marketing this technology are elaborated.

Porous silicon-cyclodextrin based polymer composites for drug delivery applications.

PubMed

Hernandez-Montelongo, J; Naveas, N; Degoutin, S; Tabary, N; Chai, F; Spampinato, V; Ceccone, G; Rossi, F; Torres-Costa, V; Manso-Silvan, M; Martel, B

2014-09-22

One of the main applications of porous silicon (PSi) in biomedicine is drug release, either as a single material or as a part of a composite. PSi composites are attractive candidates for drug delivery systems because they can display new chemical and physical characteristics, which are not exhibited by the individual constituents alone. Since cyclodextrin-based polymers have been proven efficient materials for drug delivery, in this work β-cyclodextrin-citric acid in-situ polymerization was used to functionalize two kinds of PSi (nanoporous and macroporous). The synthesized composites were characterized by microscopy techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact angle, TGA and TBO titration) and a preliminary biological assay was performed. Both systems were tested as drug delivery platforms with two different model drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory), in two different media: pure water and PBS solution. Results show that both kinds of PSi/β-cyclodextrin-citric acid polymer composites, nano- and macro-, provide enhanced release control for drug delivery applications than non-functionalized PSi samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

Network-Based Professional Development: A Comparison of Statewide Initiatives.

ERIC Educational Resources Information Center

Shotsberger, Paul G.; Stammen, Ronald; Vetter, Ronald; Blue, Gloria; Greer, Edrie

This paper addresses opportunities and issues related to the use of the World Wide Web and high-speed networks as a delivery vehicle for training educators who are geographically dispersed. The benefits and potential pitfalls of using networks as educational platforms are explored from the perspective of various systems specifically being…

Picturebooks 2.0: Transmedial Features across Narrative Platforms

ERIC Educational Resources Information Center

Serafini, Frank; Kachorsky, Dani; Aguilera, Earl

2015-01-01

Like other multimodal texts, the design, publication, and delivery of contemporary picture-books have been impacted by the digital revolution and the affordances of digital reading devices. Print-based picture-books are being published alongside digital narratives, and new digital picture-books are being created that no long begin as print-based…

Online Continuing Education for Health Professionals: Does Sticky Design Promote Practice-Relevance?

ERIC Educational Resources Information Center

Zaghab, Roxanne Ward; Maldonado, Carlos; Whitehead, Dongsook; Bartlett, Felicia; de Bittner, Magaly Rodriguez

2015-01-01

Online continuing education (CE) holds promise as an effective method for rapid dissemination of emerging evidence-based practices in health care. Yet, the field of CE continues to develop and delivery is predominately face-to-face programs. Practice-oriented online educational methods and e-learning platforms are not fully utilized. Educational…

Efficient Evaluation System for Learning Management Systems

ERIC Educational Resources Information Center

Cavus, Nadire

2009-01-01

A learning management system (LMS) provides the platform for web-based learning environment by enabling the management, delivery, tracking of learning, testing, communication, registration process and scheduling. There are many LMS systems on the market that can be obtained for free or through payment. It has now become an important task to choose…

Targeting the undruggable: Advances and obstacles in current RNAi therapy

PubMed Central

Wu, Sherry Y.; Lopez-Berestein, Gabriel; Calin, George A.; Sood, Anil K.

2014-01-01

RNA interference (RNAi) therapeutics represents a rapidly emerging platform for personalized cancer treatment. Recent advances in delivery, target selection, and safety of RNAi cancer therapy provide unprecedented opportunities for clinical translation. Here, we discuss these advances and present strategies for making RNAi-based therapy a viable part of cancer management. PMID:24920658

Achieving Complex Learning Outcomes through Adoption of a Pedagogical Perspective: A Model for Computer Technology Delivered Instruction

ERIC Educational Resources Information Center

Bellard, Breshanica

2018-01-01

Professionals responsible for the delivery of education and training using technology systems and platforms can facilitate complex learning through application of relevant strategies, principles and theories that support how learners learn and that support how curriculum should be designed in a technology based learning environment. Technological…

Reducing audio stimulus presentation latencies across studies, laboratories, and hardware and operating system configurations.

PubMed

Babjack, Destiny L; Cernicky, Brandon; Sobotka, Andrew J; Basler, Lee; Struthers, Devon; Kisic, Richard; Barone, Kimberly; Zuccolotto, Anthony P

2015-09-01

Using differing computer platforms and audio output devices to deliver audio stimuli often introduces (1) substantial variability across labs and (2) variable time between the intended and actual sound delivery (the sound onset latency). Fast, accurate audio onset latencies are particularly important when audio stimuli need to be delivered precisely as part of studies that depend on accurate timing (e.g., electroencephalographic, event-related potential, or multimodal studies), or in multisite studies in which standardization and strict control over the computer platforms used is not feasible. This research describes the variability introduced by using differing configurations and introduces a novel approach to minimizing audio sound latency and variability. A stimulus presentation and latency assessment approach is presented using E-Prime and Chronos (a new multifunction, USB-based data presentation and collection device). The present approach reliably delivers audio stimuli with low latencies that vary by ≤1 ms, independent of hardware and Windows operating system (OS)/driver combinations. The Chronos audio subsystem adopts a buffering, aborting, querying, and remixing approach to the delivery of audio, to achieve a consistent 1-ms sound onset latency for single-sound delivery, and precise delivery of multiple sounds that achieves standard deviations of 1/10th of a millisecond without the use of advanced scripting. Chronos's sound onset latencies are small, reliable, and consistent across systems. Testing of standard audio delivery devices and configurations highlights the need for careful attention to consistency between labs, experiments, and multiple study sites in their hardware choices, OS selections, and adoption of audio delivery systems designed to sidestep the audio latency variability issue.

Airship platform for high-resolution space technology telescope

NASA Astrophysics Data System (ADS)

Miller, John A.

1995-06-01

This paper sets out to describe the utilization of an unmanned lighter-than-air vehicle as a sub- orbital airborne mission platform for the deployment of space technology telescopes allowing innovative space quality astronomy to be conducted. The paper describes how a low cost airship of relatively simple design can be produced that will be capable of operating in an unmanned remotely piloted mode from a base, fly to a pressure altitude, shut down engines, and operate in a free balloon stage for the period of experimental research. It will be shown that ballooning will allow the platform to be completely free from vibration, and in conjunction with high altitude and polar weather conditions minimize perturbation caused by weather. This paper outlines the technical features of the airship, the projected mission interfaces and the modus operandi of Airship delivery, ground base and missions operations, and final recovery.

Recent advances in recombinant protein-based malaria vaccines.

PubMed

Draper, Simon J; Angov, Evelina; Horii, Toshihiro; Miller, Louis H; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-12-22

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle-including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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.

Nanoparticle hardness controls the internalization pathway for drug delivery

NASA Astrophysics Data System (ADS)

Li, Ye; Zhang, Xianren; Cao, Dapeng

2015-01-01

Nanoparticle (NP)-based drug delivery systems offer fundamental advantages over current therapeutic agents that commonly display a longer circulation time, lower toxicity, specific targeted release, and greater bioavailability. For successful NP-based drug delivery it is essential that the drug-carrying nanocarriers can be internalized by the target cells and transported to specific sites, and the inefficient internalization of nanocarriers is often one of the major sources for drug resistance. In this work, we use the dissipative particle dynamics simulation to investigate the effect of NP hardness on their internalization efficiency. Three simplified models of NP platforms for drug delivery, including polymeric NP, liposome and solid NP, are designed here to represent increasing nanocarrier hardness. Simulation results indicate that NP hardness controls the internalization pathway for drug delivery. Rigid NPs can enter the cell by a pathway of endocytosis, whereas for soft NPs the endocytosis process can be inhibited or frustrated due to wrapping-induced shape deformation and non-uniform ligand distribution. Instead, soft NPs tend to find one of three penetration pathways to enter the cell membrane via rearranging their hydrophobic and hydrophilic segments. Finally, we show that the interaction between nanocarriers and drug molecules is also essential for effective drug delivery.

ROS-Responsive Microspheres for On Demand Antioxidant Therapy in a Model of Diabetic Peripheral Arterial Disease

PubMed Central

Poole, KM; Nelson, CE; Joshi, RV; Martin, JR; Gupta, MK; Haws, SC; Kavanaugh, TE; Skala, MC; Duvall, CL

2014-01-01

A new microparticle-based delivery system was synthesized from reactive oxygen species (ROS)-responsive poly(propylene sulfide) (PPS) and tested for “on demand” antioxidant therapy. PPS is hydrophobic but undergoes a phase change to become hydrophilic upon oxidation and thus provides a useful platform for ROS-demanded drug release. This platform was tested for delivery of the promising anti-inflammatory and antioxidant therapeutic molecule curcumin, which is currently limited in use in its free form due to poor pharmacokinetic properties. PPS microspheres efficiently encapsulated curcumin through oil-in-water emulsion and provided sustained, on demand release that was modulated in vitro by hydrogen peroxide concentration. The cytocompatible, curcumin-loaded microspheres preferentially targeted and scavenged intracellular ROS in activated macrophages, reduced in vitro cell death in the presence of cytotoxic levels of ROS, and decreased tissue-level ROS in vivo in the diabetic mouse hind limb ischemia model of peripheral arterial disease. Interestingly, due to the ROS scavenging behavior of PPS, the blank microparticles also showed inherent therapeutic properties that were synergistic with the effects of curcumin in these assays. Functionally, local delivery of curcumin-PPS microspheres accelerated recovery from hind limb ischemia in diabetic mice, as demonstrated using non-invasive imaging techniques. This work demonstrates the potential for PPS microspheres as a generalizable vehicle for ROS-demanded drug release and establishes the utility of this platform for improving local curcumin bioavailability for treatment of chronic inflammatory diseases. PMID:25522975

Innovative Models of Dental Care Delivery and Coverage: Patient-Centric Dental Benefits Based on Digital Oral Health Risk Assessment.

PubMed

Martin, John; Mills, Shannon; Foley, Mary E

2018-04-01

Innovative models of dental care delivery and coverage are emerging across oral health care systems causing changes to treatment and benefit plans. A novel addition to these models is digital risk assessment, which offers a promising new approach that incorporates the use of a cloud-based technology platform to assess an individual patient's risk for oral disease. Risk assessment changes treatment by including risk as a modifier of treatment and as a determinant of preventive services. Benefit plans are being developed to use risk assessment to predetermine preventive benefits for patients identified at elevated risk for oral disease. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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.

CVN 78 Gerald R. Ford Class Nuclear Aircraft Carrier (CVN 78)

DTIC Science & Technology

2013-12-01

Capabil... -Follow-on Ship (CVN 79) DAB Program Review - • Start Construction - • Delivery .-:K IOT &E IOT &E Start .-:41 IOT &E Complete e(41 Follow-on...Ship (CVN 80) DAB Program Review -Platform-Level Integration D ... ....., Milestone C .. EMALS EMALS Delivery (with Ship) .-:o; IOC ..:<! IOT ...E IOT &E Start ..:<! IOT &E Complete -· Platform-Level Integration .. ...:<! CVN 78 Milestones SAR Baseline Dev Est Current APB Development

Strategy for selecting nanotechnology carriers to overcome immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics.

PubMed

Dobrovolskaia, Marina A; McNeil, Scott E

2015-07-01

Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation. This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents. NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.

Steam distribution and energy delivery optimization using wireless sensors

NASA Astrophysics Data System (ADS)

Olama, Mohammed M.; Allgood, Glenn O.; Kuruganti, Teja P.; Sukumar, Sreenivas R.; Djouadi, Seddik M.; Lake, Joe E.

2011-05-01

The Extreme Measurement Communications Center at Oak Ridge National Laboratory (ORNL) explores the deployment of a wireless sensor system with a real-time measurement-based energy efficiency optimization framework in the ORNL campus. With particular focus on the 12-mile long steam distribution network in our campus, we propose an integrated system-level approach to optimize the energy delivery within the steam distribution system. We address the goal of achieving significant energy-saving in steam lines by monitoring and acting on leaking steam valves/traps. Our approach leverages an integrated wireless sensor and real-time monitoring capabilities. We make assessments on the real-time status of the distribution system by mounting acoustic sensors on the steam pipes/traps/valves and observe the state measurements of these sensors. Our assessments are based on analysis of the wireless sensor measurements. We describe Fourier-spectrum based algorithms that interpret acoustic vibration sensor data to characterize flows and classify the steam system status. We are able to present the sensor readings, steam flow, steam trap status and the assessed alerts as an interactive overlay within a web-based Google Earth geographic platform that enables decision makers to take remedial action. We believe our demonstration serves as an instantiation of a platform that extends implementation to include newer modalities to manage water flow, sewage and energy consumption.

Thick-tissue bioreactor as a platform for long-term organotypic culture and drug delivery.

PubMed

Markov, Dmitry A; Lu, Jenny Q; Samson, Philip C; Wikswo, John P; McCawley, Lisa J

2012-11-07

We have developed a novel, portable, gravity-fed, microfluidics-based platform suitable for optical interrogation of long-term organotypic cell culture. This system is designed to provide convenient control of cell maintenance, nutrients, and experimental reagent delivery to tissue-like cell densities housed in a transparent, low-volume microenvironment. To demonstrate the ability of our Thick-Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density cellular arrays, we observed the morphogenic growth of human mammary epithelial cell lines, MCF-10A and their invasive variants, cultured under three-dimensional (3D) conditions inside our system. Over the course of 21 days, these cells typically develop into hollow "mammospheres" if cultured in standard 3D Matrigel. This complex morphogenic process requires alterations in a variety of cellular functions, including degradation of extracellular matrix that is regulated by cell-produced matrix proteinases. For our "drug" delivery testing and validation experiments we have introduced proteinase inhibitors into the fluid supply system, and we observed both reduced proteinase activity and inhibited cellular morphogenesis. The size inhibition results correlated well with the overall proteinase activities of the tested cells.

Potent Immune Responses in Rhesus Macaques Induced by Nonviral Delivery of a Self-amplifying RNA Vaccine Expressing HIV Type 1 Envelope With a Cationic Nanoemulsion

PubMed Central

Bogers, Willy M.; Oostermeijer, Herman; Mooij, Petra; Koopman, Gerrit; Verschoor, Ernst J.; Davis, David; Ulmer, Jeffrey B.; Brito, Luis A.; Cu, Yen; Banerjee, Kaustuv; Otten, Gillis R.; Burke, Brian; Dey, Antu; Heeney, Jonathan L.; Shen, Xiaoying; Tomaras, Georgia D.; Labranche, Celia; Montefiori, David C.; Liao, Hua-Xin; Haynes, Barton; Geall, Andrew J.; Barnett, Susan W.

2015-01-01

Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. The SAM vaccine platform is based on a synthetic, self-amplifying mRNA delivered by a nonviral delivery system. The safety and immunogenicity of an HIV SAM vaccine encoding a clade C envelope glycoprotein formulated with a cationic nanoemulsion (CNE) delivery system was evaluated in rhesus macaques. The HIV SAM vaccine induced potent cellular immune responses that were greater in magnitude than those induced by self-amplifying mRNA packaged in a viral replicon particle (VRP) or by a recombinant HIV envelope protein formulated with MF59 adjuvant, anti-envelope binding (including anti-V1V2), and neutralizing antibody responses that exceeded those induced by the VRP vaccine. These studies provide the first evidence in nonhuman primates that HIV vaccination with a relatively low dose (50 µg) of formulated self-amplifying mRNA is safe and immunogenic. PMID:25234719

Nano to micro delivery systems: targeting angiogenesis in brain tumors.

PubMed

Gilert, Ariel; Machluf, Marcelle

2010-10-08

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain.

Nano to micro delivery systems: targeting angiogenesis in brain tumors

PubMed Central

2010-01-01

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain. PMID:20932320

Supramolecular Drug Delivery Systems Based on Water-Soluble Pillar[n]arenes.

PubMed

Wu, Xuan; Gao, Lei; Hu, Xiao-Yu; Wang, Leyong

2016-06-01

Supramolecular drug delivery systems (SDDSs), including various kinds of nanostructures that are assembled by reversible noncovalent interactions, have attracted considerable attention as ideal drug carriers owing to their fascinating ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, which provides a flexible and robust platform for designing and developing functional and smart supramolecular nano-drug carriers. Pillar[n]arenes represent a new generation of macrocyclic hosts, which have unique structures and excellent properties in host-guest chemistry. This account describes recent progress in our group to develop pillararene-based stimuli-responsive supramolecular nanostructures constructed by reversible host-guest interactions for controllable anticancer drug delivery. The potential applications of these supramolecular drug carriers in cancer treatment and the fundamental questions facing SDDSs are also discussed. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Edible plants for oral delivery of biopharmaceuticals.

PubMed

Merlin, Matilde; Pezzotti, Mario; Avesani, Linda

2017-01-01

Molecular farming is the use of plants for the production of high value recombinant proteins. Over the last 25 years, molecular farming has achieved the inexpensive, scalable and safe production of pharmaceutical proteins using a range of strategies. One of the most promising approaches is the use of edible plant organs expressing biopharmaceuticals for direct oral delivery. This approach has proven to be efficacious in several clinical vaccination and tolerance induction trials as well as multiple preclinical studies for disease prevention. The production of oral biopharmaceuticals in edible plant tissues could revolutionize the pharmaceutical industry by reducing the cost of production systems based on fermentation, and also eliminating expensive downstream purification, cold storage and transportation costs. This review considers the unique features that make plants ideal as platforms for the oral delivery of protein-based therapeutics and describes recent developments in the production of plant derived biopharmaceuticals for oral administration. © 2016 The British Pharmacological Society.

Determining the True Cost to Deliver Total Hip and Knee Arthroplasty Over the Full Cycle of Care: Preparing for Bundling and Reference-Based Pricing.

PubMed

DiGioia, Anthony M; Greenhouse, Pamela K; Giarrusso, Michelle L; Kress, Justina M

2016-01-01

The Affordable Care Act accelerates health care providers' need to prepare for new care delivery platforms and payment models such as bundling and reference-based pricing (RBP). Thriving in this environment will be difficult without knowing the true cost of care delivery at the level of the clinical condition over the full cycle of care. We describe a project in which we identified true costs for both total hip and total knee arthroplasty. With the same tool, we identified cost drivers in each segment of care delivery and collected patient experience information. Combining cost and experience information with outcomes data we already collect allows us to drive costs down while protecting outcomes and experiences, and compete successfully in bundling and RBP programs. Copyright © 2016 Elsevier Inc. All rights reserved.

PLGA-Chitosan nanoparticle-mediated gene delivery for oral cancer treatment: A brief review

NASA Astrophysics Data System (ADS)

Bakar, L. M.; Abdullah, M. Z.; Doolaanea, A. A.; Ichwan, S. J. A.

2017-08-01

Cancer becomes a serious issue on society with increasing of their growth and proliferation, either in well economic developed countries or not. Recent years, oral cancer is one of the most threatening diseases impairing the quality of life of the patient. Scientists have emphasised on application of gene therapy for oral cancer by using nanoparticle as transportation vectors as a new alternative platform in order to overcome the limitations of conventional approaches. In modern medicine, nanotechnologies’ application, such as nanoparticles-mediated gene delivery, is one of promising tool for therapeutic devices. The objective of this article is to present a brief review summarizes on the current progress of nanotechnology-based gene delivery treatment system targeted for oral cancer.

Architectural and Functional Design and Evaluation of E-Learning VUIS Based on the Proposed IEEE LTSA Reference Model.

ERIC Educational Resources Information Center

O'Droma, Mairtin S.; Ganchev, Ivan; McDonnell, Fergal

2003-01-01

Presents a comparative analysis from the Institute of Electrical and Electronics Engineers (IEEE) Learning Technology Standards Committee's (LTSC) of the architectural and functional design of e-learning delivery platforms and applications, e-learning course authoring tools, and learning management systems (LMSs), with a view of assessing how…

Problematic but Possible: Online Teaching and Learning in Post-Registration Programmes

ERIC Educational Resources Information Center

Cassar, Maria; Trapani, Josef

2014-01-01

This artifact identifies the main challenges experienced by the authors, both nurse educators, in the delivery of a module on evidence based practice exclusively through the use of an e-learning platform. The module has been running for the past four years as part of an entirely online post registration programme for qualified health professionals…

Probabilities and Predictions: Modeling the Development of Scientific Problem-Solving Skills

ERIC Educational Resources Information Center

Stevens, Ron; Johnson, David F.; Soller, Amy

2005-01-01

The IMMEX (Interactive Multi-Media Exercises) Web-based problem set platform enables the online delivery of complex, multimedia simulations, the rapid collection of student performance data, and has already been used in several genetic simulations. The next step is the use of these data to understand and improve student learning in a formative…

Internet-enabled solutions for health care business problems.

PubMed

Kennedy, R; Geisler, M

1997-01-01

Many health care delivery organizations have built, installed, or made use of Nets. As single entities merge with others, and independent institutions become part of much larger delivery networks, the need for collaboration is critical. With the formation of such partnerships, existing platforms will become increasingly available from which it will be possible to build disparate technologies that must somehow be part of a single working "system." Nets can enable this leveraging, allowing access from multiple technological platforms. The collaboration, distribution, application integration, and messaging possibilities with the Nets are unprecedented. We believe that meeting a health care delivery organization's needs without these benefits will soon be unthinkable. While Nets are not the answer to the challenges facing health care delivery today, they certainly are a large contributor to the solution.

Periadventitial drug delivery for the prevention of intimal hyperplasia following open surgery.

PubMed

Chaudhary, Mirnal A; Guo, Lian-Wang; Shi, Xudong; Chen, Guojun; Gong, Shaoqin; Liu, Bo; Kent, K Craig

2016-07-10

Intimal hyperplasia (IH) remains a major cause of poor patient outcomes after surgical revascularization to treat atherosclerosis. A multitude of drugs have been shown to prevent the development of IH. Moreover, endovascular drug delivery following angioplasty and stenting has been achieved with a marked diminution in the incidence of restenosis. Despite advances in endovascular drug delivery, there is currently no clinically available method of periadventitial drug delivery suitable for open vascular reconstructions. Herein we provide an overview of the recent literature regarding innovative polymer platforms for periadventitial drug delivery in preclinical models of IH as well as insights about barriers to clinical translation. A comprehensive PubMed search confined to the past 15years was performed for studies of periadventitial drug delivery. Additional searches were performed for relevant clinical trials, patents, meeting abstracts, and awards of NIH funding. Most of the research involving direct periadventitial delivery without a drug carrier was published prior to 2000. Over the past 15years there have been a surge of reports utilizing periadventitial drug-releasing polymer platforms, most commonly bioresorbable hydrogels and wraps. These methods proved to be effective for the inhibition of IH in various animal models (e.g. balloon angioplasty, wire injury, and vein graft), but very few have advanced to clinical trials. There are a number of barriers that may account for this lack of translation. Promising new approaches including the use of nanoparticles will be described. No periadventitial drug delivery system has reached clinical application. For periadventitial delivery, polymer hydrogels, wraps, and nanoparticles exhibit overlapping and complementary properties. The ideal periadventitial delivery platform would allow for sustained drug release yet exert minimal mechanical and inflammatory stresses to the vessel wall. A clinically applicable strategy for periadventitial drug delivery would benefit thousands of patients undergoing open vascular reconstruction each year. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuum of Care Services for Maternal and Child Health using mobile technology - a health system strengthening strategy in low and middle income countries.

PubMed

Balakrishnan, Ramkrishnan; Gopichandran, Vijayaprasad; Chaturvedi, Sharadprakash; Chatterjee, Rahul; Mahapatra, Tanmay; Chaudhuri, Indrajit

2016-07-07

Mobile phone technology is utilized for better delivery of health services worldwide. In low-and-middle income countries mobile phones are now ubiquitous. Thus leveraging mHealth applications in health sector is becoming popular rapidly in these countries. To assess the effectiveness of the Continuum of Care Services (CCS) mHealth platform in terms of strengthening the delivery of maternal and child health (MCH) services in a district in Bihar, a resource-poor state in India. The CommCare mHealth platform was customized to CCS as one of the innovations under a project funded by the Bill and Melinda Gates Foundation to improve the maternal and newborn health services in Bihar. The intervention was rolled out in one project district in Bihar, during July 2012. More than 550 frontline workers out of a total of 3000 including Accredited Social Health Activists, Anganwadi Workers, Auxilliary Nurse Midwives and Lady Health Supervisors were trained to use the mHealth platform. The service delivery components namely early registration of pregnant women, three antenatal visits, tetanus toxoid immunization of the mother, iron and folic acid tablet supply, institutional delivery, postnatal home visits and early initiation of breastfeeding were used as indicators for good quality services. The resultant coverage of these services in the implementation area was compared with rest of Bihar and previous year statistics of the same area. The time lag between delivery of a service and its record capture in the maternal and child tracking system (MCTS) database was computed in a random sample of 16,000 beneficiaries. The coverage of services among marginalized and non-marginalized castes was compared to indicate equity of service delivery. Health system strengthening was viewed from the angle of coverage, quality, equity and efficiency of services. The implementation blocks had higher coverage of all the eight indicator services compared to rest of Bihar and the previous year. There was equity of services across castes for all the indicators. Timely capture of data was also ensured compared to paper-based reporting. By virtue of its impact on quality, efficiency and equity of service delivery, health care manpower efficiency and governance, the mHealth inclusion at service provision level can be one of the potential strategy to strengthen the health system.

3D tumor microtissues as an in vitro testing platform for microenvironmentally-triggered drug delivery systems.

PubMed

Brancato, Virginia; Gioiella, Filomena; Profeta, Martina; Imparato, Giorgia; Guarnieri, Daniela; Urciuolo, Francesco; Melone, Pietro; Netti, Paolo A

2017-07-15

Therapeutic approaches based on nanomedicine have garnered great attention in cancer research. In vitro biological models that better mimic in vivo conditions are crucial tools to more accurately predict their therapeutic efficacy in vivo. In this work, a new 3D breast cancer microtissue has been developed to recapitulate the complexity of the tumor microenvironment and to test its efficacy as screening platform for drug delivery systems. The proposed 3D cancer model presents human breast adenocarcinoma cells and cancer-associated fibroblasts embedded in their own ECM, thus showing several features of an in vivo tumor, such as overexpression of metallo-proteinases (MMPs). After demonstrating at molecular and protein level the MMP2 overexpression in such tumor microtissues, we used them to test a recently validated formulation of endogenous MMP2-responsive nanoparticles (NP). The presence of the MMP2-sensitive linker allows doxorubicin release from NP only upon specific enzymatic cleavage of the peptide. The same NP without the MMP-sensitive linker and healthy breast microtissues were also produced to demonstrate NP specificity and selectivity. Cell viability after NP treatment confirmed that controlled drug delivery is achieved only in 3D tumor microtissues suggesting that the validation of therapeutic strategies in such 3D tumor model could predict human response. A major issue of modern cancer research is the development of accurate and predictive experimental models of human tumors consistent with tumor microenvironment and applicable as screening platforms for novel therapeutic strategies. In this work, we developed and validated a new 3D microtissue model of human breast tumor as a testing platform of anti-cancer drug delivery systems. To this aim, biodegradable nanoparticles responsive to physiological changes specifically occurring in tumor microenvironment were used. Our findings clearly demonstrate that the breast tumor microtissue well recapitulates in vivo physiological features of tumor tissue and elicits a specific response to microenvironmentally-responsive nanoparticles compared to healthy tissue. We believe this study is of particular interest for cancer research and paves the way to exploit tumor microtissues for several testing purposes. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Technology-assisted Interventions for Parents of Young Children: Emerging Practices, Current Research, and Future Directions

PubMed Central

Hall, Cristin M.; Bierman, Karen L.

2016-01-01

Technology can potentially expand the reach and cut the costs of providing effective, evidence-based interventions. This paper reviews existing publications that describe the application and evaluation of technology-assisted interventions for parents of young children. A broad review of the early childhood literature revealed 48 studies describing technology-assisted parent education and interventions. Across these studies, multiple forms of technology were used, including web-based platforms, discussion forums, mobile devices, and video conferencing. Results are described moving from feasibility and acceptability of technology-based delivery systems to more rigorous evaluations examining their impact on parent and child outcomes. Potential exists for technology to deliver interventions to parents. Limitations are discussed including differential acceptability and elevated attrition associated with internet-only intervention delivery. PMID:27773964

Technology-assisted Interventions for Parents of Young Children: Emerging Practices, Current Research, and Future Directions.

PubMed

Hall, Cristin M; Bierman, Karen L

Technology can potentially expand the reach and cut the costs of providing effective, evidence-based interventions. This paper reviews existing publications that describe the application and evaluation of technology-assisted interventions for parents of young children. A broad review of the early childhood literature revealed 48 studies describing technology-assisted parent education and interventions. Across these studies, multiple forms of technology were used, including web-based platforms, discussion forums, mobile devices, and video conferencing. Results are described moving from feasibility and acceptability of technology-based delivery systems to more rigorous evaluations examining their impact on parent and child outcomes. Potential exists for technology to deliver interventions to parents. Limitations are discussed including differential acceptability and elevated attrition associated with internet-only intervention delivery.

Development of a Just-in-Time Adaptive mHealth Intervention for Insomnia: Usability Study.

PubMed

Pulantara, I Wayan; Parmanto, Bambang; Germain, Anne

2018-05-17

Healthy sleep is a fundamental component of physical and brain health. Insomnia, however, is a prevalent sleep disorder that compromises functioning, productivity, and health. Therefore, developing efficient treatment delivery methods for insomnia can have significant societal and personal health impacts. Cognitive behavioral therapy for insomnia (CBTI) is the recommended first-line treatment of insomnia but access is currently limited for patients, since treatment must occur in specialty sleep clinics, which suffer from an insufficient number of trained clinicians. Smartphone-based interventions offer a promising means for improving the delivery of CBTI. Furthermore, novel features such as real-time monitoring and assessment, personalization, dynamic adaptations of the intervention, and context awareness can enhance treatment personalization and effectiveness, and reduce associated costs. Ultimately, this "Just in Time Adaptive Intervention" for insomnia-an intervention approach that is acceptable to patients and clinicians, and is based on mobile health (mHealth) platform and tools-can significantly improve patient access and clinician delivery of evidence-based insomnia treatments. This study aims to develop and assess the usability of a Just in Time Adaptive Intervention application platform called iREST ("interactive Resilience Enhancing Sleep Tactics") for use in behavioral insomnia interventions. iREST can be used by both patients and clinicians. The development of iREST was based on the Iterative and Incremental Development software development model. Requirement analysis was based on the case study's description, workflow and needs, clinician inputs, and a previously conducted BBTI military study/implementation of the Just in Time Adaptive Intervention architecture. To evaluate the usability of the iREST mHealth tool, a pilot usability study was conducted. Additionally, this study explores the feasibility of using an off-the-shelf wearable device to supplement the subjective assessment of patient sleep patterns. The iREST app was developed from the mobile logical architecture of Just in Time Adaptive Intervention. It consists of a cross-platform smartphone app, a clinician portal, and secure 2-way communications platform between the app and the portal. The usability study comprised 19 Active Duty Service Members and Veterans between the ages of 18 and 60. Descriptive statistics based on in-app questionnaires indicate that on average, 12 (mean 12.23, SD 8.96) unique devices accessed the clinician portal per day for more than two years, while the app was rated as "highly usable", achieving a mean System Usability Score score of 85.74 (SD 12.37), which translates to an adjective rating of "Excellent". The participants also gave high scores on "ease of use and learnability" with an average score of 4.33 (SD 0.65) on a scale of 1 to 5. iREST provides a feasible platform for the implementation of Just in Time Adaptive Intervention in mHealth-based and remote intervention settings. The system was rated highly usable and its cross-platformness made it readily implemented within the heavily segregated smartphone market. The use of wearables to track sleep is promising; yet the accuracy of this technology needs further improvement. Ultimately, iREST demonstrates that mHealth-based Just in Time Adaptive Intervention is not only feasible, but also works effectively. ©I Wayan Pulantara, Bambang Parmanto, Anne Germain. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 17.05.2018.

Patient specific optimization-based treatment planning for catheter-based ultrasound hyperthermia and thermal ablation

NASA Astrophysics Data System (ADS)

Prakash, Punit; Chen, Xin; Wootton, Jeffery; Pouliot, Jean; Hsu, I.-Chow; Diederich, Chris J.

2009-02-01

A 3D optimization-based thermal treatment planning platform has been developed for the application of catheter-based ultrasound hyperthermia in conjunction with high dose rate (HDR) brachytherapy for treating advanced pelvic tumors. Optimal selection of applied power levels to each independently controlled transducer segment can be used to conform and maximize therapeutic heating and thermal dose coverage to the target region, providing significant advantages over current hyperthermia technology and improving treatment response. Critical anatomic structures, clinical target outlines, and implant/applicator geometries were acquired from sequential multi-slice 2D images obtained from HDR treatment planning and used to reconstruct patient specific 3D biothermal models. A constrained optimization algorithm was devised and integrated within a finite element thermal solver to determine a priori the optimal applied power levels and the resulting 3D temperature distributions such that therapeutic heating is maximized within the target, while placing constraints on maximum tissue temperature and thermal exposure of surrounding non-targeted tissue. This optimizationbased treatment planning and modeling system was applied on representative cases of clinical implants for HDR treatment of cervix and prostate to evaluate the utility of this planning approach. The planning provided significant improvement in achievable temperature distributions for all cases, with substantial increase in T90 and thermal dose (CEM43T90) coverage to the hyperthermia target volume while decreasing maximum treatment temperature and reducing thermal dose exposure to surrounding non-targeted tissues and thermally sensitive rectum and bladder. This optimization based treatment planning platform with catheter-based ultrasound applicators is a useful tool that has potential to significantly improve the delivery of hyperthermia in conjunction with HDR brachytherapy. The planning platform has been extended to model thermal ablation, including the addition of temperature dependent attenuation, perfusion, and tissue damage. Pilot point control at the target boundaries was implemented to control power delivery to each transducer section, simulating an approach feasible for MR guided procedures. The computer model of thermal ablation was evaluated on representative patient anatomies to demonstrate the feasibility of using catheter-based ultrasound thermal ablation for treatment of benign prostate hyperplasia (BPH) and prostate cancer, and to assist in designing applicators and treatment delivery strategies.

Evaluating Student Perceptions of Course Delivery Platforms

ERIC Educational Resources Information Center

Bramorski, Tom; Madan, Manu S.

2016-01-01

In this paper we evaluate effectiveness of course delivery mode on three dimensions: values, networking opportunities and learning. While students and their future employers are two important customers for the business program, we focus on the perception of students regarding the effectiveness of course delivery mode on program performance. The…

An Automated Microfluidic Multiplexer for Fast Delivery of C. elegans Populations from Multiwells

PubMed Central

Ghorashian, Navid; Gökçe, Sertan Kutal; Guo, Sam Xun; Everett, William Neil; Ben-Yakar, Adela

2013-01-01

Automated biosorter platforms, including recently developed microfluidic devices, enable and accelerate high-throughput and/or high-resolution bioassays on small animal models. However, time-consuming delivery of different organism populations to these systems introduces a major bottleneck to executing large-scale screens. Current population delivery strategies rely on suction from conventional well plates through tubing periodically exposed to air, leading to certain disadvantages: 1) bubble introduction to the sample, interfering with analysis in the downstream system, 2) substantial time drain from added bubble-cleaning steps, and 3) the need for complex mechanical systems to manipulate well plate position. To address these concerns, we developed a multiwell-format microfluidic platform that can deliver multiple distinct animal populations from on-chip wells using multiplexed valve control. This Population Delivery Chip could operate autonomously as part of a relatively simple setup that did not require any of the major mechanical moving parts typical of plate-handling systems to address a given well. We demonstrated automatic serial delivery of 16 distinct C. elegans worm populations to a single outlet without introducing any bubbles to the samples, causing cross-contamination, or damaging the animals. The device achieved delivery of more than 90% of the population preloaded into a given well in 4.7 seconds; an order of magnitude faster than delivery modalities in current use. This platform could potentially handle other similarly sized model organisms, such as zebrafish and drosophila larvae or cellular micro-colonies. The device’s architecture and microchannel dimensions allow simple expansion for processing larger numbers of populations. PMID:24069313

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels.

PubMed

Alsaab, Hashem; Bonam, Sindhu Prabha; Bahl, Dherya; Chowdhury, Pallabita; Alexander, Kenneth; Boddu, Sai Hs

2016-01-01

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Chlorotoxin-conjugated graphene oxide for targeted delivery of an anticancer drug

PubMed Central

Wang, Hao; Gu, Wei; Xiao, Ning; Ye, Ling; Xu, Qunyuan

2014-01-01

Current chemotherapy for glioma is rarely satisfactory due to low therapeutic efficiency and systemic side effects. We have developed a glioma-targeted drug delivery system based on graphene oxide. Targeted peptide chlorotoxin-conjugated graphene oxide (CTX-GO) sheets were successfully synthesized and characterized. Doxorubicin was loaded onto CTX-GO (CTX-GO/DOX) with high efficiency (570 mg doxorubicin per gram CTX-GO) via noncovalent interactions. Doxorubicin release was pH-dependent and showed sustained-release properties. Cytotoxicity experiments demonstrated that CTX-GO/DOX mediated the highest rate of death of glioma cells compared with free doxorubicin or graphene oxide loaded with doxorubicin only. Further, conjugation with chlorotoxin enhanced accumulation of doxorubicin within glioma cells. These findings indicate that CTX-GO is a promising platform for drug delivery and provide a rationale for developing a glioma-specific drug delivery system. PMID:24672236

Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells and Tissues Following Combat Associated Trauma

DTIC Science & Technology

2013-09-01

death pathways such as apoptosis subsequent to acute trauma as soon as possible, ideally by self- administration of a drug or a biologic that can be... Drugs to Ocular Tissues Including Retina and Cornea . Mol Ther, 2007;16(1):107- 14. 3. Read SP, Cashman SM, and Kumar-Singh R: POD...1 AD_________________ Award Number: W81XWH-12-1-0374 TITLE: Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells

Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape.

PubMed

Sahari, Ali; Traore, Mahama A; Scharf, Birgit E; Behkam, Bahareh

2014-10-01

Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).

An emerging platform for drug delivery: aerogel based systems.

PubMed

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.

Tellurium-containing polymer micelles: competitive-ligand-regulated coordination responsive systems.

PubMed

Cao, Wei; Gu, Yuwei; Meineck, Myriam; Li, Tianyu; Xu, Huaping

2014-04-02

Nanomaterials capable of achieving tunable cargo release kinetics are of significance in a fundamental sense and various biological or medical applications. We report a competitive coordination system based on a novel tellurium-containing polymer and its ligand-regulated release manners. Tellurium was introduced to water-soluble polymers for the first time as drug delivery vehicles. The coordination chemistry between platinum and tellurium was designed to enable the load of platinum-based drugs. Through the competitive coordination of biomolecules, the drugs could be released in a controlled manner. Furthermore, the release kinetics could be modulated by the competitive ligands involved due to their different coordination ability. This tellurium-containing polymer may enrich the family of delivery systems and provide a new platform for future biomedical nanotechnologies.

Nanotechnology for protein delivery: Overview and perspectives.

PubMed

Yu, Mikyung; Wu, Jun; Shi, Jinjun; Farokhzad, Omid C

2016-10-28

Protein-based therapeutics have made a significant impact in the treatment of a variety of important human diseases. However, given their intrinsically vulnerable structure and susceptibility to enzymatic degradation, many therapeutic proteins such as enzymes, growth factors, hormones, and cytokines suffer from poor physicochemical/biological stability and immunogenicity that may limit their potential benefits, and in some cases limit their utility. Furthermore, when protein therapeutics are developed for intracellular targets, their internalization and biological activity may be limited by inefficient membrane permeability and/or endosomal escape. Development of effective protein delivery strategies is therefore essential to further enhance therapeutic outcomes to enable widespread medical applications. This review discusses the advantages and limitations of marketed and developmental-stage protein delivery strategies, and provides a focused overview of recent advances in nanotechnology platforms for the systemic delivery of therapeutic proteins. In addition, we also highlight nanoparticle-mediated non-invasive administration approaches (e.g., oral, nasal, pulmonary, and transdermal routes) for protein delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Organ-on-a-chip platforms for studying drug delivery systems.

PubMed

Bhise, Nupura S; Ribas, João; Manoharan, Vijayan; Zhang, Yu Shrike; Polini, Alessandro; Massa, Solange; Dokmeci, Mehmet R; Khademhosseini, Ali

2014-09-28

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems - microscale recapitulations of complex organ functions - promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

Capsid-like supramolecular dendritic systems as pH-responsive nanocarriers for drug penetration and site-specific delivery.

PubMed

Li, Yachao; Lai, Yusi; Xu, Xianghui; Zhang, Xiao; Wu, Yahui; Hu, Cheng; Gu, Zhongwei

2016-02-01

Supramolecular dendritic systems emerge as a promising new-generation bioinspired nanoplatform for nanomedicine. Herein, we report capsid-like mimics self-assembled from peptide dendrimers and functionalized peptides to enhance drug penetration and site-specific delivery for tumor therapy. These drug-loaded supramolecular dendritic systems are endowed with capsid-like component and nanostructure by a facile supramolecular approach. As expected, the drug-loaded capsid-like nanocarriers show some desirable advantages for antitumor drug delivery: a) well-defined nanostructure to improve drug location at tumor site, b) capsid-like architecture to enhance drug penetration, c) high internalization, pH-controlled release and nuclear delivery to jointly achieve site-specific delivery. Based on these merits, the drug-loaded capsid nanocarriers provide efficient tumor suppression to 4T1 tumor bearing BALB/c mice and decrease the DOX-induced toxicity during treatment course. Dendrimers have been tested in many clinical trials as nanocarriers, without great success due to many limitations. Here, the authors attempted to address these issues by developing supramolecular dendritic systems, which mimic capsids in viruses. Both in-vitro and in-vivo studies showed promising results. This work should provide a platform for further development of dendrimer-based nanocarriers for drug delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

LumenRECON Guidewire: Pilot Study of a Novel, Nonimaging Technology for Accurate Vessel Sizing and Delivery of Therapy in Femoropopliteal Disease.

PubMed

Nair, Pradeep K; Carr, Jeffrey G; Bigelow, Brian; Bhatt, Deepak L; Berwick, Zachary C; Adams, George

2018-01-01

Proper vessel sizing during endovascular interventions is crucial to avoid adverse procedural and clinical outcomes. LumenRECON (LR) is a novel, nonimaging, 0.035-inch wire-based technology that uses the physics-based principle of Ohm's law to provide a simple, real-time luminal size while also providing a platform for therapy delivery. This study evaluated the accuracy, reliability, and safety of the LR system in patients presenting for a femoropopliteal artery intervention. This multicenter, prospective pilot study of 24 patients presenting for peripheral intervention compared LR measurements of femoropopliteal artery size to angiographic visual estimation, duplex ultrasound, quantitative angiography, and intravascular ultrasound. The primary effectiveness and safety end point was comparison against core laboratory adjudicated intravascular ultrasound values and major adverse events, respectively. Additional preclinical studies were also performed in vitro and in vivo in swine to determine the accuracy of the LR guidewire system. No intra- or postprocedure device-related adverse events occurred. A balloon or stent was successfully delivered in 12 patients (50%) over the LR wire. Differences in repeatability between successive LR measurements was 2.5±0.40% ( R 2 =0.96) with no significant bias. Differences in measurements of LR to other modalities were 0.5±1.7%, 5.0±1.8%, -1.5±2.0%, and 6.8±3.4% for intravascular ultrasound core laboratory, quantitative angiography, angiographic, and duplex ultrasound, respectively. This study demonstrates that through a physics-based principle, LR provides a real-time, safe, reproducible, and accurate vessel size of the femoropopliteal artery during intervention and can additionally serve as a conduit for therapy delivery over its wire-based platform. © 2018 American Heart Association, Inc.

Theory and modeling of particles with DNA-mediated interactions

NASA Astrophysics Data System (ADS)

Licata, Nicholas A.

2008-05-01

In recent years significant attention has been attracted to proposals which utilize DNA for nanotechnological applications. Potential applications of these ideas range from the programmable self-assembly of colloidal crystals, to biosensors and nanoparticle based drug delivery platforms. In Chapter I we introduce the system, which generically consists of colloidal particles functionalized with specially designed DNA markers. The sequence of bases on the DNA markers determines the particle type. Due to the hybridization between complementary single-stranded DNA, specific, type-dependent interactions can be introduced between particles by choosing the appropriate DNA marker sequences. In Chapter II we develop a statistical mechanical description of the aggregation and melting behavior of particles with DNA-mediated interactions. In Chapter III a model is proposed to describe the dynamical departure and diffusion of particles which form reversible key-lock connections. In Chapter IV we propose a method to self-assemble nanoparticle clusters using DNA scaffolds. A natural extension is discussed in Chapter V, the programmable self-assembly of nanoparticle clusters where the desired cluster geometry is encoded using DNA-mediated interactions. In Chapter VI we consider a nanoparticle based drug delivery platform for targeted, cell specific chemotherapy. In Chapter VII we present prospects for future research: the connection between DNA-mediated colloidal crystallization and jamming, and the inverse problem in self-assembly.

A nanoparticle-based epigenetic modulator for efficient gene modulation

NASA Astrophysics Data System (ADS)

Pongkulapa, Thanapat

Modulation of gene expression through chromatin remodeling involves epigenetic mechanisms, such as histone acetylation. Acetylation is tightly regulated by two classes of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). Molecules that can regulate these enzymes by altering (activating or inhibiting) their functions have become a valuable tool for understanding cell development and diseases. HAT activators, i.e. N-(4-Chloro-(3-trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB), have shown a therapeutic potential for many diseases, including cancer and neurodegeneration. However, these compounds encounter a solubility and a membrane permeability issue, which restricts their full potential for practical usage, especially for in vivo applications. To address this issue, in this work, we developed a nanoparticle-based HAT activator CTB, named Au-CTB, by incorporating a new CTB analogue onto gold nanoparticles (AuNPs) along with a poly(ethylene glycol) moiety and a nuclear localization signal (NLS) peptide to assist with solubility and membrane permeability. We found that our new CTB analogue and Au-CTB could activate HAT activity. Significantly, an increase in potency to activate HAT activity by Au-CTB proved the effectiveness of using the nanoparticle delivery platform. In addition, the versatility of Au-CTB platform permits the attachment of multiple ligands with tunable ratios on the nanoparticle surface via facile surface functionalization of gold nanoparticles. Due to its high delivery efficiency and versatility, Au-CTB can be a powerful platform for applications in epigenetic regulation of gene expression.

A M-Health Platform for Supporting Clinical Data Integration and Service Delivery: An Example from Augmentative and Alternative Communication Intervention

ERIC Educational Resources Information Center

Wang, Erh-Hsuan

2016-01-01

Improving the quality of healthcare while simultaneously reducing its overall costs remains a challenge. One of the recommended approaches for achieving this goal is to build high quality data collection and reporting systems to facilitate evidence-based practice (EBP), which emphasizes the importance of using the solid evidence available to make…

Nanotechnology-based drug delivery systems for control of microbial biofilms: a review.

PubMed

Dos Santos Ramos, Matheus Aparecido; Da Silva, Patrícia Bento; Spósito, Larissa; De Toledo, Luciani Gaspar; Bonifácio, Bruna Vidal; Rodero, Camila Fernanda; Dos Santos, Karen Cristina; Chorilli, Marlus; Bauab, Taís Maria

2018-01-01

Since the dawn of civilization, it has been understood that pathogenic microorganisms cause infectious conditions in humans, which at times, may prove fatal. Among the different virulent properties of microorganisms is their ability to form biofilms, which has been directly related to the development of chronic infections with increased disease severity. A problem in the elimination of such complex structures (biofilms) is resistance to the drugs that are currently used in clinical practice, and therefore, it becomes imperative to search for new compounds that have anti-biofilm activity. In this context, nanotechnology provides secure platforms for targeted delivery of drugs to treat numerous microbial infections that are caused by biofilms. Among the many applications of such nanotechnology-based drug delivery systems is their ability to enhance the bioactive potential of therapeutic agents. The present study reports the use of important nanoparticles, such as liposomes, microemulsions, cyclodextrins, solid lipid nanoparticles, polymeric nanoparticles, and metallic nanoparticles, in controlling microbial biofilms by targeted drug delivery. Such utilization of these nanosystems has led to a better understanding of their applications and their role in combating biofilms.

Nanotechnology-based drug delivery systems for control of microbial biofilms: a review

PubMed Central

Dos Santos Ramos, Matheus Aparecido; Da Silva, Patrícia Bento; Spósito, Larissa; De Toledo, Luciani Gaspar; Bonifácio, Bruna Vidal; Rodero, Camila Fernanda; Dos Santos, Karen Cristina; Chorilli, Marlus; Bauab, Taís Maria

2018-01-01

Since the dawn of civilization, it has been understood that pathogenic microorganisms cause infectious conditions in humans, which at times, may prove fatal. Among the different virulent properties of microorganisms is their ability to form biofilms, which has been directly related to the development of chronic infections with increased disease severity. A problem in the elimination of such complex structures (biofilms) is resistance to the drugs that are currently used in clinical practice, and therefore, it becomes imperative to search for new compounds that have anti-biofilm activity. In this context, nanotechnology provides secure platforms for targeted delivery of drugs to treat numerous microbial infections that are caused by biofilms. Among the many applications of such nanotechnology-based drug delivery systems is their ability to enhance the bioactive potential of therapeutic agents. The present study reports the use of important nanoparticles, such as liposomes, microemulsions, cyclodextrins, solid lipid nanoparticles, polymeric nanoparticles, and metallic nanoparticles, in controlling microbial biofilms by targeted drug delivery. Such utilization of these nanosystems has led to a better understanding of their applications and their role in combating biofilms. PMID:29520143

Nanoscale “fluorescent stone”: Luminescent Calcium Fluoride Nanoparticles as Theranostic Platforms

PubMed Central

Li, Zhanjun; Zhang, Yuanwei; Huang, Ling; Yang, Yuchen; Zhao, Yang; El-Banna, Ghida; Han, Gang

2016-01-01

Calcium Fluoride (CaF2) based luminescent nanoparticles exhibit unique, outstanding luminescent properties, and represent promising candidates as nanoplatforms for theranostic applications. There is an urgent need to facilitate their further development and applications in diagnostics and therapeutics as a novel class of nanotools. Here, in this critical review, we outlined the recent significant progresses made in CaF2-related nanoparticles: Firstly, their physical chemical properties, synthesis chemistry, and nanostructure fabrication are summarized. Secondly, their applications in deep tissue bio-detection, drug delivery, imaging, cell labeling, and therapy are reviewed. The exploration of CaF2-based luminescent nanoparticles as multifunctional nanoscale carriers for imaging-guided therapy is also presented. Finally, we discuss the challenges and opportunities in the development of such CaF2-based platform for future development in regard to its theranostic applications. PMID:27877242

Preparation of multifunctional glyconanoparticles as a platform for potential carbohydrate-based anticancer vaccines.

PubMed

Ojeda, Rafael; de Paz, Jose Luis; Barrientos, Africa G; Martín-Lomas, Manuel; Penadés, Soledad

2007-02-26

A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently developed in our laboratory. Ten different multifunctional gold glyconanoparticles incorporating sialylTn and Lewis(y) antigens, T-cell helper peptides (TT) and glucose in well defined average proportions and with differing density have been synthesised in one step and characterised using NMR and TEM. Size and nature of the linker were crucial to control kinetics of S-Au bond formation and to achieve the desired ligand ratio on the gold clusters. The technology presented here opens the way for tailoring polyvalent anticancer vaccines candidates and drug delivery carriers with defined average chemical composition.

Engineered CRISPR Systems for Next Generation Gene Therapies.

PubMed

Pineda, Michael; Moghadam, Farzaneh; Ebrahimkhani, Mo R; Kiani, Samira

2017-09-15

An ideal in vivo gene therapy platform provides safe, reprogrammable, and precise strategies which modulate cell and tissue gene regulatory networks with a high temporal and spatial resolution. Clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial adoptive immune system, and its CRISPR-associated protein 9 (Cas9), have gained attention for the ability to target and modify DNA sequences on demand with unprecedented flexibility and precision. The precision and programmability of Cas9 is derived from its complexation with a guide-RNA (gRNA) that is complementary to a desired genomic sequence. CRISPR systems open-up widespread applications including genetic disease modeling, functional screens, and synthetic gene regulation. The plausibility of in vivo genetic engineering using CRISPR has garnered significant traction as a next generation in vivo therapeutic. However, there are hurdles that need to be addressed before CRISPR-based strategies are fully implemented. Some key issues center on the controllability of the CRISPR platform, including minimizing genomic-off target effects and maximizing in vivo gene editing efficiency, in vivo cellular delivery, and spatial-temporal regulation. The modifiable components of CRISPR systems: Cas9 protein, gRNA, delivery platform, and the form of CRISPR system delivered (DNA, RNA, or ribonucleoprotein) have recently been engineered independently to design a better genome engineering toolbox. This review focuses on evaluating CRISPR potential as a next generation in vivo gene therapy platform and discusses bioengineering advancements that can address challenges associated with clinical translation of this emerging technology.

Development of an inducible platform for intercellular protein delivery.

PubMed

Siller, Richard; Dufour, Eric; Lycke, Max; Wilmut, Ian; Jung, Yong-Wook; Park, In Hyun; Sullivan, Gareth J

2017-04-30

A challenge to protein based therapies is the ability to produce biologically active proteins and their ensured delivery. Various approaches have been utilised including fusion of protein transduction domains with a protein or biomolecule of interest. A compounding issue is lack of specificity, efficiency and indeed whether the protein fusions are actually translocated into the cell and not merely an artefact of the fixation process. Here we present a novel platform, allowing the inducible export and uptake of a protein of interest. The system utilises a combination of the Tetracyline repressor system, combined with a fusion protein containing the N-terminal signal peptide from human chorionic gonadotropin beta-subunit, and a C-terminal poly-arginine domain for efficient uptake by target cells. This novel platform was validated using enhanced green fluorescent protein as the gene of interest. Doxycycline efficiently induced expression of the fusion protein. The human chorionic gonadotropin beta-subunit facilitated the export of the fusion protein into the cell culture media. Finally, the fusion protein was able to efficiently enter into neighbouring cells (target cells), mediated by the poly-arginine cell penetrating peptide. Importantly we have addressed the issue of whether the observed uptake is an artefact of the fixation process or indeed genuine translocation. In addition this platform provides a number of potential applications in diverse areas such as stem cell biology, immune therapy and cancer targeting therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the feasibility of using uniaxial accelerometers with an online support platform in the delivery of a community-based exercise referral scheme.

PubMed

Hawkins, Jemma L; Oliver, Emily J; Wyatt-Williams, Jeannie; Scale, Elaine; van Woerden, Hugo C

2014-10-01

Exercise referral schemes are established within community-based health care; however, they have been criticized for failing to evidence long-term behavior change relative to usual care. As such, recent reviews have called for refinement of their delivery with a focus on embedded strategies targeting client motivation. This research letter presents findings from an initial pilot trial conducted within Wales' National Exercise Referral Scheme (NERS), examining the feasibility of using validated physical activity monitoring devices and an accompanying online platform within standard scheme delivery. 30 individuals referred to generic or cardiovascular pathways were offered the system; of these 17 agreed to participate. Common reasons for declining were clustered into lack of technology literacy or access, condition severity, or fear of costs associated with losing the device. Analysis of follow-up interviews after 4 weeks of use indicated that while participants found the monitoring devices practical and informative, only a minority (n = 4) were using the system in full. Crucially, the system element most aligned with contemporary theories of motivation (the online portal) was not used as expected. In addition, feedback from exercise referral professionals indicated that there were demands for support from clients, which might be mitigated by more effective independent system use. Recommendations for larger scale trials using similar systems include consideration of targeted patient groups, equity of access, and providing adequate technological support that is currently beyond the capacity of the NERS system. © The Author(s) 2014.

Course Delivery Platform Changes and Instructional Delivery Methods: Student Attitudes and Perceptions

ERIC Educational Resources Information Center

Garner, William E.; Pack, Tresvil G.; Szirony, Gary M.; Beeson, Eric T.

2013-01-01

The purposes of this study were to examine students' perceptions and attitudes toward changes in Distance Education (DE) course management systems and to evaluate their instructional delivery preferences. Students (N = 145) enrolled in an online master's degree program on either a full- or part-time basis completed an online survey instrument…

Myocardial gene delivery using molecular cardiac surgery with recombinant adeno-associated virus vectors in vivo

PubMed Central

White, JD; Thesier, DM; Swain, JBD; Katz, MG; Tomasulo, C; Henderson, A; Wang, L; Yarnall, C; Fargnoli, A; Sumaroka, M; Isidro, A; Petrov, M; Holt, D; Nolen-Walston, R; Koch, WJ; Stedman, HH; Rabinowitz, J; Bridges, CR

2013-01-01

We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the relative efficacy of single-stranded (ss) adeno-associated virus (AAV)6, ssAAV9 and self-complimentary (sc)AAV6-encoding enhanced green fluorescent protein, driven by the constitutive cytomegalovirus promoter to transduce the ovine myocardium in situ. MCARD allows for the unprecedented delivery of up to 48 green fluorescent protein genome copies per cell globally in the sheep left ventricular (LV) myocardium. We demonstrate that scAAV6-mediated MCARD delivery results in global, cardiac-specific LV gene expression in the ovine heart and provides for considerably more robust and cardiac-specific gene delivery than other available delivery techniques such as intramuscular injection or intracoronary injection; thus, representing a potential, clinically translatable platform for heart failure gene therapy. PMID:21228882

Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription

NASA Astrophysics Data System (ADS)

Jang, Mihue; Kim, Jong Hwan; Nam, Hae Yun; Kwon, Ick Chan; Ahn, Hyung Jun

2015-08-01

For therapeutic applications of siRNA, there are technical challenges with respect to targeted and systemic delivery. We here report a new siRNA carrier, RNAtr NPs, in a way that multiple tandem copies of RNA hairpins as a result of rolling circle transcription (RCT) can be readily adapted in tumour-targeted and systemic siRNA delivery. RNAtr NPs provide a means of condensing large amounts of multimeric RNA transcripts into the compact nanoparticles, especially without the aid of polycationic agents, and thus reduce the risk of immunogenicity and cytotoxicity by avoiding the use of synthetic polycationic reagents. This strategy allows the design of a platform technology for systemic delivery of siRNA to tumour sites, because RCT reaction, which enzymatically generates RNA polymers in multiple copy numbers at low cost, can lead to directly accessible routes to targeted and systemic delivery. Therefore, RNAtr NPs suggest great potentials as the siRNA therapeutics for cancer treatment.

Delivery of Small Interfering RNA by Peptide-Targeted Mesoporous Silica Nanoparticle-Supported Lipid Bilayers

PubMed Central

Ashley, Carlee E.; Carnes, Eric C.; Epler, Katharine E.; Padilla, David P.; Phillips, Genevieve K.; Castillo, Robert E.; Wilkinson, Dan C.; Wilkinson, Brian S.; Burgard, Cameron A.; Sewell, Robin M.; Townson, Jason L.; Chackerian, Bryce; Willman, Cheryl L.; Peabody, David S.; Wharton, Walker; Brinker, C. Jeffrey

2012-01-01

The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous silica nanoparticle-supported lipid bilayers (or ‘protocells’), exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid nanoparticles and are markedly more stable when incubated under physiological conditions. Protocells loaded with a cocktail of siRNAs bind to cells in a manner dependent on the presence of an appropriate targeting peptide and, through an endocytic pathway followed by endosomal disruption, promote delivery of the silencing nucleotides to the cytoplasm. The expression of each of the genes targeted by the siRNAs was shown to be repressed at the protein level, resulting in a potent induction of growth arrest and apoptosis. Incubation of control cells that lack expression of the antigen recognized by the targeting peptide with siRNA-loaded protocells induced neither repression of protein expression nor apoptosis, indicating the precise specificity of cytotoxic activity. In terms of loading capacity, targeting capabilities, and potency of action, protocells provide unique attributes as a delivery platform for therapeutic oligonucleotides. PMID:22309035

Flexible biodegradable citrate-based polymeric step-index optical fiber.

PubMed

Shan, Dingying; Zhang, Chenji; Kalaba, Surge; Mehta, Nikhil; Kim, Gloria B; Liu, Zhiwen; Yang, Jian

2017-10-01

Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment.

PubMed

Li, Ruixiang; He, Yuwei; Zhang, Shuya; Qin, Jing; Wang, Jianxin

2018-01-01

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

The conceptual framework and assessment methodology for the systematic reviews of community-based interventions for the prevention and control of infectious diseases of poverty.

PubMed

Lassi, Zohra S; Salam, Rehana A; Das, Jai K; Bhutta, Zulfiqar A

2014-01-01

This paper describes the conceptual framework and the methodology used to guide the systematic reviews of community-based interventions (CBIs) for the prevention and control of infectious diseases of poverty (IDoP). We adapted the conceptual framework from the 3ie work on the 'Community-Based Intervention Packages for Preventing Maternal Morbidity and Mortality and Improving Neonatal Outcomes' to aid in the analyzing of the existing CBIs for IDoP. The conceptual framework revolves around objectives, inputs, processes, outputs, outcomes, and impacts showing the theoretical linkages between the delivery of the interventions targeting these diseases through various community delivery platforms and the consequent health impacts. We also describe the methodology undertaken to conduct the systematic reviews and the meta-analyses.

Development of replication-competent viral vectors for HIV vaccine delivery

PubMed Central

Parks, Christopher L.; Picker, Louis J.; King, C. Richter

2014-01-01

Purpose of review Briefly describe some of the replication-competent (RC) vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. Recent findings RC viral vectors have advanced to the stage were decisions can be made regarding future development of HIV vaccines. The viruses being used as RC vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. RC viral vectors encoding SIV or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of pre-existing immunity. Summary A variety of DNA and RNA viruses are being used to develop RC viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be safe and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials. PMID:23925000

High-Throughput Identification of Combinatorial Ligands for DNA Delivery in Cell Culture

NASA Astrophysics Data System (ADS)

Svahn, Mathias G.; Rabe, Kersten S.; Barger, Geoffrey; EL-Andaloussi, Samir; Simonson, Oscar E.; Didier, Boturyn; Olivier, Renaudet; Dumy, Pascal; Brandén, Lars J.; Niemeyer, Christof M.; Smith, C. I. Edvard

2008-10-01

Finding the optimal combinations of ligands for tissue-specific delivery is tedious even if only a few well-established compounds are tested. The cargo affects the receptor-ligand interaction, especially when it is charged like DNA. The ligand should therefore be evaluated together with its cargo. Several viruses have been shown to interact with more than one receptor, for efficient internalization. We here present a DNA oligonucleotide-based method for inexpensive and rapid screening of biotin labeled ligands for combinatorial effects on cellular binding and uptake. The oligonucleotide complex was designed as a 44 bp double-stranded DNA oligonucleotide with one central streptavidin molecule and a second streptavidin at the terminus. The use of a highly advanced robotic platform ensured stringent processing and execution of the experiments. The oligonucleotides were fluorescently labeled and used for detection and analysis of cell-bound, internalized and intra-cellular compartmentalized constructs by an automated line-scanning confocal microscope, IN Cell Analyzer 3000. All possible combinations of 22 ligands were explored in sets of 2 and tested on 6 different human cell lines in triplicates. In total, 10 000 transfections were performed on the automation platform. Cell-specific combinations of ligands were identified and their relative position on the scaffold oligonucleotide was found to be of importance. The ligands were found to be cargo dependent, carbohydrates were more potent for DNA delivery whereas cell penetrating peptides were more potent for delivery of less charged particles.

Microstructured fibres: a positive impact on defence technology?

NASA Astrophysics Data System (ADS)

O'Driscoll, E. J.; Watson, M. A.; Delmonte, T.; Petrovich, M. N.; Feng, X.; Flanagan, J. C.; Hayes, J. R.; Richardson, D. J.

2006-09-01

In this paper we seek to assess the potential impact of microstructured fibres for security and defence applications. Recent literature has presented results on using microstructured fibre for delivery of high power, high quality radiation and also on the use of microstructured fibre for broadband source generation. Whilst these two applications may appear contradictory to one another the inherent design flexibility of microstructured fibres allows fibres to be fabricated for the specific application requirements, either minimising (for delivery) or maximising (for broadband source generation) the nonlinear effects. In platform based laser applications such as infrared counter measures, remote sensing and laser directed-energy weapons, a suitable delivery fibre providing high power, high quality light delivery would allow a laser to be sited remotely from the sensor/device head. This opens up the possibility of several sensor/device types sharing the same multi-functional laser, thus reducing the complexity and hence the cost of such systems. For applications requiring broadband source characteristics, microstructured fibres can also offer advantages over conventional sources. By exploiting the nonlinear effects it is possible to realise a multifunctional source for applications such as active hyperspectral imaging, countermeasures, and biochemical sensing. These recent results suggest enormous potential for these novel fibre types to influence the next generation of photonic systems for security and defence applications. However, it is important to establish where the fibres can offer the greatest advantages and what research still needs to be done to drive the technology towards real platform solutions.

Cloud Computing-based Platform for Drought Decision-Making using Remote Sensing and Modeling Products: Preliminary Results for Brazil

NASA Astrophysics Data System (ADS)

Vivoni, E.; Mascaro, G.; Shupe, J. W.; Hiatt, C.; Potter, C. S.; Miller, R. L.; Stanley, J.; Abraham, T.; Castilla-Rubio, J.

2012-12-01

Droughts and their hydrological consequences are a major threat to food security throughout the world. In arid and semiarid regions dependent on irrigated agriculture, prolonged droughts lead to significant and recurring economic and social losses. In this contribution, we present preliminary results on integrating a set of multi-resolution drought indices into a cloud computing-based visualization platform. We focused our initial efforts on Brazil due to a severe, on-going drought in a large agricultural area in the northeastern part of the country. The online platform includes drought products developed from: (1) a MODIS-based water stress index (WSI) based on inferences from normalized difference vegetation index and land surface temperature fields, (2) a volumetric water content (VWC) index obtained from application of the NASA CASA model, and (3) a set of AVHRR-based vegetation health indices obtained from NOAA/NESDIS. The drought indices are also presented in terms of anomalies with respect to a baseline period. Since our main objective is to engage stakeholders and decision-makers in Brazil, we incorporated other relevant geospatial data into the platform, including irrigation areas, dams and reservoirs, administrative units and annual climate information. We will also present a set of use cases developed to help stakeholders explore, query and provide feedback that allowed fine-tuning of the drought product delivery, presentation and analysis tools. Finally, we discuss potential next steps in development of the online platform, including applications at finer resolutions in specific basins and at a coarser global scale.

Electrospinning: An enabling nanotechnology platform for drug delivery and regenerative medicine.

PubMed

Chen, Shixuan; Li, Ruiquan; Li, Xiaoran; Xie, Jingwei

2018-05-02

Electrospinning provides an enabling nanotechnology platform for generating a rich variety of novel structured materials in many biomedical applications including drug delivery, biosensing, tissue engineering, and regenerative medicine. In this review article, we begin with a thorough discussion on the method of producing 1D, 2D, and 3D electrospun nanofiber materials. In particular, we emphasize on how the 3D printing technology can contribute to the improvement of traditional electrospinning technology for the fabrication of 3D electrospun nanofiber materials as drug delivery devices/implants, scaffolds or living tissue constructs. We then highlight several notable examples of electrospun nanofiber materials in specific biomedical applications including cancer therapy, guiding cellular responses, engineering in vitro 3D tissue models, and tissue regeneration. Finally, we finish with conclusions and future perspectives of electrospun nanofiber materials for drug delivery and regenerative medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.

PubMed

Wilson, A Nolan; Guiseppi-Elie, Anthony

2014-01-30

A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and possessing a covalently tethered peptide-drug conjugate was engineered to achieve stasis, via a closed control loop, of the external biochemical activity of the actuating protease. The delivery platform contains a peptide-drug conjugate covalently tethered to the hydrogel matrix, which in the presence of the appropriate protease, was cleaved and the drug released into the bathing environment. This platform was developed and investigated in silico using a finite element modeling (FEM) approach. Firstly, the primary governing phenomena guiding drug release profiles were investigated, and it was confirmed that under transport-limited conditions, the diffusion of the enzyme within the hydrogel and the coupled enzyme kinetics accurately model the system and are in agreement with published results. Secondly, the FEM model was used to investigate the release of a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu-MAG-283 by MMP9 in order to achieve targeted homeostasis of MMP-9 activity, such as in the pathophysiology of chronic wounds, via closed-loop feedback control. The key engineering parameters for the delivery device are the radii of the hydrogel microspheres and the concentration of the peptide-inhibitor conjugate. Homeostatic drug delivery, where the focus turns away from the drug release rate and turns toward achieving targeted control of biochemical activity within a biochemical pathway, is an emerging approach in drug delivery methodologies for which the potential has not yet been fully realized. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of a 3D patient-specific planning platform for interstitial and transurethral ultrasound thermal therapy

NASA Astrophysics Data System (ADS)

Prakash, Punit; Diederich, Chris J.

2010-03-01

Interstitial and transurethral catheter-based ultrasound devices are under development for treatment of prostate cancer and BPH, uterine fibroids, liver tumors and other soft tissue disease. Accurate 3D thermal modeling is essential for designing site-specific applicators, exploring treatment delivery strategies, and integration of patient-specific treatment planning of thermal ablations. We are developing a comprehensive 3D modeling and treatment planning platform for ultrasound ablation of tissue using catheter-based applicators. We explored the applicability of assessing thermal effects in tissue using critical temperature, thermal dose and Arrhenius thermal damage thresholds and performed a comparative analysis of dynamic tissue properties critical to accurate modeling. We used the model to assess the feasibility of automatic feedback control with MR thermometry, and demonstrated the utility of the modeling platform for 3D patient-specific treatment planning. We have identified critical temperature, thermal dose and thermal damage thresholds for assessing treatment endpoint. Dynamic changes in tissue attenuation/absorption and perfusion must be included for accurate prediction of temperature profiles and extents of the ablation zone. Lastly, we demonstrated use of the modeling platform for patient-specific treatment planning.

Bio-inspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair

PubMed Central

Lee, Yuhan; Xu, Chenjie; Sebastin, Monisha; Lee, Albert; Holwell, Nathan; Xu, Calvin; Miranda-Nieves, David; Mu, Luye; Lin, Charles

2015-01-01

Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, we have developed a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate. Negatively charged alginate was used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ~30w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures. PMID:26227833

Fabrication Methods and Performance of Low-Permeability Microfluidic Components for a Miniaturized Wearable Drug Delivery System

PubMed Central

Mescher, Mark J.; Swan, Erin E. Leary; Fiering, Jason; Holmboe, Maria E.; Sewell, William F.; Kujawa, Sharon G.; McKenna, Michael J.; Borenstein, Jeffrey T.

2010-01-01

In this paper, we describe low-permeability components of a microfluidic drug delivery system fabricated with versatile micromilling and lamination techniques. The fabrication process uses laminate sheets which are machined using XY milling tables commonly used in the printed-circuit industry. This adaptable platform for polymer microfluidics readily accommodates integration with silicon-based sensors, printed-circuit, and surface-mount technologies. We have used these methods to build components used in a wearable liquid-drug delivery system for in vivo studies. The design, fabrication, and performance of membrane-based fluidic capacitors and manual screw valves provide detailed examples of the capability and limitations of the fabrication method. We demonstrate fluidic capacitances ranging from 0.015 to 0.15 μL/kPa, screw valves with on/off flow ratios greater than 38 000, and a 45× reduction in the aqueous fluid loss rate to the ambient due to permeation through a silicone diaphragm layer. PMID:20852729

Bioinspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair.

PubMed

Lee, Yuhan; Xu, Chenjie; Sebastin, Monisha; Lee, Albert; Holwell, Nathan; Xu, Calvin; Miranda Nieves, David; Mu, Luye; Langer, Robert S; Lin, Charles; Karp, Jeffrey M

2015-11-18

Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ≈30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ordered DNA-Surfactant Hybrid Nanospheres Triggered by Magnetic Cationic Surfactants for Photon- and Magneto-Manipulated Drug Delivery and Release.

PubMed

Xu, Lu; Wang, Yitong; Wei, Guangcheng; Feng, Lei; Dong, Shuli; Hao, Jingcheng

2015-12-14

Here we construct for the first time ordered surfactant-DNA hybrid nanospheres of double-strand (ds) DNA and cationic surfactants with magnetic counterion, [FeCl3Br](-). The specificity of the magnetic cationic surfactants that can compact DNA at high concentrations makes it possible for building ordered nanospheres through aggregation, fusion, and coagulation. Cationic surfactants with conventional Br(-) cannot produce spheres under the same condition because they lose the DNA compaction ability. When a light-responsive magnetic cationic surfactant is used to produce nanospheres, a dual-controllable drug-delivery platform can be built simply by the applications of external magnetic force and alternative UV and visible light. These nanospheres obtain high drug absorption efficiency, slow release property, and good biocompatibility. There is potential for effective magnetic-field-based targeted drug delivery, followed by photocontrollable drug release. We deduce that our results might be of great interest for making new functional nucleic-acid-based nanomachines and be envisioned to find applications in nanotechnology and biochemistry.

SU-F-T-508: A Collimator-Based 3-Dimensional Grid Therapy Technique in a Small Animal Radiation Research Platform

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

Jin, J; Kong, V; Zhang, H

Purpose: Three dimensional (3D) Grid Therapy using MLC-based inverse-planning has been proposed to achieve the features of both conformal radiotherapy and spatially fractionated radiotherapy, which may deliver very high dose in a single fraction to portions of a large tumor with relatively low normal tissue dose. However, the technique requires relatively long delivery time. This study aims to develop a collimator-based 3D grid therapy technique. Here we report the development of the technique in a small animal radiation research platform. Methods: Similar as in the MLC-based technique, 9 non-coplanar beams in special channeling directions were used for the 3D gridmore » therapy technique. Two specially designed grid collimators were fabricated, and one of them was selectively used to match the corresponding gantry/couch angles so that the grid opening of all 9 beams are met in the 3D space in the target. A stack of EBT3 films were used as 3D dosimetry to demonstrate the 3D grid-like dose distribution in the target. Three 1-mm beams were delivered to the stack of films in the area outside the target for alignment when all the films were scanned to reconstruct the 3D dosimtric image. Results: 3D film dosimetry showed a lattice-like dose distribution in the 3D target as well as in the axial, sagittal and coronal planes. The dose outside the target also showed a grid like dose distribution, and the average dose gradually decreased with the distance to the target. The peak to valley ratio was approximately 5:1. The delivery time was 7 minutes for 18 Gy peak dose, comparing to 6 minutes to deliver a 18-Gy 3D conformal plan. Conclusion: We have demonstrated the feasibility of the collimator-based 3D grid therapy technique which can significantly reduce delivery time comparing to MLC-based inverse planning technique.« less

RNA-based micelles: A novel platform for paclitaxel loading and delivery.

PubMed

Shu, Yi; Yin, Hongran; Rajabi, Mehdi; Li, Hui; Vieweger, Mario; Guo, Sijin; Shu, Dan; Guo, Peixuan

2018-04-28

RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures for biotechnological and biomedical applications. In addition to current self-assembly strategies utilizing base pairing, motif piling and tertiary interactions, we reported for the first time the formation of RNA based micellar nanoconstruct with a cholesterol molecule conjugated onto one helical end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic RNA micelles consist of a hydrophilic RNA head and a covalently linked hydrophobic lipid tail that can spontaneously assemble in aqueous solution via hydrophobic interaction. Taking advantage of pRNA 3WJ branched structure, the assembled RNA micelles are capable of escorting multiple functional modules. As a proof of concept for delivery for therapeutics, Paclitaxel was loaded into the RNA micelles with significantly improved water solubility. The successful construction of the drug loaded RNA micelles was confirmed and characterized by agarose gel electrophoresis, atomic force microscopy (AFM), dynamic light scattering (DLS), and fluorescence Nile Red encapsulation assay. The estimate critical micelle formation concentration ranges from 39 nM to 78 nM. The Paclitaxel loaded RNA micelles can internalize into cancer cells and inhibit their proliferation. Further studies showed that the Paclitaxel loaded RNA micelles induced cancer cell apoptosis in a Caspase-3 dependent manner but RNA micelles alone exhibited low cytotoxicity. Finally, the Paclitaxel loaded RNA micelles targeted to tumor in vivo without accumulation in healthy tissues and organs. There is also no or very low induction of pro-inflammatory response. Therefore, multivalence, cancer cell permeability, combined with controllable assembly, low or non toxic nature, and tumor targeting are all promising features that make our pRNA micelles a suitable platform for potential drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of ICG concentration on the optical properties of erythrocyte-derived nano-vectors

NASA Astrophysics Data System (ADS)

Tang, Jack; Bahmani, Baharak; Burns, Joshua; Nuñez, Vicente; Mac, Jenny; Bacon, Danielle; Vullev, Valentine; Sun, Victor; Jia, Wangcun; Nelson, J. S.; Anvari, Bahman

2015-03-01

Erythrocyte-based nanoparticle platforms can offer long circulation times not offered by traditional drug delivery methods. We have developed a novel erythrocyte-based nanoparticle doped with indocyanine green (ICG), the only FDA-approved near-infrared chromophore. Here, we report on the absorption and fluorescence emission characteristics of these nanoparticles fabricated using ICG concentrations in the range of 161-323 μM. These nanoparticles may serve as biocompatible optical materials for various clinical imaging and phototherapeutic applications.

GFP-complementation assay to detect functional CPP and protein delivery into living cells

PubMed Central

Milech, Nadia; Longville, Brooke AC; Cunningham, Paula T; Scobie, Marie N; Bogdawa, Heique M; Winslow, Scott; Anastasas, Mark; Connor, Theresa; Ong, Ferrer; Stone, Shane R; Kerfoot, Maria; Heinrich, Tatjana; Kroeger, Karen M; Tan, Yew-Foon; Hoffmann, Katrin; Thomas, Wayne R; Watt, Paul M; Hopkins, Richard M

2015-01-01

Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell’s membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes, and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging, and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease. PMID:26671759

A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

NASA Astrophysics Data System (ADS)

Rotenstreich, Ygal; Tzameret, Adi; Kalish, Sapir E.; Belkin, Michael; Meir, Amilia; Treves, Avraham J.; Nagler, Arnon; Sher, Ifat

2015-03-01

Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.

Application of in situ polymerization for design and development of oral drug delivery systems.

PubMed

Ngwuluka, Ndidi

2010-12-01

Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

Micro-seismic measurements of cliff motion under wave impact and implications for the development of near-horizontal shore platforms

NASA Astrophysics Data System (ADS)

Dickson, Mark E.; Pentney, Rachael

2012-05-01

Few high-resolution measurements of process-form interactions have been taken on rock coasts, but recent studies in California have shown that portable seismometers enable useful proxy measurements of wave-energy delivery to cliffs. Here we describe measurements over 20 days of high frequency ground motion of cliffs formed in sedimentary (flysch) rocks at Okakari Point, north of Auckland, New Zealand. Three sensors were located in a shore-normal array inland from the cliff top and a fourth sensor was bolted to a ledge 2 m above the cliff toe. The nearshore wave field in front of the cliff and shore platform was monitored using a shore-normal array of 5 wave gauges. The instrumentation provided measurements of wave-energy delivery and consequent ground motion, including the first observations of motion at the top and bottom of cliffs. Results showed that horizontal ground motion is dominant at the cliff top, whereas vertical motion is dominant at the cliff toe. Power spectra show that several high frequency peaks occur in data from the cliff toe, whereas a single, broader peak frequency occurs at the cliff top resulting from signal modification as seismic waves pass through tens of metres of cliff rock. A 100 m wide shore platform at the cliff toe fundamentally controls the patterns of observed energy delivery. The shore platform is nearly horizontal, elevated close to high water level, and abruptly plunges into water > 10 m deep at its seaward edge. As expected, the magnitude of ground motion at all sensors is greatest during larger waves. Measurements further show that ground motion, both at the bottom and top of the cliff, is strongest at low tide and weakest at high tide. This observation is opposite to that noted at Santa Cruz, where ground motion was greatest at high tide. At Okakari Point the most significant high frequency ground motions occur at low tide when waves are forced to break (sometimes violently) against the seaward edge of the shore platform. Four distinctive frequency peaks between 1 and 50 Hz increase in magnitude as tidal stage drops, implying that wave breaking against the outside edge of the shore platform represents an important source of vibration. A detailed understanding of the energy source (e.g. short duration shock pressures) and rock resonance is not provided by this study. However, quantifying the spatial and temporal patterns of energy delivery places strong emphasis on the important role of shore platform geometry in filtering wave-energy delivery to the cliff. During the 20-day experiment most wave energy was delivered to the outside edge of the shore platform, not the cliff toe. The geomorphic role of high-frequency shaking from wave impacts remains to be clearly demonstrated, but if wave impacts are capable of eroding rock then the data from this study imply that under present conditions the outside edge of the shore platform may be subject to higher erosion rates than the cliff toe. It is possible that the shore platform is currently being destroyed rather than created, but a longer programme of measurements is required to test this notion.

Supplementary immunization activities (SIAs) in South Africa: comprehensive economic evaluation of an integrated child health delivery platform.

PubMed

Verguet, Stéphane; Jassat, Waasila; Bertram, Melanie Y; Tollman, Stephen M; Murray, Christopher J L; Jamison, Dean T; Hofman, Karen J

2013-03-01

Supplementary immunization activity (SIA) campaigns provide children with an additional dose of measles vaccine and deliver other interventions, including vitamin A supplements, deworming medications, and oral polio vaccines. To assess the cost-effectiveness of the full SIA delivery platform in South Africa (SA). We used an epidemiologic cost model to estimate the cost-effectiveness of the 2010 SIA campaign. We used province-level campaign data sourced from the District Health Information System, SA, and from planning records of provincial coordinators of the Expanded Programme on Immunization. The data included the number of children immunized with measles and polio vaccines, the number of children given vitamin A supplements and Albendazole tablets, and costs. The campaign cost $37 million and averted a total of 1,150 deaths (95% uncertainty range: 990-1,360). This ranged from 380 deaths averted in KwaZulu-Natal to 20 deaths averted in the Northern Cape. Vitamin A supplementation alone averted 820 deaths (95% UR: 670-1,040); measles vaccination alone averted 330 deaths (95% UR: 280-370). Incremental cost-effectiveness was $27,100 (95% UR: $18,500-34,400) per death averted nationally, ranging from $11,300 per death averted in the Free State to $91,300 per death averted in the Eastern Cape. Cost-effectiveness of the SIA child health delivery platform varies substantially across SA provinces, and it is substantially more cost-effective when vitamin A supplementation is included in the interventions administered. Cost-effectiveness assessments should consider health system delivery platforms that integrate multiple interventions, and they should be conducted at the sub-national level.

Overmanned and Undertrained: Preparing UAS Crewmembers for Unmanned Close Air Support

DTIC Science & Technology

2012-03-22

collection and artillery observation platform to a much more sophisticated mission platform capable of unmanned cargo delivery, laser designation, electronic...VMU Mission Essential Task List ..............................................................................30 iv Table of Contents...Marine Corps ...........................................................................2 VMU Squadrons: Aircraft, Operations, and Missions

DNA-Based Nanobiosensors as an Emerging Platform for Detection of Disease

PubMed Central

Abu-Salah, Khalid M.; Zourob, Mohammed M.; Mouffouk, Fouzi; Alrokayan, Salman A.; Alaamery, Manal A.; Ansari, Anees A.

2015-01-01

Detection of disease at an early stage is one of the biggest challenges in medicine. Different disciplines of science are working together in this regard. The goal of nanodiagnostics is to provide more accurate tools for earlier diagnosis, to reduce cost and to simplify healthcare delivery of effective and personalized medicine, especially with regard to chronic diseases (e.g., diabetes and cardiovascular diseases) that have high healthcare costs. Up-to-date results suggest that DNA-based nanobiosensors could be used effectively to provide simple, fast, cost-effective, sensitive and specific detection of some genetic, cancer, and infectious diseases. In addition, they could potentially be used as a platform to detect immunodeficiency, and neurological and other diseases. This review examines different types of DNA-based nanobiosensors, the basic principles upon which they are based and their advantages and potential in diagnosis of acute and chronic diseases. We discuss recent trends and applications of new strategies for DNA-based nanobiosensors, and emphasize the challenges in translating basic research to the clinical laboratory. PMID:26102488

A high-throughput microparticle microarray platform for dendritic cell-targeting vaccines.

PubMed

Acharya, Abhinav P; Clare-Salzler, Michael J; Keselowsky, Benjamin G

2009-09-01

Immunogenomic approaches combined with advances in adjuvant immunology are guiding progress toward rational design of vaccines. Furthermore, drug delivery platforms (e.g., synthetic particles) are demonstrating promise for increasing vaccine efficacy. Currently there are scores of known antigenic epitopes and adjuvants, and numerous synthetic delivery systems accessible for formulation of vaccines for various applications. However, the lack of an efficient means to test immune cell responses to the abundant combinations available represents a significant blockade on the development of new vaccines. In order to overcome this barrier, we report fabrication of a new class of microarray consisting of antigen/adjuvant-loadable poly(D,L lactide-co-glycolide) microparticles (PLGA MPs), identified as a promising carrier for immunotherapeutics, which are co-localized with dendritic cells (DCs), key regulators of the immune system and prime targets for vaccines. The intention is to utilize this high-throughput platform to optimize particle-based vaccines designed to target DCs in vivo for immune system-related disorders, such as autoimmune diseases, cancer and infection. Fabrication of DC/MP arrays leverages the use of standard contact printing miniarraying equipment in conjunction with surface modification to achieve co-localization of particles/cells on isolated islands while providing background non-adhesive surfaces to prevent off-island cell migration. We optimized MP overspotting pin diameter, accounting for alignment error, to allow construction of large, high-fidelity arrays. Reproducible, quantitative delivery of as few as 16+/-2 MPs per spot was demonstrated and two-component MP dosing arrays were constructed, achieving MP delivery which was independent of formulation, with minimal cross-contamination. Furthermore, quantification of spotted, surface-adsorbed MP degradation was demonstrated, potentially useful for optimizing MP release properties. Finally, we demonstrate DC co-localization with PLGA MPs on isolated islands and that DCs do not migrate between islands for up to 24 h. Using this platform, we intend to analyze modulation of DC function by providing multi-parameter combinatorial cues in the form of proteins, peptides and other immuno-modulatory molecules encapsulated in or tethered on MPs. Critically, the miniaturization attained enables high-throughput investigation of rare cell populations by reducing the requirement for cells and reagents by many-fold, facilitating advances in personalized vaccines which target DCs in vivo.

SU-F-T-149: Development of the Monte Carlo Simulation Platform Using Geant4 for Designing Heavy Ion Therapy Beam Nozzle

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

Shin, Jae-ik; Yoo, SeungHoon; Cho, Sungho

Purpose: The significant issue of particle therapy such as proton and carbon ion was a accurate dose delivery from beam line to patient. For designing the complex delivery system, Monte Carlo simulation can be used for the simulation of various physical interaction in scatters and filters. In this report, we present the development of Monte Carlo simulation platform to help design the prototype of particle therapy nozzle and performed the Monte Carlo simulation using Geant4. Also we show the prototype design of particle therapy beam nozzle for Korea Heavy Ion Medical Accelerator (KHIMA) project in Korea Institute of Radiological andmore » Medical Science(KIRAMS) at Republic of Korea. Methods: We developed a simulation platform for particle therapy beam nozzle using Geant4. In this platform, the prototype nozzle design of Scanning system for carbon was simply designed. For comparison with theoretic beam optics, the beam profile on lateral distribution at isocenter is compared with Mont Carlo simulation result. From the result of this analysis, we can expected the beam spot property of KHIMA system and implement the spot size optimization for our spot scanning system. Results: For characteristics study of scanning system, various combination of the spot size from accerlator with ridge filter and beam monitor was tested as simple design for KHIMA dose delivery system. Conclusion: In this report, we presented the part of simulation platform and the characteristics study. This study is now on-going in order to develop the simulation platform including the beam nozzle and the dose verification tool with treatment planning system. This will be presented as soon as it is become available.« less

Use of measles supplemental immunization activities (SIAs) as a delivery platform for other maternal and child health interventions: opportunities and challenges.

PubMed

Johri, Mira; Sharma, Jitendar K; Jit, Mark; Verguet, Stéphane

2013-02-18

Measles supplementary immunization activities (SIAs) offer children in countries with weaker immunization delivery systems like India a second opportunity for measles vaccination. They could also provide a platform to deliver additional interventions, but the feasibility and acceptability of including add-ons is uncertain. We surveyed Indian programme officers involved in the current (2010-2012) measles SIAs concerning opportunities and challenges of using SIAs as a delivery platform for other maternal and child health interventions. Respondents felt that an expanded SIA strategy including add-ons could be of great value in improving access and efficiency. They viewed management challenges, logistics, and safety as the most important potential barriers. They proposed that additional interventions be selected using several criteria, of which importance of the health problem, safety, and contribution to health equity figured most prominently. For children, they recommended inclusion of basic interventions to address nutritional deficiencies, diarrhoea and parasites over vaccines. For mothers, micronutrient interventions were highest ranked. Copyright © 2012 Elsevier Ltd. All rights reserved.

Soft electroporation for delivering molecules into tightly adherent mammalian cells through 3D hollow nanoelectrodes.

PubMed

Caprettini, Valeria; Cerea, Andrea; Melle, Giovanni; Lovato, Laura; Capozza, Rosario; Huang, Jian-An; Tantussi, Francesco; Dipalo, Michele; De Angelis, Francesco

2017-08-17

Electroporation of in-vitro cultured cells is widely used in biological and medical areas to deliver molecules of interest inside cells. Since very high electric fields are required to electroporate the plasma membrane, depending on the geometry of the electrodes the required voltages can be very high and often critical to cell viability. Furthermore, in traditional electroporation configuration based on planar electrodes there is no a priori certain feedback about which cell has been targeted and delivered and the addition of fluorophores may be needed to gain this information. In this study we present a nanofabricated platform able to perform intracellular delivery of membrane-impermeable molecules by opening transient nanopores into the lipid membrane of adherent cells with high spatial precision and with the application of low voltages (1.5-2 V). This result is obtained by exploiting the tight seal that the cells present with 3D fluidic hollow gold-coated nanostructures that act as nanochannels and nanoelectrodes at the same time. The final soft-electroporation platform provides an accessible approach for controlled and selective drug delivery on ordered arrangements of cells.

Is there an app for that? Mobile phones and secondary prevention of cardiovascular disease.

PubMed

Neubeck, Lis; Cartledge, Susie; Dawkes, Susan; Gallagher, Robyn

2017-09-01

Advances in technology coupled with increased penetration of mobile phones and smart devices are rapidly changing healthcare delivery. Mobile phone applications ('apps'), text messages, and Internet platforms used alone or in combination are now providing interventions targeting people with multiple cardiovascular risk factors. The present article will review the emerging evidence regarding apps and discuss their potential role in providing secondary prevention interventions via mobile phones. Seven recent randomized controlled trials used text messages or apps for six to 12 months, with or without differing combinations of other technology platforms. All studies, involved cardiac and diabetes populations, and demonstrated at least one positive improvement to cardiovascular risk factor profiles. When measured, acceptability of the intervention was high. Mobile apps and technology can deliver positive outcomes in the management of cardiovascular risk factors. However, because of the complexity of combination interventions, it is difficult to determine the 'active' ingredient. A future challenge for researchers and clinicians will be to respond quickly to these rapidly evolving interventions in order to ensure the delivery of effective, evidence-based outcomes.

Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

NASA Astrophysics Data System (ADS)

Hao, Liangliang

Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct novel SNA-based nanomaterials with desired properties and applying targeting moieties to the SNA platform to achieve cell type specific gene regulation effects. Due to the flexibility of the SNA approach, the SNA platform can potentially be applied to many genetic disorders through tailored target specificities.

Application of robotics in gastrointestinal endoscopy: A review

PubMed Central

Yeung, Baldwin Po Man; Chiu, Philip Wai Yan

2016-01-01

Multiple robotic flexible endoscope platforms have been developed based on cross specialty collaboration between engineers and medical doctors. However, significant number of these platforms have been developed for the natural orifice transluminal endoscopic surgery paradigm. Increasing amount of evidence suggest the focus of development should be placed on advanced endolumenal procedures such as endoscopic submucosal dissection instead. A thorough literature analysis was performed to assess the current status of robotic flexible endoscopic platforms designed for advanced endolumenal procedures. Current efforts are mainly focused on robotic locomotion and robotic instrument control. In the future, advances in actuation and servoing technology, optical analysis, augmented reality and wireless power transmission technology will no doubt further advance the field of robotic endoscopy. Globally, health systems have become increasingly budget conscious; widespread acceptance of robotic endoscopy will depend on careful design to ensure its delivery of a cost effective service. PMID:26855540

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

NASA Astrophysics Data System (ADS)

Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery.

PubMed

Badeau, Barry A; Comerford, Michael P; Arakawa, Christopher K; Shadish, Jared A; DeForest, Cole A

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Synthesis of Nanodiamond-Daunorubicin Conjugates to Overcome Multidrug Chemoresistance in Leukemia

PubMed Central

Man, Han B.; Kim, Hansung; Kim, Ho-Joong; Robinson, Erik; Liu, Wing Kam; Chow, Edward Kai-Hua; Ho, Dean

2013-01-01

Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains. PMID:23916889

Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

PubMed

Keeney, Michael; Chung, Michael T; Zielins, Elizabeth R; Paik, Kevin J; McArdle, Adrian; Morrison, Shane D; Ransom, Ryan C; Barbhaiya, Namrata; Atashroo, David; Jacobson, Gunilla; Zare, Richard N; Longaker, Michael T; Wan, Derrick C; Yang, Fan

2016-08-01

Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016. © 2016 Wiley Periodicals, Inc.

Enhanced effectiveness of tocotrienol-based nano-emulsified system for topical delivery against skin carcinomas.

PubMed

Pham, Jimmy; Nayel, Amy; Hoang, Christina; Elbayoumi, Tamer

2016-06-01

The potent anti-proliferative and pro-apoptotic actions of tocotrienols (T3) against cancer, but not normal tissues, have been hampered by their limited systemic bioavailabilty. Recent expansive development of diverse nanoemulsion (NE) vehicles emphasized their vast potential to improve the effective dosing of different clinical and experimental drugs of lipophilic nature, such as T3. The emphasis of the present work is to develop a pharmaceutically scalable, low-energy nano-emulsification approach for optimized incorporation of T3-rich palm oil (Tocomin®), possessing anticancer activity as a potential cutaneous delivery platform for adjunctive therapy of skin carcinomas, either alone or in combination with other chemotherapeutic agents. Different Tocomin®-NEs, obtained with different homogenization strategies, were screened based on physicochemical uniformity (droplet size, charge and polydispersity) and subjected to stress physical stability testing, along with chemical content analysis (≥90% Tocomin® - incorporation efficiency). Adopted hybrid nano-emulsification of Tocomin®, correlated with highest preservation of DPPH-radical scavenging capacity of active T3 in prototype formulation, Tocomin®-NE, which effectively permeated diffusion cell membranes 4-folds higher than propyleneglycol (PG)-admixed Tocomin® control. Against two different cell models of human cutaneous carcinoma, Tocomin®-hybrid NE demonstrated significantly stronger cytotoxic profiles (p ≤ 0.01), visible in both concentration- and time- dependent manners, with at least 5-folds lower IC50 values, compared to those estimated for the closest Tocomin®-control. The proposed hybrid nano-emulsified formulation of Tocomin® provides simple and stable delivery platform, for effective topical application against keratinocyte tumors.

Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

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

Acar, Handan; Samaeekia, Ravand; Schnorenberg, Mathew R.

Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are twomore » major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.« less

Polymeric Micelles: Recent Advancements in the Delivery of Anticancer Drugs.

PubMed

Gothwal, Avinash; Khan, Iliyas; Gupta, Umesh

2016-01-01

Nanotechnology, in health and medicine, extensively improves the safety and efficacy of different therapeutic agents, particularly the aspects related to drug delivery and targeting. Among various nano-carriers, polymer based macromolecular approaches have resulted in improved drug delivery for the diseases like cancers, diabetes, autoimmune disorders and many more. Polymeric micelles consisting of hydrophilic exterior and hydrophobic core have established a record of anticancer drug delivery from the laboratory to commercial reality. The nanometric size, tailor made functionality, multiple choices of polymeric micelle synthesis and stability are the unique properties, which have attracted scientists and researchers around the world to work upon in this opportunistic drug carrier. The capability of polymeric micelles as nano-carriers are nowhere less significant than nanoparticles, liposomes and other nanocarriers, as per as the commercial feasibility and presence is concerned. In fact polymeric micelles are among the most extensively studied delivery platforms for the effective treatment of different cancers as well as non-cancerous disorders. The present review highlights the sequential and recent developments in the design, synthesis, characterization and evaluation of polymeric micelles to achieve the effective anticancer drug delivery. The future possibilities and clinical outcome have also been discussed, briefly.

Theory and modeling of particles with DNA-mediated interactions

NASA Astrophysics Data System (ADS)

Licata, Nicholas A.

In recent years significant attention has been attracted to proposals which utilize DNA for nanotechnological applications. Potential applications of these ideas range from the programmable self-assembly of colloidal crystals, to biosensors and nanoparticle based drug delivery platforms. In Chapter I we introduce the system, which generically consists of colloidal particles functionalized with specially designed DNA markers. The sequence of bases on the DNA markers determines the particle type. Due to the hybridization between complementary single-stranded DNA, specific, type-dependent interactions can be introduced between particles by choosing the appropriate DNA marker sequences. In Chapter II we develop a statistical mechanical description of the aggregation and melting behavior of particles with DNA-mediated interactions. A quantitative comparison between the theory and experiments is made by calculating the experimentally observed melting profile. In Chapter III a model is proposed to describe the dynamical departure and diffusion of particles which form reversible key-lock connections. The model predicts a crossover from localized to diffusive behavior. The random walk statistics for the particles' in plane diffusion is discussed. The lateral motion is analogous to dispersive transport in disordered semiconductors, ranging from standard diffusion with a renormalized diffusion coefficient to anomalous, subdiffusive behavior. In Chapter IV we propose a method to self-assemble nanoparticle clusters using DNA scaffolds. An optimal concentration ratio is determined for the experimental implementation of our self-assembly proposal. A natural extension is discussed in Chapter V, the programmable self-assembly of nanoparticle clusters where the desired cluster geometry is encoded using DNA-mediated interactions. We determine the probability that the system self-assembles the desired cluster geometry, and discuss the connections to jamming in granular and colloidal systems. In Chapter VI we consider a nanoparticle based drug delivery platform for targeted, cell specific chemotherapy. A key-lock model is proposed to describe the results of in-vitro experiments, and the situation in-vivo is discussed. The cooperative binding, and hence the specificity to cancerous cells, is kinetically limited. The implications for optimizing the design of nanoparticle based drug delivery platforms is discussed. In Chapter VII we present prospects for future research: the connection between DNA-mediated colloidal crystallization and jamming, and the inverse problem in self-assembly.

Hyaluronic acid for anticancer drug and nucleic acid delivery.

PubMed

Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

2016-02-01

Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results. Copyright © 2015 Elsevier B.V. All rights reserved.

Perfluorocarbon Nanoparticles:. A Theranostic Platform Technology

NASA Astrophysics Data System (ADS)

Lanza, Gregory M.; Winter, Patrick M.; Caruthers, Shelton D.; Hughes, Michael S.; Hu, Grace; Pan, Dipanjan; Schmieder, Anne H.; Pham, Christine; Wickline, Samuel A.

2013-09-01

Nanomedicine clearly offers unique tools to address intractable medical problems in cancer and cardiovascular disease from entirely new perspectives. Among the theranostic options emerging in this new wave of biotechnology development, the perfluorocarbon nanoparticles have shown robust potential in vivo for diagnosing, characterizing, treating and following proliferating cancers, progressive atherosclerosis, rheumatoid arthritis and much more. These molecular imaging agents have been demonstrated for use with ultrasound, MRI, CT, and SPECT/CT. Moreover, the synergism of imaging for confirmation of therapeutic delivery, for dosimetry, and for noninvasively following early treatment responses is discussed. Image-guided drug delivery based on nanotechnology is emerging as a powerful clinical opportunity, and PFC nanoparticles are among the leading technologies reaching clinical testing today with this potential.

Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer.

PubMed

Zhang, Lianru; Li, Rutian; Chen, Hong; Wei, Jia; Qian, Hanqing; Su, Shu; Shao, Jie; Wang, Lifeng; Qian, Xiaoping; Liu, Baorui

2017-01-01

Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic- co -glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI) was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% ( P =0.002). Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization.

New platforms for multi-functional ocular lenses: engineering double-sided functionalized nano-coatings.

PubMed

Mehta, Prina; Justo, Lucas; Walsh, Susannah; Arshad, Muhammad S; Wilson, Clive G; O'Sullivan, Ciara K; Moghimi, Seyed M; Vizirianakis, Ioannis S; Avgoustakis, Konstantinos; Fatouros, Dimitris G; Ahmad, Zeeshan

2015-05-01

A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing matrix, both sides of ocular lenses were coated using a modified scaled-up masking electrohydrodynamic atomization (EHDA) technique (flow rates variable between 5 and 10 µL/min, applied voltage 4-11 kV). Each side was coated (using a specially designed flip-able well) selectively with a pre-determined morphology and model drug substance. PVP nanoparticles (inner side, to be in contact with the cornea, mean size

Microfluidic electroporation for delivery of small molecules and genes into cells using a common DC power supply.

PubMed

Wang, Hsiang-Yu; Lu, Chang

2008-06-15

Electroporation is an efficient method of introducing foreign impermeant molecules such as drugs and genes into cells. Conventional electroporation has been based on the application of short electrical pulses (electropulsation). Electropulsation requires specialized equipment and cannot be integrated easily with techniques such as electrophoresis which is based on constant voltage. Here we demonstrate the delivery of small molecules and genes into cells, using a microfluidic electroporation technique based on constant direct current (DC) voltage that we developed earlier. We demonstrate the delivery of two molecules into Chinese hamster ovary (CHO-K1) cells: a membrane impermeable nucleic acid dye (SYTOX Green) and a plasmid vector carrying the gene for green fluorescent protein (pEGFP-C1). Our devices can exert field variations to flowing cells that are analogous to the application of single or multiple pulses by having different geometries. We investigate the effects of the electrical parameters and different geometries of the device on the transfection efficiency and cell viability. Our technique provides a simple solution to electroporation-based drug and gene delivery by eliminating the need for a pulse generator. We envision that these simple microscale electroporation devices will have the potential to work in parallel on a microchip platform and such technology will allow high-throughput functional screening of drugs and genes. (c) 2008 Wiley Periodicals, Inc.

Geosynchronous platform definition study. Volume 5: Geosynchronous platform synthesis

NASA Technical Reports Server (NTRS)

1973-01-01

The development is described of the platform configurations, support subsystems, mission equipment, and servicing concepts. A common support module is developed; subsystem concepts are traded off; data relay, TDRS, earth observational, astro-physics, and advanced navigation and traffic control mission equipment concepts are postulated; and ancillary equipment required for delivery and on-orbit servicing interfaces with geosynchronous platforms is grossly defined. The general approach was to develop a platform concept capable of evolving through three on-orbit servicing modes: remote, EVA, and shirtsleeve. The definition of the equipment is to the assembly level. Weight, power, and volumetric data are compiled for all the platforms.

Hybrid biosynthetic gene therapy vector development and dual engineering capacity.

PubMed

Jones, Charles H; Ravikrishnan, Anitha; Chen, Mingfu; Reddinger, Ryan; Kamal Ahmadi, Mahmoud; Rane, Snehal; Hakansson, Anders P; Pfeifer, Blaine A

2014-08-26

Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.

Development of collagen-hydroxyapatite scaffolds incorporating PLGA and alginate microparticles for the controlled delivery of rhBMP-2 for bone tissue engineering.

PubMed

Quinlan, Elaine; López-Noriega, Adolfo; Thompson, Emmet; Kelly, Helena M; Cryan, Sally Ann; O'Brien, Fergal J

2015-01-28

The spatiotemporally controlled delivery of the pro-osteogenic factor rhBMP-2 would overcome most of the severe secondary effects linked to the products delivering this protein for bone regeneration. With this in mind, the aim of the present work was to develop a controlled rhBMP-2 release system using collagen-hydroxyapatite (CHA) scaffolds, which had been previously optimized for bone regeneration, as delivery platforms to produce a device with enhanced capacity for bone repair. Spray-drying and emulsion techniques were used to encapsulate bioactive rhBMP-2 in alginate and PLGA microparticles, with a high encapsulation efficiency. After incorporation of these microparticles into the scaffolds, rhBMP-2 was delivered in a sustained fashion for up to 28days. When tested in vitro with osteoblasts, these eluting materials showed an enhanced pro-osteogenic effect. From these results, an optimal rhBMP-2 eluting scaffold composition was selected and implanted in critical-sized calvarial defects in a rat model, where it demonstrated an excellent healing capacity in vivo. These platforms have an immense potential in the field of tissue regeneration; by tuning the specific therapeutic molecule to the tissue of interest and by utilizing different collagen-based scaffolds, similar systems can be developed for enhancing the healing of a diverse range of tissues and organs. Copyright © 2014 Elsevier B.V. All rights reserved.

An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery

NASA Astrophysics Data System (ADS)

Najer, Adrian; Wu, Dalin; Nussbaumer, Martin G.; Schwertz, Geoffrey; Schwab, Anatol; Witschel, Matthias C.; Schäfer, Anja; Diederich, François; Rottmann, Matthias; Palivan, Cornelia G.; Beck, Hans-Peter; Meier, Wolfgang

2016-08-01

Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol-disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30-50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL-1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (+/-)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block.Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol-disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30-50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL-1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (+/-)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block. Electronic supplementary information (ESI) available: Detailed experimental procedures, additional schemes and supplementary data including NMR, FTIR, TEM, DLS, UV-Vis, FCS, and fluorescence microscopy images. See DOI: 10.1039/c6nr04290b

Selective Gene Delivery for Integrating Exogenous DNA into Plastid and Mitochondrial Genomes Using Peptide-DNA Complexes.

PubMed

Yoshizumi, Takeshi; Oikawa, Kazusato; Chuah, Jo-Ann; Kodama, Yutaka; Numata, Keiji

2018-05-14

Selective gene delivery into organellar genomes (mitochondrial and plastid genomes) has been limited because of a lack of appropriate platform technology, even though these organelles are essential for metabolite and energy production. Techniques for selective organellar modification are needed to functionally improve organelles and produce transplastomic/transmitochondrial plants. However, no method for mitochondrial genome modification has yet been established for multicellular organisms including plants. Likewise, modification of plastid genomes has been limited to a few plant species and algae. In the present study, we developed ionic complexes of fusion peptides containing organellar targeting signal and plasmid DNA for selective delivery of exogenous DNA into the plastid and mitochondrial genomes of intact plants. This is the first report of exogenous DNA being integrated into the mitochondrial genomes of not only plants, but also multicellular organisms in general. This fusion peptide-mediated gene delivery system is a breakthrough platform for both plant organellar biotechnology and gene therapy for mitochondrial diseases in animals.

Multiple emulsions as effective platforms for controlled anti-cancer drug delivery.

PubMed

Dluska, Ewa; Markowska-Radomska, Agnieszka; Metera, Agata; Tudek, Barbara; Kosicki, Konrad

2017-09-01

Developing pH-responsive multiple emulsion platforms for effective glioblastoma multiforme therapy with reduced toxicity, a drug release study and modeling. Cancer cell line: U87 MG, multiple emulsions with pH-responsive biopolymer and encapsulated doxorubicin (DOX); preparation of multiple emulsions in a Couette-Taylor flow biocontactor, in vitro release study of DOX (fluorescence intensity analysis), in vitro cytotoxicity study (alamarBlue cell viability assay) and numerical simulation of DOX release rates. The multiple emulsions offered a high DOX encapsulation efficiency (97.4 ± 1%) and pH modulated release rates of a drug. Multiple emulsions with a low concentration of DOX (0.02 μM) exhibited broadly advanced cell (U87 MG) cytotoxicity than free DOX solution used at the same concentration. Emulsion platforms could be explored for potential delivery of chemotherapeutics in glioblastoma multiforme therapy.

HIFU Monitoring and Control with Dual-Mode Ultrasound Arrays

NASA Astrophysics Data System (ADS)

Casper, Andrew Jacob

The biological effects of high-intensity focused ultrasound (HIFU) have been known and studied for decades. HIFU has been shown capable of treating a wide variety of diseases and disorders. However, despite its demonstrated potential, HIFU has been slow to gain clinical acceptance. This is due, in part, to the difficulty associated with robustly monitoring and controlling the delivery of the HIFU energy. The non-invasive nature of the surgery makes the assessment of treatment progression difficult, leading to long treatment times and a significant risk of under treatment. This thesis research develops new techniques and systems for robustly monitoring HIFU therapies for the safe and efficacious delivery of the intended treatment. Systems and algorithms were developed for the two most common modes of HIFU delivery systems: single-element and phased array applicators. Delivering HIFU with a single element transducer is a widely used technique in HIFU therapies. The simplicity of a single element offers many benefits in terms of cost and overall system complexity. Typical monitoring schemes rely on an external device (e.g. diagnostic ultrasound or MRI) to assess the progression of therapy. The research presented in this thesis explores using the same element to both deliver and monitor the HIFU therapy. The use of a dual-mode ultrasound transducer (DMUT) required the development of an FPGA based single-channel arbitrary waveform generator and high-speed data acquisition unit. Data collected from initial uncontrolled ablations led to the development of monitoring and control algorithms which were implemented directly on the FPGA. Close integration between the data acquisition and arbitrary waveform units allowed for fast, low latency control over the ablation process. Results are presented that demonstrate control of HIFU therapies over a broad range of intensities and in multiple in vitro tissues. The second area of investigation expands the DMUT research to an ultrasound phased-array. The phased-array allows for electronic steering of the HIFU focus and imaging of the acoustic medium. Investigating the dual-mode ultrasound array (DMUA) required the design and construction of a novel ultrasound-guided focused ultrasound (USgFUS) platform. The platform consisted of custom hardware designed for the unique requirements of operating a phased-array in both therapeutic and imaging modes. The platform also required the development of FPGA based signal processing and GPU based beamforming algorithms for online monitoring of the therapy process. The results presented in this thesis represent the first demonstration of a real-time USgFUS platform based around a DMUA. Experimental imaging and therapy results from series of animal experiments, including a 12 animal GLP study, are presented. In addition, in vitro control results, which build upon the DMUT work, are presented.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

PubMed Central

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-01-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles.

PubMed

Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu; Liu, Guohua

2017-04-01

Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH=7.0 phosphate buffered saline (PBS) solution without 365nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH=5.0 PBS) and 365nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomaterials for mRNA Delivery

PubMed Central

Islam, Mohammad Ariful; Reesor, Emma K. G.; Xu, Yingjie; Zope, Harshal R.; Zetter, Bruce R.; Shi, Jinjun

2015-01-01

Messenger RNA (mRNA) has recently emerged with remarkable potential as an effective alternative to DNA-based therapies because of several unique advantages. mRNA does not require nuclear entry for transfection activity and has a negligible chance of integrating into the host genome which excludes the possibility of potentially detrimental genomic alternations. Chemical modification of mRNA has further enhanced its stability and decreased its activation of innate immune responses. Additionally, mRNA has been found to have rapid expression and predictable kinetics. Nevertheless, the ubiquitous application of mRNA remains challenging given its unfavorable attributes, such as large size, negative charge and susceptibility to enzymatic degradation. Further refinement of mRNA delivery modalities is therefore essential for its development as a therapeutic tool. This review provides an exclusive overview of current state-of-the-art biomaterials and nanotechnology platforms for mRNA delivery, and discusses future prospects to bring these exciting technologies into clinical practice. PMID:26280625

Targeted Immunomodulation Using Antigen-Conjugated Nanoparticles

PubMed Central

McCarthy, Derrick P.; Hunter, Zoe N.; Chackerian, Bryce; Shea, Lonnie D.; Miller, Stephen D.

2014-01-01

The growing prevalence of nanotechnology in the fields of biology, medicine and the pharmaceutical industry is confounded by the relatively small amount of data on the impact of these materials on the immune system. In addition to concerns surrounding the potential toxicity of nanoparticle (NP)-based delivery systems, there is also a demand for a better understanding of the mechanisms governing interactions of NPs with the immune system. Nanoparticles can be tailored to suppress, enhance, or subvert recognition by the immune system. This “targeted immunomodulation” can be achieved by delivery of unmodified particles, or by modifying particles to deliver drugs, proteins/peptides or genes to a specific site. In order to elicit the desired, beneficial immune response, considerations should be made at every step of the design process: the NP platform itself, ligands and other modifiers, the delivery route, and the immune cells that will encounter the conjugated NPs can all impact host immune responses. PMID:24616452

Degradable polymeric nano-films and particles as delivery platforms for vaccines and immunotherapeutics

NASA Astrophysics Data System (ADS)

Su, Xingfang

Degradable polymeric materials provide opportunities for the development of improved vaccines and immunotherapies by acting as platforms that facilitate the delivery of molecules to appropriate tissue and cellular locations to achieve therapeutic outcomes. To this end, we have designed and characterized nano-films and particles employing a hydrolytically degradable polymer for the delivery of vaccine antigens and immunotherapeutics. We first describe protein- and oligonucleotide-loaded layer-by-layer (LbL)-assembled multilayer thin films constructed based on electrostatic interactions between a cationic poly(beta-amino ester) (PBAE, denoted Poly-1) with a model protein antigen, ovalbumin (OVA), and/or immunostimulatory CpG oligonucleotides for transcutaneous delivery. Linear growth of nanoscale Poly-I/OVA bilayers was observed. Dried OVA protein-loaded films rapidly deconstructed when rehydrated in saline solutions, releasing OVA as non-aggregated/non-degraded protein, suggesting that the structure of biomolecules integrated into these multilayer films are preserved during release. Using confocal fluorescence microscopy and an in vivo murine ear skin model, we demonstrated delivery of OVA from LbL films into barrier-disrupted skin, uptake of the protein by skin-resident antigen-presenting cells (Langerhans cells), and transport of the antigen to the skin-draining lymph nodes. Dual incorporation of OVA and CpG oligonucleotides into the nanolayers of LbL films enabled dual release of the antigen and adjuvant with distinct kinetics for each component; OVA was rapidly released while CpG was released in a relatively sustained manner. Applied as skin patches, these films delivered OVA and CpG to Langerhans Cells in the skin. To our knowledge, this is the first demonstration of LbL films applied for the delivery of biomolecules into skin. This approach provides a new route for storage of vaccines and other immunotherapeutics in a solid-state thin film for subsequent delivery into the immunologically-rich milieu of the skin. In parallel, we also developed biodegradable core-shell nanoparticles with a PBAE core enveloped by a phospholipid bilayer shell for cytosolic delivery, with a view towards delivery of messenger RNA (mRNA)-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. mRNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of ˜30%. Particles also promoted cytosolic uptake of co-delivered anti-tumor toxins in tumor cells resulting in synergistic killing, demonstrating potential for cancer therapy. In vivo, particles loaded with mRNA administered intranasally or intratracheally in mice led to the enhanced expression of the reporter protein luciferase compared to naked mRNA This system may thus be promising for noninvasive delivery of mRNA-based vaccines. (Copies available exclusively from MIT Libraries, libraries.mit.edu/docs - docs mit.edu)

Supplementary immunization activities (SIAs) in South Africa: comprehensive economic evaluation of an integrated child health delivery platform

PubMed Central

Verguet, Stéphane; Jassat, Waasila; Bertram, Melanie Y.; Tollman, Stephen M.; Murray, Christopher J. L.; Jamison, Dean T.; Hofman, Karen J.

2013-01-01

Background Supplementary immunization activity (SIA) campaigns provide children with an additional dose of measles vaccine and deliver other interventions, including vitamin A supplements, deworming medications, and oral polio vaccines. Objective To assess the cost-effectiveness of the full SIA delivery platform in South Africa (SA). Design We used an epidemiologic cost model to estimate the cost-effectiveness of the 2010 SIA campaign. We used province-level campaign data sourced from the District Health Information System, SA, and from planning records of provincial coordinators of the Expanded Programme on Immunization. The data included the number of children immunized with measles and polio vaccines, the number of children given vitamin A supplements and Albendazole tablets, and costs. Results The campaign cost $37 million and averted a total of 1,150 deaths (95% uncertainty range: 990–1,360). This ranged from 380 deaths averted in KwaZulu-Natal to 20 deaths averted in the Northern Cape. Vitamin A supplementation alone averted 820 deaths (95% UR: 670–1,040); measles vaccination alone averted 330 deaths (95% UR: 280–370). Incremental cost-effectiveness was $27,100 (95% UR: $18,500–34,400) per death averted nationally, ranging from $11,300 per death averted in the Free State to $91,300 per death averted in the Eastern Cape. Conclusions Cost-effectiveness of the SIA child health delivery platform varies substantially across SA provinces, and it is substantially more cost-effective when vitamin A supplementation is included in the interventions administered. Cost-effectiveness assessments should consider health system delivery platforms that integrate multiple interventions, and they should be conducted at the sub-national level. PMID:23458088

Systems-level thinking for nanoparticle-mediated therapeutic delivery to neurological diseases.

PubMed

Curtis, Chad; Zhang, Mengying; Liao, Rick; Wood, Thomas; Nance, Elizabeth

2017-03-01

Neurological diseases account for 13% of the global burden of disease. As a result, treating these diseases costs $750 billion a year. Nanotechnology, which consists of small (~1-100 nm) but highly tailorable platforms, can provide significant opportunities for improving therapeutic delivery to the brain. Nanoparticles can increase drug solubility, overcome the blood-brain and brain penetration barriers, and provide timed release of a drug at a site of interest. Many researchers have successfully used nanotechnology to overcome individual barriers to therapeutic delivery to the brain, yet no platform has translated into a standard of care for any neurological disease. The challenge in translating nanotechnology platforms into clinical use for patients with neurological disease necessitates a new approach to: (1) collect information from the fields associated with understanding and treating brain diseases and (2) apply that information using scalable technologies in a clinically-relevant way. This approach requires systems-level thinking to integrate an understanding of biological barriers to therapeutic intervention in the brain with the engineering of nanoparticle material properties to overcome those barriers. To demonstrate how a systems perspective can tackle the challenge of treating neurological diseases using nanotechnology, this review will first present physiological barriers to drug delivery in the brain and common neurological disease hallmarks that influence these barriers. We will then analyze the design of nanotechnology platforms in preclinical in vivo efficacy studies for treatment of neurological disease, and map concepts for the interaction of nanoparticle physicochemical properties and pathophysiological hallmarks in the brain. WIREs Nanomed Nanobiotechnol 2017, 9:e1422. doi: 10.1002/wnan.1422 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Photoacoustic bio-quantification of graphene based nanomaterials at a single cell level (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nedosekin, Dmitry A.; Nolan, Jacqueline; Biris, Alexandru S.; Zharov, Vladimir P.

2017-03-01

Arkansas Nanomedicine Center at the University of Arkansas for Medical Sciences in collaboration with other Arkansas Universities and the FDA-based National Center of Toxicological Research in Jefferson, AR is developing novel techniques for rapid quantification of graphene-based nanomaterials (GBNs) in various biological samples. All-carbon GBNs have wide range of potential applications in industry, agriculture, food processing and medicine; however, quantification of GBNs is difficult in carbon reach biological tissues. The accurate quantification of GBNs is essential for research on material toxicity and the development of GBNs-based drug delivery platforms. We have developed microscopy and cytometry platforms for detection and quantification of GBNs in single cells, tissue and blood samples using photoacoustic contrast of GBNs. We demonstrated PA quantification of individual graphene uptake by single cells. High-resolution PA microscopy provided mapping of GBN distribution within live cells to establish correlation with intracellular toxic phenomena using apoptotic and necrotic assays. This new methodology and corresponding technical platform provide the insight on possible toxicological risks of GBNs at singe cells levels. In addition, in vivo PA image flow cytometry demonstrated the capability to monitor of GBNs pharmacokinetics in mouse model and to map the resulting biodistribution of GBNs in mouse tissues. The integrated PA platform provided an unprecedented sensitivity toward GBNs and allowed to enhance conventional toxicology research by providing a direct correlation between uptake of GBNs at a single cell level and cell viability status.

Are CD-ROM LANs a Thing of the Past?

ERIC Educational Resources Information Center

Mehta, Apurva

1996-01-01

Remote access to full-text and CD-ROM databases using the Internet has advantages over a CD-ROM local area network. Topics include speed, document delivery, multiple platforms, technical support, licensing, copyright, and access to graphics. Considerations of duplication of information, platform compatibility, print versus digital media, back…

Growth and Decline of Second Life as an Educational Platform

ERIC Educational Resources Information Center

Mark, Christine Libby

2014-01-01

"Second Life," a 3D online immersive virtual environment, emerged in 2003 and was predicted to become the predominant online course delivery platform by 2013. Educational institutions initially rushed to create a presence in the "Second Life;" however, after 2009 those same institutions were disappointed by their experiences…

Acceptability of Bedside Resuscitation With Intact Umbilical Cord to Clinicians and Patients' Families in the United States.

PubMed

Katheria, Anup C; Sorkhi, Samuel R; Hassen, Kasim; Faksh, Arij; Ghorishi, Zahra; Poeltler, Debra

2018-01-01

While delayed umbilical cord clamping in preterm infants has shown to improve long-term neurological outcomes, infants who are thought to need resuscitation do not receive delayed cord clamping even though they may benefit the most. A mobile resuscitation platform allows infants to be resuscitated at the mother's bedside with the cord intact. The newborn is supplied with placental blood during the resuscitation in view of the mother. The objective of the study is to assess the usability and acceptability of mobile resuscitation platform, LifeStart trolley, among the infants' parents and perinatal providers. A resuscitation platform was present during every delivery that required advanced neonatal providers for high-risk deliveries. Perinatal providers and parents of the infants were given a questionnaire shortly after the delivery. 60 neonatal subjects were placed on the trolley. The majority of deliveries were high risk for meconium-stained amniotic fluid (43%), and non-reassuring fetal heart rate (45%). About 50% of neonatal providers felt that there were some concerns regarding access to the baby. No parents were uncomfortable with the bedside neonatal interventions, and most parents perceived that communication was improved because of the proximity to the care team. Bedside resuscitation with umbilical cord intact through the use of a mobile resuscitation trolley is feasible, safe, and effective, but about half of the perinatal providers expressed concerns. Logistical issues such as improved space management and/or delivery setup should be considered in centers planning to perform neonatal resuscitation with an intact cord.

Quality control of next-generation sequencing library through an integrative digital microfluidic platform.

PubMed

Thaitrong, Numrin; Kim, Hanyoup; Renzi, Ronald F; Bartsch, Michael S; Meagher, Robert J; Patel, Kamlesh D

2012-12-01

We have developed an automated quality control (QC) platform for next-generation sequencing (NGS) library characterization by integrating a droplet-based digital microfluidic (DMF) system with a capillary-based reagent delivery unit and a quantitative CE module. Using an in-plane capillary-DMF interface, a prepared sample droplet was actuated into position between the ground electrode and the inlet of the separation capillary to complete the circuit for an electrokinetic injection. Using a DNA ladder as an internal standard, the CE module with a compact LIF detector was capable of detecting dsDNA in the range of 5-100 pg/μL, suitable for the amount of DNA required by the Illumina Genome Analyzer sequencing platform. This DMF-CE platform consumes tenfold less sample volume than the current Agilent BioAnalyzer QC technique, preserving precious sample while providing necessary sensitivity and accuracy for optimal sequencing performance. The ability of this microfluidic system to validate NGS library preparation was demonstrated by examining the effects of limited-cycle PCR amplification on the size distribution and the yield of Illumina-compatible libraries, demonstrating that as few as ten cycles of PCR bias the size distribution of the library toward undesirable larger fragments. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

PubMed

Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

2012-11-26

Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P<0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

Postpartum family planning: current evidence on successful interventions.

PubMed

Blazer, Cassandra; Prata, Ndola

2016-01-01

We reviewed existing evidence of the efficacy of postpartum family planning interventions targeting women in the 12 months postpartum period in low- and middle-income countries. We searched for studies from January 1, 2004 to September 19, 2015, using the US Preventive Services Task Force recommendations to assess evidence quality. Our search resulted in 26 studies: 11 based in sub-Saharan Africa, six in the Middle East and North Africa, and nine in Asia. Twenty of the included studies assessed health facility-based interventions. Three were focused on community interventions, two had community and facility components, and one was a workplace program. Overall quality of the evidence was moderate, including evidence for counseling interventions. Male partner involvement, integration with other service delivery platforms, such as prevention of mother-to-child transmission of HIV and immunization, and innovative product delivery programs may increase knowledge and use during the postpartum period. Community-based and workplace strategies need a much stronger base of evidence to prompt recommendations.

Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

NASA Astrophysics Data System (ADS)

Hankins, Patrick Leon

While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT-CT imaging studies showed the preferential accumulation of these nanobins in an orthotopic model of breast cancer. Due to their biocompatibility, robustness, and extensive history in the clinic, liposomes are an ideal drug delivery vehicle for the development of targeted therapies. The data presented in this thesis demonstrates the potential for active targeting to increase the therapeutic index of nanoscale drug delivery systems by increasing antitumor effect while simultaneously preventing drug uptake in peripheral tissue. In particular, targeting nanoparticles to the uPA system is a promising strategy for the treatment of many advanced, metastatic cancers.

Cancer Nanotechnology: Opportunities for Prevention, Diagnosis, and Therapy.

PubMed

Zeineldin, Reema; Syoufjy, Joan

2017-01-01

Nanotechnological innovations over the last 16 years have brought about the potential to revolutionize specific therapeutic drug delivery to cancer tissue without affecting normal tissues. In addition, there are new nanotechnology-based platforms for diagnosis of cancers and for theranostics, i.e., integrating diagnosis with therapy and follow-up of effectiveness of therapy. This chapter presents an overview of these nanotechnology-based advancements in the areas of prevention, diagnosis, therapy, and theranostics for cancer. In addition, we stress the need to educate bio- and medical students in the field of nanotechnology.

Integration of Diagnostics into Ground Equipment Study. Volume 1

DTIC Science & Technology

2004-07-30

Marine Corps V-22, CH-53E, MH-53E, SH- 60B, MH- 60S /R, AH-1Z and UH -1Y aircraft. In addition, 30 systems are in delivery to the US Army Aviation Applied...simultaneous) can be connected to the VMEP system, which is based on a PC-104 platform and a 233MHz processor. The AH-64 Apache and UH - 60 Blackhawk are outfitted...34A Model-Based Health and Usage Monitoring and Diagnostic System for the UH - 60 Helicopter," Proceedings of the American Helicopter Society 57th

Anisotropic biodegradable lipid coated particles for spatially dynamic protein presentation.

PubMed

Meyer, Randall A; Mathew, Mohit P; Ben-Akiva, Elana; Sunshine, Joel C; Shmueli, Ron B; Ren, Qiuyin; Yarema, Kevin J; Green, Jordan J

2018-05-01

There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical despite emerging evidence that non-spherical shapes can provide important advantages including reduced non-specific elimination and increased target-specific binding. We combine control of core particle geometry with control of particle surface functionality by developing anisotropic, biodegradable ellipsoidal particles with lipid coatings. We demonstrate that these lipid coated ellipsoidal particles maintain advantageous properties of lipid polymer hybrid particles, such as the ability for modular protein conjugation to the particle surface using versatile bioorthogonal ligation reactions. In addition, they exhibit biomimetic membrane fluidity and demonstrate lateral diffusive properties characteristic of natural membrane proteins. These ellipsoidal particles simultaneously provide benefits of non-spherical particles in terms of stability and resistance to non-specific phagocytosis by macrophages as well as enhanced targeted binding. These biomaterials provide a novel and flexible platform for numerous biomedical applications. The research reported here documents the ability of non-spherical polymeric particles to be coated with lipids to form anisotropic biomimetic particles. In addition, we demonstrate that these lipid-coated biodegradable polymeric particles can be conjugated to a wide variety of biological molecules in a "click-like" fashion. This is of interest due to the multiple types of cellular mimicry enabled by this biomaterial based technology. These features include mimicry of the highly anisotropic shape exhibited by cells, surface presentation of membrane bound protein mimetics, and lateral diffusivity of membrane bound substrates comparable to that of a plasma membrane. This platform is demonstrated to facilitate targeted cell binding while being resistant to non-specific cellular uptake. Such a platform could allow for investigations into how physical parameters of a particle and its surface affect the interface between biomaterials and cells, as well as provide biomimetic technology platforms for drug delivery and cellular engineering. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Integrating Neglected Tropical Disease and Immunization Programs: The Experiences of the Tanzanian Ministry of Health

PubMed Central

Mwingira, Upendo John; Means, Arianna Rubin; Chikawe, Maria; Kilembe, Bernard; Lyimo, Dafrossa; Crowley, Kathryn; Rusibamayila, Neema; Nshala, Andreas; Mphuru, Alex

2016-01-01

Global health practitioners are increasingly advocating for the integration of community-based health-care platforms as a strategy for increasing the coverage of programs, encouraging program efficiency, and promoting universal health-care goals. To leverage the strengths of compatible programs and avoid geographic and temporal duplications in efforts, the Tanzanian Ministry of Health and Social Welfare coordinated immunization and neglected tropical disease programs for the first time in 2014. Specifically, a measles and rubella supplementary vaccine campaign, mass drug administration (MDA) of ivermectin and albendazole, and Vitamin A were provisionally integrated into a shared community-based delivery platform. Over 21 million people were targeted by the integrated campaign, with the immunization program and MDA program reaching 97% and 93% of targeted individuals, respectively. The purpose of this short report is to share the Tanzanian experience of launching and managing this integrated campaign with key stakeholders. PMID:27246449

A multiplexable TALE-based binary expression system for in vivo cellular interaction studies.

PubMed

Toegel, Markus; Azzam, Ghows; Lee, Eunice Y; Knapp, David J H F; Tan, Ying; Fa, Ming; Fulga, Tudor A

2017-11-21

Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE-VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.

Method for Targeted Therapeutic Delivery of Proteins into Cells | NCI Technology Transfer Center | TTC

Cancer.gov

The Protein Expression Laboratory at the National Cancer Institute in Frederick, MD is seeking statements of capability or interest from parties interested in collaborative research to further develop a platform technology for the targeted intra-cellular delivery of proteins using virus-like particles (VLPs).

Therapeutic Potency of Nanoformulations of siRNAs and shRNAs in Animal Models of Cancers.

PubMed

Karim, Md Emranul; Tha, Kyi Kyi; Othman, Iekhsan; Borhan Uddin, Mohammad; Chowdhury, Ezharul Hoque

2018-05-26

RNA Interference (RNAi) has brought revolutionary transformations in cancer management in the past two decades. RNAi-based therapeutics including siRNA and shRNA have immense scope to silence the expression of mutant cancer genes specifically in a therapeutic context. Although tremendous progress has been made to establish catalytic RNA as a new class of biologics for cancer management, a lot of extracellular and intracellular barriers still pose a long-lasting challenge on the way to clinical approval. A series of chemically suitable, safe and effective viral and non-viral carriers have emerged to overcome physiological barriers and ensure targeted delivery of RNAi. The newly invented carriers, delivery techniques and gene editing technology made current treatment protocols stronger to fight cancer. This review has provided a platform about the chronicle of siRNA development and challenges of RNAi therapeutics for laboratory to bedside translation focusing on recent advancement in siRNA delivery vehicles with their limitations. Furthermore, an overview of several animal model studies of siRNA- or shRNA-based cancer gene therapy over the past 15 years has been presented, highlighting the roles of genes in multiple cancers, pharmacokinetic parameters and critical evaluation. The review concludes with a future direction for the development of catalytic RNA vehicles and design strategies to make RNAi-based cancer gene therapy more promising to surmount cancer gene delivery challenges.

A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria.

PubMed

Giddam, Ashwini Kumar; Reiman, Jennifer M; Zaman, Mehfuz; Skwarczynski, Mariusz; Toth, Istvan; Good, Michael F

2016-10-15

Although attenuated malaria parasitized red blood cells (pRBCs) are promising vaccine candidates, their application in humans may be restricted for ethical and regulatory reasons. Therefore, we developed an organic microparticle-based delivery platform as a whole parasite malaria-antigen carrier to mimic pRBCs. Killed blood stage parasites were encapsulated within liposomes that are targeted to antigen presenting cells (APCs). Mannosylated lipid core peptides (MLCPs) were used as targeting ligands for the liposome-encapsulated parasite antigens. MLCP-liposomes, but not unmannosylated liposomes, were taken-up efficiently by APCs which then significantly upregulated expression of MHC-ll and costimulatory molecules, CD80 and CD86. Two such vaccines using rodent model systems were constructed - one with Plasmodium chabaudi and the other with P. yoelii. MLCP-liposome vaccines were able to control the parasite burden and extended the survival of mice. Thus, we have demonstrated an alternative delivery system to attenuated pRBCs with similar vaccine efficacy and added clinical advantages. Such liposomes are promising candidates for a human malaria vaccine. Attenuated whole parasite-based vaccines, by incorporating all parasite antigens, are very promising candidates, but issues relating to production, storage and safety concerns are significantly slowing their development. We therefore developed a semi-synthetic whole parasite malaria vaccine that is easily manufactured and stored. Two such prototype vaccines (a P. chabaudi and a P. yoelii vaccine) have been constructed. They are non-infectious, highly immunogenic and give good protection profiles. This semi-synthetic delivery platform is an exciting strategy to accelerate the development of a licensed malaria vaccine. Moreover, this strategy can be potentially applied to a wide range of pathogens. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Delivery of a urology online course using Moodle versus didactic lectures methods.

PubMed

Reis, Leonardo Oliveira; Ikari, Osamu; Taha-Neto, Khaled A; Gugliotta, Antonio; Denardi, Fernandes

2015-02-01

To subjectively and objectively compare an accessible interactive electronic library using Moodle with lectures for urology teaching of medical students. Forty consecutive fourth-year medical students and one urology teacher were exposed to two teaching methods (4 weeks each) in the form of problem-based learning: - lectures and - student-centered group discussion based on Moodle (modular object-oriented dynamic learning environment) full time online delivered (24/7) with video surgeries, electronic urology cases and additional basic principles of the disease process. All 40 students completed the study. While 30% were moderately dissatisfied with their current knowledge base, online learning course delivery using Moodle was considered superior to the lectures by 86% of the students. The study found the following observations: (1) the increment in learning grades ranged from 7.0 to 9.7 for students in the online Moodle course compared to 4.0-9.6 to didactic lectures; (2) the self-reported student involvement in the online course was characterized as large by over 60%; (3) the teacher-student interaction was described as very frequent (50%) and moderately frequent (50%); and (4) more inquiries and requisitions by students as well as peer assisting were observed from the students using the Moodle platform. The Moodle platform is feasible and effective, enthusing medical students to learn, improving immersion in the urology clinical rotation and encouraging the spontaneous peer assisted learning. Future studies should expand objective evaluations of knowledge acquisition and retention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development of a PEGylated-Based Platform for Efficient Delivery of Dietary Antioxidants Across the Blood-Brain Barrier.

PubMed

Fernandes, Carlos; Pinto, Miguel; Martins, Cláudia; Gomes, Maria João; Sarmento, Bruno; Oliveira, Paulo J; Remião, Fernando; Borges, Fernanda

2018-05-16

The uptake and transport of dietary antioxidants remains the most important setback for their application in therapy. To overcome the limitations, a PEGylated-based platform was developed to improve the delivery properties of two dietary hydroxycinnamic (HCA) antioxidants-caffeic and ferulic acids. The antioxidant properties of the new polymer-antioxidant conjugates (PEGAntiOxs), prepared by linking poly(ethylene glycol) (PEG) to the cinnamic acids by a one-step Knovenagel condensation reaction, were evaluated. PEGAntiOxs present a higher lipophilicity than the parent compounds (caffeic and ferulic acids) and similar, or higher, antioxidant properties. PEGAntiOxs were not cytotoxic at the tested concentrations in SH-SY5Y, Caco-2, and hCMEC/D3 cells. By contrast, cytotoxic effects in hCMEC/D3 and SH-SY5Y cells were observed, at 50 and 100 μM, for caffeic and ferulic acids. PEGAntiOxs operate as antioxidants against several oxidative stress-cellular inducers in a neuronal cell-based model, and were able to inhibit glycoprotein-P in Caco-2 cells. PEGAntiOxs can cross hCMEC/D3 monolayer cells, a model of the blood-brain barrier (BBB) endothelial membrane. In summary, PEGAntiOxs are valid antioxidant prototypes that can uphold the antioxidant properties of HCAs, reduce their cytotoxicity, and improve their BBB permeability. PEGAntiOxs can be used in the near future as drug candidates to prevent or slow oxidative stress associated with neurodegenerative diseases.

5-Azacytidine delivered by mesoporous silica nanoparticles regulates the differentiation of P19 cells into cardiomyocytes

NASA Astrophysics Data System (ADS)

Cheng, Jin; Ding, Qian; Wang, Jia; Deng, Lin; Yang, Lu; Tao, Lei; Lei, Haihong; Lu, Shaoping

2016-01-01

Heart disease is one of the deadliest diseases causing mortality due to the limited regenerative capability of highly differentiated cardiomyocytes. Stem cell-based therapy in tissue engineering is one of the most exciting and rapidly growing areas and raises promising prospects for cardiac repair. In this study, we have synthesized FITC-mesoporous silica nanoparticles (FMSNs) based on a sol-gel method (known as Stöber's method) as a drug delivery platform to transport 5-azacytidine in P19 embryonic carcinoma stem cells. The surfactant CTAB is utilized as a liquid crystal template to self-aggregate into micelles, resulting in the synthesis of MSNs. Based on the cell viability assay, treatment with FMSNs + 5-azacytidine resulted in much more significant inhibition of the proliferation than 5-azacytidine alone. To study the mechanism, we have tested the differentiation genes and cardiac marker genes in P19 cells and found that these genes have been up-regulated in P19 embryonic carcinoma stem cells treated with FMSNs + 5-azacytidine + poly(allylamine hydrochloride) (PAH), with the changes of histone modifications on the regulatory region. In conclusion, with FMSNs as drug delivery platforms, 5-azacytidine can be more efficiently delivered into stem cells and can be used to monitor and track the transfection process in situ to clarify their effects on stem cell functions and the differentiation process, which can serve as a promising tool in tissue engineering and other biomedical fields.

Practice innovation: the need for nimble data platforms to implement precision oncology care.

PubMed

Elfiky, Aymen; Zhang, Dongyang; Krishnan Nair, Hari K

2015-01-01

Given the drive toward personalized, value-based, and coordinated cancer care delivery, modern knowledge-based practice is being shaped within the context of an increasingly technology-driven healthcare landscape. The ultimate promise of 'precision medicine' is predicated on taking advantage of the range of new capabilities for integrating disease- and individual-specific data to define new taxonomies as part of a systems-based knowledge network. Specifically, with cancer being a constantly evolving complex disease process, proper care of an individual will require the ability to seamlessly integrate multi-dimensional 'omic' and clinical data. Importantly, however, the challenges of curating knowledge from multiple dynamic data sources and translating to practice at the point-of-care highlight parallel needs. As patients, caregivers, and their environments become more proactive in clinical care and management, practical success of precision medicine is equally dependent on the development of proper infrastructures for evolving data integration, platforms for knowledge representation in a clinically-relevant context, and implementation within a provider's work-life and workflow.

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

PubMed Central

Fan, Yuchen; Moon, James J.

2016-01-01

Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. PMID:27038091

Coating barium titanate nanoparticles with polyethylenimine improves cellular uptake and allows for coupled imaging and gene delivery

PubMed Central

Dempsey, Christopher; Lee, Isac; Cowan, Katie; Suh, Junghae

2015-01-01

Barium titanate nanoparticles (BT NP) belong to a class of second harmonic generating (SHG) nanoprobes that have recently demonstrated promise in biological imaging. Unfortunately, BT NPs display low cellular uptake efficiencies, which may be a problem if cellular internalization is desired or required for a particular application. To overcome this issue, while concomitantly developing a particle platform that can also deliver nucleic acids into cells, we coated the BT NPs with the cationic polymer polyethylenimine (PEI) – one of the most effective nonviral gene delivery agents. Coating of BT with PEI yielded complexes with positive zeta potentials and resulted in an 8-fold increase in cellular uptake of the BT NPs. Importantly, we were able to achieve high levels of gene delivery with the BT-PEI/DNA complexes, supporting further efforts to generate BT platforms for coupled imaging and gene therapy. PMID:23973999

Patient-controlled analgesia: therapeutic interventions using transdermal electro-activated and electro-modulated drug delivery.

PubMed

Indermun, Sunaina; Choonara, Yahya E; Kumar, Pradeep; Du Toit, Lisa C; Modi, Girish; Luttge, Regina; Pillay, Viness

2014-02-01

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within is the possibility of further developing transdermal drug delivery for chronic pain treatment using iontophoresis-based microneedle array patches. A concerted effort was made to review critically all available therapies designed for the treatment of chronic pain. The drug delivery systems developed for this purpose and nondrug routes are elaborated on, in a systematic manner. Recent developments and future goals in transdermal delivery as a means to overcome the individual limitations of the aforementioned delivery routes are represented as well. The approval of patch-like devices that contain both the microelectronic-processing mechanism and the active medicament in a small portable device is still awaited by the pharmaceutical industry. This anticipated platform may provide transdermal electro-activated and electro-modulated drug delivery systems a feasible attempt in chronic pain treatment. Iontophoresis has been proven an effective mode used to administer ionized drugs in physiotherapeutic, diagnostic, and dermatological applications and may be an encouraging probability for the development of devices and aids in the treatment of chronic pain. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Knowledge as a Service at the Point of Care.

PubMed

Shellum, Jane L; Freimuth, Robert R; Peters, Steve G; Nishimura, Rick A; Chaudhry, Rajeev; Demuth, Steve J; Knopp, Amy L; Miksch, Timothy A; Milliner, Dawn S

2016-01-01

An electronic health record (EHR) can assist the delivery of high-quality patient care, in part by providing the capability for a broad range of clinical decision support, including contextual references (e.g., Infobuttons), alerts and reminders, order sets, and dashboards. All of these decision support tools are based on clinical knowledge; unfortunately, the mechanisms for managing rules, order sets, Infobuttons, and dashboards are often unrelated, making it difficult to coordinate the application of clinical knowledge to various components of the clinical workflow. Additional complexity is encountered when updating enterprise-wide knowledge bases and delivering the content through multiple modalities to different consumers. We present the experience of Mayo Clinic as a case study to examine the requirements and implementation challenges related to knowledge management across a large, multi-site medical center. The lessons learned through the development of our knowledge management and delivery platform will help inform the future development of interoperable knowledge resources.

Knowledge as a Service at the Point of Care

PubMed Central

Shellum, Jane L.; Freimuth, Robert R.; Peters, Steve G.; Nishimura, Rick A.; Chaudhry, Rajeev; Demuth, Steve J.; Knopp, Amy L.; Miksch, Timothy A.; Milliner, Dawn S.

2016-01-01

An electronic health record (EHR) can assist the delivery of high-quality patient care, in part by providing the capability for a broad range of clinical decision support, including contextual references (e.g., Infobuttons), alerts and reminders, order sets, and dashboards. All of these decision support tools are based on clinical knowledge; unfortunately, the mechanisms for managing rules, order sets, Infobuttons, and dashboards are often unrelated, making it difficult to coordinate the application of clinical knowledge to various components of the clinical workflow. Additional complexity is encountered when updating enterprise-wide knowledge bases and delivering the content through multiple modalities to different consumers. We present the experience of Mayo Clinic as a case study to examine the requirements and implementation challenges related to knowledge management across a large, multi-site medical center. The lessons learned through the development of our knowledge management and delivery platform will help inform the future development of interoperable knowledge resources. PMID:28269911

Biodegradable protein-based rockets for drug transportation and light-triggered release.

PubMed

Wu, Zhiguang; Lin, Xiankun; Zou, Xian; Sun, Jianmin; He, Qiang

2015-01-14

We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These rockets can rapidly deliver the doxorubicin to the targeted cancer cell with a speed of up to 68 μm/s, through a combination of biocatalytic bubble propulsion and magnetic guidance. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for rapid release of the loaded doxorubicin and efficient killing of the surrounding cancer cells. Such biodegradable and multifunctional protein-based microrockets provide a convenient and efficient platform for the rapid delivery and controlled release of therapeutic drugs.

Versatile Nanosystem-Based Cancer Theranostics: Design Inspiration and Predetermined Routing

PubMed Central

Opoku-Damoah, Yaw; Wang, Ruoning; Zhou, Jianping; Ding, Yang

2016-01-01

The relevance of personalized medicine, aimed at a more individualized drug therapy, has inspired research into nano-based concerted diagnosis and therapeutics (theranostics). As the intention is to “kill two birds with one stone”, scientists have already described the emerging concept as a treasured tailor for the future of cancer therapy, wherein the main idea is to design “smart” nanosystems to concurrently discharge both therapeutic and diagnostic roles. These nanosystems are expected to offer a relatively clearer view of the ingenious cellular trafficking pathway, in-situ diagnosis, and therapeutic efficacy. We herein present a detailed review of versatile nanosystems, with prominent examples of recently developed intelligent delivery strategies which have gained attention in the field of theranostics. These nanotheranostics include various mechanisms programmed in novel platforms to enable predetermined delivery of cargo to specific sites, as well as techniques to overcome the notable challenges involved in the efficacy of theranostics. PMID:27217832

Assessing the potential of the Woman's Condom for vaginal drug delivery

PubMed Central

Kramzer, Lindsay F.; Cohen, Jessica; Schubert, Jesse; Dezzutti, Charlene S.; Moncla, Bernard J.; Friend, David; Rohan, Lisa C.

2015-01-01

Background The Woman's Condom is a new female condom that uses a dissolvable polyvinyl alcohol (PVA) capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman's Condom capsule, offering a unique drug delivery platform. Study Design UC781 capsules were fabricated using methods from the development of the Woman's Condom capsules as well as those used in vaginal film development. Capsules were characterized to evaluate physical/chemical attributes, Lactobacillus compatibility, in vitro safety and bioactivity, and condom compatibility. Results Two UC781 capsule platforms were assessed. Capsule masses (mg; mean ± SD) for platforms 1 and 2 were 116.50 ± 18.22 and 93.80 ± 8.49, respectively. Thicknesses were 0.0034 ± 0.0004 in and 0.0033 ± 0.0004 in. Disintegration times were 11 ± 3 sec and 5 ± 1 sec. Puncture strengths were 21.72 ± 3.30 N and 4.02 ± 0.83 N. Water content measured 6.98 ± 1.17 % and 7.04 ± 1.92 %. UC781 content was 0.59 ± 0.05 mg and 0.77 ± 0.11 mg. Both platforms retained in vitro bioactivity and were non-toxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules with the Woman's Condom pouch did not decrease condom mechanical integrity. Conclusions UC781 was loaded into a polymeric capsule similar to that of the Woman's Condom product. This study highlights the potential use of the Woman's Condom as a platform for vaginal delivery of drugs relevant to sexual/reproductive health, including those for short or long-acting HIV prevention. PMID:25998936

Initial experience using a femtosecond laser cataract surgery system at a UK National Health Service cataract surgery day care centre

PubMed Central

Dhallu, Sandeep K; Maurino, Vincenzo; Wilkins, Mark R

2016-01-01

Objectives To describe the initial outcomes following installation of a cataract surgery laser system. Setting National Health Service cataract surgery day care unit in North London, UK. Participants 158 eyes of 150 patients undergoing laser-assisted cataract surgery. Interventions Laser cataract surgery using the AMO Catalys femtosecond laser platform. Primary and secondary outcome measures Primary outcome measure: intraoperative complications including anterior and posterior capsule tears. Secondary outcome measures: docking to the laser platform, successful treatment delivery, postoperative visual acuities. Results Mean case age was 67.7±10.8 years (range 29–88 years). Docking was successful in 94% (148/158 cases), and in 4% (6/148 cases) of these, the laser delivery was aborted part way during delivery due to patient movement. A total of 32 surgeons, of grades from junior trainee to consultant, performed the surgeries. Median case number per surgeon was 3 (range from 1–20). The anterior capsulotomy was complete in 99.3% of cases, there were no anterior capsule tears (0%). There were 3 cases with posterior capsule rupture requiring anterior vitrectomy, and 1 with zonular dialysis requiring anterior vitrectomy (4/148 eyes, 2.7%). These 4 cases were performed by trainee surgeons, and were either their first laser cataract surgery (2 surgeons) or their first and second laser cataract surgeries (1 surgeon). Conclusions Despite the learning curve, docking and laser delivery were successfully performed in almost all cases, and surgical complication rates and visual outcomes were similar to those expected based on national data. Complications were predominately confined to trainee surgeons, and with the exception of intraoperative pupil constriction appeared unrelated to the laser-performed steps. PMID:27466243

Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems

NASA Astrophysics Data System (ADS)

Curry, Dennis; Cameron, Amanda; MacDonald, Bruce; Nganou, Collins; Scheller, Hope; Marsh, James; Beale, Stefanie; Lu, Mingsheng; Shan, Zhi; Kaliaperumal, Rajendran; Xu, Heping; Servos, Mark; Bennett, Craig; Macquarrie, Stephanie; Oakes, Ken D.; Mkandawire, Martin; Zhang, Xu

2015-11-01

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates. Electronic supplementary information (ESI) available: DOX-AuNP absorption spectra and colored solution images, citrate displacement data, original DOX-AuNP loading isotherm, XPS data and TEM micrographs, modelling data. See DOI: 10.1039/c5nr05826k

Interest in Health Behavior Intervention Delivery Modalities Among Cancer Survivors: A Cross-Sectional Study

PubMed Central

Basen-Engquist, Karen; Cox, Matthew G; Lyons, Elizabeth J; Carmack, Cindy L; Blalock, Janice A; Demark-Wahnefried, Wendy

2016-01-01

Background Effective, broad-reaching channels are important for the delivery of health behavior interventions in order to meet the needs of the growing population of cancer survivors in the United States. New technology presents opportunities to increase the reach of health behavior change interventions and therefore their overall impact. However, evidence suggests that older adults may be slower in their adoption of these technologies than the general population. Survivors’ interest for more traditional channels of delivery (eg, clinic) versus new technology-based channels (eg, smartphones) may depend on a variety of factors, including demographics, current health status, and the behavior requiring intervention. Objective The aim of this study was to determine the factors that predict cancer survivors’ interest in new technology-based health behavior intervention modalities versus traditional modalities. Methods Surveys were mailed to 1871 survivors of breast, prostate, and colorectal cancer. Participants’ demographics, diet and physical activity behaviors, interest in health behavior interventions, and interest in intervention delivery modalities were collected. Using path analysis, we explored the relationship between four intervention modality variables (ie, clinic, telephone, computer, and smartphone) and potential predictors of modality interest. Results In total, 1053 respondents to the survey (56.3% response rate); 847 provided complete data for this analysis. Delivery channel interest was highest for computer-based interventions (236/847, 27.9% very/extremely interested) and lowest for smartphone–based interventions (73/847, 8.6%), with interest in clinic-based (147/847, 17.3%) and telephone-delivered (143/847, 16.9%) falling in between. Use of other technology platforms, such as Web cameras and social networking sites, was positively predictive of interest in technology-based delivery channels. Older survivors were less likely to report interest in smartphone–based diet interventions. Physical activity, fruit and vegetable consumption, weight status, and age moderated relationships between interest in targeted intervention behavior and modality. Conclusions This study identified several predictors of survivor interest in various health behavior intervention delivery modalities. Overall, computer-based interventions were found to be most acceptable, while smartphones were the least. Factors related to survivors’ current technology use and health status play a role in their interest for technology-based intervention versus more traditional delivery channels. Future health behavior change research in this population should consider participants’ demographic, clinical, and lifestyle characteristics when selecting a delivery channel. Furthermore, current health behavior interventions for older cancer survivors may be best delivered over the Internet. Smartphone interventions may be feasible in the future following further adoption and familiarization by this particular population. PMID:28410164

Gene Delivery into Plant Cells for Recombinant Protein Production

PubMed Central

Chen, Qiang

2015-01-01

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. PMID:26075275

The Cardiovascular Intensive Care Unit-An Evolving Model for Health Care Delivery.

PubMed

Loughran, John; Puthawala, Tauqir; Sutton, Brad S; Brown, Lorrel E; Pronovost, Peter J; DeFilippis, Andrew P

2017-02-01

Prior to the advent of the coronary care unit (CCU), patients having an acute myocardial infarction (AMI) were managed on the general medicine wards with reported mortality rates of greater than 30%. The first CCUs are believed to be responsible for reducing mortality attributed to AMI by as much as 40%. This drastic improvement can be attributed to both advances in medical technology and in the process of health care delivery. Evolving considerably since the 1960s, the CCU is now more appropriately labeled as a cardiac intensive care unit (CICU) and represents a comprehensive system designed for the care of patients with an array of advanced cardiovascular disease, an entity that reaches far beyond its early association with AMI. Grouping of patients by diagnosis to a common physical space, dedicated teams of health care providers, as well as the development and implementation of evidence-based treatment algorithms have resulted in the delivery of safer, more efficient care, and most importantly better patient outcomes. The CICU serves as a platform for an integrated, team-based patient care delivery system that addresses a broad spectrum of patient needs. Lessons learned from this model can be broadly applied to address the urgent need to improve outcomes and efficiency in a variety of health care settings.

Robotics-assisted mass spectrometry assay platform enabled by open-source electronics.

PubMed

Chiu, Shih-Hao; Urban, Pawel L

2015-02-15

Mass spectrometry (MS) is an important analytical technique with numerous applications in clinical analysis, biochemistry, environmental analysis, geology and physics. Its success builds on the ability of MS to determine molecular weights of analytes, and elucidate their structures. However, sample handling prior to MS requires a lot of attention and labor. In this work we were aiming to automate processing samples for MS so that analyses could be conducted without much supervision of experienced analysts. The goal of this study was to develop a robotics and information technology-oriented platform that could control the whole analysis process including sample delivery, reaction-based assay, data acquisition, and interaction with the analyst. The proposed platform incorporates a robotic arm for handling sample vials delivered to the laboratory, and several auxiliary devices which facilitate and secure the analysis process. They include: multi-relay board, infrared sensors, photo-interrupters, gyroscopes, force sensors, fingerprint scanner, barcode scanner, touch screen panel, and internet interface. The control of all the building blocks is achieved through implementation of open-source electronics (Arduino), and enabled by custom-written programs in C language. The advantages of the proposed system include: low cost, simplicity, small size, as well as facile automation of sample delivery and processing without the intervention of the analyst. It is envisaged that this simple robotic system may be the forerunner of automated laboratories dedicated to mass spectrometric analysis of biological samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.

PubMed

Rabanel, Jean-Michel; Faivre, Jimmy; Paka, Ghislain Djiokeng; Ramassamy, Charles; Hildgen, Patrice; Banquy, Xavier

2015-10-01

We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers. Copyright © 2015 Elsevier B.V. All rights reserved.

Suppression of inflammation in a mouse model of rheumatoid arthritis using targeted lipase-labile fumagillin prodrug nanoparticles.

PubMed

Zhou, Hui-Fang; Yan, Huimin; Senpan, Angana; Wickline, Samuel A; Pan, Dipanjan; Lanza, Gregory M; Pham, Christine T N

2012-11-01

Nanoparticle-based therapeutics are emerging technologies that have the potential to greatly impact the treatment of many human diseases. However, drug instability and premature release from the nanoparticles during circulation currently preclude clinical translation. Herein, we use a lipase-labile (Sn 2) fumagillin prodrug platform coupled with a unique lipid surface-to-surface targeted delivery mechanism, termed contact-facilitated drug delivery, to counter the premature drug release and overcome the inherent photo-instability of fumagillin, an established anti-angiogenic agent. We show that α(v)β(3)-integrin targeted fumagillin prodrug nanoparticles, administered at 0.3 mg of fumagillin prodrug/kg of body weight suppress the clinical disease indices of KRN serum-mediated arthritis in a dose-dependent manner when compared to treatment with the control nanoparticles with no drug. This study demonstrates the effectiveness of this lipase-labile prodrug nanocarrier in a relevant preclinical model that approximates human rheumatoid arthritis. The lipase-labile prodrug paradigm offers a translatable approach that is broadly applicable to many targeted nanosystems and increases the translational potential of this platform for many diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vaccines 'on demand': science fiction or a future reality.

PubMed

Ulmer, Jeffrey B; Mansoura, Monique K; Geall, Andrew J

2015-02-01

Self-amplifying mRNA vaccines are being developed as a platform technology with potential to be used for a broad range of targets. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, Ebola, cytomegalovirus, human immunodeficiency virus and malaria. This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform. The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity. The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising. Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats.

Control, communication and monitoring of intravaginal drug delivery in dairy cows.

PubMed

Cross, Peter S; Künnemeyer, Rainer; Bunt, Craig R; Carnegie, Dale A; Rathbone, Michael J

2004-09-10

We present the design of an electronically controlled drug delivery system. The intravaginally located device is a low-invasive platform that can measure and react inside the cow vagina while providing external control and monitoring ability. The electronics manufactured from off the shelf components occupies 16 mL of a Theratron syringe. A microcontroller reads and logs sensor data and controls a gascell. The generated gas pressure propels the syringe piston and releases the formulation. A two way radio link allows communication between other devices or a base station. Proof of principle experiments confirm variable-rate, arbitrary profile drug delivery qualified by internal sensors. A total volume of 30 mL was dispensed over a 7-day-period with a volume error of +/- 1 mL or +/- 7% for larger volumes. Delivery was controlled or overridden via the wireless link, and proximity to other devices was detected and recorded. The results suggest that temperature and activity sensing or social grouping determined via proximity can be used to detect oestrus and trigger appropriate responses.

Fabrication of Plasmonic Nanorod-Embedded Dipeptide Microspheres via the Freeze-Quenching Method for Near-Infrared Laser-Triggered Drug-Delivery Applications.

PubMed

Erdogan, Hakan; Yilmaz, Mehmet; Babur, Esra; Duman, Memed; Aydin, Halil M; Demirel, Gokhan

2016-05-09

Control of drug release by an external stimulus may provide remote controllability, low toxicity, and reduced side effects. In this context, varying physical external stimuli, including magnetic and electric fields, ultrasound, light, and pharmacological stimuli, have been employed to control the release rate of drug molecules in a diseased region. However, the design and development of alternative on-demand drug-delivery systems that permit control of the dosage of drug released via an external stimulus are still required. Here, we developed near-infrared laser-activatable microspheres based on Fmoc-diphenylalanine (Phe-Phe) dipeptides and plasmonic gold nanorods (AuNRs) via a simple freeze-quenching approach. These plasmonic nanoparticle-embedded microspheres were then employed as a smart drug-delivery platform for native, continuous, and pulsatile doxorubicin (DOX) release. Remarkable sustained, burst, and on-demand DOX release from the fabricated microspheres were achieved by manipulating the laser exposure time. Our results demonstrate that AuNR-embedded dipeptide microspheres have great potential for controlled drug-delivery systems.

Development of an acid-resistant Salmonella Typhi Ty21a attenuated vector for improved oral vaccine delivery

USDA-ARS?s Scientific Manuscript database

The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, T...

Enhancement of antigen-specific CD4 + and CD8 + T cell responses using a self-assembled biologic nanolipoprotein particle vaccine

DOE PAGES

Weilhammer, Dina; Dunkle, Alexis D.; Blanchette, Craig D.; ...

2017-02-14

To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. Here, we utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4 + and CD8 + T cells in vitro compared to co-administration of free OVA andmore » MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4 + and CD8 + T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.« less

Enhancement of antigen-specific CD4 + and CD8 + T cell responses using a self-assembled biologic nanolipoprotein particle vaccine

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

Weilhammer, Dina; Dunkle, Alexis D.; Blanchette, Craig D.

To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. Here, we utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4 + and CD8 + T cells in vitro compared to co-administration of free OVA andmore » MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4 + and CD8 + T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.« less

Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms

PubMed Central

Lopez, Felipe L; Ernest, Terry B; Tuleu, Catherine; Gul, Mine Orlu

2015-01-01

Introduction: Most conventional drug delivery systems are not acceptable for pediatric patients as they differ in their developmental status and dosing requirements from other subsets of the population. Technology platforms are required to aid the development of age-appropriate medicines to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability. Areas covered: The current approaches and novel developments in the field of age-appropriate drug delivery for pediatric patients are critically discussed including patient-centric formulations, administration devices and packaging systems. Expert opinion: Despite the incentives provided by recent regulatory modifications and the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable the manufacture of licensed age-appropriate formulations. Harmonization of endeavors from regulators, industry and academia by sharing learning associated with data obtained from pediatric investigation plans, product development pathways and scientific projects would be the way forward to speed up bench-to-market age appropriate formulation development. A collaborative approach will benefit not only pediatrics, but other patient populations such as geriatrics would also benefit from an accelerated patient-centric approach to drug delivery. PMID:26165848

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

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

Fischer, Nicholas O.; Weilhammer, Dina R.; Dunkle, Alexis

Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. In order to begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We also found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP wasmore » also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Though only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.« less

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

PubMed Central

Fischer, Nicholas O.; Weilhammer, Dina R.; Dunkle, Alexis; Thomas, Cynthia; Hwang, Mona; Corzett, Michele; Lychak, Cheri; Mayer, Wasima; Urbin, Salustra; Collette, Nicole; Chiun Chang, Jiun; Loots, Gabriela G.; Rasley, Amy; Blanchette, Craig D.

2014-01-01

Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. To begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Although only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics. PMID:24675794

Dosimetric verification of gated delivery of electron beams using a 2D ion chamber array

PubMed Central

Yoganathan, S. A.; Das, K. J. Maria; Raj, D. Gowtham; Kumar, Shaleen

2015-01-01

The purpose of this study was to compare the dosimetric characteristics; such as beam output, symmetry and flatness between gated and non-gated electron beams. Dosimetric verification of gated delivery was carried for all electron beams available on Varian CL 2100CD medical linear accelerator. Measurements were conducted for three dose rates (100 MU/min, 300 MU/min and 600 MU/min) and two respiratory motions (breathing period of 4s and 8s). Real-time position management (RPM) system was used for the gated deliveries. Flatness and symmetry values were measured using Imatrixx 2D ion chamber array device and the beam output was measured using plane parallel ion chamber. These detector systems were placed over QUASAR motion platform which was programmed to simulate the respiratory motion of target. The dosimetric characteristics of gated deliveries were compared with non-gated deliveries. The flatness and symmetry of all the evaluated electron energies did not differ by more than 0.7 % with respect to corresponding non-gated deliveries. The beam output variation of gated electron beam was less than 0.6 % for all electron energies except for 16 MeV (1.4 %). Based on the results of this study, it can be concluded that Varian CL2100 CD is well suitable for gated delivery of non-dynamic electron beams. PMID:26170552

Targeted Nanoparticles for Image-guided Treatment of Triple Negative Breast Cancer: Clinical Significance and Technological Advances

PubMed Central

Miller-Kleinhenz, Jasmine M.; Bozeman, Erica N.

2015-01-01

Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. PMID:25966677

AmI and deployment considerations in AAL services provision for elderly independent living: the MonAMI project.

PubMed

Falcó, Jorge L; Vaquerizo, Esteban; Lain, Luis; Artigas, Jose Ignacio; Ibarz, Alejandro

2013-07-12

The MonAMI project aims to investigate the feasibility of the deployment of open platforms for Ambient Assisted Living (AAL) services provision based on Ambient Intelligence (AmI) and to test user acceptance and the usability of the services. Services were designed to provide support in the areas of environmental control, security, well-being and leisure. These services were installed and evaluated in a Spanish geriatric residence. The participants included elderly persons with disabilities, nursing home care givers and informal carers. The concept of the open platform proved to be satisfactory for the provision of the services in a context aware framework. Furthermore, the usability of the technology was viewed positively and the overall results indicate that this system has the potential to prolong independent living at home for elderly people with disabilities. Deployment was proven successful and awareness of open-platform AAL service delivery was raised in local communities throughout Europe.

AmI and Deployment Considerations in AAL Services Provision for Elderly Independent Living: The MonAMI Project

PubMed Central

Falcó, Jorge L.; Vaquerizo, Esteban; Lain, Luis; Artigas, Jose Ignacio; Ibarz, Alejandro

2013-01-01

The MonAMI project aims to investigate the feasibility of the deployment of open platforms for Ambient Assisted Living (AAL) services provision based on Ambient Intelligence (AmI) and to test user acceptance and the usability of the services. Services were designed to provide support in the areas of environmental control, security, well-being and leisure. These services were installed and evaluated in a Spanish geriatric residence. The participants included elderly persons with disabilities, nursing home care givers and informal carers. The concept of the open platform proved to be satisfactory for the provision of the services in a context aware framework. Furthermore, the usability of the technology was viewed positively and the overall results indicate that this system has the potential to prolong independent living at home for elderly people with disabilities. Deployment was proven successful and awareness of open-platform AAL service delivery was raised in local communities throughout Europe. PMID:23857262

A Survey of Geosensor Networks: Advances in Dynamic Environmental Monitoring

PubMed Central

Nittel, Silvia

2009-01-01

In the recent decade, several technology trends have influenced the field of geosciences in significant ways. The first trend is the more readily available technology of ubiquitous wireless communication networks and progress in the development of low-power, short-range radio-based communication networks, the miniaturization of computing and storage platforms as well as the development of novel microsensors and sensor materials. All three trends have changed the type of dynamic environmental phenomena that can be detected, monitored and reacted to. Another important aspect is the real-time data delivery of novel platforms today. In this paper, I will survey the field of geosensor networks, and mainly focus on the technology of small-scale geosensor networks, example applications and their feasibility and lessons learnt as well as the current research questions posed by using this technology today. Furthermore, my objective is to investigate how this technology can be embedded in the current landscape of intelligent sensor platforms in the geosciences and identify its place and purpose. PMID:22346721

An augmented SMS intervention to improve access to antenatal CD4 testing and ART initiation in HIV-infected pregnant women: a cluster randomized trial.

PubMed

Dryden-Peterson, Scott; Bennett, Kara; Hughes, Michael D; Veres, Adrian; John, Oaitse; Pradhananga, Rosina; Boyer, Matthew; Brown, Carolyn; Sakyi, Bright; van Widenfelt, Erik; Keapoletswe, Koona; Mine, Madisa; Moyo, Sikhulile; Asmelash, Aida; Siedner, Mark; Mmalane, Mompati; Shapiro, Roger L; Lockman, Shahin

2015-01-01

Less than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART. We conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD4 collection and to receive CD4 results via an automated SMS platform with active patient tracing. CD4 testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed. Three-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD4-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD4 phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47-1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD4 test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53-2.13, P = 0.87). The augmented SMS-based intervention delivered CD4 results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD4 testing or ART initiation, as obstacles other than CD4 impeded ART initiation during pregnancy.

Research priorities for adolescent health in low- and middle-income countries: A mixed-methods synthesis of two separate exercises.

PubMed

Nagata, Jason M; Hathi, Sejal; Ferguson, B Jane; Hindin, Michele J; Yoshida, Sachiyo; Ross, David A

2018-06-01

In order to clarify priorities and stimulate research in adolescent health in low- and middle-income countries (LMICs), the World Health Organization (WHO) conducted two priority-setting exercises based on the Child Health and Nutrition Research Initiative (CHNRI) methodology related to 1) adolescent sexual and reproductive health and 2) eight areas of adolescent health including communicable diseases prevention and management, injuries and violence, mental health, non-communicable diseases management, nutrition, physical activity, substance use, and health policy. Although the CHNRI methodology has been utilized in over 50 separate research priority setting exercises, none have qualitatively synthesized the ultimate findings across studies. The purpose of this study was to conduct a mixed-method synthesis of two research priority-setting exercises for adolescent health in LMICs based on the CHNRI methodology and to situate the priority questions within the current global health agenda. All of the 116 top-ranked questions presented in each exercise were analyzed by two independent reviewers. Word clouds were generated based on keywords from the top-ranked questions. Questions were coded and content analysis was conducted based on type of delivery platform, vulnerable populations, and the Survive, Thrive, and Transform framework from the United Nations Global Strategy for Women's, Children's, and Adolescents' Health, 2016-2030. Within the 53 top-ranked intervention-related questions that specified a delivery platform, the platforms specified were schools (n = 17), primary care (n = 12), community (n = 11), parenting (n = 6), virtual media (n = 5), and peers (n = 2). Twenty questions specifically focused on vulnerable adolescents, including those living with HIV, tuberculosis, mental illness, or neurodevelopmental disorders; victims of gender-based violence; refugees; young persons who inject drugs; sex workers; slum dwellers; out-of-school youth; and youth in armed conflict. A majority of the top-ranked questions (108/116) aligned with one or a combination of the Survive (n = 39), Thrive (n = 67), and Transform (n = 28) agendas. This study advances the CHNRI methodology by conducting the first mixed-methods synthesis of multiple research priority-setting exercises by analyzing keywords (using word clouds) and themes (using content analysis).

IAServ: an intelligent home care web services platform in a cloud for aging-in-place.

PubMed

Su, Chuan-Jun; Chiang, Chang-Yu

2013-11-12

As the elderly population has been rapidly expanding and the core tax-paying population has been shrinking, the need for adequate elderly health and housing services continues to grow while the resources to provide such services are becoming increasingly scarce. Thus, increasing the efficiency of the delivery of healthcare services through the use of modern technology is a pressing issue. The seamless integration of such enabling technologies as ontology, intelligent agents, web services, and cloud computing is transforming healthcare from hospital-based treatments to home-based self-care and preventive care. A ubiquitous healthcare platform based on this technological integration, which synergizes service providers with patients' needs to be developed to provide personalized healthcare services at the right time, in the right place, and the right manner. This paper presents the development and overall architecture of IAServ (the Intelligent Aging-in-place Home care Web Services Platform) to provide personalized healthcare service ubiquitously in a cloud computing setting to support the most desirable and cost-efficient method of care for the aged-aging in place. The IAServ is expected to offer intelligent, pervasive, accurate and contextually-aware personal care services. Architecturally the implemented IAServ leverages web services and cloud computing to provide economic, scalable, and robust healthcare services over the Internet.

IAServ: An Intelligent Home Care Web Services Platform in a Cloud for Aging-in-Place

PubMed Central

Su, Chuan-Jun; Chiang, Chang-Yu

2013-01-01

As the elderly population has been rapidly expanding and the core tax-paying population has been shrinking, the need for adequate elderly health and housing services continues to grow while the resources to provide such services are becoming increasingly scarce. Thus, increasing the efficiency of the delivery of healthcare services through the use of modern technology is a pressing issue. The seamless integration of such enabling technologies as ontology, intelligent agents, web services, and cloud computing is transforming healthcare from hospital-based treatments to home-based self-care and preventive care. A ubiquitous healthcare platform based on this technological integration, which synergizes service providers with patients’ needs to be developed to provide personalized healthcare services at the right time, in the right place, and the right manner. This paper presents the development and overall architecture of IAServ (the Intelligent Aging-in-place Home care Web Services Platform) to provide personalized healthcare service ubiquitously in a cloud computing setting to support the most desirable and cost-efficient method of care for the aged-aging in place. The IAServ is expected to offer intelligent, pervasive, accurate and contextually-aware personal care services. Architecturally the implemented IAServ leverages web services and cloud computing to provide economic, scalable, and robust healthcare services over the Internet. PMID:24225647

Integration of Technology-based Behavioral Health Interventions in Substance Abuse and Addiction Services.

PubMed

Ramsey, Alex

2015-08-01

The past decade has witnessed revolutionary changes to the delivery of health services, ushered in to a great extent by the introduction of electronic health record systems. More recently, a new class of technological advancements-technology-based behavioral health interventions, which involve the delivery of evidence-informed practices via computers, web-based applications, mobile phones, wearable sensors, or other technological platforms-has emerged and is primed to once again radically shift current models for behavioral healthcare. Despite the promise and potential of these new therapeutic approaches, a greater understanding of the impact of technology-based interventions on cornerstone issues of mental health and addiction services-namely access, quality, and cost -is needed. The current review highlights 1) relevant conceptual frameworks that guide this area of research, 2) key studies that inform the relevance of technology-based interventions for behavioral healthcare access, quality, and cost, 3) pressing methodological issues that require attention, 4) unresolved questions that warrant further investigation, and 5) practical implications that underscore important new directions for this emerging area of research.

Rational Design of Iron Oxide Nanoparticles as Targeted Nanomedicines for Cancer Therapy

NASA Astrophysics Data System (ADS)

Kievit, Forrest M.

2011-07-01

Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired biological response. Of the nanomaterials studied, superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as one of top candidates for cancer therapy due to their intrinsic superparamagnetism that enables non-invasive magnetic resonance imaging (MRI) and biodegradability favorable for in vivo application. This dissertation is aimed at development of SPION-based nanomedicines to overcome the current limitations in cancer therapy. These limitations include non-specificity of therapy which can harm healthy tissue, the difficulty in delivering nucleic acids for gene therapy, the formation of drug resistance, and the inability to detect and treat micrometastases. First, a SPION-based non-viral gene delivery vehicle was developed through functionalization of the SPION core with a co-polymer designed to provide stable binding of DNA and low toxicity which showed excellent gene delivery in vitro and in vivo. This SPION-based non-viral gene delivery vehicle was then activated with a targeting agent to improve gene delivery throughout a xenograft tumor of brain cancer. It was found that targeting did not promote the accumulation of SPIONs at the tumor site, but rather improved the distribution of SPIONs throughout the tumor so a higher proportion of cells received treatment. Next, the high surface area of SPIONs was utilized for loading large amounts of drug which was shown to overcome the multidrug resistance acquired by many cancer cells. Drug bound to SPIONs showed significantly higher multidrug resistant cell uptake as compared to free drug which translated into improved cell kill. Also, an antibody activated SPION was developed and was shown to be able to target micrometastases in a transgenic animal model of metastatic breast cancer. These SPION-based nanomedicines provide a platform for the future development of therapies that are hoped to overcome the current limitations in cancer therapy. Finally, a three-dimensional in vitro tumor tissue culture model was developed for mimicking the tumor microenvironment in which cultured cells showed higher malignancy than traditional two-dimensional and three-dimensional models. This in vitro model should provided researches with a better tool for testing novel nanomedicines in vitro before moving to the more costly in vivo experiments.

Using Time-Driven Activity-Based Costing as a Key Component of the Value Platform: A Pilot Analysis of Colonoscopy, Aortic Valve Replacement and Carpal Tunnel Release Procedures.

PubMed

Martin, Jacob A; Mayhew, Christopher R; Morris, Amanda J; Bader, Angela M; Tsai, Mitchell H; Urman, Richard D

2018-04-01

Time-driven activity-based costing (TDABC) is a methodology that calculates the costs of healthcare resources consumed as a patient moves along a care process. Limited data exist on the application of TDABC from the perspective of an anesthesia provider. We describe the use of TDABC, a bottom-up costing strategy and financial outcomes for three different medical-surgical procedures. In each case, a multi-disciplinary team created process maps describing the care delivery cycle for a patient encounter using the TDABC methodology. Each step in a process map delineated an activity required for delivery of patient care. The resources (personnel, equipment and supplies) associated with each step were identified. A per minute cost for each resource expended was generated, known as the capacity cost rate, and multiplied by its time requirement. The total cost for an episode of care was obtained by adding the cost of each individual resource consumed as the patient moved along a clinical pathway. We built process maps for colonoscopy in the gastroenterology suite, calculated costs of an aortic valve replacement by comparing surgical aortic valve replacement (SAVR) versus transcatheter aortic valve replacement (TAVR) techniques, and determined the cost of carpal tunnel release in an operating room versus an ambulatory procedure room. TDABC is central to the value-based healthcare platform. Application of TDABC provides a framework to identify process improvements for health care delivery. The first case demonstrates cost-savings and improved wait times by shifting some of the colonoscopies scheduled with an anesthesiologist from the main hospital to the ambulatory facility. In the second case, we show that the deployment of an aortic valve via the transcatheter route front loads the costs compared to traditional, surgical replacement. The last case demonstrates significant cost savings to the healthcare system associated with re-organization of staff required to execute a carpal tunnel release.

Using Time-Driven Activity-Based Costing as a Key Component of the Value Platform: A Pilot Analysis of Colonoscopy, Aortic Valve Replacement and Carpal Tunnel Release Procedures

PubMed Central

Martin, Jacob A.; Mayhew, Christopher R.; Morris, Amanda J.; Bader, Angela M.; Tsai, Mitchell H.; Urman, Richard D.

2018-01-01

Background Time-driven activity-based costing (TDABC) is a methodology that calculates the costs of healthcare resources consumed as a patient moves along a care process. Limited data exist on the application of TDABC from the perspective of an anesthesia provider. We describe the use of TDABC, a bottom-up costing strategy and financial outcomes for three different medical-surgical procedures. Methods In each case, a multi-disciplinary team created process maps describing the care delivery cycle for a patient encounter using the TDABC methodology. Each step in a process map delineated an activity required for delivery of patient care. The resources (personnel, equipment and supplies) associated with each step were identified. A per minute cost for each resource expended was generated, known as the capacity cost rate, and multiplied by its time requirement. The total cost for an episode of care was obtained by adding the cost of each individual resource consumed as the patient moved along a clinical pathway. Results We built process maps for colonoscopy in the gastroenterology suite, calculated costs of an aortic valve replacement by comparing surgical aortic valve replacement (SAVR) versus transcatheter aortic valve replacement (TAVR) techniques, and determined the cost of carpal tunnel release in an operating room versus an ambulatory procedure room. Conclusions TDABC is central to the value-based healthcare platform. Application of TDABC provides a framework to identify process improvements for health care delivery. The first case demonstrates cost-savings and improved wait times by shifting some of the colonoscopies scheduled with an anesthesiologist from the main hospital to the ambulatory facility. In the second case, we show that the deployment of an aortic valve via the transcatheter route front loads the costs compared to traditional, surgical replacement. The last case demonstrates significant cost savings to the healthcare system associated with re-organization of staff required to execute a carpal tunnel release. PMID:29511420

Medical Device Plug-and-Play Interoperability Standards and Technology Leadership

DTIC Science & Technology

2012-10-01

External Network Pump Adapter PulseOx Adapter • MD MP3 cart is a platform for the development of smart pump control algorithms • It includes...delivery with bounded latency Medical Device Mobile PnP Prototype Platform (MD MP3 ) • Got MDCF code to run on the BeagleBoard development boards we are

Integrated Microsensors for Autonomous Microrobots

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

ADKINS, DOUGLAS R.; BYRNE, RAYMOND H.; HELLER, EDWIN J.

2003-02-01

This report describes the development of a miniature mobile microrobot device and several microsystems needed to create a miniature microsensor delivery platform. This work was funded under LDRD No.10785, entitled, ''Integrated Microsensors for Autonomous Microrobots''. The approach adopted in this project was to develop a mobile platform, to which would be attached wireless RF remote control and data acquisition in addition to various microsensors. A modular approach was used to produce a versatile microrobot platform and reduce power consumption and physical size.

Nanodiamonds as platforms for biology and medicine.

PubMed

Man, Han B; Ho, Dean

2013-02-01

Nanoparticles possess a wide range of exceptional properties applicable to biology and medicine. In particular, nanodiamonds (NDs) are being studied extensively because they possess unique characteristics that make them suitable as platforms for diagnostics and therapeutics. This carbon-based material (2-8 nm) is medically relevant because it unites several key properties necessary for clinical applications, such as stability and compatibility in biological environments, and scalability in production. Research by the Ho group and others has yielded ND particles with a variety of capabilities ranging from delivery of chemotherapeutic drugs to targeted labeling and uptake studies. In addition, encouraging new findings have demonstrated the ability for NDs to effectively treat chemoresistant tumors in vivo. In this review, we highlight the progress made toward bringing nanodiamonds from the bench to the bedside.

Gadolinium-doped hollow CeO2-ZrO2 nanoplatform as multifunctional MRI/CT dual-modal imaging agent and drug delivery vehicle.

PubMed

Wei, Zuwu; Wu, Ming; Li, Zuanfang; Lin, Zhan; Zeng, Jinhua; Sun, Haiyan; Liu, Xiaolong; Liu, Jingfeng; Li, Buhong; Zeng, Yongyi

2018-11-01

Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO 2 -ZrO 2 /DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO 2 -ZrO 2 /DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging.

Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

PubMed

Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

2015-10-01

Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Long term orbital storage of cryogenic propellants for advanced space transportation missions

NASA Technical Reports Server (NTRS)

Schuster, John R.; Brown, Norman S.

1987-01-01

A comprehensive study has developed the major features of a large capacity orbital propellant depot for the space-based, cryogenic OTV. The study has treated both the Dual-Keel Space Station and co-orbiting platforms as the accommodations base for the propellant storage facilities, and trades have examined both tethered and hard-docked options. Five tank set concepts were developed for storing the propellants, and along with layout options for the station and platform, were evaluated from the standpoints of servicing, propellant delivery, boiloff, micrometeoroid/debris shielding, development requirements, and cost. These trades led to the recommendation that an all-passive storage concept be considered for the platform and an actively refrigerated concept providing for reliquefaction of all boiloff be considered for the Space Station. The tank sets are modular, each storing up to 45,400 kg of LO2/LH2, and employ many advanced features to provide for microgravity fluid management and to limit boiloff. The features include such technologies as zero-gravity mass gauging, total communication capillary liquid acquisition devices, autogenous pressurization, thermodynamic vent systems, thick multilayer insulation, vapor-cooled shields, solar-selective coatings, advanced micrometeoroid/debris protection systems, and long-lived cryogenic refrigeration systems.

Automated reagent-dispensing system for microfluidic cell biology assays.

PubMed

Ly, Jimmy; Masterman-Smith, Michael; Ramakrishnan, Ravichandran; Sun, Jing; Kokubun, Brent; van Dam, R Michael

2013-12-01

Microscale systems that enable measurements of oncological phenomena at the single-cell level have a great capacity to improve therapeutic strategies and diagnostics. Such measurements can reveal unprecedented insights into cellular heterogeneity and its implications into the progression and treatment of complicated cellular disease processes such as those found in cancer. We describe a novel fluid-delivery platform to interface with low-cost microfluidic chips containing arrays of microchambers. Using multiple pairs of needles to aspirate and dispense reagents, the platform enables automated coating of chambers, loading of cells, and treatment with growth media or other agents (e.g., drugs, fixatives, membrane permeabilizers, washes, stains, etc.). The chips can be quantitatively assayed using standard fluorescence-based immunocytochemistry, microscopy, and image analysis tools, to determine, for example, drug response based on differences in protein expression and/or activation of cellular targets on an individual-cell level. In general, automation of fluid and cell handling increases repeatability, eliminates human error, and enables increased throughput, especially for sophisticated, multistep assays such as multiparameter quantitative immunocytochemistry. We report the design of the automated platform and compare several aspects of its performance to manually-loaded microfluidic chips.

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

NASA Astrophysics Data System (ADS)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

Poster — Thur Eve — 28: Enabling trajectory-based radiotherapy on a TrueBeam accelerator with the Eclipse treatment planning system

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

Mullins, J; Asiev, K; DeBlois, F

2014-08-15

The TrueBeam linear accelerator platform has a developer's mode which permits the user dynamic control over many of the machine's mechanical and radiation systems. Using this research tool, synchronous couch and gantry motion can be programmed to simulate isocentric treatment with a shortened SAD, with benefits such as smaller projected MLC leaf widths and an increased dose rate. In this work, water tank measurements were used to commission a virtual linear accelerator with an 85 cm SAD in Eclipse, from which several arc-based radiotherapy treatments were generated, including an inverse optimized VMAT delivery. For each plan, the pertinent treatment deliverymore » information was extracted from control points specified in the Eclipse-exported DICOM files using the pydicom package in Python, allowing construction of an XML control file. The dimensions of the jaws and MLC positions, defined for an 85 cm SAD in Eclipse, were scaled for delivery on a conventional SAD linear accelerator, and translational couch motion was added as a function of gantry angle to simulate delivery at 85 cm SAD. Ionization chamber and Gafchromic film measurements were used to compare the radiation delivery to dose calculations in Eclipse. With the exception of the VMAT delivery, ionization chamber measurements agreed within 3.3% of the Eclipse calculations. For the VMAT delivery, the ionization chamber was located in an inhomogeneous region, but gamma evaluation of the Gafchromic film plane resulted in a 94.5% passing rate using criteria of 3 mm/3%. The results indicate that Eclipse calculation infrastructure can be used.« less

Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi

2011-01-01

An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

Refolding of proteins from inclusion bodies: rational design and recipes.

PubMed

Basu, Anindya; Li, Xiang; Leong, Susanna Su Jan

2011-10-01

The need to develop protein biomanufacturing platforms that can deliver proteins quickly and cost-effectively is ever more pressing. The rapid rate at which genomes can now be sequenced demands efficient protein production platforms for gene function identification. There is a continued need for the biotech industry to deliver new and more effective protein-based drugs to address new diseases. Bacterial production platforms have the advantage of high expression yields, but insoluble expression of many proteins necessitates the development of diverse and optimised refolding-based processes. Strategies employed to eliminate insoluble expression are reviewed, where it is concluded that inclusion bodies are difficult to eliminate for various reasons. Rational design of refolding systems and recipes are therefore needed to expedite production of recombinant proteins. This review article discusses efforts towards rational design of refolding systems and recipes, which can be guided by the development of refolding screening platforms that yield both qualitative and quantitative information on the progression of a given refolding process. The new opportunities presented by light scattering technologies for developing rational protein refolding buffer systems which in turn can be used to develop new process designs armed with better monitoring and controlling functionalities are discussed. The coupling of dynamic and static light scattering methodologies for incorporation into future bioprocess designs to ensure delivery of high-quality refolded proteins at faster rates is also discussed.

A smartphone-based platform to test the performance of wireless mobile networks and preliminary findings

NASA Astrophysics Data System (ADS)

Geng, Xinli; Xu, Hao; Qin, Xiaowei

2016-10-01

During the last several years, the amount of wireless network traffic data increased fast and relative technologies evolved rapidly. In order to improve the performance and Quality of Experience (QoE) of wireless network services, the analysis of field network data and existing delivery mechanisms comes to be a promising research topic. In order to achieve this goal, a smartphone based platform named Monitor and Diagnosis of Mobile Applications (MDMA) was developed to collect field data. Based on this tool, the web browsing service of High Speed Downlink Packet Access (HSDPA) network was tested. The top 200 popular websites in China were selected and loaded on smartphone for thousands times automatically. Communication packets between the smartphone and the cell station were captured for various scenarios (e.g. residential area, urban roads, bus station etc.) in the selected city. A cross-layer database was constructed to support the off-line analysis. Based on the results of client-side experiments and analysis, the usability of proposed portable tool was verified. The preliminary findings and results for existing web browsing service were also presented.

Mobile Phone Cognitive Bias Modification Research Platform for Substance Use Disorders: Protocol for a Feasibility Study.

PubMed

Zhang, Melvyn; Ying, JiangBo; Song, Guo; Fung, Daniel Ss; Smith, Helen

2018-06-12

Cognitive biases refer to automatic attentional and interpretational tendencies, which could be retained by cognitive bias modification interventions. Cristea et al and Jones et al have published reviews (in 2016 and 2017 respectively) on the effectiveness of such interventions. The advancement of technologies such as electronic health (eHealth) and mobile health (mHealth) has led to them being harnessed for the delivery of cognitive bias modification. To date, at least eight studies have demonstrated the feasibility of mobile technologies for the delivery of cognitive bias modification. Most of the studies are limited to a description of the conventional cognitive bias modification methodology that has been adopted. None of the studies shared the developmental process for the methodology involved, such that future studies could adopt it in the cost-effective replication of such interventions. It is important to have a common platform that could facilitate the design and customization of cognitive bias modification interventions for a variety of psychiatric and addictive disorders. It is the aim of the current research protocol to describe the design of a research platform that allows for customization of cognitive bias modification interventions for addictive disorders. A multidisciplinary team of 2 addiction psychiatrists, a psychologist with expertise in cognitive bias modification, and a computer engineer, were involved in the development of the intervention. The proposed platform would comprise of a mobile phone version of the cognitive bias task which is controlled by a server that could customize the algorithm for the tasks and collate the reaction-time data in realtime. The server would also allow the researcher to program the specific set of images that will be present in the task. The mobile phone app would synchronize with the backend server in real-time. An open-sourced cross-platform gaming software from React Native was used in the current development. Multimedia Appendix 1 contains a video demonstrating the operation of the app, as well as a sample dataset of the reaction times (used for the computation of attentional biases) captured by the app. The current design can be utilized for cognitive bias modification across a spectrum of disorders and is not limited to one disorder. It will be of value for future research to utilize the above platform and compare the efficacy of mHealth approaches, such as the one described in this study, with conventional Web-based approaches in the delivery of attentional bias modification interventions. RR1-10.2196/9740. ©Melvyn Zhang, JiangBo Ying, Guo Song, Daniel SS Fung, Helen Smith. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 12.06.2018.

Alternative foaming agents for topical treatment of ulcerative colitis.

PubMed

Asama, Martin; Hall, Alex; Qi, Yijun; Moreau, Branden; Walthier, Heidi; Schaschwary, Matthew; Bristow, Blaine; Wang, Qun

2018-05-01

Approximately 907,000 Americans currently suffer from ulcerative colitis, a condition characterized by inflammation of the large intestine or rectum. Treatment of this disease often includes anti-inflammatory medication or immunosuppressants. Here foams are an attractive delivery platform, offering relatively high bioavailability, low systemic exposure, and improved patient comfort. However, the surfactants that generate these foams may adversely affect the diseased mucosa. Therefore, this project evaluated two alternative surfactants for use in topical drug delivery platforms: sodium caseinate and l-α-phosphatidylcholine. Both were compared to the biocompatible surfactant Pluronic ® F-127 using stability and density tests, and biocompatibility tests performed on mini-guts. Sodium caseinate foams were less stable but denser than Pluronic ® foams; however, they exhibited an unexpectedly low shelf-life. l-α-phosphatidylcholine was an unsuccessful primary foaming agent owing to poor foamability at low concentrations. Mini-gut growth rates were not significantly altered by surfactants, while morphology and an MTT assay identified Pluronic ® as the most biocompatible surfactant at higher concentrations. These results clarify the possible challenges that the tested surfactants may present in topical delivery platforms and show the relevance of permeability to tissue-surfactant interaction tests. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1448-1456, 2018. © 2017 Wiley Periodicals, Inc.

Pros and cons of the liposome platform in cancer drug targeting.

PubMed

Gabizon, Alberto A; Shmeeda, Hilary; Zalipsky, Samuel

2006-01-01

Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-à-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.

Transgene Delivery using Poly(amino ether)-Gold Nanorod Assemblies

PubMed Central

Ramos, James; Rege, Kaushal

2012-01-01

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach; polymers from a poly(amino ether) library recently synthesized in our laboratory were employed to generate the PAE-GNR assemblies. PAE-GNR assemblies demonstrate long-term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. The roles of polyelectrolyte chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. Our results indicate that stable and effective PAE-GNR assemblies are a promising engineered platform for transgene delivery. PAE-GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform. PMID:22170455

In Vitro and In Vivo Investigation of the Potential of Amorphous Microporous Silica as a Protein Delivery Vehicle

PubMed Central

Vanmellaert, Lieve; Vermaelen, Peter; Deroose, Christophe M.; Naert, Ignace; Cardoso, Marcio Vivan; Martens, Johan A.

2013-01-01

Delivering growth factors (GFs) at bone/implant interface needs to be optimized to achieve faster osseointegration. Amorphous microporous silica (AMS) has a potential to be used as a carrier and delivery platform for GFs. In this work, adsorption (loading) and release (delivery) mechanism of a model protein, bovine serum albumin (BSA), from AMS was investigated in vitro as well as in vivo. In general, strong BSA adsorption to AMS was observed. The interaction was stronger at lower pH owing to favorable electrostatic interaction. In vitro evaluation of BSA release revealed a peculiar release profile, involving a burst release followed by a 6 h period without appreciable BSA release and a further slower release later. Experimental data supporting this observation are discussed. Apart from understanding protein/biomaterial (BSA/AMS) interaction, determination of in vivo protein release is an essential aspect of the evaluation of a protein delivery system. In this regard micropositron emission tomography (μ-PET) was used in an exploratory experiment to determine in vivo BSA release profile from AMS. Results suggest stronger in vivo retention of BSA when adsorbed on AMS. This study highlights the possible use of AMS as a controlled protein delivery platform which may facilitate osseointegration. PMID:23991413

Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB–siRNA conjugates

PubMed Central

Cuellar, Trinna L.; Barnes, Dwight; Nelson, Christopher; Tanguay, Joshua; Yu, Shang-Fan; Wen, Xiaohui; Scales, Suzie J.; Gesch, Julie; Davis, David; van Brabant Smith, Anja; Leake, Devin; Vandlen, Richard; Siebel, Christian W.

2015-01-01

Delivery of siRNA is a key hurdle to realizing the therapeutic promise of RNAi. By targeting internalizing cell surface antigens, antibody–siRNA complexes provide a possible solution. However, initial reports of antibody–siRNA complexes relied on non-specific charged interactions and have not been broadly applicable. To assess and improve this delivery method, we built on an industrial platform of therapeutic antibodies called THIOMABs, engineered to enable precise covalent coupling of siRNAs. We report that such coupling generates monomeric antibody–siRNA conjugates (ARCs) that retain antibody and siRNA activities. To broadly assess this technology, we generated a battery of THIOMABs against seven targets that use multiple internalization routes, enabling systematic manipulation of multiple parameters that impact delivery. We identify ARCs that induce targeted silencing in vitro and extend tests to target prostate carcinoma cells following systemic administration in mouse models. However, optimal silencing was restricted to specific conditions and only observed using a subset of ARCs. Trafficking studies point to ARC entrapment in endocytic compartments as a limiting factor, independent of the route of antigen internalization. Our broad characterization of multiple parameters using therapeutic-grade conjugate technology provides a thorough assessment of this delivery technology, highlighting both examples of success as well as remaining challenges. PMID:25550431

Assessing Google Cardboard Virtual Reality as a Content Delivery System in Business Classrooms

ERIC Educational Resources Information Center

Lee, Seung Hwan; Sergueeva, Ksenia; Catangui, Mathew; Kandaurova, Maria

2017-01-01

In the past, researchers have explored virtual reality (VR) as an educational tool primarily for training or therapeutic purposes. In this research, the authors examine the potential for using Google Cardboard VR in business classrooms as a content delivery platform. They specifically investigate how VR (viewing a 3-dimensional, 360° video)…

Evaluation of Free Platforms for Delivery of Massive Open Online Courses (MOOCS)

ERIC Educational Resources Information Center

Zancanaro, Airton; Nunes, Carolina Schmitt; Domingues, Maria Jose Carvalho de Souza

2017-01-01

For the hosting, management and delivery of Massive Open Online Courses (MOOC) it is necessary a technological infrastructure that supports it. Various educational institutions do not have or do not wish to invest in such a structure, possibly because MOOCs are not yet part of official programs of universities, but initiatives by a particular…

A Novel Theranostic Platform for Targeted Cancer Therapy and Treatment Monitoring | Division of Cancer Prevention

Cancer.gov

DESCRIPTION (provided by applicant): Cancer treatment currently relies heavily upon administration of cytotoxic drugs that attack both cancerous and healthy cells due to limited selectivity of drugs. Therapeutic efficacy and systemic toxicity can be improved by employing a multifunctional drug delivery system that allows targeted drug delivery, controlled drug release and

Affective Learning Outcomes in Workplace Training: A Test of Synchronous vs. Asynchronous Online Learning Environments

ERIC Educational Resources Information Center

Cleveland-Innes, Martha; Ally, Mohamed

2004-01-01

Research employing an experimental design pilot-tested two delivery platforms, WebCT™ and vClass™, for the generation of affective learning outcomes in the workplace. Using a sample of volunteer participants in the help-desk industry, participants were randomly assigned to one of the two types of delivery software. Thirty-eight subjects…

The Death of the Large Lecture Hall, the Rise of Peer-to-Peer Course Delivery?

ERIC Educational Resources Information Center

Navarro, Peter

2015-01-01

This article reports the results of a pilot project conducted at the University of California--Irvine (UCI) involving the simultaneous online delivery of a course to both University of California undergraduates and enrollees on the Coursera Massive Open Online Course (MOOC) platform. Survey results from a robust sampling of UCI undergraduates…

Continuing progress toward controlled intracellular delivery of semiconductor quantum dots

PubMed Central

Breger, Joyce; Delehanty, James B; Medintz, Igor L

2015-01-01

The biological applications of luminescent semiconductor quantum dots (QDs) continue to grow at a nearly unabated pace. This growth is driven, in part, by their unique photophysical and physicochemical properties which have allowed them to be used in many different roles in cellular biology including: as superior fluorophores for a wide variety of cellular labeling applications; as active platforms for assembly of nanoscale sensors; and, more recently, as a powerful tool to understand the mechanisms of nanoparticle mediated drug delivery. Given that controlled cellular delivery is at the intersection of all these applications, the latest progress in delivering QDs to cells is examined here. A brief discussion of relevant considerations including the importance of materials preparation and bioconjugation along with the continuing issue of endosomal sequestration is initially provided for context. Methods for the cellular delivery of QDs are then highlighted including those based on passive exposure, facilitated strategies that utilize peptides or polymers and fully active modalities such as electroporation and other mechanically based methods. Following on this, the exciting advent of QD cellular delivery using multiple or combined mechanisms is then previewed. Several recent methods reporting endosomal escape of QD materials in cells are also examined in detail with a focus on the mechanisms by which access to the cytosol is achieved. The ongoing debate over QD cytotoxicity is also discussed along with a perspective on how this field will continue to evolve in the future. PMID:25154379

DNA nanomaterials for preclinical imaging and drug delivery.

PubMed

Jiang, Dawei; England, Christopher G; Cai, Weibo

2016-10-10

Besides being the carrier of genetic information, DNA is also an excellent biological organizer to establish well-designed nanostructures in the fields of material engineering, nanotechnology, and biomedicine. DNA-based materials represent a diverse nanoscale system primarily due to their predictable base pairing and highly regulated conformations, which greatly facilitate the construction of DNA nanostructures with distinct shapes and sizes. Integrating the emerging advancements in bioconjugation techniques, DNA nanostructures can be readily functionalized with high precision for many purposes ranging from biosensors to imaging to drug delivery. Recent progress in the field of DNA nanotechnology has exhibited collective efforts to employ DNA nanostructures as smart imaging agents or delivery platforms within living organisms. Despite significant improvements in the development of DNA nanostructures, there is limited knowledge regarding the in vivo biological fate of these intriguing nanomaterials. In this review, we summarize the current strategies for designing and purifying highly-versatile DNA nanostructures for biological applications, including molecular imaging and drug delivery. Since DNA nanostructures may elicit an immune response in vivo, we also present a short discussion of their potential toxicities in biomedical applications. Lastly, we discuss future perspectives and potential challenges that may limit the effective preclinical and clinical employment of DNA nanostructures. Due to their unique properties, we predict that DNA nanomaterials will make excellent agents for effective diagnostic imaging and drug delivery, improving patient outcome in cancer and other related diseases in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.

Including customers in health service design.

PubMed

Perrott, Bruce E

2013-01-01

This article will explore the concept and meaning of codesign as it applies to the delivery of health services. The results of a pilot study in health codesign will be used as a research based case discussion, thus providing a platform to suggest future research that could lead to building more robust knowledge of how the consumers of health services may be more effectively involved in the process of developing and delivering the type of services that are in line with expectations of the various stakeholder groups.

A Targeted Multifunctional Platform for Imaging and Treatment of Breast Cancer and Its Metastases Based on Adenoviral Vectors and Magnetic Nanoparticles

DTIC Science & Technology

2007-08-01

selective or are genetically modified to be selective for replication competence in tu- mor cells. In this regard, herpesvirus samiri (HVS) was de...logy 76, 4559-4566 Ring CJ (2002) Cytolytic viruses as potential anti -cancer agents . The Journal of General Virology 83, 491-502 Riviere C, Danos O...precursors for tumor stroma and targeted-delivery vehicles for anti - cancer agents . Journal of the National Cancer Institute 96, 1593-1603 Takanami

HPLC-Assisted Automated Oligosaccharide Synthesis: Implementation of the Autosampler as a Mode of the Reagent Delivery.

PubMed

Pistorio, Salvatore G; Nigudkar, Swati S; Stine, Keith J; Demchenko, Alexei V

2016-10-07

The development of a useful methodology for simple, scalable, and transformative automation of oligosaccharide synthesis that easily interfaces with existing methods is reported. The automated synthesis can now be performed using accessible equipment where the reactants and reagents are delivered by the pump or the autosampler and the reactions can be monitored by the UV detector. The HPLC-based platform for automation is easy to setup and adapt to different systems and targets.

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices.

PubMed

Linko, Veikko; Ora, Ari; Kostiainen, Mauri A

2015-10-01

DNA molecules can be assembled into custom predesigned shapes via hybridization of sequence-complementary domains. The folded structures have high spatial addressability and a tremendous potential to serve as platforms and active components in a plethora of bionanotechnological applications. DNA is a truly programmable material, and its nanoscale engineering thus opens up numerous attractive possibilities to develop novel methods for therapeutics. The tailored molecular devices could be used in targeting cells and triggering the cellular actions in the biological environment. In this review we focus on the DNA-based assemblies - primarily DNA origami nanostructures - that could perform complex tasks in cells and serve as smart drug-delivery vehicles in, for example, cancer therapy, prodrug medication, and enzyme replacement therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spherical photography and virtual tours for presenting crime scenes and forensic evidence in new zealand courtrooms.

PubMed

Tung, Nicole D; Barr, Jason; Sheppard, Dion J; Elliot, Douglas A; Tottey, Leah S; Walsh, Kevan A J

2015-05-01

The delivery of forensic science evidence in a clear and understandable manner is an important aspect of a forensic scientist's role during expert witness delivery in a courtroom trial. This article describes an Integrated Evidence Platform (IEP) system based on spherical photography which allows the audience to view the crime scene via a virtual tour and view the forensic scientist's evidence and results in context. Equipment and software programmes used in the creation of the IEP include a Nikon DSLR camera, a Seitz Roundshot VR Drive, PTGui Pro, and Tourweaver Professional Edition. The IEP enables a clear visualization of the crime scene, with embedded information such as photographs of items of interest, complex forensic evidence, the results of laboratory analyses, and scientific opinion evidence presented in context. The IEP has resulted in significant improvements to the pretrial disclosure of forensic results, enhanced the delivery of evidence in court, and improved the jury's understanding of the spatial relationship between results. © 2015 American Academy of Forensic Sciences.

Lipid-Based Nanoparticles as a Potential Delivery Approach in the Treatment of Rheumatoid Arthritis

PubMed Central

Chuang, Shih-Yi; Lin, Chih-Hung; Huang, Tse-Hung

2018-01-01

Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease, results in immune dysfunction and destruction of joints and cartilages. Small molecules and biological therapies have been applied in a wide variety of inflammatory disorders, but their utility as a therapeutic agent is limited by poor absorption, rapid metabolism, and serious side effects. To improve these limitations, nanoparticles, which are capable of encapsulating and protecting drugs from degradation before they reach the target site in vivo, may serve as drug delivery systems. The present research proposes a platform for different lipid nanoparticle approaches for RA therapy, taking advantage of the newly emerging field of lipid nanoparticles to develop a targeted theranostic system for application in the treatment of RA. This review aims to present the recent major application of lipid nanoparticles that provide a biocompatible and biodegradable delivery system to effectively improve RA targeting over free drugs via the presentation of tissue-specific targeting of ligand-controlled drug release by modulating nanoparticle composition. PMID:29342965

Increasing clinical presence of mobile communication technology: avoiding the pitfalls.

PubMed

Visvanathan, Akila; Gibb, Alan P; Brady, Richard R W

2011-10-01

Mobile communication technologies are employed in many diverse areas of healthcare delivery to provide improved quality and efficiency of communication and facilitate increased rapidity of data or information transfer. Mobile phones enable healthcare professionals to possess a portable platform from which to provide many healthcare-related applications and are a popular means to directly communicate with colleagues and patients. As involvement of mobile communication technology in healthcare delivery continues to rapidly expand, there are also important considerations of relevance to patient safety and security as a result. Here, we review the previous evidence of reported clinical risks associated with mobile communication technology, such as electromagnetic interference, confidentiality and data security, distraction/noise, infection control, and cross contamination. In conclusion, although mobile phones provide much putative potential improvement to healthcare delivery, further evaluation and research are required to both inform and protect health professionals and users of such technology in the healthcare environment and provide the evidence base to support the provision of clear and comprehensive guidelines.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

PubMed

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

Hybrid protein-synthetic polymer nanoparticles for drug delivery.

PubMed

Koseva, Neli S; Rydz, Joanna; Stoyanova, Ekaterina V; Mitova, Violeta A

2015-01-01

Among the most common nanoparticulate systems, the polymeric nanocarriers have a number of key benefits, which give a great choice of delivery platforms. Nevertheless, polymeric nanoparticles possess some limitations that include use of toxic solvents in the production process, polymer degradation, drug leakage outside the diseased tissue, and polymer cytotoxicity. The combination of polymers of biological and synthetic origin is an appealing modern strategy for the production of novel nanocarriers with unprecedented properties. Proteins' interface can play an important role in determining bioactivity and toxicity and gives perspective for future development of the polymer-based nanoparticles. The design of hybrid constructs composed of synthetic polymer and biological molecules such as proteins can be considered as a straightforward tool to integrate a broad spectrum of properties and biofunctions into a single device. This review discusses hybrid protein-synthetic polymer nanoparticles with different structures and levels in complexity and functionality, in view of their applications as drug delivery systems. © 2015 Elsevier Inc. All rights reserved.

Osmolarity as a contributing factor in topical drug delivery

NASA Astrophysics Data System (ADS)

Funke, Claire; Szeri, Andrew J.

2017-11-01

Gels and dissolvable solids are drug delivery platforms being evaluated for application of active pharmaceutical ingredients, termed microbicides, which act topically against infection by sexually transmitted HIV. In previous work, we have investigated how dilution by naturally produced fluid from the vaginal mucosa affects drug transport into the vaginal wall. We expand on this work by no longer assuming a constant flux and instead developing a relation for fluid transport based on osmolarity - thus allowing fluid to pass both into and out of epithelial cells. This relation shows that varying the osmolarity of the applied solution can have a significant effect on the amount of drug delivered to its target while holding the applied amount constant. This effect is modulated by a dimensionless group that relates the rates of solute and solvent transport. Ultimately, our goal is to develop a tool to understand better how to manipulate solution osmolarity in order to improve drug delivery within safety parameters for mucosal tissue.

Nanoparticles in targeted cancer therapy: mesoporous silica nanoparticles entering preclinical development stage.

PubMed

Rosenholm, Jessica M; Mamaeva, Veronika; Sahlgren, Cecilia; Lindén, Mika

2012-01-01

Nanotechnology may help overcome persisting limitations of current cancer treatment and thus contribute to the creation of more effective, safer and more affordable therapies. While some nanotechnology-based drug delivery systems are already being marketed and others are in clinical trial, most still remain in the preclinical development stage. Mesoporous silica nanoparticles have been highlighted as an interesting drug delivery platform, due to their flexibility and high drug load potential. Although numerous reports demonstrate sophisticated drug delivery mechanisms in vitro, the therapeutic benefit of these systems for in vivo applications have been under continuous debate. This has been due to nontranslatable conditions used in the in vitro studies, as well as contradictory conclusions drawn from preclinical (in vivo) studies. However, recent studies have indicated that the encouraging cellular studies could in fact be repeated also in vivo. Here, we report on these recent advances regarding therapeutic efficacy, targeting and safety issues related to the application of mesoporous silica nanoparticles in cancer therapy.

Enzymatic- and temperature-sensitive controlled release of ultrasmall superparamagnetic iron oxides (USPIOs).

PubMed

Yu, Shann S; Scherer, Randy L; Ortega, Ryan A; Bell, Charleson S; O'Neil, Conlin P; Hubbell, Jeffrey A; Giorgio, Todd D

2011-02-27

Drug and contrast agent delivery systems that achieve controlled release in the presence of enzymatic activity are becoming increasingly important, as enzymatic activity is a hallmark of a wide array of diseases, including cancer and atherosclerosis. Here, we have synthesized clusters of ultrasmall superparamagnetic iron oxides (USPIOs) that sense enzymatic activity for applications in magnetic resonance imaging (MRI). To achieve this goal, we utilize amphiphilic poly(propylene sulfide)-bl-poly(ethylene glycol) (PPS-b-PEG) copolymers, which are known to have excellent properties for smart delivery of drug and siRNA. Monodisperse PPS polymers were synthesized by anionic ring opening polymerization of propylene sulfide, and were sequentially reacted with commercially available heterobifunctional PEG reagents and then ssDNA sequences to fashion biofunctional PPS-bl-PEG copolymers. They were then combined with hydrophobic 12 nm USPIO cores in the thin-film hydration method to produce ssDNA-displaying USPIO micelles. Micelle populations displaying complementary ssDNA sequences were mixed to induce crosslinking of the USPIO micelles. By design, these crosslinking sequences contained an EcoRV cleavage site. Treatment of the clusters with EcoRV results in a loss of R2 negative contrast in the system. Further, the USPIO clusters demonstrate temperature sensitivity as evidenced by their reversible dispersion at ~75°C and re-clustering following return to room temperature. This work demonstrates proof of concept of an enzymatically-actuatable and thermoresponsive system for dynamic biosensing applications. The platform exhibits controlled release of nanoparticles leading to changes in magnetic relaxation, enabling detection of enzymatic activity. Further, the presented functionalization scheme extends the scope of potential applications for PPS-b-PEG. Combined with previous findings using this polymer platform that demonstrate controlled drug release in oxidative environments, smart theranostic applications combining drug delivery with imaging of platform localization are within reach. The modular design of these USPIO nanoclusters enables future development of platforms for imaging and drug delivery targeted towards proteolytic activity in tumors and in advanced atherosclerotic plaques.

Porous silicon advances in drug delivery and immunotherapy

PubMed Central

Savage, D; Liu, X; Curley, S; Ferrari, M; Serda, RE

2013-01-01

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. PMID:23845260

A novel local anti-colorectal cancer drug delivery system: negative lipidoid nanoparticles with a passive target via a size-dependent pattern

NASA Astrophysics Data System (ADS)

Ding, Weifeng; Wang, Feng; Zhang, Jianfeng; Guo, Yibing; Ju, Shaoqing; Wang, Huimin

2013-09-01

The nontoxic, targeted and effective delivery of nucleic acid drugs remains an important challenge for clinical development. Here, we describe a novel negative lipidoid nanoparticle delivery system, providing entrapment-based transfection agents for local delivery of siRNA to the colorectal cancer focus. The delivery system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14 glyceride and cholesterol at a desired molar ratio to realize the anionic surface charge of particles, which could alleviate to a larger degree the inflammatory response and immune stimulation of the organism, embodying dramatic biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to ameliorate the stability of the delivery system and protection of nucleic acids by extending the tail length of the carbons, crucial also to neutralize the positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo experiments revealed that a particle size of 90 nm perfectly realized a passive target in a size-dependent manner and did not affect the function of the liver and kidneys by a local delivery method, enema. We clarified that the uptake of negative lipidoid nanoparticles internalized through a lipid raft endocytotic pathway with low cytotoxicity, strong biocompatibility and high efficacy. This study suggests that negative lipidoid nanoparticles with enema delivery costitute, uniquely and appropriately, a local anti-colorectal cancer nucleic acid drug delivery platform, and the application of similar modes may be feasible in other therapeutic settings.

Operational Experience of an Open-Access, Subscription-Based Mass Spectrometry and Proteomics Facility.

PubMed

Williamson, Nicholas A

2018-03-01

This paper discusses the successful adoption of a subscription-based, open-access model of service delivery for a mass spectrometry and proteomics facility. In 2009, the Mass Spectrometry and Proteomics Facility at the University of Melbourne (Australia) moved away from the standard fee for service model of service provision. Instead, the facility adopted a subscription- or membership-based, open-access model of service delivery. For a low fixed yearly cost, users could directly operate the instrumentation but, more importantly, there were no limits on usage other than the necessity to share available instrument time with all other users. All necessary training from platform staff and many of the base reagents were also provided as part of the membership cost. These changes proved to be very successful in terms of financial outcomes for the facility, instrument access and usage, and overall research output. This article describes the systems put in place as well as the overall successes and challenges associated with the operation of a mass spectrometry/proteomics core in this manner. Graphical abstract ᅟ.

Operational Experience of an Open-Access, Subscription-Based Mass Spectrometry and Proteomics Facility

NASA Astrophysics Data System (ADS)

Williamson, Nicholas A.

2018-03-01

This paper discusses the successful adoption of a subscription-based, open-access model of service delivery for a mass spectrometry and proteomics facility. In 2009, the Mass Spectrometry and Proteomics Facility at the University of Melbourne (Australia) moved away from the standard fee for service model of service provision. Instead, the facility adopted a subscription- or membership-based, open-access model of service delivery. For a low fixed yearly cost, users could directly operate the instrumentation but, more importantly, there were no limits on usage other than the necessity to share available instrument time with all other users. All necessary training from platform staff and many of the base reagents were also provided as part of the membership cost. These changes proved to be very successful in terms of financial outcomes for the facility, instrument access and usage, and overall research output. This article describes the systems put in place as well as the overall successes and challenges associated with the operation of a mass spectrometry/proteomics core in this manner. [Figure not available: see fulltext.

An integrated microrobotic platform for on-demand, targeted therapeutic interventions.

PubMed

Fusco, Stefano; Sakar, Mahmut Selman; Kennedy, Stephen; Peters, Christian; Bottani, Rocco; Starsich, Fabian; Mao, Angelo; Sotiriou, Georgios A; Pané, Salvador; Pratsinis, Sotiris E; Mooney, David; Nelson, Bradley J

2014-02-12

The presented microrobotic platform combines together the advantages of self-folding NIR light sensitive polymer bilayers, magnetic alginate microbeads, and a 3D manipulation system, to propose a solution for targeted, on-demand drug and cell delivery. First feasibility studies are presented together with the potential of the full design. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells

PubMed Central

Shalek, Alex K.; Robinson, Jacob T.; Karp, Ethan S.; Lee, Jin Seok; Ahn, Dae-Ro; Yoon, Myung-Han; Sutton, Amy; Jorgolli, Marsela; Gertner, Rona S.; Gujral, Taranjit S.; MacBeath, Gavin; Yang, Eun Gyeong; Park, Hongkun

2010-01-01

A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells using surface-modified vertical silicon nanowires. The method relies on the ability of the silicon nanowires to penetrate a cell’s membrane and subsequently release surface-bound molecules directly into the cell’s cytosol, thus allowing highly efficient delivery of biomolecules without chemical modification or viral packaging. This modality enables one to assess the phenotypic consequences of introducing a broad range of biological effectors (DNAs, RNAs, peptides, proteins, and small molecules) into almost any cell type. We show that this platform can be used to guide neuronal progenitor growth with small molecules, knock down transcript levels by delivering siRNAs, inhibit apoptosis using peptides, and introduce targeted proteins to specific organelles. We further demonstrate codelivery of siRNAs and proteins on a single substrate in a microarray format, highlighting this technology’s potential as a robust, monolithic platform for high-throughput, miniaturized bioassays. PMID:20080678

A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: rheological, mucoadhesive and in vitro release properties.

PubMed

Mayol, Laura; Quaglia, Fabiana; Borzacchiello, Assunta; Ambrosio, Luigi; La Rotonda, Maria I

2008-09-01

The influence of hyaluronic acid (HA) on the gelation properties of poloxamers blends has been studied with the aim of engineering thermosensitive and mucoadhesive polymeric platforms for drug delivery. The gelation temperature (T(gel)), viscoelastic properties and mucoadhesive force of the systems were investigated and optimised by means of rheological analyses. Poloxamers micellar diameter was evaluated by photon correlation spectroscopy (PCS). Moreover in order to explore the feasibility of these platforms for drug delivery, the optimised systems were loaded with acyclovir and its release properties studied in vitro. By formulating poloxamers/HA platforms, at specific concentrations, it was possible to obtain a thermoreversible gel with a T(gel) close to body temperature. The addition of HA did not hamper the self assembling process of poloxamers just delaying the gelation temperature of few Celsius degrees. Furthermore, HA presence led to a strong increase of the poloxamer rheological properties thus indicating possible HA interactions with micelles through secondary bonds, such as hydrogen ones, which reinforce the gel structure. These interactions could also explain PCS results which show, in systems containing HA, aggregates with hydrodynamic diameters much higher than those of poloxamer micelles. Mucoadhesion experiments showed a rheological synergism between poloxamers/HA gels and mucin dispersion which led to a change of the flow behaviour from a quite Newtonian one of the separate solutions to a pseudoplastic one of their mixture. In vitro release experiments indicated that the optimised platform was able to prolong and control acyclovir release for more than 6h.

3D printed lattices as an activation and expansion platform for T cell therapy.

PubMed

Delalat, Bahman; Harding, Frances; Gundsambuu, Batjargal; De-Juan-Pardo, Elena M; Wunner, Felix M; Wille, Marie-Luise; Jasieniak, Marek; Malatesta, Kristen A L; Griesser, Hans J; Simula, Antonio; Hutmacher, Dietmar W; Voelcker, Nicolas H; Barry, Simon C

2017-09-01

One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation. This 3D technology platform facilitate the expansion of therapeutic human T cell subsets, including regulatory, effector, and cytotoxic T cells while maintaining the correct phenotype. Lentiviral gene delivery to T cells is enhanced in the presence of the lattices. Incorporation of the lattice format into existing cell culture vessels such as the G-Rex system is feasible. This cell expansion platform is user-friendly and expedites cell recovery and scale-up, making it ideal for translating T cell therapies from bench to bedside. Copyright © 2017 Elsevier Ltd. All rights reserved.

Supporting the Delivery of Total Knee Replacements Care for Both Patients and Their Clinicians With a Mobile App and Web-Based Tool: Randomized Controlled Trial Protocol.

PubMed

Hussain, M Sazzad; Li, Jane; Brindal, Emily; van Kasteren, Yasmin; Varnfield, Marlien; Reeson, Andrew; Berkovsky, Shlomo; Freyne, Jill

2017-03-01

Total knee replacement (TKR) surgeries have increased in recent years. Exercise programs and other interventions following surgery can facilitate the recovery process. With limited clinician contact time, patients with TKR have a substantial burden of self-management and limited communication with their care team, thus often fail to implement an effective rehabilitation plan. We have developed a digital orthopedic rehabilitation platform that comprises a mobile phone app, wearable activity tracker, and clinical Web portal in order to engage patients with self-management tasks for surgical preparation and recovery, thus addressing the challenges of adherence to and completion of TKR rehabilitation. The study will determine the efficacy of the TKR platform in delivering information and assistance to patients in their preparation and recovery from TKR surgery and a Web portal for clinician care teams (ie, surgeons and physiotherapists) to remotely support and monitor patient progress. The study will evaluate the TKR platform through a randomized controlled trial conducted at multiple sites (N=5) in a number of states in Australia with 320 patients undergoing TKR surgery; the trial will run for 13 months for each patient. Participants will be randomized to either a control group or an intervention group, both receiving usual care as provided by their hospital. The intervention group will receive the app and wearable activity tracker. Participants will be assessed at 4 different time points: 4 weeks before surgery, immediately before surgery, 12 weeks after surgery, and 52 weeks after surgery. The primary outcome measure is the Oxford Knee Score. Secondary outcome measures include quality of life (Short-Form Health Survey); depression, anxiety, and stress (Depression, Anxiety, and Stress Scales); self-motivation; self-determination; self-efficacy; and the level of satisfaction with the knee surgery and care delivery. The study will also collect quantitative usage data related to all components (app, activity tracker, and Web portal) of the TKR platform and qualitative data on the perceptions of the platform as a tool for patients, carers, and clinicians. Finally, an economic evaluation of the impact of the platform will be conducted. Development of the TKR platform has been completed and deployed for trial. The research protocol is approved by 2 human research ethics committees in Australia. A total of 5 hospitals in Australia (2 in New South Wales, 2 in Queensland, and 1 in South Australia) are expected to participate in the trial. The TKR platform is designed to provide flexibility in care delivery and increased engagement with rehabilitation services. This trial will investigate the clinical and behavioral efficacy of the app and impact of the TKR platform in terms of service satisfaction, acceptance, and economic benefits of the provision of digital services. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616000504415; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370536 (Archived by WebCite at http://www.webcitation.org/6oKES0Gp1). ©M Sazzad Hussain, Jane Li, Emily Brindal, Yasmin van Kasteren, Marlien Varnfield, Andrew Reeson, Shlomo Berkovsky, Jill Freyne. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.03.2017.

Magnetic timing valves for fluid control in paper-based microfluidics.

PubMed

Li, Xiao; Zwanenburg, Philip; Liu, Xinyu

2013-07-07

Multi-step analytical tests, such as an enzyme-linked immunosorbent assay (ELISA), require delivery of multiple fluids into a reaction zone and counting the incubation time at different steps. This paper presents a new type of paper-based magnetic valves that can count the time and turn on or off a fluidic flow accordingly, enabling timed fluid control in paper-based microfluidics. The timing capability of these valves is realized using a paper timing channel with an ionic resistor, which can detect the event of a solution flowing through the resistor and trigger an electromagnet (through a simple circuit) to open or close a paper cantilever valve. Based on this principle, we developed normally-open and normally-closed valves with a timing period up to 30.3 ± 2.1 min (sufficient for an ELISA on paper-based platforms). Using the normally-open valve, we performed an enzyme-based colorimetric reaction commonly used for signal readout of ELISAs, which requires a timed delivery of an enzyme substrate to a reaction zone. This design adds a new fluid-control component to the tool set for developing paper-based microfluidic devices, and has the potential to improve the user-friendliness of these devices.

Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer.

PubMed

Truffi, Marta; Fiandra, Luisa; Sorrentino, Luca; Monieri, Matteo; Corsi, Fabio; Mazzucchelli, Serena

2016-05-01

Nowadays cancer represents a prominent challenge in clinics. Main achievements in cancer management would be the development of highly accurate and specific diagnostic tools for early detection of cancer onset, and the generation of smart drug delivery systems for targeted chemotherapy release in cancer cells. In this context, protein-based nanocages hold a tremendous potential as devices for theranostics purposes. In particular, ferritin has emerged as an excellent and promising protein-based nanocage thanks to its unique architecture, surface properties and high biocompatibility. By exploiting natural recognition of the Transferrin Receptor 1, which is overexpressed on tumor cells, ferritin nanocages may ensure a proper drug delivery and release. Moreover, researchers have applied surface functionalities on ferritin cages for further providing active tumor targeting. Encapsulation strategies of non metal-containing drugs within ferritin cages have been explored and successfully performed with encouraging results. Various preclinical studies have demonstrated that nanoformulation within ferritin nanocages significantly improved targeted therapy and accurate imaging of cancer cells. Aims of this review are to describe structure and functions of ferritin nanocages, and to provide an overview about the nanotechnological approaches implemented for applying them to cancer diagnosis and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sonoproduction of liposomes and protein particles as templates for delivery purposes.

PubMed

Silva, Raquel; Ferreira, Helena; Cavaco-Paulo, Artur

2011-10-10

The development of nano and micro delivery systems (DS), so small in size, is growing in importance, such as in drug targeting. In an era where nano is the new trend, micro and nano materials are in the forefront of progress. These systems can be produced by a diversity of methods. However, the use of high-intensity ultrasound offers an easy and versatile tool for nano- and microstructured materials that are often unavailable by conventional methods. Similarly to the synthesis methods that can be used, several starting materials can be applied to produce particulate systems. In this review, the recent strategic development of DS is discussed with emphasis on liposomes and polymer-based, specially protein-based, nanomedicine platforms for drug delivery. Among the variety of applications that materials in the particulate form can have, the control release of drugs is probably the most prominent one, as these have been in the forefront line of interest for biomedical applications. The basic concepts of sonochemical process pertaining to DS are summarized as well as the role of sonochemical procedure to their preparation. The different applications of these systems wrap up this review.

Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: Synthesis, characterization and implications for anticancer drug delivery

PubMed Central

Kim, Jong Oh; Oberoi, Hardeep S.; Desale, Swapnil; Kabanov, Alexander V.; Bronich, Tatiana K.

2014-01-01

Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics. PMID:23998716

Clinical cancer diagnosis using optical fiber-delivered coherent anti-stokes ramon scattering microscopy

NASA Astrophysics Data System (ADS)

Gao, Liang

This thesis describes the development of a combined label-free imaging and analytical strategy for intraoperative characterization of cancer lesions using the coherent anti-Stokes Raman scattering imaging (CARS) technique. A cell morphology-based analytical platform is developed to characterize CARS images and, hence, provide diagnostic information using disease-related pathology features. This strategy is validated for three different applications, including margin detection for radical prostatectomy, differential diagnosis of lung cancer, as well as detection and differentiation of breast cancer subtypes for in situ analysis of margin status during lumpectomy. As the major contribution of this thesis, the developed analytical strategy shows high accuracy and specificity for all three diseases and thus has introduced the CARS imaging technique into the field of human cancer diagnosis, which holds substantial potential for clinical translations. In addition, I have contributed a project aimed at miniaturizing the CARS imaging device into a microendoscope setup through a fiber-delivery strategy. A four-wave-mixing (FWM) background signal, which is caused by simultaneous delivery of the two CARS-generating excitation laser beams, is initially identified. A polarization-based strategy is then introduced and tested for suppression of this FWM noise. The approach shows effective suppression of the FWM signal, both on microscopic and prototype endoscopic setups, indicating the potential of developing a novel microendoscope with a compatible size for clinical use. These positive results show promise for the development of an all-fiber-based, label-free imaging and analytical platform for minimally invasive detection and diagnosis of cancers during surgery or surgical-biopsy, thus improving surgical outcomes and reducing patients' suffering.

Virus-mimetic polyplex particles for systemic and inflammation-specific targeted delivery of large genetic contents.

PubMed

Kang, S; Lu, K; Leelawattanachai, J; Hu, X; Park, S; Park, T; Min, I M; Jin, M M

2013-11-01

Systemic and target-specific delivery of large genetic contents has been difficult to achieve. Although viruses effortlessly deliver kilobase-long genome into cells, its clinical use has been hindered by serious safety concerns and the mismatch between native tropisms and desired targets. Nonviral vectors, in contrast, are limited by low gene transfer efficiency and inherent cytotoxicity. Here we devised virus-mimetic polyplex particles (VMPs) based on electrostatic self-assembly among polyanionic peptide (PAP), cationic polymer polyethyleneimine (PEI) and nucleic acids. We fused PAP to the engineered ligand-binding domain of integrin αLβ2 to target intercellular adhesion molecule-1 (ICAM-1), an inducible marker of inflammation. Fully assembled VMPs packaged large genetic contents, bound specifically to target molecules, elicited receptor-mediated endocytosis and escaped endosomal pathway, resembling intracellular delivery processes of viruses. Unlike conventional PEI-mediated transfection, molecular interaction-dependent gene delivery of VMPs was unaffected by the presence of serum and achieved higher efficiency without toxicity. By targeting overexpressed ICAM-1, VMPs delivered genes specifically to inflamed endothelial cells and macrophages both in vitro and in vivo. Simplicity and versatility of the platform and inflammation-specific delivery may open up opportunities for multifaceted gene therapy that can be translated into the clinic and treat a broad range of debilitating immune and inflammatory diseases.

Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming and Utilizing Biological Barriers to Peptide Drug Delivery.

PubMed

Yan, Jin; He, Wangxiao; Yan, Siqi; Niu, Fan; Liu, Tianya; Ma, Bohan; Shao, Yongping; Yan, Yuwei; Yang, Guang; Lu, Wuyuan; Du, Yaping; Lei, Bo; Ma, Peter X

2018-02-27

Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.

Nano-assembly and Controlled Release Kinetics of Nanoelements from Nanoporous Templates

NASA Astrophysics Data System (ADS)

Gultepe, E.; Nagesha, D.; McNulty, J.; Sridhar, S.

2008-03-01

Nanotemplates and nanoparticles have potential for use in the area of nanomanufacturing and biomedical applications. We are using highly ordered nanoporous alumina as a template for drug delivery and to assemble nanoelements such as latex beads and single wall carbon nanotubes (SWNT) by the means of electrophoresis and/or dielectrophoresis. The results of 100% assembly of latex beads and controlled elution of drugs from nanoporous templates will be discussed. Vertically assembled SWNT and with the I-V characteristic as 3D interconnects, will also be presented. We have developed a variety of platforms incorporating superparamagnetic iron oxide nanoparticles for targeted delivery, magnetic hyperthermia and as a contrast agent for magnetic resonance imaging. The results of cell studies on these platforms will be discussed.

Contactless and non-invasive delivery of micro-particles lying on a non-customized rigid surface by using acoustic radiation force.

PubMed

Meng, Jianxin; Mei, Deqing; Jia, Kun; Fan, Zongwei; Yang, Keji

2014-07-01

In the existing acoustic micro-particle delivery methods, the micro-particles always lie and slide on the surface of platform in the whole delivery process. To avoid the damage and contamination of micro-particles caused by the sliding motion, this paper deals with a novel approach to trap micro-particles from non-customized rigid surfaces and freely manipulate them. The delivery process contains three procedures: detaching, transporting, and landing. Hence, the micro-particles no longer lie on the surface, but are levitated in the fluid, during the long range transporting procedure. It is very meaningful especially for the fragile and easily contaminated targets. To quantitatively analyze the delivery process, a theoretical model to calculate the acoustic radiation force exerting upon a micro-particle near the boundary in half space is built. An experimental device is also developed to validate the delivery method. A 100 μm diameter micro-silica bead adopted as the delivery target is detached from the upper surface of an aluminum platform and levitated in the fluid. Then, it is transported along the designated path with high precision in horizontal plane. The maximum deviation is only about 3.3 μm. During the horizontal transportation, the levitation of the micro-silica bead is stable, the maximum fluctuation is less than 1 μm. The proposed method may extend the application of acoustic radiation force and provide a promising tool for microstructure or cell manipulation. Copyright © 2014 Elsevier B.V. All rights reserved.

WMS and WFS Standards Implementation of Weather Data

NASA Astrophysics Data System (ADS)

Armstrong, M.

2005-12-01

CustomWeather is private weather company that delivers global weather data products. CustomWeather has built a mapping platform according to OGC standards. Currently, both a Web Mapping Service (WMS) and Web Feature Service (WFS) are supported by CustomWeather. Supporting open geospatial standards has lead to number of positive changes internally to the processes of CustomWeather, along with those of the clients accessing the data. Quite a number of challenges surfaced during this process, particularly with respect to combining a wide variety of raw modeling and sensor data into a single delivery platform. Open standards have, however, made the delivery of very different data products rather seamless. The discussion will address the issues faced in building an OGC-based mapping platform along with the limitations encountered. While the availability of these data products through open standards is still very young, there have already been many adopters in the utility and navigation industries. The discussion will take a closer look at the different approach taken by these two industries as they utilize interoperability standards with existing data. Insight will be given in regards to applications already taking advantage of this new technology and how this is affecting decision-making processes. CustomWeather has observed considerable interest and potential benefit in this technology from developing countries. Weather data is a key element in disaster management. Interoperability is literally opening up a world of data and has the potential to quickly enable functionality that would otherwise take considerable time to implement. The discussion will briefly touch on our experience.

Interest in Health Behavior Intervention Delivery Modalities Among Cancer Survivors: A Cross-Sectional Study.

PubMed

Martin, Emily C; Basen-Engquist, Karen; Cox, Matthew G; Lyons, Elizabeth J; Carmack, Cindy L; Blalock, Janice A; Demark-Wahnefried, Wendy

2016-02-11

Effective, broad-reaching channels are important for the delivery of health behavior interventions in order to meet the needs of the growing population of cancer survivors in the United States. New technology presents opportunities to increase the reach of health behavior change interventions and therefore their overall impact. However, evidence suggests that older adults may be slower in their adoption of these technologies than the general population. Survivors' interest for more traditional channels of delivery (eg, clinic) versus new technology-based channels (eg, smartphones) may depend on a variety of factors, including demographics, current health status, and the behavior requiring intervention. The aim of this study was to determine the factors that predict cancer survivors' interest in new technology-based health behavior intervention modalities versus traditional modalities. Surveys were mailed to 1871 survivors of breast, prostate, and colorectal cancer. Participants' demographics, diet and physical activity behaviors, interest in health behavior interventions, and interest in intervention delivery modalities were collected. Using path analysis, we explored the relationship between four intervention modality variables (ie, clinic, telephone, computer, and smartphone) and potential predictors of modality interest. In total, 1053 respondents to the survey (56.3% response rate); 847 provided complete data for this analysis. Delivery channel interest was highest for computer-based interventions (236/847, 27.9% very/extremely interested) and lowest for smartphone-based interventions (73/847, 8.6%), with interest in clinic-based (147/847, 17.3%) and telephone-delivered (143/847, 16.9%) falling in between. Use of other technology platforms, such as Web cameras and social networking sites, was positively predictive of interest in technology-based delivery channels. Older survivors were less likely to report interest in smartphone-based diet interventions. Physical activity, fruit and vegetable consumption, weight status, and age moderated relationships between interest in targeted intervention behavior and modality. This study identified several predictors of survivor interest in various health behavior intervention delivery modalities. Overall, computer-based interventions were found to be most acceptable, while smartphones were the least. Factors related to survivors' current technology use and health status play a role in their interest for technology-based intervention versus more traditional delivery channels. Future health behavior change research in this population should consider participants' demographic, clinical, and lifestyle characteristics when selecting a delivery channel. Furthermore, current health behavior interventions for older cancer survivors may be best delivered over the Internet. Smartphone interventions may be feasible in the future following further adoption and familiarization by this particular population. ©Emily C Martin, Karen Basen-Engquist, Matthew G Cox, Elizabeth J Lyons, Cindy L Carmack, Janice A Blalock, Wendy Demark-Wahnefried. Originally published in JMIR Cancer (http://cancer.jmir.org), 11.02.2016.

Ionic liquids in drug delivery.

PubMed

Shamshina, Julia L; Barber, Patrick S; Rogers, Robin D

2013-10-01

To overcome potential problems with solid-state APIs, such as polymorphism, solubility and bioavailability, pure liquid salt (ionic liquid) forms of active pharmaceutical ingredients (API-ILs) are considered here as a design strategy. After a critical review of the current literature, the recent development of the API-ILs strategy is presented, with a particular focus on the liquefaction of drugs. A variety of IL tools for control over the liquid salt state of matter are discussed including choice of counterion to produce an IL from a given API; the concept of oligomeric ions that enables liquefaction of solid ILs by changing the stoichiometry or complexity of the ions; formation of 'liquid co-crystals' where hydrogen bonding is the driving force in the liquefaction of a neutral acid-base complex; combining an IL strategy with the prodrug strategy to improve the delivery of solid APIs; using ILs as delivery agents via trapping a drug in a micelle and finally ILs designed with tunable hydrophilic-lipophilic balance that matches the structural requirements needed to solubilize poorly water-soluble APIs. The authors believe that API-IL approaches may save failed lead candidates, extend the patent life of current APIs, lead to new delivery options or even new pharmaceutical action. They encourage the pharmaceutical industry to invest more research into the API-IL platform as it could lead to fast-tracked approval based on similarities to the APIs already approved.

Self-assembled amphiphilic zein-lactoferrin micelles for tumor targeted co-delivery of rapamycin and wogonin to breast cancer.

PubMed

Sabra, Sally A; Elzoghby, Ahmed O; Sheweita, Salah A; Haroun, Medhat; Helmy, Maged W; Eldemellawy, Maha A; Xia, Ying; Goodale, David; Allan, Alison L; Rohani, Sohrab

2018-07-01

Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy. Copyright © 2018. Published by Elsevier B.V.

Controllable Synthesis of a Smart Multifunctional Nanoscale Metal-Organic Framework for Magnetic Resonance/Optical Imaging and Targeted Drug Delivery.

PubMed

Gao, Xuechuan; Zhai, Manjue; Guan, Weihua; Liu, Jingjuan; Liu, Zhiliang; Damirin, Alatangaole

2017-02-01

As a result of their extraordinarily large surfaces and well-defined pores, the design of a multifunctional metal-organic framework (MOF) is crucial for drug delivery but has rarely been reported. In this paper, a novel drug delivery system (DDS) based on nanoscale MOF was developed for use in cancer diagnosis and therapy. This MOF-based tumor targeting DDS was fabricated by a simple postsynthetic surface modification process. First, magnetic mesoporous nanomaterial Fe-MIL-53-NH 2 was used for encapsulating the drug and served as a magnetic resonance contrast agent. Moreover, the Fe-MIL-53-NH 2 nanomaterial exhibited a high loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, the fluorescence imaging agent 5-carboxyfluorescein (5-FAM) and the targeting reagent folic acid (FA) were conjugated to the 5-FU-loaded Fe-MIL-53-NH 2 , resulting in the advanced DDS Fe-MIL-53-NH 2 -FA-5-FAM/5-FU. Owing to the multifunctional surface modification, the obtained DDS Fe-MIL-53-NH 2 -FA-5-FAM/5-FU shows good biocompatibility, tumor enhanced cellular uptake, strong cancer cell growth inhibitory effect, excellent fluorescence imaging, and outstanding magnetic resonance imaging capability. Taken together, this study integrates diagnostic and treatment aspects into a single platform by a simple and efficient strategy, aiming for facilitating new possibilities for MOF use for multifunctional drug delivery.

Regional Multiteam Systems in Cancer Care Delivery

PubMed Central

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

Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend Particles.

PubMed

Zhan, Xi; Tran, Kenny K; Wang, Liguo; Shen, Hong

2015-07-01

A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity.

Controlled endolysosomal release of agents by pH-responsive polymer blend particles

PubMed Central

Zhan, Xi; Tran, Kenny K.; Wang, Liguo; Shen, Hong

2015-01-01

Purpose A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly (lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. Methods We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. Results We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. Conclusions This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity. PMID:25592550

Streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular and tumor delivery of enzymes.

PubMed

Kim, Kyoung-Ran; Hwang, Dohyeon; Kim, Juhyeon; Lee, Chang-Yong; Lee, Wonseok; Yoon, Dae Sung; Shin, Dongyun; Min, Sun-Joon; Kwon, Ick Chan; Chung, Hak Suk; Ahn, Dae-Ro

2018-06-28

Despite the extremely high substrate specificity and catalytically amplified activity of enzymes, the lack of efficient cellular internalization limits their application as therapeutics. To overcome this limitation and to harness enzymes as practical biologics for targeting intracellular functions, we developed the streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular delivery of various enzymes. The hybrid consists of streptavidin, which provides a stoichiometrically controlled loading site for the enzyme cargo and an L-DNA (mirror DNA) tetrahedron, which provides the intracellular delivery potential. Due to the cell-penetrating ability of the mirror DNA tetrahedron of this hybrid, enzymes loaded on streptavidin can be efficiently delivered into the cells, intracellularly expressing their activity. In addition, we demonstrate tumor delivery of enzymes in an animal model by utilizing the potential of the hybrid to accumulate in tumors. Strikingly, the hybrid is able to transfer the apoptotic enzyme specifically into tumor cells, leading to strong suppression of tumor growth without causing significant damage to other tissues. These results suggest that the hybrid may allow anti-proliferative enzymes and proteins to be utilized as anticancer drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

A rapid, maskless 3D prototyping for fabrication of capillary circuits: Toward urinary protein detection.

PubMed

Yan, Sheng; Zhu, Yuanqing; Tang, Shi-Yang; Li, Yuxing; Zhao, Qianbin; Yuan, Dan; Yun, Guolin; Zhang, Jun; Zhang, Shiwu; Li, Weihua

2018-04-01

Proteinuria is an established risk marker for progressive renal function loss and patients would significantly benefit from a point-of-care testing. Although extensive work has been done to develop the microfluidic devices for the detection of urinary protein, they need the complicated operation and bulky peripherals. Here, we present a rapid, maskless 3D prototyping for fabrication of capillary fluidic circuits using laser engraving. The capillary circuits can be fabricated in a short amount of time (<10 min) without the requirements of clean-room facilities and photomasks. The advanced capillary components (e.g., trigger valves, retention valves and retention bursting valves) were fabricated, enabling the sequential liquid delivery and sample-reagent mixing. With the integration of smartphone-based detection platform, the microfluidic device can quantify the urinary protein via a colorimetric analysis. By eliminating the bulky and expensive equipment, this smartphone-based detection platform is portable for on-site quantitative detection. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ICE System: Interruptible control expert system. M.S. Thesis

NASA Technical Reports Server (NTRS)

Vezina, James M.

1990-01-01

The Interruptible Control Expert (ICE) System is based on an architecture designed to provide a strong foundation for real-time production rule expert systems. Three principles are adopted to guide the development of ICE. A practical delivery platform must be provided, no specialized hardware can be used to solve deficiencies in the software design. Knowledge of the environment and the rule-base is exploited to improve the performance of a delivered system. The third principle of ICE is to respond to the most critical event, at the expense of the more trivial tasks. Minimal time is spent on classifying the potential importance of environmental events with the majority of the time used for finding the responses. A feature of the system, derived from all three principles, is the lack of working memory. By using a priori information, a fixed amount of memory can be specified for the hardware platform. The absence of working memory removes the dangers of garbage collection during the continuous operation of the controller.

Nanostructured Platforms for the Sustained and Local Delivery of Antibiotics in the Treatment of Osteomyelitis

PubMed Central

Uskoković, Vuk

2015-01-01

This article provides a critical view of the current state of the development of nanoparticulate and other solid-state carriers for the local delivery of antibiotics in the treatment of osteomyelitis. Mentioned are the downsides of traditional means for treating bone infection, which involve systemic administration of antibiotics and surgical debridement, along with the rather imperfect local delivery options currently available in the clinic. Envisaged are more sophisticated carriers for the local and sustained delivery of antimicrobials, including bioresorbable polymeric, collagenous, liquid crystalline, and bioglass- and nanotube-based carriers, as well as those composed of calcium phosphate, the mineral component of bone and teeth. A special emphasis is placed on composite multifunctional antibiotic carriers of a nanoparticulate nature and on their ability to induce osteogenesis of hard tissues demineralized due to disease. An ideal carrier of this type would prevent the long-term, repetitive, and systemic administration of antibiotics and either minimize or completely eliminate the need for surgical debridement of necrotic tissue. Potential problems faced by even hypothetically “perfect” antibiotic delivery vehicles are mentioned too, including (i) intracellular bacterial colonies involved in recurrent, chronic osteomyelitis; (ii) the need for mechanical and release properties to be adjusted to the area of surgical placement; (iii) different environments in which in vitro and in vivo testings are carried out; (iv) unpredictable synergies between drug delivery system components; and (v) experimental sensitivity issues entailing the increasing subtlety of the design of nanoplatforms for the controlled delivery of therapeutics. PMID:25746204

Nanoporous Anodic Alumina Platforms: Engineered Surface Chemistry and Structure for Optical Sensing Applications

PubMed Central

Kumeria, Tushar; Santos, Abel; Losic, Dusan

2014-01-01

Electrochemical anodization of pure aluminum enables the growth of highly ordered nanoporous anodic alumina (NAA) structures. This has made NAA one of the most popular nanomaterials with applications including molecular separation, catalysis, photonics, optoelectronics, sensing, drug delivery, and template synthesis. Over the past decades, the ability to engineer the structure and surface chemistry of NAA and its optical properties has led to the establishment of distinctive photonic structures that can be explored for developing low-cost, portable, rapid-response and highly sensitive sensing devices in combination with surface plasmon resonance (SPR) and reflective interference spectroscopy (RIfS) techniques. This review article highlights the recent advances on fabrication, surface modification and structural engineering of NAA and its application and performance as a platform for SPR- and RIfS-based sensing and biosensing devices. PMID:25004150

Using e-technologies in clinical trials

PubMed Central

Rosa, Carmen; Campbell, Aimee N. C.; Miele, Gloria M.; Brunner, Meg; Winstanley, Erin L.

2015-01-01

Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored. PMID:26176884

Development of the European Small Geostationary Satellite SGEO

NASA Astrophysics Data System (ADS)

Lübberstedt, H.; Schneider, A.; Schuff, H.; Miesner, Th.; Winkler, A.

2008-08-01

The SGEO product portfolio, ranging from Satellite platform delivery up to in-orbit delivery of a turnkey system including satellite and ground control station, is designed for applications ranging from TV Broadcast to multimedia applications, Internet access, mobile or fixed services in a wide range of frequency bands. Furthermore, Data Relay missions such as the European Data Relay Satellite (EDRS) as well as other institutional missions are targeted. Key design features of the SGEO platform are high flexibility and modularity in order to accommodate a very wide range of future missions, a short development time below two years and the objective to build the system based on ITAR free subsystems and components. The system will provide a long lifetime of up to 15 years in orbit operations with high reliability. SGEO is the first European satellite to perform all orbit control tasks solely by electrical propulsion (EP). This design provides high mass efficiency and the capability for direct injection into geostationary orbit without chemical propulsion (CP). Optionally, an Apogee Engine Module based on CP will provide the perigee raising manoeuvres in case of a launch into geostationary transfer orbit (GTO). This approach allows an ideal choice out of a wide range of launcher candidates in dependence of the required payload capacity. SGEO will offer to the market a versatile and high performance satellite system with low investment risk for the customer and a short development time. This paper provides an overview of the SGEO system key features and the current status of the SGEO programme.

Using e-technologies in clinical trials.

PubMed

Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L

2015-11-01

Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored. Published by Elsevier Inc.

Mobile Technology for Community Health in Ghana: what happens when technical functionality threatens the effectiveness of digital health programs?

PubMed

LeFevre, Amnesty E; Mohan, Diwakar; Hutchful, David; Jennings, Larissa; Mehl, Garrett; Labrique, Alain; Romano, Karen; Moorthy, Anitha

2017-03-14

Despite the growing use of technology in the health sector, little evidence is available on the technological performance of mobile health programs nor on the willingness of target users to utilize these technologies as intended (behavioral performance). In this case study of the Mobile Technology for Health (MOTECH) program in Ghana, we assess the platform's effectiveness in delivering messages, along with user response across sites in five districts from 2011 to 2014. MOTECH is comprised of "Client Data Application" (CDA) which allows providers to digitize and track service delivery information for women and infants and "Mobile Midwife" (MM) which sends automated educational voice messages to the mobile phones of pregnant and postpartum women. Using a naturalist study design, we draw upon system generated data to evaluate message delivery, client engagement, and provider responsiveness to MOTECH over time and by level of facility. A total of 7,370 women were enrolled in MM during pregnancy and 14,867 women were enrolled postpa1rtum. While providers were able to register and upload patient-level health information using CDA, the majority of these uploads occurred in Community-based facilities versus Health Centers. For MM, 25% or less of expected messages were received by pregnant women, despite the majority (>77%) owning a private mobile phone. While over 80% of messages received by pregnant women were listened to, postpartum rates of listening declined over time. Only 25% of pregnant women received and listened to at least 1 first trimester message. By 6-12 months postpartum, less than 6% of enrolled women were exposed to at least one message. Caution should be exercised in assuming that digital health programs perform as intended. Evaluations should measure the technological, behavioral, health systems, and/or community factors which may lead to breaks in the impact pathway and influence findings on effectiveness. The MOTECH platform's technological limitations in 'pushing' out voice messages highlights the need for more timely use of data to mitigate delivery challenges and improve exposure to health information. Alternative message delivery channels (USSD or SMS) could improve the platform's ability to deliver messages but may not be appropriate for illiterate users. Not applicable.

Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.

PubMed

Miller-Kleinhenz, Jasmine M; Bozeman, Erica N; Yang, Lily

2015-01-01

Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. © 2015 Wiley Periodicals, Inc.

Olsalazine-Based Metal-Organic Frameworks as Biocompatible Platforms for H2 Adsorption and Drug Delivery.

PubMed

Levine, Dana J; Runčevski, Tomče; Kapelewski, Matthew T; Keitz, Benjamin K; Oktawiec, Julia; Reed, Douglas A; Mason, Jarad A; Jiang, Henry Z H; Colwell, Kristen A; Legendre, Christina M; FitzGerald, Stephen A; Long, Jeffrey R

2016-08-17

The drug olsalazine (H4olz) was employed as a ligand to synthesize a new series of mesoporous metal-organic frameworks that are expanded analogues of the well-known M2(dobdc) materials (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate; M-MOF-74). The M2(olz) frameworks (M = Mg, Fe, Co, Ni, and Zn) exhibit high surface areas with large hexagonal pore apertures that are approximately 27 Å in diameter. Variable temperature H2 adsorption isotherms revealed strong adsorption at the open metal sites, and in situ infrared spectroscopy experiments on Mg2(olz) and Ni2(olz) were used to determine site-specific H2 binding enthalpies. In addition to its capabilities for gas sorption, the highly biocompatible Mg2(olz) framework was also evaluated as a platform for the delivery of olsalazine and other encapsulated therapeutics. The Mg2(olz) material (86 wt % olsalazine) was shown to release the therapeutic linker through dissolution of the framework under simulated physiological conditions. Furthermore, Mg2(olz) was used to encapsulate phenethylamine (PEA), a model drug for a broad class of bioactive compounds. Under simulated physiological conditions, Mg2(olz)(PEA)2 disassembled to release PEA from the pores and olsalazine from the framework itself, demonstrating that multiple therapeutic components can be delivered together at different rates. The low toxicity, high surface areas, and coordinatively unsaturated metal sites make these M2(olz) materials promising for a range of potential applications, including drug delivery in the treatment of gastrointestinal diseases.

Olsalazine-Based Metal–Organic Frameworks as Biocompatible Platforms for H 2 Adsorption and Drug Delivery

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

Levine, Dana J.; Runčevski, Tomče; Kapelewski, Matthew T.

The drug olsalazine (H4olz) was employed as a ligand to synthesize a new series of mesoporous metal–organic frameworks that are expanded analogues of the well-known M2(dobdc) materials (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate; M-MOF-74). The M2(olz) frameworks (M = Mg, Fe, Co, Ni, and Zn) exhibit high surface areas with large hexagonal pore apertures that are approximately 27 Å in diameter. Variable temperature H2 adsorption isotherms revealed strong adsorption at the open metal sites, and in situ infrared spectroscopy experiments on Mg2(olz) and Ni2(olz) were used to determine site-specific H2 binding enthalpies. In addition to its capabilities for gas sorption, the highly biocompatiblemore » Mg2(olz) framework was also evaluated as a platform for the delivery of olsalazine and other encapsulated therapeutics. The Mg2(olz) material (86 wt % olsalazine) was shown to release the therapeutic linker through dissolution of the framework under simulated physiological conditions. Furthermore, Mg2(olz) was used to encapsulate phenethylamine (PEA), a model drug for a broad class of bioactive compounds. Under simulated physiological conditions, Mg2(olz)(PEA)2 disassembled to release PEA from the pores and olsalazine from the framework itself, demonstrating that multiple therapeutic components can be delivered together at different rates. The low toxicity, high surface areas, and coordinatively unsaturated metal sites make these M2(olz) materials promising for a range of potential applications, including drug delivery in the treatment of gastrointestinal diseases.« less

Integrating a novel SN38 prodrug into the PEGylated liposomal system as a robust platform for efficient cancer therapy in solid tumors.

PubMed

Fang, Tao; Dong, Yuehan; Zhang, Xiaomin; Xie, Ke; Lin, Li; Wang, Hangxiang

2016-10-15

Liposomal nanoassemblies have been used extensively as carriers for the delivery of both lipophilic and hydrophilic drugs. They represent a mature, versatile technology with considerable potential for improving the pharmacokinetics of drugs. However, the formulation of many chemotherapeutics into liposome systems has posed a significant challenge due to their incompatible physicochemical properties, as was the case with camptothecin-based chemotherapeutics. Here, we present a rational paradigm of potent chemotherapeutics that were reconstructed and subsequently integrated into liposomal nanoassemblies. Using SN38 (7-ethyl-10-hydroxy camptothecin) as a model drug, a lipophilic prodrug 1 (designated as LA-SN38) was constructed by tethering the linoleic acid (LA) moiety via esterification, which was further facilitated to form liposomal nanoparticles (LipoNP) through supramolecular nanoassembly. The resulting 1-loaded LipoNP exhibited sustained drug release kinetics and decreased cellular uptake by macrophage cells. Uptake by tumor cells was enhanced relative to our previous supramolecular nanoparticles (SNP 1), which were derived from the self-assembling prodrug 1. Notably, LipoNP outperformed SNP 1 in terms of pharmacokinetics and in vivo therapeutic efficacy in both human BEL-7402 hepatocellular carcinoma (HCC) and HCT-116 colorectal cancer-derived xenograft mouse models. These results were likely due to the improved systemic circulation and preferential accumulation of nanodrugs in tumors. Hence, our results suggest that the combination of liposomal delivery platforms with rational prodrug engineering may emerge as a promising approach for the effective and safe delivery of anticancer chemotherapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of facile drug delivery platform of ranibizumab fabricated PLGA-PEGylated magnetic nanoparticles for age-related macular degeneration therapy.

PubMed

Yan, Jian; Peng, Xifeng; Cai, Yulian; Cong, Wendong

2018-06-01

The present anti-angiogenic therapies for neovascular age-related macular degeneration require effective drug delivery systems for transfer drug molecules. Ranibizumab is an active humanized monoclonal antibody that counteracts active forms of vascular endothelial growth factor A in the neovascular age-related macular degeneration therapy. The development of ranibizumab-related therapies, we have designed the effective drug career with engineered magnetic nanoparticles (Fe 3 O 4 ) as a facile platform of ranibizumab delivery for the treatment of neovascular age-related macular degeneration. Ranibizumab conjugated iron oxide (Fe 3 O 4 )/PEGylated poly lactide-co-glycolide (PEG-PLGA) was successfully designed and the synthesized materials are analyzed different analytical techniques. The microscopic techniques (Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM)) are clearly displayed that spherical nanoparticles into the PEG-PLGA matrix and presence of elements and chemical interactions confirmed by the results of energy dispersive X-ray analysis (EDX) and Fourier trans-form infrared (FTIR) spectroscopic methods. The in vitro anti-angiogenic evaluation of Fe 3 O 4 /PEG-PLGA polymer nanomaterial efficiently inhibits the tube formation in the Matrigel-based assay method by using human umbilical vein endothelial cells. Ranibizumab treated Fe 3 O 4 /PEG-PLGA polymer nanomaterials not disturbed cell proliferation and the results could not display the any significant differences in human endothelial cells. The present investigated results describe that Fe 3 O 4 /PEG-PLGA polymer nanomaterials can be highly favorable and novel formulation for the treatment of neovascular age-related macular degeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthetic Nanovaccines Against Respiratory Pathogens (SYNARP). Addendum

DTIC Science & Technology

2014-09-01

and c) block ionomer complexes (BIC) for targeted delivery of DNA (or protein) antigen to the antigen presenting cells (APCs) (Platform C). The...immune cells to elicit most efficient immune response. The proposal was focusing on achieving the following specific technical objectives: 1) Develop...muscle in a mouse (Platform B & C). ACCOMPLISHED YEAR 3 Task 1: Determine optimal antigen-containing BPN that activate dendritic cells (DCs

Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides.

PubMed

Tan, Roger S; Naruchi, Kentaro; Amano, Maho; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2015-09-18

A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems.

Assessing the potential of the Woman's Condom for vaginal drug delivery.

PubMed

Kramzer, Lindsay F; Cohen, Jessica; Schubert, Jesse; Dezzutti, Charlene S; Moncla, Bernard J; Friend, David; Rohan, Lisa C

2015-09-01

The Woman's Condom is a new female condom that uses a dissolvable polyvinyl alcohol capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman's Condom capsule, offering a unique drug delivery platform. UC781 capsules were fabricated using methods from the development of the Woman's Condom capsules as well as those used in vaginal film development. Capsules were characterized to evaluate physical/chemical attributes, Lactobacillus compatibility, in vitro safety and bioactivity, and condom compatibility. Two UC781 capsule platforms were assessed. Capsule masses (mg; mean±SD) for platforms 1 and 2 were 116.50±18.22 and 93.80±8.49, respectively. Thicknesses were 0.0034±0.0004 in and 0.0033±0.0004 in. Disintegration times were 11±3 s and 5±1 s. Puncture strengths were 21.72±3.30 N and 4.02±0.83 N. Water content measured 6.98±1.17% and 7.04±1.92%. UC781 content was 0.59±0.05 mg and 0.77±0.11 mg. Both platforms retained in vitro bioactivity and were nontoxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules with the Woman's Condom pouch did not decrease condom mechanical integrity. UC781 was loaded into a polymeric capsule similar to that of the Woman's Condom product. This study highlights the potential use of the Woman's Condom as a platform for vaginal delivery of drugs relevant to sexual/reproductive health, including those for short- or long-acting HIV prevention. We determined the proof-of-concept feasibility of incorporation of an HIV-preventative microbicide into the Woman's Condom capsule. This study highlights various in vitro physical and chemical evaluations as well as bioactivity and safety assessments necessary for vaginal product development related to female sexual and reproductive health. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessing learning outcomes and cost effectiveness of an online sleep curriculum for medical students.

PubMed

Bandla, Hari; Franco, Rose A; Simpson, Deborah; Brennan, Kimberly; McKanry, Jennifer; Bragg, Dawn

2012-08-15

Sleep disorders are highly prevalent across all age groups but often remain undiagnosed and untreated, resulting in significant health consequences. To overcome an inadequacy of available curricula and learner and instructor time constraints, this study sought to determine if an online sleep medicine curriculum would achieve equivalent learner outcomes when compared with traditional, classroom-based, face-to-face instruction at equivalent costs. Medical students rotating on a required clinical clerkship received instruction in 4 core clinical sleep-medicine competency domains in 1 of 2 delivery formats: a single 2.5-hour face-to-face workshop or 4 asynchronous e-learning modules. Immediate learning outcomes were assessed in a subsequent clerkship using a multiple-choice examination and standardized patient station, with long-term outcomes assessed through analysis of students' patient write-ups for inclusion of sleep complaints and diagnoses before and after the intervention. Instructional costs by delivery format were tracked. Descriptive and inferential statistical analyses compared learning outcomes and costs by instructional delivery method (face-to-face versus e-learning). Face-to-face learners, compared with online learners, were more satisfied with instruction. Learning outcomes (i.e., multiple-choice examination, standardized patient encounter, patient write-up), as measured by short-term and long-term assessments, were roughly equivalent. Design, delivery, and learner-assessment costs by format were equivalent at the end of 1 year, due to higher ongoing teaching costs associated with face-to-face learning offsetting online development and delivery costs. Because short-term and long-term learner performance outcomes were roughly equivalent, based on delivery method, the cost effectiveness of online learning is an economically and educationally viable instruction platform for clinical clerkships.

Clinically translatable nanotheranostic platforms for peripheral nerve regeneration: design with outcome in mind

NASA Astrophysics Data System (ADS)

Janjic, Jelena M.; Gorantla, Vijay S.

2018-02-01

Neuroinflammation is a dynamic immune phenomenon that changes in severity with time after neurotrauma and has a profound impact on neuroregeneration, tissue healing and neuropathic pain, which is a common consequence of peripheral nerve injury (PNI). Macrophages are key cellular mediators of neuroinflammation. Macrophage-targeted nanotherapies, such as complex (perfluorocarbon/hydrocarbon) multimodal nanoemulsions (NEs) provide highly specific imaging signatures of neuroinflammation and hence indirect surrogate metrics of regeneration. We present a novel strategy where these NEs incorporating multiple imaging modalities and biosensors are delivered locally to directly target key cellular players of neuroregeneration. Two representative formulations of a nanotheranostic platform for local delivery of cell targeted NEs are presented: 1) A dual (macrophage and neuronal) targeted nanoparticle laden hydrogel for synergistic modulation of neuroinflammation and analgesia following PNI; and 2) neurotherapeutic loaded nanoparticles with extended release profile for sustained support of neuroregeneration. Each platform is capable of dual imaging payloads (NIRF, MRI and/or PET) and/or cell specific targeting moieties for controlled drug release. In vitro and pilot in vivo results will be presented. Theranostic nanosystem based platforms offer a unique opportunity to sequentially monitor cellular and molecular events at the site of neuronal injury, enabling dynamic, in-vivo mechanistic insights rather than static, ex-vivo histopathologic evaluation. Given their targeted capabilities, these platforms can help achieve personalized treatments that are customized and optimized for patients with PNI.

Porous silicon advances in drug delivery and immunotherapy.

PubMed

Savage, David J; Liu, Xuewu; Curley, Steven A; Ferrari, Mauro; Serda, Rita E

2013-10-01

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. Copyright © 2013 Elsevier Ltd. All rights reserved.

Usability studies on e-learning platforms: Preliminary study in USM

NASA Astrophysics Data System (ADS)

Emang, Devinna Win Anak Boniface; Lukman, Raja Nurul Izzati Raja; Kamarulzaman, Muhammad Izzat Syafiq; Zaaba, Zarul Fitri

2017-10-01

This paper explores the end-users' experienced in regards to the usability issues in E-learning platform. An online survey utilising 116 participants were conducted to investigate the end-users understanding and satisfaction on E-learning platform in the Universiti Sains Malaysia (USM). The results indicates that mainly students still experiencing significant challenges in E-learning platform in regards to accessibility, technical terminologies and functionality. On the other hand, the 10 heuristic guideline is chosen to be a referral point to compare five E-learning platforms in order to assess each performance on regards to the usability criteria. Overall, USM E-learning platform can be considered in a good shape. However, there are more works to be done to improve the delivery system of the E-learning if it would like to sustain for a long period of time. Although the result is at the preliminary stage, it provides useful insights to improve the E-learning platform as one of the most popular education platform in Malaysia.

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy

PubMed Central

Wickens, Jennifer M.; Alsaab, Hashem O.; Kesharwani, Prashant; Bhise, Ketki; Amin, Mohd Cairul Iqbal Mohd; Tekade, Rakesh Kumar; Gupta, Umesh; Iyer, Arun K.

2016-01-01

The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy. PMID:28017836

Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases

PubMed Central

Patel, Sulabh P.; Vaishya, Ravi; Patel, Ashaben; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K.

2016-01-01

This manuscript is focused on the development of pentablock (PB) copolymer based sustained release formulation for the treatment of posterior segment ocular diseases. We have successfully synthesized biodegradable and biocompatible PB copolymers for the preparation of nanoparticles (NPs) and thermosensitive gel. Achieving high drug loading with hydrophilic biotherapeutics (peptides /proteins) is a challenging task. Moreover, small intravitreal injection volume (≤100 μL) requires high loading to develop a long term (6 months) sustained release formulation. We have successfully investigated various formulation parameters to achieve maximum peptide/protein (octreotide, insulin, lysozyme, IgG-Fab, IgG, and catalase) loading in PB NPs. Improvement in drug loading can facilitate delivery of larger doses of therapeutic proteins via limited injection volume. A composite formulation comprised of NPs in gel system exhibited sustained release (without burst effect) of peptides and proteins, may serve as a platform technology for the treatment of posterior segment ocular diseases. PMID:26964498

Lighter-Than-Air (LTA) "AirStation": Unmanned Aircraft System (UAS) Carrier Concept

NASA Technical Reports Server (NTRS)

Hochstetler, Ronald D.; Bosma, John; Chachad, Girish H.; Blanken, Matthew L.

2016-01-01

The advantages of utilizing an airship as an airborne carrier for support and deployment of Unmanned Aircraft Systems (UAS) are examined. Whether as a stand-alone platform or in concert with conventional aircraft, the airship UAS carrier provides a number of compelling benefits for both military and civilian missions. As a mobile base it can remain operational despite political fallout that may render ground or ocean based UAS sites unavailable. It offers the psychological impact of a power projection tool that has few geographical limits, and holds promise as a new method for cost-saving intelligence gathering. It is also adaptable for civilian variants for supporting: emergency response, security/surveillance, delivery of medical/food supplies, as well as commercial package delivery to metropolitan and remote communities. This paper presents the background on airship-aircraft operations, and explores the general airship carrier concept. Additionally, a catalog of contemporary technologies available to support the airship carrier concept are discussed, and essential elements for an Air-Station Development program proposed.

miRNA-based therapies: Strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents

PubMed Central

Baumann, V; Winkler, J

2015-01-01

The discovery of microRNAs as important regulatory agents for gene expression has expanded the therapeutic opportunities for oligonucleotides. In contrast to siRNA, miRNA-targeted therapy is able to influence not only a single gene, but entire cellular pathways or processes. It is possible to supplement down regulated or non-functional miRNAs by synthetic oligonucleotides, as well as alleviating effects caused by overexpression of malignant miRNAs through artificial antagonists, either oligonucleotides or small molecules. Chemical oligonucleotide modifications together with an efficient delivery system seem to be mandatory for successful therapeutic application. While miRNA-based therapy benefits from the decades of research spent on other therapeutic oligonucleotides, there are some specific challenges associated with miRNA therapy, mainly caused by the short target sequence. The current status and recent progress of miRNA-targeted therapeutics is described and future challenges and potential applications in treatment of cancer and viral infections are discussed. PMID:25495987

Programmable In Vitro Coencapsidation of Guest Proteins for Intracellular Delivery by Virus-like Particles.

PubMed

Dashti, Noor H; Abidin, Rufika S; Sainsbury, Frank

2018-05-22

Bioinspired self-sorting and self-assembling systems using engineered versions of natural protein cages are being developed for biocatalysis and therapeutic delivery. The packaging and intracellular delivery of guest proteins is of particular interest for both in vitro and in vivo cell engineering. However, there is a lack of bionanotechnology platforms that combine programmable guest protein encapsidation with efficient intracellular uptake. We report a minimal peptide anchor for in vivo self-sorting of cargo-linked capsomeres of murine polyomavirus (MPyV) that enables controlled encapsidation of guest proteins by in vitro self-assembly. Using Förster resonance energy transfer, we demonstrate the flexibility in this system to support coencapsidation of multiple proteins. Complementing these ensemble measurements with single-particle analysis by super-resolution microscopy shows that the stochastic nature of coencapsidation is an overriding principle. This has implications for the design and deployment of both native and engineered self-sorting encapsulation systems and for the assembly of infectious virions. Taking advantage of the encoded affinity for sialic acids ubiquitously displayed on the surface of mammalian cells, we demonstrate the ability of self-assembled MPyV virus-like particles to mediate efficient delivery of guest proteins to the cytosol of primary human cells. This platform for programmable coencapsidation and efficient cytosolic delivery of complementary biomolecules therefore has enormous potential in cell engineering.

Evaluation of poly(lactic-co-glycolic acid) and poly(dl-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection.

PubMed

Aniagyei, Stella E; Sims, Lee B; Malik, Danial A; Tyo, Kevin M; Curry, Keegan C; Kim, Woihwan; Hodge, Daniel A; Duan, Jinghua; Steinbach-Rankins, Jill M

2017-03-01

More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(dl-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions.

PubMed

Whitlow, Jonathan; Pacelli, Settimio; Paul, Arghya

2017-09-10

With recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable features have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made toward the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrasonic nebulization platforms for pulmonary drug delivery.

PubMed

Yeo, Leslie Y; Friend, James R; McIntosh, Michelle P; Meeusen, Els N T; Morton, David A V

2010-06-01

Since the 1950s, ultrasonic nebulizers have played an important role in pulmonary drug delivery. As the process in which aerosol droplets are generated is independent and does not require breath-actuation, ultrasonic nebulizers, in principle, offer the potential for instantaneously fine-tuning the dose administered to the specific requirements of a patient, taking into account the patient's breathing pattern, physiological profile and disease state. Nevertheless, owing to the difficulties and limitations associated with conventional designs and technologies, ultrasonic nebulizers have never been widely adopted, and have in recent years been in a state of decline. An overview is provided on the advances in new miniature ultrasonic nebulization platforms in which large increases in lung dose efficiency have been reported. In addition to a discussion of the underlying mechanisms governing ultrasonic nebulization, in which there appears to be widely differing views, the advantages and shortcomings of conventional ultrasonic nebulization technology are reviewed and advanced state-of-the-art technologies that have been developed recently are discussed. Recent advances in ultrasonic nebulization technology demonstrate significant potential for the development of smart, portable inhalation therapy platforms for the future. Nevertheless, there remain considerable challenges that need to be addressed before such personalized delivery systems can be realized. These have to be addressed across the spectrum from fundamental physics through to in vivo device testing and dealing with the relevant regulatory framework.

From print to digital (1985-2015): APA's evolving role in psychological publishing.

PubMed

VandenBos, Gary R

2017-11-01

Knowledge dissemination plays an important role in all scientific fields. The American Psychological Association's (APA) journal publication program was established in 1927. During the 1960s, the Psychological Abstracts publication was computerized. In the mid-1980s, a reenergizing of APA Publishing began, with the establishment of the APA Books Program, as well as the movement of abstracts to CD-ROMs. This article describes the 30-year program of expansion of APA Publishing, covering the period from 1985 through 2015. This period saw the journals program grow from 15 journals to 89 journals, the abstract program grow into an Internet-based delivery system, the creation of the APA's own PsycNET delivery platform, the creation of 6 addition databases, and the establishment of dictionaries and handbooks of psychology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

From a Content Delivery Portal to a Knowledge Management System for Standardized Cancer Documentation.

PubMed

Schlue, Danijela; Mate, Sebastian; Haier, Jörg; Kadioglu, Dennis; Prokosch, Hans-Ulrich; Breil, Bernhard

2017-01-01

Heterogeneous tumor documentation and its challenges of interpretation of medical terms lead to problems in analyses of data from clinical and epidemiological cancer registries. The objective of this project was to design, implement and improve a national content delivery portal for oncological terms. Data elements of existing handbooks and documentation sources were analyzed, combined and summarized by medical experts of different comprehensive cancer centers. Informatics experts created a generic data model based on an existing metadata repository. In order to establish a national knowledge management system for standardized cancer documentation, a prototypical tumor wiki was designed and implemented. Requirements engineering techniques were applied to optimize this platform. It is targeted to user groups such as documentation officers, physicians and patients. The linkage to other information sources like PubMed and MeSH was realized.

Note: Four-port microfluidic flow-cell with instant sample switching

NASA Astrophysics Data System (ADS)

MacGriff, Christopher A.; Wang, Shaopeng; Tao, Nongjian

2013-10-01

A simple device for high-speed microfluidic delivery of liquid samples to a surface plasmon resonance sensor surface is presented. The delivery platform is comprised of a four-port microfluidic cell, two ports serve as inlets for buffer and sample solutions, respectively, and a high-speed selector valve to control the alternate opening and closing of the two outlet ports. The time scale of buffer/sample switching (or sample injection rise and fall time) is on the order of milliseconds, thereby minimizing the opportunity for sample plug dispersion. The high rates of mass transport to and from the central microfluidic sensing region allow for SPR-based kinetic analysis of binding events with dissociation rate constants (kd) up to 130 s-1. The required sample volume is only 1 μL, allowing for minimal sample consumption during high-speed kinetic binding measurement.

Polymeric capsule-cushioned leukocyte cell membrane vesicles as a biomimetic delivery platform

NASA Astrophysics Data System (ADS)

Gao, Changyong; Wu, Zhiguang; Lin, Zhihua; Lin, Xiankun; He, Qiang

2016-02-01

We report a biomimetic delivery of microsized capsule-cushioned leukocyte membrane vesicles (CLMVs) through the conversion of freshly reassembled leukocyte membrane vesicles (LMVs), including membrane lipids and membrane-bound proteins onto the surface of layer-by-layer assembled polymeric multilayer microcapsules. The leukocyte membrane coating was verified by using electron microscopy, a quartz crystal microbalance, dynamic light scattering, and confocal laser scanning microscopy. The resulting CLMVs have the ability to effectively evade clearance by the immune system and thus prolong the circulation time in mice. Moreover, we also show that the right-side-out leukocyte membrane coating can distinctly improve the accumulation of capsules in tumor sites through the molecular recognition of membrane-bound proteins of CLMVs with those of tumor cells in vitro and in vivo. The natural cell membrane camouflaged polymeric multilayer capsules with the immunosuppressive and tumor-recognition functionalities of natural leukocytes provide a new biomimetic delivery platform for disease therapy.We report a biomimetic delivery of microsized capsule-cushioned leukocyte membrane vesicles (CLMVs) through the conversion of freshly reassembled leukocyte membrane vesicles (LMVs), including membrane lipids and membrane-bound proteins onto the surface of layer-by-layer assembled polymeric multilayer microcapsules. The leukocyte membrane coating was verified by using electron microscopy, a quartz crystal microbalance, dynamic light scattering, and confocal laser scanning microscopy. The resulting CLMVs have the ability to effectively evade clearance by the immune system and thus prolong the circulation time in mice. Moreover, we also show that the right-side-out leukocyte membrane coating can distinctly improve the accumulation of capsules in tumor sites through the molecular recognition of membrane-bound proteins of CLMVs with those of tumor cells in vitro and in vivo. The natural cell membrane camouflaged polymeric multilayer capsules with the immunosuppressive and tumor-recognition functionalities of natural leukocytes provide a new biomimetic delivery platform for disease therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08407e

Level-2 Milestone 6007: Sierra Early Delivery System Deployed to Secret Restricted Network

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

Bertsch, A. D.

This report documents the delivery and installation of Shark, a CORAL Sierra early delivery system deployed on the LLNL SRD network. Early ASC program users have run codes on the machine in support of application porting for the final Sierra system which will be deployed at LLNL in CY2018. In addition to the SRD resource, Shark, unclassified resources, Rzmanta and Ray, have been deployed on the LLNL Restricted Zone and Collaboration Zone networks in support of application readiness for the Sierra platform.

Low Yield Nuclear Experiments: Should They Be Permitted Within a Comprehensive Test Ban Treaty?

DTIC Science & Technology

1996-10-01

GRAVITY BOMB 83 AF A W87 ICBM REENTRY VEHICLE 86 AF A W88 SLBM REENTRY VEHICLE 89 NAVY C SAFETY FEATURES: A--(ENDS, IHE, FRP) B--(ENDS, IHE) C--(ENDS) o...NUCLEAR WEAPON DELIVERY PLATFORMS (NUCLEAR POSTURE REVIEW) STRATEGIC DELIVERY VEHICLES 20 B-2 BOMBERS USAF 66 B-52 BOMBERS USAF 500/450 MINUTEMAN III...ICBMs USAF 14 TRIBENT SUBMARINES USN W/ 24 D-5 MISSILES EACH TACTICAL DELIVERY VEHICLES DUAL CAPABLE AIRCRAFT USAF/USN SEA-LAUNCH CRUISE MISSILES USN

Evaluating the Usability of Authoring Environments for Serious Games.

PubMed

Slootmaker, Aad; Hummel, Hans; Koper, Rob

2017-08-01

Background . The EMERGO method and online platform enable the development and delivery of scenario-based serious games that foster students to acquire professional competence. One of the main goals of the platform is to provide a user-friendly authoring environment for creating virtual environments where students can perform authentic tasks. Aim . We present the findings of an in-depth qualitative case study of the platform's authoring environment and compare our findings on usability with those found for comparable environments in literature. Method . We carried out semi-structured interviews, with two experienced game developers who have authored a game for higher education, and a literature review of comparable environments. Findings . The analysis shows that the usability of the authoring environment is problematic, especially regarding understandability and learnability , which is in line with findings of comparable environments. Other findings are that authoring is well integrated with the EMERGO method and that functionality and reliability of the authoring environment are valued. Practical implications . The lessons learned are presented in the form of general guidelines to improve the understandability and learnability of authoring environments for serious games .

CHRONIOUS: an open, ubiquitous and adaptive chronic disease management platform for chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) and renal insufficiency.

PubMed

Rosso, R; Munaro, G; Salvetti, O; Colantonio, S; Ciancitto, F

2010-01-01

CHRONIOUS is an highly innovative Information and Communication Technologies (ICT) research Initiative that aspires to implement its vision for ubiquitous health and lifestyle monitoring. The 17 European project partners are strictly working together since February 2008 to realize and open platform to manage and monitor elderly patients with chronic diseases and many difficulties to reach hospital centers for routine controls. The testing activities will be done in Italy and Spain involving COPD (Chronic Obstructive Pulmonary Disease) and CKD (Chronic Kidney Disease) patients, these being widespread and highly expensive in terms of social and economic costs. Patients, equipped by wearable technologies and sensors and interacting with lifestyle interfaces, will be assisted by healthcare personnel able to check the health record and critical conditions through the Chronious platform data analysis and decision support system. Additionally, the new ontology based literature search engine will help the clinicians in the standardization of care delivery process. This paper is to present the main project objectives and its principal components from the intelligent system point of view.

Protein-lipid nanohybrids as emerging platforms for drug and gene delivery: Challenges and outcomes.

PubMed

Gaber, Mohamed; Medhat, Waseem; Hany, Mark; Saher, Nourhan; Fang, Jia-You; Elzoghby, Ahmed

2017-05-28

Nanoparticulate drug delivery systems have been long used to deliver a vast range of drugs and bioactives owing to their ability to demonstrate novel physical, chemical, and/or biological properties. An exponential growth has spurred in research and development of these nanocarriers which led to the evolution of a great number of diverse nanosystems including liposomes, nanoemulsions, solid lipid nanoparticles (SLNs), micelles, dendrimers, polymeric nanoparticles (NPs), metallic NPs, and carbon nanotubes. Among them, lipid-based nanocarriers have made the largest progress whether commercially or under development. Despite this progress, these lipid-based nanocarriers suffer from several limitations that led to the development of many protein-coated lipid nanocarriers. To less extent, protein-based nanocarriers suffer from limitations that led to the fabrication of some lipid bilayer enveloping protein nanocarriers. This review discusses in-depth some limitations associated with the lipid-based or protein-based nanocarriers and the fruitful outcomes brought by protein-lipid hybridization. Also discussed are the various hybridization techniques utilized to formulate these protein-lipid nanohybrids and the mechanisms involved in the drug loading process. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering DNA scaffolds for delivery of anticancer therapeutics.

PubMed

Sun, Wujin; Gu, Zhen

2015-07-01

Engineering DNA nanostructures with programmability in size, shape and surface chemistry holds tremendous promise in biomedical applications. As an emerging platform for drug delivery, DNA nanostructures have been extensively studied for delivering anticancer therapeutics, including small-molecule drug, nucleic acids and proteins. In this mini-review, current advances in utilizing DNA scaffolds as drug carriers for cancer treatment were summarized and future challenges were also discussed.

Biopolymers for Antitumor Implantable Drug Delivery Systems: Recent Advances and Future Outlook.

PubMed

Talebian, Sepehr; Foroughi, Javad; Wade, Samantha J; Vine, Kara L; Dolatshahi-Pirouz, Alireza; Mehrali, Mehdi; Conde, João; Wallace, Gordon G

2018-05-13

In spite of remarkable improvements in cancer treatments and survivorship, cancer still remains as one of the major causes of death worldwide. Although current standards of care provide encouraging results, they still cause severe systemic toxicity and also fail in preventing recurrence of the disease. In order to address these issues, biomaterial-based implantable drug delivery systems (DDSs) have emerged as promising therapeutic platforms, which allow local administration of drugs directly to the tumor site. Owing to the unique properties of biopolymers, they have been used in a variety of ways to institute biodegradable implantable DDSs that exert precise spatiotemporal control over the release of therapeutic drug. Here, the most recent advances in biopolymer-based DDSs for suppressing tumor growth and preventing tumor recurrence are reviewed. Novel emerging biopolymers as well as cutting-edge polymeric microdevices deployed as implantable antitumor DDSs are discussed. Finally, a review of a new therapeutic modality within the field, which is based on implantable biopolymeric DDSs, is given. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Layer-by-layer assembled fluorescent probes in the second near-infrared window for systemic delivery and detection of ovarian cancer

PubMed Central

Dang, Xiangnan; Gu, Li; Qi, Jifa; Correa, Santiago; Zhang, Geran; Belcher, Angela M.; Hammond, Paula T.

2016-01-01

Fluorescence imaging in the second near-infrared window (NIR-II, 1,000–1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes, are constructed into biocompatible nanoparticles using the layer-by-layer (LbL) platform due to its modular and versatile nature. The LbL platform has previously been demonstrated to enable incorporation of diagnostic agents, drugs, and nucleic acids such as siRNA while providing enhanced blood plasma half-life and tumor targeting. This work carries out head-to-head comparisons of currently available NIR-II probes with identical LbL coatings with regard to their biodistribution, pharmacokinetics, and toxicities. Overall, rare-earth-based down-conversion nanoparticles demonstrate optimal biological and optical performance and are evaluated as a diagnostic probe for high-grade serous ovarian cancer, typically diagnosed at late stage. Successful detection of orthotopic ovarian tumors is achieved by in vivo NIR-II imaging and confirmed by ex vivo microscopic imaging. Collectively, these results indicate that LbL-based NIR-II probes can serve as a promising theranostic platform to effectively and noninvasively monitor the progression and treatment of serous ovarian cancer. PMID:27114520

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

NASA Astrophysics Data System (ADS)

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-SS-BEN) capable of intracellular release of BENSpm using thiolytically sensitive dithiobenzyl carbamate linker. Similar activity on SSAT enzyme induction by Lipo-SS-BEN compared with BENSpm free drug verified the success of this prodrug design. Biodegradability of Lipo-SS-BEN contributed to decreased toxicity compared with nondegradable control LipoBEN. However, decreased enhancement of TRAIL activity was observed for Lipo-SS-BEN when compared with BENSpm, indicating that the lipid-related toxicity diminished the synergism. In addition, compared with LipoBEN and DOTAP, decreased transfection efficiency of Lipo-SS-BEN demonstrated instability of Lipo-SS-BEN in extracellular environment. In order to design a dual delivery vector with reduced vector toxicity and improved linker stability, we employed dendritic polyglycerol (PG) as a safe carrier backbone, onto which BENSpm was conjugated through carbamate linkage (PG-BEN). Polymers with norspermine (PG-Nor) shell and amine-terminated PG (PG-NH2) were synthesized as controls. The BENSpm dual vector PG-BEN demonstrated superior gene delivery function, and showed decreased toxicity compared with the control polymers. However, compared with BENSpm, which depleted all natural polyamines, PG-BEN only down-regulated intracellular putrescine levels. In addition, no free BENSpm was detected in PG-BEN treated cells. These results suggested that in order to take full advantage of BENSpm anticancer activity, alternative linker chemistry needs to be further explored. We then incorporated bis(2-hydroxyethyl) disulfide as a self-immolative linker to synthesize polymer prodrugs of BENSpm (DSS-BEN). The proposed mechanism of BENSpm release from DSS-BEN contains two steps: disulfide bond is first cleaved in the reducing intracellular space, then the intermediate further undergoes slow intramolecular cyclization to release free BENSpm. Cell line-dependent BENSpm release after DSS-BEN treatment was observed using HPLC analysis, demonstrating the success of our linker strategy. DSS-BEN showed comparable transfection efficiency as polyethylenimine and showed decreased toxicity in several cell lines compared with the nondegradable control DCC-BEN. We further demonstrated that DSS-BEN could act synergistically with several therapeutic agents, making it a promising delivery platform for combination therapy in cancer. In all, we have successfully developed a dual delivery vector based on BENSpm, which fulfills its function as a gene delivery vector as well as a prodrug of BENSpm, and possesses synergistic potential to augment the effect of the co-delivered agents.

In situ monitoring of intracellular controlled drug release from mesoporous silica nanoparticles coated with pH-responsive charge-reversal polymer.

PubMed

Zhang, Peng; Wu, Tong; Kong, Ji-Lie

2014-10-22

Therapeutic platforms such as chemotherapy that respond to physical and biological stimuli are highly desirable for effective cancer therapy. In this study, pH-responsive charge-reversal, polymer-coated mesoporous silica nanoparticles [PAH-cit/APTES-MSNs; PAH-cit refers to poly(allylamine)-citraconic anhydride; APTES refers to (3-aminopropyl)triethoxysilane] were synthesized for application as drug-delivery systems for the treatment of malignant cells. Confocal laser scanning microscopy (CLSM) revealed that the PAH-cit/APTES-MSNs nanocomposite effectively delivered and released doxorubicin hydrochloride to the nucleus of HeLa (human cervical carcinoma) cells. Additionally, the real-time dynamic drug-release process was monitored by CLSM. The current pH-controlled-smart-release platform holds promise in drug-delivery and cancer therapy-related applications.

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications.

PubMed

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

To address the limitations of traditional drug delivery, TiO 2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future.

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

PubMed Central

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

2017-01-01

To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. PMID:28053530

The Science of a Sundae: Using the Principle of Colligative Properties in Food Science Outreach Activities for Middle and High School Students

ERIC Educational Resources Information Center

Wickware, Carmen L.; Day, Charles T.C.; Adams, Michael; Orta-Ramirez, Alicia; Snyder, Abigail B.

2017-01-01

The opportunities for outreach activities for professionals and academics in food science are extensive, as too are the range of participants' experience levels and platforms for delivery. Here, we present a set of activities that are readily adaptable for a range of students (ages 10 to 18) in multiple platforms (demonstration table and hands-on…

Hermes: Seamless delivery of containerized bioinformatics workflows in hybrid cloud (HTC) environments

NASA Astrophysics Data System (ADS)

Kintsakis, Athanassios M.; Psomopoulos, Fotis E.; Symeonidis, Andreas L.; Mitkas, Pericles A.

Hermes introduces a new "describe once, run anywhere" paradigm for the execution of bioinformatics workflows in hybrid cloud environments. It combines the traditional features of parallelization-enabled workflow management systems and of distributed computing platforms in a container-based approach. It offers seamless deployment, overcoming the burden of setting up and configuring the software and network requirements. Most importantly, Hermes fosters the reproducibility of scientific workflows by supporting standardization of the software execution environment, thus leading to consistent scientific workflow results and accelerating scientific output.

Carbon Nanotube Arrays for Intracellular Delivery and Biological Applications

NASA Astrophysics Data System (ADS)

Golshadi, Masoud

Introducing nucleic acids into mammalian cells is a crucial step to elucidate biochemical pathways, modify gene expression in immortalized cells, primary cells, and stem cells, and intoduces new approaches for clinical diagnostics and therapeutics. Current gene transfer technologies, including lipofection, electroporation, and viral delivery, have enabled break-through advances in basic and translational science to enable derivation and programming of embryonic stem cells, advanced gene editing using CRISPR (Clustered regularly interspaced short palindromic repeats), and development of targeted anti-tumor therapy using chimeric antigen receptors in T-cells (CAR-T). Despite these successes, current transfection technologies are time consuming and limited by the inefficient introduction of test molecules into large populations of target cells, and the cytotoxicity of the techniques. Moreover, many cell types cannot be consistently transfected by lipofection or electroporation (stem cells, T-cells) and viral delivery has limitations to the size of experimental DNA that can be packaged. In this dissertation, a novel coverslip-like platform consisting of an array of aligned hollow carbon nanotubes (CNTs) embedded in a sacrificial template is developed that enhances gene transfer capabilities, including high efficiency, low toxicity, in an expanded range of target cells, with the potential to transfer mixed combinations of protein and nucleic acids. The CNT array devices are fabricated by a scalable template-based manufacturing method using commercially available membranes, eliminating the need for nano-assembly. High efficient transfection has been demonstrated by delivering various cargos (nanoparticles, dye and plasmid DNA) into populations of cells, achieving 85% efficiency of plasmid DNA delivery into immortalized cells. Moreover, the CNT-mediated transfection of stem cells shows 3 times higher efficiency compared to current lipofection methods. Evaluating the cell-CNT interaction elucidates the importance of the geometrical properties of CNT arrays (CNT exposed length and surface morphology) on transfection efficiency. The results indicate that densely-packed and shortly-exposed CNT arrays with planar surface will enhance gene delivery using this new platform. This technology offers a significant increase in efficiency and cell viability, along with the ease of use compared to current standard methods, which demonstrates its potential to accelerate the development of new cell models to study intractable diseases, decoding the signaling pathways, and drug discovery.

Generation of Multiple Metadata Formats from a Geospatial Data Repository

NASA Astrophysics Data System (ADS)

Hudspeth, W. B.; Benedict, K. K.; Scott, S.

2012-12-01

The Earth Data Analysis Center (EDAC) at the University of New Mexico is partnering with the CYBERShARE and Environmental Health Group from the Center for Environmental Resource Management (CERM), located at the University of Texas, El Paso (UTEP), the Biodiversity Institute at the University of Kansas (KU), and the New Mexico Geo- Epidemiology Research Network (GERN) to provide a technical infrastructure that enables investigation of a variety of climate-driven human/environmental systems. Two significant goals of this NASA-funded project are: a) to increase the use of NASA Earth observational data at EDAC by various modeling communities through enabling better discovery, access, and use of relevant information, and b) to expose these communities to the benefits of provenance for improving understanding and usability of heterogeneous data sources and derived model products. To realize these goals, EDAC has leveraged the core capabilities of its Geographic Storage, Transformation, and Retrieval Engine (Gstore) platform, developed with support of the NSF EPSCoR Program. The Gstore geospatial services platform provides general purpose web services based upon the REST service model, and is capable of data discovery, access, and publication functions, metadata delivery functions, data transformation, and auto-generated OGC services for those data products that can support those services. Central to the NASA ACCESS project is the delivery of geospatial metadata in a variety of formats, including ISO 19115-2/19139, FGDC CSDGM, and the Proof Markup Language (PML). This presentation details the extraction and persistence of relevant metadata in the Gstore data store, and their transformation into multiple metadata formats that are increasingly utilized by the geospatial community to document not only core library catalog elements (e.g. title, abstract, publication data, geographic extent, projection information, and database elements), but also the processing steps used to generate derived modeling products. In particular, we discuss the generation and service delivery of provenance, or trace of data sources and analytical methods used in a scientific analysis, for archived data. We discuss the workflows developed by EDAC to capture end-to-end provenance, the storage model for those data in a delivery format independent data structure, and delivery of PML, ISO, and FGDC documents to clients requesting those products.

Cellphone-based devices for bioanalytical sciences

PubMed Central

Vashist, Sandeep Kumar; Mudanyali, Onur; Schneider, E.Marion; Zengerle, Roland; Ozcan, Aydogan

2014-01-01

During the last decade, there has been a rapidly growing trend toward the use of cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have been used for digital microscopy, cytometry, read-out of immunoassays and lateral flow tests, electrochemical and surface plasmon resonance based bio-sensing, colorimetric detection and healthcare monitoring, among others. Cellphone can be considered as one of the most prospective devices for the development of next-generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare delivery and personalized medicine. With more than 6.5 billion cellphone subscribers worldwide and approximately 1.6 billion new devices being sold each year, cellphone technology is also creating new business and research opportunities. Many cellphone-based devices, such as those targeted for diabetic management, weight management, monitoring of blood pressure and pulse rate, have already become commercially-available in recent years. In addition to such monitoring platforms, several other CBDs are also being introduced, targeting e.g., microscopic imaging and sensing applications for medical diagnostics using novel computational algorithms and components already embedded on cellphones. This manuscript aims to review these recent developments in CBDs for bioanalytical sciences along with some of the challenges involved and the future opportunities. PMID:24287630

From volume to value? Can a value-based approach help deliver the ambitious aims of the NHS cardiovascular disease outcomes strategy?

PubMed

Dunbar-Rees, Rupert; Panch, Trishan; Dancy, Mark

2014-06-01

The last year has seen the publication of two papers which will radically shape the future organisation of healthcare in general, and cardiovascular disease in particular: Cardiovascular Outcomes Strategy (Department of Health) and The Strategy That Will Fix Healthcare (Harvard Business Review). Both publications set out a health delivery mechanism based around improvement of outcomes for groups of patients with similar needs. Instead of organising care around disease categories, it is proposed that the cardiovascular diseases are treated as a single family of diseases. We are reaching the limits of what an activity-based system organised around existing provider structures can sustainably deliver. Unless we find delivery systems which reduce costs while at the same time improving outcomes that are meaningful to patients, then we will be faced with a future of healthcare rationing. The increasing burden of chronic disease and ongoing quality concerns in delivery systems has created a 'burning platform', which must be addressed if we are to maintain a system which offers high-quality care free at the point of delivery. This paper explores what an outcomes and value-based system could look like when applied to cardiovascular disease. It explores what it means for providers and patients if we start to think about outcomes by patients with similar needs, rather than by intervention, or by clinical specialty. As a specific example, the paper explores the features of an Integrated Circulation Service, what the challenges and implications might be, and whether there is any evidence that this would deliver improved outcomes, at a lower cost to the system.

Analysis of outcomes in radiation oncology: An integrated computational platform

PubMed Central

Liu, Dezhi; Ajlouni, Munther; Jin, Jian-Yue; Ryu, Samuel; Siddiqui, Farzan; Patel, Anushka; Movsas, Benjamin; Chetty, Indrin J.

2009-01-01

Radiotherapy research and outcome analyses are essential for evaluating new methods of radiation delivery and for assessing the benefits of a given technology on locoregional control and overall survival. In this article, a computational platform is presented to facilitate radiotherapy research and outcome studies in radiation oncology. This computational platform consists of (1) an infrastructural database that stores patient diagnosis, IMRT treatment details, and follow-up information, (2) an interface tool that is used to import and export IMRT plans in DICOM RT and AAPM/RTOG formats from a wide range of planning systems to facilitate reproducible research, (3) a graphical data analysis and programming tool that visualizes all aspects of an IMRT plan including dose, contour, and image data to aid the analysis of treatment plans, and (4) a software package that calculates radiobiological models to evaluate IMRT treatment plans. Given the limited number of general-purpose computational environments for radiotherapy research and outcome studies, this computational platform represents a powerful and convenient tool that is well suited for analyzing dose distributions biologically and correlating them with the delivered radiation dose distributions and other patient-related clinical factors. In addition the database is web-based and accessible by multiple users, facilitating its convenient application and use. PMID:19544785

An organophosphonate strategy for functionalizing silicon photonic biosensors

PubMed Central

Shang, Jing; Cheng, Fang; Dubey, Manish; Kaplan, Justin M.; Rawal, Meghana; Jiang, Xi; Newburg, David S.; Sullivan, Philip A.; Andrade, Rodrigo B.; Ratner, Daniel M.

2012-01-01

Silicon photonic microring resonators have established their potential for label-free and low-cost biosensing applications. However, the long-term performance of this optical sensing platform requires robust surface modification and biofunctionalization. Herein, we demonstrate a conjugation strategy based on an organophosphonate surface coating and vinyl sulfone linker to biofunctionalize silicon resonators for biomolecular sensing. To validate this method, a series of glycans, including carbohydrates and glycoconjugates, were immobilized on divinyl sulfone (DVS)/organophosphonate-modified microrings and used to characterize carbohydrate-protein and norovirus particle interactions. This biofunctional platform was able to orthogonally detect multiple specific carbohydrate-protein interactions simultaneously. Additionally, the platform was capable of reproducible binding after multiple regenerations by high-salt, high-pH or low-pH solutions and after 1-month storage in ambient conditions. This remarkable stability and durability of the organophosphonate immobilization strategy will facilitate the application of silicon microring resonators in various sensing conditions, prolong their lifetime, and minimize the cost for storage and delivery; these characteristics are requisite for developing biosensors for point-of-care and distributed diagnostics and other biomedical applications. In addition, the platform demonstrated its ability to characterize carbohydrate-mediated host-virus interactions, providing a facile method for discovering new anti-viral agents to prevent infectious disease. PMID:22220731

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines nears the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be delivered to the VAB, where they will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines backs up inside the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines backs in to the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines arrives inside the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines arrives at the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

New service platforms for NASA's Space Launch System booster engines, secured on two flatbed trucks, are on their way to the agency's Kennedy Space Center in Florida. They are being transported from fabricator Met-Con Inc. in Cocoa, Florida. The platforms will be delivered to the Vehicle Assembly Building, where they will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

One of two new work platforms for NASA's Space Launch System booster engines is secured on dunnage inside the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

Research priorities for adolescent health in low- and middle-income countries: A mixed-methods synthesis of two separate exercises

PubMed Central

Nagata, Jason M; Hathi, Sejal; Ferguson, B Jane; Hindin, Michele J; Yoshida, Sachiyo; Ross, David A

2018-01-01

Background In order to clarify priorities and stimulate research in adolescent health in low- and middle-income countries (LMICs), the World Health Organization (WHO) conducted two priority-setting exercises based on the Child Health and Nutrition Research Initiative (CHNRI) methodology related to 1) adolescent sexual and reproductive health and 2) eight areas of adolescent health including communicable diseases prevention and management, injuries and violence, mental health, non-communicable diseases management, nutrition, physical activity, substance use, and health policy. Although the CHNRI methodology has been utilized in over 50 separate research priority setting exercises, none have qualitatively synthesized the ultimate findings across studies. The purpose of this study was to conduct a mixed-method synthesis of two research priority-setting exercises for adolescent health in LMICs based on the CHNRI methodology and to situate the priority questions within the current global health agenda. Methods All of the 116 top-ranked questions presented in each exercise were analyzed by two independent reviewers. Word clouds were generated based on keywords from the top-ranked questions. Questions were coded and content analysis was conducted based on type of delivery platform, vulnerable populations, and the Survive, Thrive, and Transform framework from the United Nations Global Strategy for Women’s, Children’s, and Adolescents’ Health, 2016-2030. Findings Within the 53 top-ranked intervention-related questions that specified a delivery platform, the platforms specified were schools (n = 17), primary care (n = 12), community (n = 11), parenting (n = 6), virtual media (n = 5), and peers (n = 2). Twenty questions specifically focused on vulnerable adolescents, including those living with HIV, tuberculosis, mental illness, or neurodevelopmental disorders; victims of gender-based violence; refugees; young persons who inject drugs; sex workers; slum dwellers; out-of-school youth; and youth in armed conflict. A majority of the top-ranked questions (108/116) aligned with one or a combination of the Survive (n = 39), Thrive (n = 67), and Transform (n = 28) agendas. Conclusions This study advances the CHNRI methodology by conducting the first mixed-methods synthesis of multiple research priority-setting exercises by analyzing keywords (using word clouds) and themes (using content analysis). PMID:29497507

An Augmented SMS Intervention to Improve Access to Antenatal CD4 Testing and ART Initiation in HIV-Infected Pregnant Women: A Cluster Randomized Trial

PubMed Central

Dryden-Peterson, Scott; Bennett, Kara; Hughes, Michael D.; Veres, Adrian; John, Oaitse; Pradhananga, Rosina; Boyer, Matthew; Brown, Carolyn; Sakyi, Bright; van Widenfelt, Erik; Keapoletswe, Koona; Mine, Madisa; Moyo, Sikhulile; Asmelash, Aida; Siedner, Mark; Mmalane, Mompati; Shapiro, Roger L.; Lockman, Shahin

2015-01-01

Background Less than one-third of HIV-infected pregnant women eligible for combination antiretroviral therapy (ART) globally initiate treatment prior to delivery, with lack of access to timely CD4 results being a principal barrier. We evaluated the effectiveness of an SMS-based intervention to improve access to timely antenatal ART. Methods We conducted a stepped-wedge cluster randomized trial of a low-cost programmatic intervention in 20 antenatal clinics in Gaborone, Botswana. From July 2011-April 2012, 2 clinics were randomly selected every 4 weeks to receive an ongoing clinic-based educational intervention to improve CD4 collection and to receive CD4 results via an automated SMS platform with active patient tracing. CD4 testing before 26 weeks gestation and ART initiation before 30 weeks gestation were assessed. Results Three-hundred-sixty-six ART-naïve women were included, 189 registering for antenatal care under Intervention and 177 under Usual Care periods. Of CD4-eligible women, 100 (59.2%) women under Intervention and 79 (50.6%) women under Usual Care completed CD4 phlebotomy before 26 weeks gestation, adjusted odds ratio (aOR, adjusted for time that a clinic initiated Intervention) 0.87 (95% confidence interval [CI]0.47–1.63, P = 0.67). The SMS-based platform reduced time to clinic receipt of CD4 test result from median of 16 to 6 days (P<0.001), was appreciated by clinic staff, and was associated with reduced operational cost. However, rates of ART initiation remained low, with 56 (36.4%) women registering under Intervention versus 37 (24.2%) women under Usual Care initiating ART prior to 30 weeks gestation, aOR 1.06 (95%CI 0.53–2.13, P = 0.87). Conclusions The augmented SMS-based intervention delivered CD4 results more rapidly and efficiently, and this type of SMS-based results delivery platform may be useful for a variety of tests and settings. However, the intervention did not appear to improve access to timely antenatal CD4 testing or ART initiation, as obstacles other than CD4 impeded ART initiation during pregnancy. PMID:25693050

A novel platform designed by Au core/inorganic shell structure conjugated onto MTX/LDH for chemo-photothermal therapy.

PubMed

Tian, De-Ying; Wang, Wei-Yuan; Li, Shu-Ping; Li, Xiao-Dong; Sha, Zhao-Lin

2016-05-30

A novel platform making up of methotrexate intercalated layered double hydroxide (MTX/LDH) hybrid doped with gold nanoparticles (NPs) may have great potential both in chemo-photothermal therapy and the simultaneous drug delivery. In this paper, a promising platform of Au@PDDA-MTX/LDH was developed for anti-tumor drug delivery and synergistic therapy. Firstly, Au NPs were coated using Layer-by-Layer (LbL) technology by alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and MTX molecules, and then the resulting core-shell structures (named as Au@PDDA-MTX) were directly conjugated onto the surface of MTX/LDH hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Here MTX was used as both the agent for surface modification and the anti-tumor drug for chemotherapy. The platform of Au@PDDA-MTX/LDH NPs not only had a high drug-loading capacity, but also showed excellent colloidal stability and interesting pH-responsive release profile. In vitro drug release studies demonstrated that MTX released from Au@PDDA-MTX/LDH was relatively slow under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. Furthermore, the combined treatment of cancer cells by using Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeted nanomedicine for cancer therapeutics: Towards precision medicine overcoming drug resistance.

PubMed

Bar-Zeev, Maya; Livney, Yoav D; Assaraf, Yehuda G

2017-03-01

Intrinsic anticancer drug resistance appearing prior to chemotherapy as well as acquired resistance due to drug treatment, remain the dominant impediments towards curative cancer therapy. Hence, novel targeted strategies to overcome cancer drug resistance constitute a key aim of cancer research. In this respect, targeted nanomedicine offers innovative therapeutic strategies to overcome the various limitations of conventional chemotherapy, enabling enhanced selectivity, early and more precise cancer diagnosis, individualized treatment as well as overcoming of drug resistance, including multidrug resistance (MDR). Delivery systems based on nanoparticles (NPs) include diverse platforms enabling a plethora of rationally designed therapeutic nanomedicines. Here we review NPs designed to enhance antitumor drug uptake and selective intracellular accumulation using strategies including passive and active targeting, stimuli-responsive drug activation or target-activated release, triggered solely in the cancer cell or in specific organelles, cutting edge theranostic multifunctional NPs delivering drug combinations for synergistic therapy, while facilitating diagnostics, and personalization of therapeutic regimens. In the current paper we review the recent findings of the past four years and discuss the advantages and limitations of the various novel NPs-based drug delivery systems. Special emphasis is put on in vivo study-based evidences supporting significant therapeutic impact in chemoresistant cancers. A future perspective is proposed for further research and development of complex targeted, multi-stage responsive nanomedical drug delivery systems for personalized cancer diagnosis and efficacious therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diffusion phenomena of cells and biomolecules in microfluidic devices.

PubMed

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-09-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules.

Diffusion phenomena of cells and biomolecules in microfluidic devices

PubMed Central

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-01-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules. PMID:26180576

Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy

PubMed Central

2017-01-01

Albumin is the most abundant circulating protein in plasma and has recently emerged as a versatile protein carrier for drug targeting and for improving the pharmacokinetic profile of peptide or protein based drugs. Three drug delivery technologies related to albumin have been developed, which include the coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugating bioactive proteins by albumin fusion technology (AFT), and encapsulation of drugs into albumin nanoparticles. This review article starts with a brief introduction of human serum albumin (HSA), and then summarizes the mainstream chemical strategies of developing HSA binding molecules for coupling with drug molecules. Moreover, we also concisely condense the recent progress of the most important clinical applications of HSA-binding platforms, and specify the current challenges that need to be met for a bright future of HSA-binding. PMID:26771036

Policy 2.0 Platform for Mobile Sensing and Incentivized Targeted Shifts in Mobility Behavior

PubMed Central

Semanjski, Ivana; Lopez Aguirre, Angel Javier; De Mol, Johan; Gautama, Sidharta

2016-01-01

Sustainable mobility and smart mobility management play important roles in achieving smart cities’ goals. In this context we investigate the role of smartphones as mobility behavior sensors and evaluate the responsivity of different attitudinal profiles towards personalized route suggestion incentives delivered via mobile phones. The empirical results are based on mobile sensed data collected from more than 3400 people’s real life over a period of six months. The findings show which user profiles are most likely to accept such incentives and how likely they are to result in more sustainable mode choices. In addition we provide insights into tendencies towards accepting more sustainable route options for different trip purposes and illustrate smart city platform potential (for collection of mobility behavior data and delivery of incentives) as a tool for development of personalized mobility management campaigns and policies. PMID:27399700

Oxygen Nanobubble Tracking by Light Scattering in Single Cells and Tissues.

PubMed

Bhandari, Pushpak; Wang, Xiaolei; Irudayaraj, Joseph

2017-03-28

Oxygen nanobubbles (ONBs) have significant potential in targeted imaging and treatment in cancer diagnosis and therapy. Precise localization and tracking of single ONBs is demonstrated based on hyperspectral dark-field microscope (HSDFM) to image and track single oxygen nanobubbles in single cells. ONBs were proposed as promising contrast-generating imaging agents due to their strong light scattering generated from nonuniformity of refractive index at the interface. With this powerful platform, we have revealed the trajectories and quantities of ONBs in cells, and demonstrated the relation between the size and diffusion coefficient. We have also evaluated the presence of ONBs in the nucleus with respect to an increase in incubation time and have quantified the uptake in single cells in ex vivo tumor tissues. Our results demonstrate that HSDFM can be a versatile platform to detect and measure cellulosic nanoparticles at the single-cell level and to assess the dynamics and trajectories of this delivery system.

Social media and your practice: navigating the surgeon-patient relationship.

PubMed

McLawhorn, Alexander S; De Martino, Ivan; Fehring, Keith A; Sculco, Peter K

2016-12-01

Utilization of social media both in the private and professional arenas has grown rapidly in the last decade. The rise of social media use within health care can be viewed as the Internet-based corollary of the patient-centered care movement, in which patient perspectives and values are central to the delivery of quality care. For orthopedic surgeons and their practices, general-purpose online social networks, such as Facebook and Twitter, are convenient platforms for marketing, providing patient education and generating referrals. Virtual health communities are used less frequently by orthopedic surgeons but provide forums for patient engagement and active surgeon-to-patient communication via blogs and ask-the-doctor platforms. This commentary reviews the current state of social media use in orthopedic practice, with particular emphasis on managing the extension of the surgeon-patient relationship online, including the unique practice risks social media poses, such as privacy concerns, potential liability, and time consumption.

RNA-Targeted Therapeutics.

PubMed

Crooke, Stanley T; Witztum, Joseph L; Bennett, C Frank; Baker, Brenda F

2018-04-03

RNA-targeted therapies represent a platform for drug discovery involving chemically modified oligonucleotides, a wide range of cellular RNAs, and a novel target-binding motif, Watson-Crick base pairing. Numerous hurdles considered by many to be impassable have been overcome. Today, four RNA-targeted therapies are approved for commercial use for indications as diverse as Spinal Muscular Atrophy (SMA) and reduction of low-density lipoprotein cholesterol (LDL-C) and by routes of administration including subcutaneous, intravitreal, and intrathecal delivery. The technology is efficient and supports approaching "undruggable" targets. Three additional agents are progressing through registration, and more are in clinical development, representing several chemical and structural classes. Moreover, progress in understanding the molecular mechanisms by which these drugs work has led to steadily better clinical performance and a wide range of mechanisms that may be exploited for therapeutic purposes. Here we summarize the progress, future challenges, and opportunities for this drug discovery platform. Copyright © 2018 Elsevier Inc. All rights reserved.

Design of a Computer-Adaptive Test to Measure English Literacy and Numeracy in the Singapore Workforce: Considerations, Benefits, and Implications

ERIC Educational Resources Information Center

Jacobsen, Jared; Ackermann, Richard; Eguez, Jane; Ganguli, Debalina; Rickard, Patricia; Taylor, Linda

2011-01-01

A computer adaptive test (CAT) is a delivery methodology that serves the larger goals of the assessment system in which it is embedded. A thorough analysis of the assessment system for which a CAT is being designed is critical to ensure that the delivery platform is appropriate and addresses all relevant complexities. As such, a CAT engine must be…

A Design of a Novel Airborne Aerosol Spectrometer for Remote Sensing Validation

NASA Astrophysics Data System (ADS)

Adler, G. A.; Brock, C. A.; Dube, W. P.; Erdesz, F.; Gordon, T.; Law, D. C.; Manfred, K.; Mason, B. J.; McLaughlin, R. J.; Richardson, M.; Wagner, N. L.; Washenfelder, R. A.; Murphy, D. M.

2016-12-01

Aerosols and their effect on the radiative properties of clouds contribute one of the largest sources of uncertainty to the Earth's energy budget. Many current global assessments, of atmospheric aerosol radiative forcing rely heavily on remote sensing observation; therefore, in situ aircraft and ground-based measurements are essential for validation of remote sensing measurements. Cavity ringdown spectrometers (CRD) measure aerosol extinction and are commonly used to validate remote sensing observations. These instruments have been deployed on aircraft based platforms over the years thus providing the opportunity to measure these properties over large areas in various conditions. However, deployment of the CRD on an aircraft platform has drawbacks. Typically, aircraft based CRDs draw sampled aerosol into a cabin based instrument through long lengths of tubing. This limits the ability of the instrument to measure: 1) Course mode aerosols (e.g. dust) 2) Aerosols at high relative humidity (above 90%) Here we describe the design of a novel aircraft based open path CRD. The open path CRD is intended to be mounted external to the cabin and has no sample tubing for aerosol delivery, thus measuring optical properties of all aerosol at the ambient conditions. However, the design of an open path CRD for operation on a wing-mounted aircraft platform has certain design complexities. The instrument's special design features include 2 CRD channels, 2 airfoils around the open Path CRD and a configuration which could be easily aligned and rigid at the same time. This novel implementation of cavity ringdown spectroscopy will provide a better assessment of the accuracy of remote sensing satellite measurements

Enzymatic- and temperature-sensitive controlled release of ultrasmall superparamagnetic iron oxides (USPIOs)

PubMed Central

2011-01-01

Background Drug and contrast agent delivery systems that achieve controlled release in the presence of enzymatic activity are becoming increasingly important, as enzymatic activity is a hallmark of a wide array of diseases, including cancer and atherosclerosis. Here, we have synthesized clusters of ultrasmall superparamagnetic iron oxides (USPIOs) that sense enzymatic activity for applications in magnetic resonance imaging (MRI). To achieve this goal, we utilize amphiphilic poly(propylene sulfide)-bl-poly(ethylene glycol) (PPS-b-PEG) copolymers, which are known to have excellent properties for smart delivery of drug and siRNA. Results Monodisperse PPS polymers were synthesized by anionic ring opening polymerization of propylene sulfide, and were sequentially reacted with commercially available heterobifunctional PEG reagents and then ssDNA sequences to fashion biofunctional PPS-bl-PEG copolymers. They were then combined with hydrophobic 12 nm USPIO cores in the thin-film hydration method to produce ssDNA-displaying USPIO micelles. Micelle populations displaying complementary ssDNA sequences were mixed to induce crosslinking of the USPIO micelles. By design, these crosslinking sequences contained an EcoRV cleavage site. Treatment of the clusters with EcoRV results in a loss of R2 negative contrast in the system. Further, the USPIO clusters demonstrate temperature sensitivity as evidenced by their reversible dispersion at ~75°C and re-clustering following return to room temperature. Conclusions This work demonstrates proof of concept of an enzymatically-actuatable and thermoresponsive system for dynamic biosensing applications. The platform exhibits controlled release of nanoparticles leading to changes in magnetic relaxation, enabling detection of enzymatic activity. Further, the presented functionalization scheme extends the scope of potential applications for PPS-b-PEG. Combined with previous findings using this polymer platform that demonstrate controlled drug release in oxidative environments, smart theranostic applications combining drug delivery with imaging of platform localization are within reach. The modular design of these USPIO nanoclusters enables future development of platforms for imaging and drug delivery targeted towards proteolytic activity in tumors and in advanced atherosclerotic plaques. PMID:21352596

Adjuvant-Loaded Spiky Gold Nanoparticles for Activation of Innate Immune Cells.

PubMed

Nam, Jutaek; Son, Sejin; Moon, James J

2017-10-01

Gold nanoparticles are versatile carriers for delivery of biomacromolecules. Here, we have developed spiky gold nanoparticles (SGNPs) that can efficiently deliver immunostimulatory agents. Our goal was to develop a platform technology for co-delivery of multiple adjuvant molecules for synergistic stimulation and maturation of innate immune cells. SGNPs were synthesized by a seed-mediated, surfactant-free synthesis method and incorporated with polyinosinic-polycytidylic acid (pIC) and DNA oligonucleotide containing unmethylated CpG motif (CpG) by an electrostatic layer-by-layer approach. Adjuvant-loaded SGNP nano-complexes were examined for their biophysical and biochemical properties and studied for immune activation using bone marrow-derived dendritic cells (BMDCs). We have synthesized SGNPs with branched nano-spikes layered with pIC and/or CpG. Adjuvant-loaded SGNP nano-complexes promoted cellular uptake of the adjuvants. Importantly, we achieved spatio-temporal control over co-delivery of pIC and CpG via SGNPs, which produced synergistic enhancement in cytokine release (IL-6, TNF-α) and upregulation of co-stimulatory markers (CD40, CD80, CD86) in BMDCs, compared with pIC, CpG, or their admixtures. SGNPs serve as a versatile delivery platform that allows flexible and on-demand cargo fabrication for strong activation of innate immune cells.

Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy.

PubMed

Xu, Xiaoding; Wu, Jun; Liu, Yanlan; Saw, Phei Er; Tao, Wei; Yu, Mikyung; Zope, Harshal; Si, Michelle; Victorious, Amanda; Rasmussen, Jonathan; Ayyash, Dana; Farokhzad, Omid C; Shi, Jinjun

2017-03-28

With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular nonliver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery. A library of oligoarginine-functionalized and sharp pH-responsive polymers was synthesized and used for self-assembly with siRNA into NPs with the features of long blood circulation and pH-triggered oligoarginine-mediated endosomal membrane penetration. By further modification with ACUPA, a small molecular ligand specifically recognizing prostate-specific membrane antigen (PSMA) receptor, this envelope-type nanoplatform with multifunctional properties can efficiently target PSMA-expressing PCa cells and silence target gene expression. Systemic delivery of the siRNA NPs can efficiently silence the expression of prohibitin 1 (PHB1), which is upregulated in PCa and other cancers, and significantly inhibit PCa tumor growth. These results suggest that this multifunctional envelope-type nanoplatform could become an effective tool for PCa-specific therapy.

Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

PubMed

Zhang, Yuanyuan; Ang, Chung Yen; Li, Menghuan; Tan, Si Yu; Qu, Qiuyu; Luo, Zhong; Zhao, Yanli

2015-08-19

In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy.

Theragnostics for tumor and plaque angiogenesis with perfluorocarbon nanoemulsions

PubMed Central

Winter, P. M.; Caruthers, S. D.; Hughes, M. S.; Hu, Grace; Schmieder, A. H.; Wickline, S. A.

2011-01-01

Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomical descriptions to complicated phenotypic characterizations based upon the recognition of unique cell-surface biochemical signatures. Although originally the purview of nuclear medicine, “molecular imaging” is now studied in conjunction with all clinically relevant imaging modalities. Of the myriad of particles that have emerged as prospective candidates for clinical translation, perfluorocarbon nanoparticles offer great potential for combining targeted imaging with drug delivery, much like the “magic bullet” envisioned by Paul Ehrlich 100 years ago. Perfluorocarbon nanoparticles, once studied in Phase III clinical trials as blood substitutes, have found new life for molecular imaging and drug delivery. The particles have been adapted for use with all clinically relevant modalities and for targeted drug delivery. In particular, their intravascular constraint due to particle size provides a distinct advantage for angiogenesis imaging and antiangiogenesis therapy. As perfluorocarbon nanoparticles have recently entered Phase I clinical study, this review provides a timely focus on the development of this platform technology and its application for angiogenesis-related pathologies. PMID:20411320

Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

NASA Astrophysics Data System (ADS)

Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

2016-09-01

Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

Targeted intracellular delivery of proteins with spatial and temporal control.

PubMed

Morales, Demosthenes P; Braun, Gary B; Pallaoro, Alessia; Chen, Renwei; Huang, Xiao; Zasadzinski, Joseph A; Reich, Norbert O

2015-02-02

While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.

Lipid Raft-Mediated Membrane Tethering and Delivery of Hydrophobic Cargos from Liquid Crystal-Based Nanocarriers.

PubMed

Nag, Okhil K; Naciri, Jawad; Oh, Eunkeu; Spillmann, Christopher M; Delehanty, James B

2016-04-20

A main goal of bionanotechnology and nanoparticle (NP)-mediated drug delivery (NMDD) continues to be the development of novel biomaterials that can controllably modulate the activity of the NP-associated therapeutic cargo. One of the desired subcellular locations for targeted delivery in NMDD is the plasma membrane. However, the controlled delivery of hydrophobic cargos to the membrane bilayer poses significant challenges including cargo precipitation and lack of specificity. Here, we employ a liquid crystal NP (LCNP)-based delivery system for the controlled partitioning of a model dye cargo from within the NP core into the plasma membrane bilayer. During synthesis of the NPs, the water-insoluble model dye cargo, 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), was efficiently incorporated into the hydrophobic LCNP core as confirmed by multiple spectroscopic analyses. Conjugation of a PEGylated cholesterol derivative to the NP surface (DiO-LCNP-PEG-Chol) facilitated the localization of the dye-loaded NPs to lipid raft microdomains in the plasma membrane in HEK 293T/17 cell. Analysis of DiO cellular internalization kinetics revealed that when delivered as a LCNP-PEG-Chol NP, the half-life of DiO membrane residence time (30 min) was twice that of free DiO (DiO(free)) (15 min) delivered from bulk solution. Time-resolved laser scanning confocal microscopy was employed to visualize the passive efflux of DiO from the LCNP core and its insertion into the plasma membrane bilayer as confirmed by Förster resonance energy transfer (FRET) imaging. Finally, the delivery of DiO as a LCNP-PEG-Chol complex resulted in the attenuation of its cytotoxicity; the NP form of DiO exhibited ∼30-40% less toxicity compared to DiO(free). Our data demonstrate the utility of the LCNP platform as an efficient vehicle for the combined membrane-targeted delivery and physicochemical modulation of molecular cargos using lipid raft-mediated tethering.

Impact of service provision platforms on maternal and newborn health in conflict areas and their acceptability in Pakistan: a systematic review.

PubMed

Lassi, Zohra S; Aftab, Wafa; Ariff, Shabina; Kumar, Rohail; Hussain, Imtiaz; Musavi, Nabiha B; Memon, Zahid; Soofi, Sajid B; Bhutta, Zulfiqar A

2015-01-01

Various models and strategies have been implemented over the years in different parts of the world to improve maternal and newborn health (MNH) in conflict affected areas. These strategies are based on specific needs and acceptability of local communities. This paper has undertaken a systematic review of global and local (Pakistan) information from conflict areas on platforms of health service provision in the last 10 years and information on acceptability from local stakeholders on effective models of service delivery; and drafted key recommendations for improving coverage of health services in conflict affected areas. The literature search revealed ten studies that described MNH service delivery platforms. The results from the systematic review showed that with utilisation of community outreach services, the greatest impacts were observed in skilled birth attendance and antenatal consultation rates. Facility level services, on the other hand, showed that labour room services for an internally displaced population (IDP) improved antenatal care coverage, contraceptive prevalence rate and maternal mortality. Consultative meetings and discussions conducted in Quetta and Peshawar (capitals of conflict affected provinces) with relevant stakeholders revealed that no systematic models of MNH service delivery, especially tailored for conflict areas, are available. During conflict, even previously available services and infrastructure suffered due to various barriers specific to times of conflict and unrest. A number of barriers that hinder MNH services were discussed. Suggestions for improving MNH services in conflict areas were also laid down by participants. The review identified some important steps that can be undertaken to mitigate the effects of conflict on MNH services, which include: improve provision and access to infrastructure and equipment; development and training of healthcare providers; and advocacy at different levels for free access to healthcare services and for the introduction of the programme model in existing healthcare system. The obligation is enormous, however, for a sustainable programme, it is important to work closely with both the IDP and host community, and collaborating with the government and non-government organisations.

Pieter Cullis' quest for a lipid-based, fusogenic delivery system for nucleic acid therapeutics: success with siRNA so what about mRNA?

PubMed

Tam, Ying K; Madden, Thomas D; Hope, Michael J

2016-11-01

For the best part of 40 years, lipids and membrane fusion have been at the center of Pieter's research. Projects range from the purely academic quest of understanding the roles of lipids in biological membranes, to the translation of this knowledge into the most advanced lipid nanoparticle (LNP) drug delivery systems in clinical trials to-date. Pieter's pioneering work in lipid polymorphism and characterizing the unique properties of unsaturated phospatidyethanolamines (PE), together with the introduction of ionizable, dialkylamino lipids to trigger membrane fusion at acidic pH, provided the foundation on which a new generation of highly potent, well-tolerated LNPs for intravenous delivery of nucleic acid therapeutics has been built. In this contribution to the special edition honoring Pieter's achievements we highlight key research conducted in Pieter's laboratory and at several biotechnology companies, some spun out of his research group, which resulted in the development of a fusogenic delivery system for siRNA therapeutics. Patisiran®, an LNP encapsulating siRNA for hepatic gene silencing, is currently in Phase III clinical trials for treatment of Transthyretin amyloidosis as are several other siRNA products employing this delivery technology. Finally, we describe more recent work in which the platform shows real promise in the rapidly growing new field of mRNA therapeutics.

A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug.

PubMed

Li, Jingwen; Lyv, Zhonglin; Li, Yanli; Liu, Huan; Wang, Jinkui; Zhan, Wenjun; Chen, Hong; Chen, Huabing; Li, Xinming

2015-05-01

Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis

PubMed Central

Fishbein, Ilia; Guerrero, David T.; Alferiev, Ivan S.; Foster, Jonathan B.; Minutolo, Nicholas G.; Chorny, Michael; Mas Monteys, Alejandro; Driesbaugh, Kathryn H.; Nagaswami, Chandrasekaran; Levy, Robert J.

2017-01-01

In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty. PMID:28832561

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

Hydroxyapatite-magnetite-MWCNT nanocomposite as a biocompatible multifunctional drug delivery system for bone tissue engineering.

PubMed

Pistone, Alessandro; Iannazzo, Daniela; Panseri, Silvia; Montesi, Monica; Tampieri, Anna; Galvagno, Signorino

2014-10-24

New magnetic hydroxyapatite-based nanomaterials as bone-specific systems for controlled drug delivery have been synthesized. The synthesized hydroxyapatite, HA, decorated with magnetite nanoparticles by a deposition method (HA/Fe3O4) and the nanocomposite system obtained using magnetic multi-walled carbon nanotubes (HA/MWCNT/Fe3O4) as a filler for HA have been characterized by chemical and morphological analyses, and their biological behavior was investigated. The systems have also been doped with clodronate in order to combine the effect of bone biomineralization induced by hydroxyapatite-based composites with the decrease of osteoclast formation induced by the drug. An analysis of the preosteoclastic RAW264.7 cell proliferation by MTT assay confirmed the high biocompatibility of the three systems. TRAP staining of RAW 264.7 conditioned with sRAKL to induce osteoclastogenesis, cultured in the presence of the systems doped and undoped with clodronate, showed the inhibitory effect of clodronate after we counted the MNC TRAP(+)cells but only in the osteoclast formation; in particular, the system HA/Fe3O4-Clo exerted a high inhibitory effect compared to the drug alone. These results demonstrate that the synthesized nanocomposites are a biocompatible magnetic drug delivery system and can represent a useful multimodal platform for applications in bone tissue engineering.

Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

NASA Astrophysics Data System (ADS)

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.

Recovery of Drug Delivery Nanoparticles from Human Plasma using an Electrokinetic Platform Technology

PubMed Central

Ibsen, Stuart; Sonnenberg, Avery; Schutt, Carolyn; Mukthavaram, Rajesh; Yeh, Yasan; Ortac, Inanc; Manouchehri, Sareh; Kesari, Santosh; Esener, Sadik

2015-01-01

The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here we present the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. We show this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low density nano-liposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. We believe that this new recovery technique is broadly applicable to the recovery of nanoparticles from high conductance fluids in a wide range of applications. PMID:26274918

Potentiation of an anthrax DNA vaccine with electroporation.

PubMed

Luxembourg, A; Hannaman, D; Nolan, E; Ellefsen, B; Nakamura, G; Chau, L; Tellez, O; Little, S; Bernard, R

2008-09-19

DNA vaccines are a promising method of immunization against biothreats and emerging infections because they are relatively easy to design, manufacture, store and distribute. However, immunization with DNA vaccines using conventional delivery methods often fails to induce consistent, robust immune responses, especially in species larger than the mouse. Intramuscular (i.m.) delivery of a plasmid encoding anthrax toxin protective antigen (PA) using electroporation (EP), a potent DNA delivery method, rapidly induced anti-PA IgG and toxin neutralizing antibodies within 2 weeks following a single immunization in multiple experimental species. The delivery procedure is particularly dose efficient and thus favorable for achieving target levels of response following vaccine administration in humans. These results suggest that EP may be a valuable platform technology for the delivery of DNA vaccines against anthrax and other biothreat agents.

From Lab to Fab: Developing a Nanoscale Delivery Tool for Scalable Nanomanufacturing

NASA Astrophysics Data System (ADS)

Safi, Asmahan A.

The emergence of nanomaterials with unique properties at the nanoscale over the past two decades carries a capacity to impact society and transform or create new industries ranging from nanoelectronics to nanomedicine. However, a gap in nanomanufacturing technologies has prevented the translation of nanomaterial into real-world commercialized products. Bridging this gap requires a paradigm shift in methods for fabricating structured devices with a nanoscale resolution in a repeatable fashion. This thesis explores the new paradigms for fabricating nanoscale structures devices and systems for high throughput high registration applications. We present a robust and scalable nanoscale delivery platform, the Nanofountain Probe (NFP), for parallel direct-write of functional materials. The design and microfabrication of NFP is presented. The new generation addresses the challenges of throughput, resolution and ink replenishment characterizing tip-based nanomanufacturing. To achieve these goals, optimized probe geometry is integrated to the process along with channel sealing and cantilever bending. The capabilities of the newly fabricated probes are demonstrated through two type of delivery: protein nanopatterning and single cell nanoinjection. The broad applications of the NFP for single cell delivery are investigated. An external microfluidic packaging is developed to enable delivery in liquid environment. The system is integrated to a combined atomic force microscope and inverted fluorescence microscope. Intracellular delivery is demonstrated by injecting a fluorescent dextran into Hela cells in vitro while monitoring the injection forces. Such developments enable in vitro cellular delivery for single cell studies and high throughput gene expression. The nanomanufacturing capabilities of NFPs are explored. Nanofabrication of carbon nanotube-based electronics presents all the manufacturing challenges characterizing of assembling nanomaterials precisely onto devices. The presented study combines top-down and bottom-approaches by integrating the catalyst patterning and carbon nanotube growth directly on structures. Large array of iron-rich catalyst are patterned on an substrate for subsequent carbon nanotubes synthesis. The dependence of probe geometry and substrate wetting is assessed by modeling and experimental studies. Finally preliminary results on synthesis of carbon nanotube by catalyst assisted chemical vapor deposition suggest increasing the catalyst yield is critical. Such work will enable high throughput nanomanufacturing of carbon nanotube based devices.

Folate receptor-specific, redox-responsive mesoporous silica nanoparticles for the simultaneous delivery of cisplatin and gemcitabine to treat cancer

NASA Astrophysics Data System (ADS)

Fink, Eric Douglas

Nanoparticles are an innovative platform for cancer treatment that reduces systemic toxicity and allows for active targeting of tumor sites to enhance the therapeutic efficacy. Mesoporous silica nanoparticles (MSNs) have emerged as an attractive drug delivery system due to their high surface area, vast functionalization potential, and biocompatibility. The main goal of this project is to develop a target-specific stimuli-responsive MSN based drug delivery system for the simultaneous delivery of cisplatin and gemcitabine. Both drugs were chemically attached to the MSNs via stimuli-responsive linkers that respond to the high reducing environment and low pH characteristic of cancer cells. The MSN materials fabricated in this work were successfully synthesized and characterized with a wide variety of spectroscopic and microscopic techniques. The loading of cisplatin and gemcitabine and their release profile under high reducing conditions were determined using atomic absorption (AA) and UV-vis spectroscopy, respectively. In vitro toxicity studies were performed on human cervical cancer (HeLa) cells in the presence of different ratios of cisplatin/gemcitabine drugs to determine the best ratio to kill HeLa cells. Based on this data, MSN materials carrying individual drugs and the corresponding combinatorial nanoparticles were fabricated and their in vitro cytotoxicity evaluated in HeLa and pancreatic cancer cells (AsPC1 and BxPC-3). The next step in this project was to further modify with folic acid to enhance its targeting ability toward cancer cells overexpressing folate receptors.

The future of neurotechnology innovation.

PubMed

Lynch, Zack

2009-06-01

Advances across several areas of neurotechnology research including stem cells treatments, new imaging technologies, drug delivery technologies and novel neuromodulation platforms promise to accelerate the development of treatments and cures for brain-related illnesses.

Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration.

PubMed

Yang, Hu; Tyagi, Puneet; Kadam, Rajendra S; Holden, Christopher A; Kompella, Uday B

2012-09-25

We report a novel hybrid polyamidoamine (PAMAM) dendrimer hydrogel/poly(lactic-co-glycolic acid) (PLGA) nanoparticle platform (HDNP) for codelivery of two antiglaucoma drugs, brimonidine and timolol maleate. This platform was not cytotoxic to human corneal epithelial cells. Cellular uptake of Nile red-encapsulating PLGA nanoparticles was significantly increased by dendrimer hydrogel. A prolonged residence time of nanoparticles was demonstrated through investigation of FluoSpheres loaded into dendrimer hydrogel. Both brimonidine and timolol maleate were slowly released in vitro over a period of 28-35 days. Following topical administration of one eye drop (30 μL of 0.7% w/v brimonidine and 3.5% w/v timolol maleate) in normotensive adult Dutch-belted male rabbits, the HDNP formulation resulted in a sustained and effective IOP reduction (18% or higher) for 4 days. Furthermore, the HDNP maintained significantly higher concentrations of brimonidine in aqueous humor and cornea as well as timolol maleate in the aqueous humor, cornea, and conjunctiva up to 7 days as compared to saline, DH, and PLGA nanoparticle dosage forms, without inducing ocular inflammation or discomfort. Histological analysis of the cornea and conjunctiva did not reveal any morphological or structural changes. Our work demonstrated that this new platform is capable of enhancing drug bioavailability and sustaining effective IOP reduction over an extended period of time. This newly developed platform can greatly reduce dosing frequency of topical formulations, thus, improving long-term patient compliance and reducing enormous societal and economic costs. Given its high structural adaptability, many other chronic ocular diseases would benefit from long-lasting drug delivery of this new platform.

Online medical care: the current state of "eVisits" in acute primary care delivery.

PubMed

Hickson, Ryan; Talbert, Jeffery; Thornbury, William C; Perin, Nathan R; Goodin, Amie J

2015-02-01

Online technologies offer the promise of an efficient, improved healthcare system. Patients benefit from increased access to care, physicians are afforded greater flexibility in care delivery, and the health system itself benefits from lower costs to provide such care. One method of incorporating online care into clinical practice, called electronic office visits or "eVisits," allows physicians to provide a consultation with patients online. We performed an analysis of the current published literature on eVisits as well as present emerging research describing the use of mobile platforms as the delivery model. We focused on the role of eVisits in acute primary care practice. A literature review was conducted using electronic databases with a variety of search terms related to the use of eVisits in primary care. Several advantages to eVisit utilization in the primary care setting were identified, namely, improvements in efficiency, continuity of care, quality of care, and access to care. Barriers to eVisit implementation were also identified, including challenges with incorporation into workflow, reimbursement, physician technological literacy, patient health literacy, overuse, security, confidentiality, and integration with existing medical technologies. Only one study of patient satisfaction with eVisit acute primary care services was identified, and this suggests that previous analyses of eVisit utilization are lacking this key component of healthcare service delivery evaluations. The delivery of primary care via eVisits on mobile platforms is still in adolescence, with few methodologically rigorous analyses of outcomes of efficiency, patient health, and satisfaction.

Human transport protein carrier for controlled photoactivation of antitumor prodrug and real-time intracellular tumor imaging.

PubMed

Li, Xi; Mu, Jing; Liu, Fang; Tan, Eddy Wei Ping; Khezri, Bahareh; Webster, Richard D; Yeow, Edwin Kok Lee; Xing, Bengang

2015-05-20

Current anticancer chemotherapy often suffers from poor tumor selectivity and serious drug resistance. Proper vectors for targeted delivery and controlled drug release play crucial roles in improving the therapeutic selectivity to tumor areas and also overcoming the resistance of cancer cells. In this work, we developed a novel human serum albumin (HSA) protein-based nanocarrier system, which combines the photoactivatable Pt(IV) antitumor prodrug for realizing the controlled release and fluorescent light-up probe for evaluations of drug action and efficacy. The constructed Pt(IV)-probe@HSA platform can be locally activated by light irradiation to release the active Pt species, which results in enhanced cell death at both drug-sensitive A2780 and cisplatin-resistant A2780cis cell lines when compared to the free prodrug molecules. Simultaneously, the cytotoxicity caused by light controlled drug release would further lead to the cellular apoptosis and trigger the activation of caspases 3, one crucial protease enzyme in apoptotic process, which could cleave the recognition peptide moiety (DEVD) with a flanking fluorescent resonance energy transfer (FRET) pair containing near-infrared (NIR) fluorophore Cy5 and quencher Qsy21 on the HSA nanocarrier surface. The turn-on fluorescence in response to caspase-3 could be assessed by fluorescence microscopy and flow cytometry analysis. Our results supported the hypothesis that such a unique design may present a successful platform for multiple roles: (i) a biocompatible protein-based nanocarrier for drug delivery, (ii) the controlled drug release with strengthened therapeutic effects, (iii) real-time monitoring of antitumor drug efficacy at the earlier stage.

Electrochemical Detection in Stacked Paper Networks.

PubMed

Liu, Xiyuan; Lillehoj, Peter B

2015-08-01

Paper-based electrochemical biosensors are a promising technology that enables rapid, quantitative measurements on an inexpensive platform. However, the control of liquids in paper networks is generally limited to a single sample delivery step. Here, we propose a simple method to automate the loading and delivery of liquid samples to sensing electrodes on paper networks by stacking multiple layers of paper. Using these stacked paper devices (SPDs), we demonstrate a unique strategy to fully immerse planar electrodes by aqueous liquids via capillary flow. Amperometric measurements of xanthine oxidase revealed that electrochemical sensors on four-layer SPDs generated detection signals up to 75% higher compared with those on single-layer paper devices. Furthermore, measurements could be performed with minimal user involvement and completed within 30 min. Due to its simplicity, enhanced automation, and capability for quantitative measurements, stacked paper electrochemical biosensors can be useful tools for point-of-care testing in resource-limited settings. © 2015 Society for Laboratory Automation and Screening.

MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid-polymer hybrid nanoparticles.

PubMed

Wu, Bo; Lu, Shu-Ting; Deng, Kai; Yu, Hui; Cui, Can; Zhang, Yang; Wu, Ming; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

2017-01-01

In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo.

Current Options and Emerging Biomaterials for Periprosthetic Joint Infection.

PubMed

Levack, Ashley E; Cyphert, Erika L; Bostrom, Mathias P; Hernandez, Christopher J; von Recum, Horst A; Carli, Alberto V

2018-04-30

Infection in the setting of total joint arthroplasty, referred to as periprosthetic joint infection (PJI), is a devastating complication requiring prolonged and costly treatment. The unique environment around an artificial joint and ability of surrounding tissues to sequester bacteria collectively make prevention, diagnosis, and treatment of this condition challenging. In light of the unique pathogenesis of PJI, this review explores the limitations of contemporary treatments and discusses novel treatment options. Recent advancements in local antibiotic delivery platforms for preventing and treating PJI include titanium nanotube arrays, synthetic polymers, resorbable hydrogels, and cyclodextrin-based drug delivery options. In particular, cyclodextrins have facilitated great advancements in other clinical disorders and have demonstrated early promise as a future option in the arena of PJI. Novel treatment modalities for PJI optimize the implant surfaces to prevent bacterial biofilm formation or provide prolonged intra-articular antibiotic dosing to eradicate bacteria.